A novel role of miR-302/367 in reprogramming.
Ever since the technique of coaxing ordinary skin cells into becoming pluripotent stem cells (iPSCs) has been developed, which have the potential to become any cell or tissue in the body, efforts were made to improve the approach because some major challenges. Increasing evidence suggests that several microRNAs (miRNAs) are involved in early embryonic development and embryonic stem cell formation, known as embryonic stem cell (ESC)-specific miRNAs, particularly the miR-302 family. We summarized here a novel approach to generate iPSCs by using miR-302 and its related miRNAs such as miR-367. The development of this miR-302/367-mediated iPSC (termed mirPSC) may provide tools to deal with the obstacles facing some current iPSC reprogramming methods. The mechanism by which miR-302/367 induce iPSC reprogramming is proposed.


Formation of Palladium η2 -Bound Chalcogenoketones across a Pd+ -C- Bond.
A series of chalcogen analogues encompassing a ketone and chalcogenoketones [{PC(=E)P}Pd(PMe3 )] (E=O, S, Se, Te) was generated from a nucleophilic palladium carbene compound, [{PC(sp2 )P}Pd(PMe3 )] ([PC(sp3 )HP]=bis[2-(diisopropylphosphino)-phenyl]methyl, iPr2 P-C6 H4 -CH-C6 H4 -PiPr2 ). The thio-, seleno-, and telluroketone were all synthesized by means of an atom transfer from the respective chalcogens. The ketone analogue, however, required the use of nitrobenzene or nitrosobenzene as the oxygen-atom transfer agent.


Association of herpes simplex virus encephalitis and paraneoplastic encephalitis - a clinico-pathological study.
A 57 year-old woman developed acute limbic encephalitis and brainstem dysfunction. Anti-HU antibodies were repeatedly detected in serum and CSF. Postmortem examination showed necrotic and hemorrhagic lesions in the temporal lobes characteristic of herpes simplex virus encephalitis, which was confirmed by immunocytochemistry, and Purkinje cell loss with proliferation of Bergman glia and myelin loss in the external aspect of the dentate nuclei characteristic of paraneoplastic encephalitis. PCR-assay performed on temporal tissue extracts was positive for HSV-1. There was no identifiable neoplasm. This unusual association raises the possibility of a link between the two diseases.


Continuous separation of cells and particles in microfluidic systems.
The progress in microfabrication and lab-on-a-chip technologies has been a major area of development for new approaches to bioanalytics and integrated concepts for cell biology. Fundamental advances in the development of elastomer based microfluidics have been driving factors for making microfluidic technology available to a larger scientific community in the past years. In line with this, microfluidic separation of cells and particles is currently developing rapidly where key areas of interest are found in designing lab-on-a-chip systems that offer controlled microenvironments for studies of fundamental cell biology. More recently industrial interests are seen in the development of micro chip based flow cytometry technology both for preclinical research and clinical diagnostics. This critical review outlines the most recent developments in microfluidic technology for cell and particle separation in continuous flow based systems. (130 references).


Killer cell immunoglobulin-like receptor genotypes in Japanese patients with type 1 diabetes.
We investigated killer cell immunoglobulin-like receptor (KIR) genotypes in 92 patients with young-onset type 1 diabetes mellitus (YT1DM: < or =35 years old), 112 patients with adult-onset type 1 diabetes mellitus (AT1DM: >35 years old) and 240 control subjects. There were no differences in the frequency of KIR genotypes between controls and all the patients with T1DM or patients grouped according to age at onset of the disorder. However, when the subjects were classified into three groups according to combinations of the presence or absence of KIR3DS1/KIR3DL1 and its ligand human leukocyte antigen (HLA)-Bw4, or KIR2DL1 and its ligand HLA-C group 2, the genotype distribution was significantly different between the patients with AT1DM and controls [chi(2)= 5.993, 2 degrees of freedom (d.f.), P= 0.0500]. These data suggest that KIR polymorphisms may be associated with the age at onset of T1DM.


Competence-induced type VI secretion might foster intestinal colonization by Vibrio cholerae: Intestinal interbacterial killing by competence-induced V. cholerae.
The human pathogen Vibrio cholerae exhibits two distinct lifestyles: one in the aquatic environment where it often associates with chitinous surfaces and the other as the causative agent of the disease cholera. While much of the research on V. cholerae has focused on the host-pathogen interaction, knowledge about the environmental lifestyle of the pathogen remains limited. We recently showed that the polymer chitin, which is extremely abundant in aquatic environments, induces natural competence as a mode of horizontal gene transfer and that this competence regulon also includes the type VI secretion system (T6SS), a molecular killing device. Here, I discuss the putative consequences that chitin-induced T6SS activation could have on intestinal colonization and how the transmission route might influence disease outcome. Moreover, I propose that common infant animal models for cholera might not sufficiently take into account T6SS-mediated interbacterial warfare between V. cholerae and the intestinal microbiota.


Early evaluation of an organised mammography screening program in Greece 2004-2009.
The aim of the current study was to present early performance indicators of a breast cancer screening program in Greece. Between March 2004 and July 2009, 9621 women aged between 40 and 69 years were recruited into programme on a voluntary basis. The participating women were residents of two adjacent administrative regions of Greece. Several performance indicators were calculated for the first and subsequent screen, separately. A total of 9621 mammograms were 1st screens and 4462 were subsequent screens. The attendance rate was almost 1.5%. The technical repeat rate was 1.7%. On the 1st screen, the recall rate was 11.4%, while the recall rate of the subsequent screens was 5.5%. The vast majority of detected cancers were invasive and only the 1/7 of cancers was identified as DCIS. As concerns tumour size of invasive cancers, the 1.9% and 16.7% was unknown, in the first and subsequent screen, respectively. Moreover, 38.5% and 44.4% of cancers detected in the 1st and subsequent screen, respectively, were less than 15 mm in diameter. Almost 1/5 of diagnosed cancers were interval cancers. This breast cancer screening programme is the first one in Greece and the attendance rate is extremely low. Taking into account that an organised screening programme may benefit women with a reduction in breast cancer mortality, there is an urgent need to develop a national-based screening programme, to increase participation and to improve the information system used to monitor programme performance.


The spreading of surfactant solutions on thin liquid films.
The spreading of a surfactant solution on a water film at first glance seems a trivial problem. However, in the last 30 years or so this has been shown to be anything like the case. There have been numerous studies which show that Marongoni driven fingering of the spreading surfactant front exists. In this paper this work has been reviewed and an attempt has been made to rationalise the results. The paper concludes with some recent observations of ours concerning the spreading of sodium dodecyl sulfate over relatively thick water films, 200 microm or less.


Identifying an Oxygenation Index Threshold for Increased Mortality in Acute Respiratory Failure.
The objective of this work was to examine current oxygenation index (OI) data and outcomes using electronic medical record data to identify a specific OI value associated with mortality. This study was a retrospective electronic medical record data review from the pediatric ICU of Phoenix Children's Hospital, with data mining for variables to calculate OIs on subjects age 1 month to 20 y mechanically ventilated > 24 h, excluding those with known intracardiac shunts or cyanotic heart disease. Age, length of hospital stay, duration of mechanical ventilation, and outcomes were also assessed. The Wilcoxon signed-rank test was used to compare continuous variables, receiver operating characteristic analysis was used in determining discriminant ability, and logistic regression was conducted to determine the odds ratio (OR) for risk of death with increasing OI. OI was calculated on 65 subjects, of whom 6 died (9%). The median maximum OI was 10 for all subjects, 17 for non-survivors, and 8 for survivors (P = .14 via Wilcoxon rank-sum test). ORs indicated a 2.4-fold increase in the odds of death (P = .09, 95% CI 0.9-6.6) for each increasing point in maximum OI. Mean OI OR revealed a 1.9-fold increase in the odds of death (P = .25, 95% CI 0.6-5.9). Receiver operating characteristic analysis indicated a higher discriminate ability for maximum OI (area under the curve = 0.68) than mean OI (area under the curve = 0.58). OI cut-points for mortality were established. Mortality was unchanged until maximum OI > 17, for which mortality nearly tripled at a value of 18% versus 6-7% for range 0-17. Limitations exist in obtaining serial OI values from current electronic medical records. Serial assessment of OI values may allow creation of alert values for increased mortality risk. Consideration of escalation of therapies for respiratory failure, such as high-frequency ventilation, inhaled nitric oxide, or extracorporeal membrane oxygenation may be warranted at lower OIs than historically reported.


Chemical modification of polymeric microchip devices.
Analytical polymeric microchips in both fluidic and array formats offer short analysis times, coupling of many sample processing and chemical reaction steps on one platform with minimal sample and reagent consumption, as well as low cost, minimal fabrication times and disposability. However, the invariable bulk properties of most commercial polymers have driven researchers to develop new modification strategies. This article critically reviews the scope and development of chemical modifications of such polymeric chips since 2003. Surface modifications were based on chemical derivatization or activation of surface layers with reagent solutions, reactive gases and irradiation. Bulk modification of polymer chips used newly incorporation of monomers with selective chemical functionalities throughout the bulk polymer material and integrated the chip modification and fabrication into a single step. Such modifications hold a great promise for establishing a true 'lab-on-chip' as can be seen from many novel applications for modulating electroosmosis, suppressing protein adsorption in microchip capillary electrophoretic separations, extraction of analytes and for zone-specific binding of enzymes and other biomolecules.


Association of oral health behaviors and status with depression: results from the Korean National Health and Nutrition Examination Survey, 2010.
To examine the association of depression with oral health behaviors and oral health status in a large nationwide sample of Korean adults. This study included 6,139 participants aged 19 years or older who participated in the fifth Korean National Health and Nutrition Examination Survey. Binary and polychotomous logistic regression analyses were used to estimate adjusted odds ratios (AORs) and 95 percent confidence intervals (CIs). Participants with lifetime depression (self-report of past or present depression) brushed their teeth less frequently (AOR = 1.30, 95 percent CI 1.03-1.65) and were more likely not to receive treatment when experiencing dental problems (AOR = 1.43, 95 percent CI 1.23-1.66) than those without lifetime depression after adjusting for sociodemographic factors, gender, and age. After adjusting for significant oral health behaviors, current smoking status, and sociodemographic factors, participants with lifetime depression had poorer oral health status than those without this disorder: uncomfortable mastication (AOR = 1.25, 95 percent CI 1.05-1.50), toothache (AOR = 1.18, 95 percent CI 1.01-1.39), temporomandibular joint symptoms (AOR = 1.41, 95 percent CI 1.08-1.85), and maxillary periodontal bleeding (AOR = 1.29, 95 percent CI 1.03-1.61 for the right side; AOR = 1.40, 95 percent CI 1.13-1.74 for the left side). Depression was significantly associated with oral health status, even after adjusting for the impact of oral health behaviors in Korean adults. Thus, our findings suggest the necessity of further investigation to detect underlying mechanisms in the relationship between depression and oral health that are not mediated by oral health behavior.


[Primary sleep in vertebrates and its role in the genesis of hypobiosis in poikilotherms and hibernation in mammals].
New data are presented on the homology between winter hibernation and hypobiosis in poikilotherms, as well as one of the resting forms of the primary sleep in vertebrates. Different stages of formation of a cycle "awakefulness-sleep" in evolution of vertebrates are discussed. On the basis of universal behavioural, somato-vegetative, neurophysiological, neurochemical correlates of resting forms, hypobiosis and winter hibernation, a discussion is made of the problem of genetic fixation in the genotype and phenotype of heterothermic mammals (hibernating ones) of those characters which are typical of the sleep in homoiothermic and poikilothermic vertebrates.


A continuous and highly effective static mixing process for antisolvent precipitation of nanoparticles of poorly water-soluble drugs.
Rapid and homogeneous mixing of the solvent and antisolvent is critical to achieve submicron drug particles by antisolvent precipitation technique. This work aims to develop a continuous and highly effective static mixing process for antisolvent precipitation of nanoparticles of poorly water-soluble drugs with spironolactone as a model drug. Continuous antisolvent production of drug nanoparticles was carried out with a SMV DN25 static mixer comprising 6-18 mixing elements. The total flow rate ranged from 1.0 to 3.0 L/min while the flow rate ratio of solvent to antisolvent was maintained at 1:9. It is found that only 6 mixing elements were sufficient to precipitate the particles in the submicron range. Increasing the number of elements would further reduce the precipitated particle size. Increasing flow rate from 1.0 to 3.0 L/min did not further reduce the particle size, while higher drug concentrations led to particle size increase. XRD and SEM results demonstrated that the freshly precipitated drug nanoparticles are in the amorphous state, which would, in presence of the mixture of solvent and antisolvent, change to crystalline form in short time. The lyophilized spironolactone nanoparticles with lactose as lyoprotectant possessed good redispersibility and showed 6.6 and 3.3 times faster dissolution rate than that of lyophilized raw drug formulation in 5 and 10 min, respectively. The developed static mixing process exhibits high potential for continuous and large-scale antisolvent precipitation of submicron drug particles.


An UPLC-MS/MS method for simultaneous determination of multiple constituents in Guizhi Fuling capsule with ultrafast positive/negative ionization switching.
Guizhi Fuling capsule (GFC), a traditional Chinese medicine (TCM) with effects of promoting blood circulation and dissipating blood stasis, has been widely used in the clinic. Because of the complex matrix and various chemical structure types, quality control of GFC remains great challenge. In the present study, an ultra performance liquid chromatography hybrid triple-quadrupole mass spectrometry (UPLC-QQQ MS) method with ultrafast positive/negative ionization switching was developed for simultaneous determination of 18 bioactive components in GFC, including methyl gallate, ethyl gallate, oxypaeoniflorin, benzoic acid, albiflorin, paeonolide, paeoniflorin, 1, 2, 3, 4, 6-pentagalloylglucose, mudanpioside C, benzoyloxypaeoniflorin, benzoylpaeoniflorin, pachymic acid, amygdalin, cinnamaldehyde, paeonol, cinnamic acid, 4-hydroxybenzoic acid, and gallic acid. Separation was performed on an Agilent Zorbax Extend-C18 column (2.1 mm × 50 mm, 1.8 μm), using a gradient elution with acetonitrile and water containing 0.1% formic acid. Cholic acid was selected as the internal standard. This newly developed method was fully validated for linearity, precision, accuracy, and stability, and then applied to quality assessment of GFC. Finally, the batch-to-batch reproducibility of GFC samples was evaluated by the cosine ration and Euclidean distance method, which showed high quality consistency. The results demonstrated that the developed method pro vided a reasonable and powerful manner for quality control of GFC.


Novel developments in non-invasive imaging of peripheral arterial disease with CT: experience with state-of-the-art, ultra-high-resolution CT and subtraction imaging.
Despite advances, challenges remain for less invasive imaging of peripheral arterial occlusive disease (PAOD) using computed tomography (CT) angiography. The application of dual-energy imaging to PAOD has been reported to improve the diagnostic accuracy of this application; however, severe arteriosclerosis with heavy arterial wall calcification still hampers definitive lesion characterisation, especially in distal and smaller arteries. Recently an ultra-high resolution scanner has been introduced. In combination with advances in post-processing, such as subtraction techniques, these developments may overcome some of the current challenges and allow far more detailed characterisation of PAOD non-invasively. The aim of this review is to describe our current experience with ultra-high resolution CT in combination with subtraction and discuss the potential advantages of their application for peripheral angiography.


Effect of source of trace minerals in either forage- or by-product-based diets fed to dairy cows: 2. Apparent absorption and retention of minerals.
Eighteen multiparous cows were used in a split-plot replicated Latin square with two 28-d periods to evaluate the effects of source of supplemental Cu, Zn, and Mn (sulfates or hydroxy) on apparent absorption of minerals when fed in either a forage- or by-product-based diet. The by-product diets were formulated to have greater concentrations of NDF and lesser concentrations of starch, and specific ingredients were chosen because they were good sources of soluble fiber and β-glucans, which bind trace minerals in nonruminants. We hypothesized that hydroxy trace minerals would interact less with digesta and have greater apparent absorption compared with sulfate minerals, and the difference in apparent absorption would be greater for the by-product diet compared with the forage-based diet. During the 56-d experiment, cows remained on the same fiber treatment but source of supplemental trace mineral was different for each 28-d period; thus, all cows were exposed to both mineral treatments. During each period cows were fed no supplemental Cu, Zn, or Mn for 16 d, followed by 12 d of feeding supplemental minerals from either sulfate or hydroxy sources. Supplemental minerals for each of the mineral sources fed provided approximately 10, 35, and 32 mg/kg of supplemental Cu, Zn, and Mn, respectively, for both fiber treatments. Total Cu, Zn, and Mn dietary concentrations, respectively, were approximately 19, 65, and 70 mg/kg for the forage diets and 21, 85, and 79 for the by-product diets. Treatment had no effect on dry matter intake (24.2 kg/d) or milk production (34.9 kg/d). Cows consuming the by-product diets had greater Zn (1,863 vs. 1,453 mg/d) and Mn (1,790 vs. 1,588 mg/d) intake compared with cows fed forage diets, but apparent Zn absorption was similar between treatments. Manganese apparent absorption was greater for the by-product diets compared with the forage diets (16 vs. 11%). A fiber by mineral interaction was observed for Cu apparent absorption, as cows fed hydroxy minerals with forage diets had greater apparent absorption compared with cows fed sulfate minerals; however, the opposite was observed with the by-product diets. Source of supplemental trace minerals and type of fiber in diets affected availability of Cu and Mn and should be considered in ration formulation.


Tuberculosis of patella.
Osteoarticular tuberculosis is rare and affects the knee in about 8% of cases and the patella in less than 0.1%. This study reports a series of five patients who were immunologically competent but living in an endemic area for tuberculosis. Treatment with antituberculous therapy and early mobilization of the knee joint led to a successful outcome in all cases without patellectomy or arthrodesis.


Correlation of contrast-enhanced ultrasonographic features with microvessel density in papillary thyroid carcinomas.
The purpose of this study was to investigate the correlation of contrast-enhanced ultrasonographic (CEUS) features with microvessel density (MVD) in papillary thyroid carcinomas (PTCs). Contrast-enhanced ultrasonography (CEUS) was performed in 62 patients (17 men and 45 women) with PTC. Tomtec software was applied to analyze the time intensity curve of CEUS. Immunohistochemistry was performed to evaluate the level of MVD in papillary thyroid carcinoma. Then the relationship between quantitative feature and the level of MVD was analyzed using SPSS 16.0 software. The mean peak intensity of PTC tissues was lower than that of peripheral thyroid parenchyma (61.9 ± 11.8% vs 100%, p < 0.05). The MVDs of CD34 and CD31 antibodies staining were 38.0 ± 6.1 and 37.9 ± 5.1 respectively in 62 PTC samples. A significantly positive correlation was observed between peak intensity and MVD in PTC tissues (PCD34 < 0.01, rCD34 = 0.838, PCD31 < 0.01, rCD31 = 0.837). The peak intensity in CEUS could reflect the MVD in PTC tissues. Therefore, quantification of CEUS seems to be helpful for assessment of MVD in PTC tissues.


Personal semantics: at the crossroads of semantic and episodic memory.
Declarative memory is usually described as consisting of two systems: semantic and episodic memory. Between these two poles, however, may lie a third entity: personal semantics (PS). PS concerns knowledge of one's past. Although typically assumed to be an aspect of semantic memory, it is essentially absent from existing models of knowledge. Furthermore, like episodic memory (EM), PS is idiosyncratically personal (i.e., not culturally-shared). We show that, depending on how it is operationalized, the neural correlates of PS can look more similar to semantic memory, more similar to EM, or dissimilar to both. We consider three different perspectives to better integrate PS into existing models of declarative memory and suggest experimental strategies for disentangling PS from semantic and episodic memory.


Changes at the glomerulo-tubular junction in renal transplants.
We studied by microscopy 377 biopsies, nephrectomies, and necropsy kidneys from 123 human renal transplants. We discovered two common abnormalities of the renal corpuscle, both affecting the glomerulo-tubular junction. Adhesion of the tip of the glomerular tuft to the origin of the tubule, as reported in various non-transplant glomerulopathies, was seen in 197 specimens (52 per cent). This change was common in material showing acute or chronic vascular rejection and glomerulopathy, and was almost universal in transplants that had been in place for over 1 year. Another change at the glomerulo-tubular junction, not previously highlighted, consisted of an infiltrate of lymphocytes or neutrophil polymorphs into the epithelium at the tubular origin. This change was seen in 145 specimens (38 per cent) and was associated with cellular rejection and ascending infection. These changes are of importance because they show two responses of the kidney to injury that involve the glomerulo-tubular junction and thus suggest that this part of the kidney has some specific properties that have been largely neglected up to now.


Incidence and significance of neutralizing antibodies to interferon beta-1a in multiple sclerosis. Multiple Sclerosis Collaborative Research Group (MSCRG)
Interferon beta is an effective treatment for relapsing multiple sclerosis (MS). As with other protein drugs, neutralizing antibodies (NAB) can develop that reduce the effectiveness of treatment. To determine the incidence and biological significance of NAB to interferon beta-la (IFN-beta-1a; Avonex; Biogen, Cambridge, MA) in MS patients. A two-step assay for NAB to IFN-beta-1a was developed and used to assay serum samples from participants in the phase III clinical trial of IFN-beta-1a, and from patients in an ongoing open-label study of IFN-beta-1a. The biological significance of NAB to IFN-beta-1a was determined by relating the NAB assay result to in vivo induction of the IFN-inducible molecules neopterin and beta-2 microglobulin, and the clinical significance was determined by comparing clinical and MRI measures of disease activity after 2 years of IFN-beta-1a therapy in patients who were NAB+ and NAB-. The incidence of NAB was compared in MS patients who had used only IFN-beta-1a with the incidence in MS patients who had used only IFN-beta-1b. In patients in the open-label study, development of NAB to IFN-beta-1a resulted in a titer-dependent reduction in neopterin induction after interferon injections. In patients in the phase III study, development of NAB was associated with a reduction in beta-2 microglobulin induction. In the phase III study, a trend toward reduced benefit of IFN-beta-1a on MRI activity in NAB+ versus NAB- patients was observed. The incidence of NAB to IFN-beta-1a in the open-label study was approximately 5% over 24 months of treatment of IFN-beta-1a therapy, but was four- to sixfold higher using the same assay for patients exposed only to IFN-beta-1b for a similar duration. There were no clinical, MRI, or CSF characteristics that were predictive of which patients would develop NAB. NAB directed against IFN-beta have in vivo biological consequences in patients with MS. The frequency with which MS patients develop NAB against IFN-beta is significantly greater with IFN-beta-1b therapy compared with IFN-beta-1a therapy. Treatment decisions in MS patients treated with IFN-beta should take into account development of NAB.


Survivors of cardiac arrest: prevention of recurrence by drug therapy as predicted by electrophysiologic testing or electrocardiographic monitoring.
Sixty-two patients (44 men and 18 women, aged 15 to 75 years) resuscitated from at least 1 cardiac arrest unrelated to acute myocardial infarction were studied. No patient was taking antiarrhythmic drugs at the time of the initial cardiac arrest. Thirty-five patients had coronary artery disease (CAD) and 27 did not. Before drug therapy, control electrophysiologic studies induced ventricular tachycardia (VT) in 43 of 58 patients (74%) (30 of 35 with CAD and 17 of 27 without CAD). At control continuous electrocardiographic monitoring for 48 hours or longer, only 19 of 62 patients (31%) had spontaneous VT, 5 of whom had no VT induced at control electrophysiologic study. Mean follow-up was 22 months. Fourteen of 41 patients, 8 of 25 with and 6 of 16 without CAD, had VT suppressed with drugs during serial electrophysiologic testing, and none had a recurrent arrhythmic event. VT was suppressed in 12 of 14 patients receiving conventional drugs. Of 27 patients with VT induced during all drug studies, 6 died from cardiac arrest and 4 had recurrent VT. Drug efficacy in 20 patients was guided by continuous electrocardiographic monitoring, and 4 of 9 patients in whom VT and ventricular pairs were suppressed by drug therapy, as documented by continuous electrocardiographic monitoring for 48 hours or longer, died of cardiac arrest. Overall, 26 patients were discharged receiving amiodarone therapy, and 5 died of cardiac arrest and 3 had recurrent sustained VT.(ABSTRACT TRUNCATED AT 250 WORDS)


Sex steroid concentrations and localization of steroidogenic enzyme expression in free-ranging female northern fur seals (Callorhinus ursinus).
Recent precipitous population declines in northern fur seal (Callorhinus ursinus) and other Alaskan pinniped populations are due in part to reduced fecundity and have emphasized deficits in basic reproductive knowledge of these species. Following estrus and mating, fertilized female pinnipeds experience an obligatory delayed implantation lasting several months and non-pregnant (pseudopregnant) females are indistinguishable by sex steroid levels during this time. The current study examined circulating steroid concentrations and ovarian expression of key steroid-synthesizing enzymes in northern fur seals to identify changes associated with embryonic implantation, data necessary for estimating early pregnancy rates of the population. Blood samples were collected from 84 female fur seals captured on an Alaskan rookery from October 15 to November 30, a period spanning the end of the delay and subsequent uterine implantation of the fertilized blastocyst in this species. Concentrations of progesterone, estradiol, and estrone measured in blood collected during boreal fall were contrasted with samples collected during late summer from post-ovulatory females and males. Serum sex steroids were also related to ovarian expression of key enzymes responsible for androgen (17alpha-hydroxylase/17,20-lyase, cytochrome b5, and 3beta-hydroxysteroid dehydrogenase) and estrogen (aromatase cytochrome P450) synthesis. Enzymes necessary for androgen synthesis were highly expressed in ovaries, and accordingly, endocrine profiles were expanded to include DHEA, androstenediol, androstenedione, and testosterone. Estradiol concentrations were universally low and free and conjugated estrone were the primary circulating estrogens in fur seal sera. No implantation-associated peak was identified for estrogens or progesterone and mean values of progesterone and estrone were actually greater in female serum samples collected during summer than fall. However, there was a significant positive relationship between fall sampling date and testosterone concentration. Additionally, DHEA concentrations in females were lower in samples collected during the implantation period than during the summer embryonic delay. These data suggest androgens may play a substantial regulatory role in the embryonic delay of northern fur seals.


Comparison of SAR in realistic fetus models of two fetal positions exposed to electromagnetic wave from business portable radio close to maternal abdomen.
Since the diversification of the electromagnetic (EM) environment is spreading, it is essential to estimate the EM energy absorption rate [specific absorption rate (SAR)] of a pregnant woman's body and her fetus under various exposure situations. For example, if pregnant women work in jobs where they might wear business portable radios around their abdomens, they should also be concerned about this issue, because the fetuses are in their abdomens. In this paper, in order to evaluate the SAR in the pregnant woman and her fetus when wearing the wireless radio terminal on her abdomen, the SAR distribution in the fetus is calculated using the numerical model of the pregnant woman by exposed to near-field of a normal mode helical antenna (NHA) with a metallic case at 150 MHz. In addition, the SAR in the fetus will be evaluated under two fetal positions. It was found that the fetal SARs are greatly affected by the distance and penetration path from the antenna to the fetal surface. In addition, the fetal SARs are lower than the RF safety guidelines for occupational exposure.


[Surgical interventions on the stomach during a glucagon-induced decrease in its tonus].
Different operations were performed on 15 patients with the Glucagon decreased tonus of the stomach and intestine. The drug was injected in doses 0.2, 0.3 and 0.5 mg. The resulting hypotonia of the stomach and duodenum facilitated performing the operations. No complications were noted.


Screening Tests for Cushing's Syndrome: Urinary Free Cortisol Role Measured by LC-MS/MS.
As initial screening for Cushing's syndrome (CS), The Endocrine Society guidelines recommend one of the following: the 1-mg dexamethasone suppression test (DST) or late-night salivary cortisol (LNSC) or urinary free cortisol (UFC) measurement. We examined the diagnostic performance of the above-mentioned tests in a series of patients. We retrospectively analyzed 137 patients with clinical conditions suggestive of hypercortisolism: 38 with confirmed CS diagnosis and 99 without (termed non-CS). UFC was measured by liquid chromatography tandem-mass spectrometry, whereas LNSC by the radioimmunometric method and serum cortisol were measured by a chemiluminescence immunoassay. Comparing CS vs non-CS, a cutoff of 138 nmol/L after 1-mg DST revealed the best specificity (SP; 97%), whereas the 50-nmol/L cutoff confirmed the best sensitivity (SE; 100%); the SE and SP for LNSC greater than 14.46 nmol/L were, respectively, 84% and 89%, whereas the SE and SP for UFC greater than 170 nmol per 24 hours, they were 97% and 91%. Overall, UFC revealed both a combined higher positive and a lower negative likelihood ratio among first-line tests (respectively 10.7 and 0.03). Computing a receiver-operating curve -contrast analysis to compare the power of each single test with that of the others, alone or combined (DST+LNSC, DST+UFC, and LNSC+UFC) or with that of all the tests together (DST+LNSC+UFC), the UFC assay was at least as good as all the other possible combinations. Measuring UFC by liquid chromatography tandem-mass spectrometry achieves the best accuracy in diagnosing CS among patients presenting with suspected hypercortisolism.


[Transfer of prophage Mu into methylotrophic bacteria in the plasmid RP4].
Bacteriophage Mu genome has been transferred into the cells of Pseudomonas methanolica and Methylobacterium sp. SKF240, that are naturally resistant to the bacteriophage, as a fragment of a hybrid plasmid RP4::Mu cts62. Temperature induction of the bacteriophage results in host cell lysis. Plasmid RP::Mu cis62 is maintained in methylotrophic cells presenting a cointegrative structure. The genetic and electrophoretic, analyses of the DNA isolated from transconjugant cells have confirmed the conclusion. Bacteriophage Mu propagation has been shown to be restricted in methylotrophic cells.


[Foreign body reaction in osteoarthrosis of the trapeziometacarpal joint treated with trapezectomy and interposition of a Dacron "anchovy". A series of 5 cases].
Osteoarthritis of the trapeziometacarpal joint is a common pathology. Numerous surgical procedures exist without any of one of them showing an obvious superiority. In our practice, when the trapezium is not big enough to allow use of a Roseland total joint arthroplasty, we used a combination of trapeziectomy and Dacron anchovy interposition. This simple and fast technique gives results similar to others in terms of pain, joint motion and strength. It appeared to be a safe technique until 2000, where an abnormal complication appeared: five implants (11% of the 46 used between 2000 and 2002) displayed a foreign body reaction both clinical and radiological, and three patients underwent revision surgery for ablation of the implant. Histological analysis confirmed this adverse reaction in all of the cases. In view of the delay between surgery and reaction we expect new cases to appear, thereby increasing the current rate. In view of the lack of any other explanation for these findings, the authors have stopped using the Dacron implant, and have instead reverted to a classical tendon interposition.


Fluoride reduces the rate of dissolution of bone.
Recently, fluoride has been used in the treatment of osteoporosis in an attempt to rebuild bone lost due to this disease. Fluoride has been shown to have a profound effect on osteoblasts and bone formation. Studies have shown that synthetic fluorapatite is more stable and less soluble than hydroxyapatite. This study was designed to determine the dissolution properties of bones from rats fed a normal diet versus rats fed a high fluoride diet. Intact and deproteinized bones were dissolved in buffered solutions, containing physiological amounts of inorganic Ca and P, at pH 3.4, 4.4 and 5.4. The data demonstrate that fluoridated bones dissolve slower than normal bones, deproteinized bones dissolve faster than intact bones and that the initial rate of dissolution of fluoridated bone is always significantly lower than that of normal bone. This may help to explain the reduced rate of osteoclastic resorption in patients undergoing fluoride therapy.


Ectrodactyly in central Africa.
Autosomal dominant ectrodactyly has been identified in several families in remote areas of central Africa. Two groups from eastern Botswana and south-western Zimbabwe belong to the Talaunda tribe and have a common ancestral origin. Another family are members of the Wadoma tribe of north-eastern Zimbabwe. A total of 24 individuals may be affected. Tenuous historical evidence suggests that the Talaunda migrated from the eastern Zambezi region late in the last century and may have the same origins as the Wadoma tribe. On this basis it is likely that the affected people have the same faulty gene, which presumably arose by mutation in a common progenitor.


Development of a loop-mediated isothermal amplification assay for rapid and sensitive detection of ostreid herpesvirus 1 DNA.
A loop-mediated isothermal amplification (LAMP) assay was developed for rapid, specific and sensitive detection of ostreid herpesvirus 1 (OsHV-1) DNA. A set of four primers was designed, based on the sequence of the ATPase subunit of the OsHV-1 DNA-packaging terminase gene. The reaction temperature and time were optimized to 64°C and 60min, respectively. LAMP products were detected by agarose gel electrophoresis or by visual inspection of a color change due to addition of fluorescent dye. The developed method was highly specific for detection of OsHV-1, and no cross-reaction was observed with other DNA viruses, such as White spot syndrome virus (WSSV), Penaeus stylirostris densovirus (PstDNV), Turbot reddish body iridovirus (TRBIV) and Lymphocystis disease virus (LCDV) found commonly in China. The lower detection limit of the LAMP assay was approximately 20 copies per reaction, and it was 100 times more sensitive than that of conventional PCR. A comparative evaluation of 10 oyster samples using LAMP and PCR assays showed overall correlation in positive and negative results for OsHV-1. These results indicate that the LAMP assay is a simple, rapid, sensitive, specific and reliable technique for the detection of OsHV-1. The LAMP technique has capacity for use for the detection of OsHV-1 both in the laboratory and on farms.


The effect of the Jessica grounding on subtidal invertebrate and plant communities at the Galápagos wreck site.
Impacts of the grounding of the oil tanker Jessica off San Cristóbal island, Galápagos, included both effects of oil on biota and also mechanical effects associated with a shallow furrow 50 m x 30 m gouged across the rocky seafloor and wreckage strewn over 7500 m(2). The wreckage represented a minor but potentially chronic source of pollution to the surrounding environment through delayed releases of oil, antifouling compounds and other toxic chemicals, and a possible source of exotic marine taxa. Investigation at the wreck site indicated that impacts on subtidal plant and macro-invertebrate communities were largely confined within 100 m of the wreck site itself. Observed population effects included significant increases in cover of opportunistic algae (filamentous green algae, filamentous red algae and Ulva sp.) and the hydroid Ectopleura media adjacent to the wreck, while densities of the green sea urchin Lytechinus semituberculatus significantly decreased from 0.3 m(-2) adjacent to the wreck to 11 m(-2) at 100 m distance.


A Randomized Trial to Evaluate the Effect of Two Topical Anesthetics on Pain Response During Frenotomy in Young Infants.
To examine the comparative effectiveness of two topical anesthetics in controlling the pain associated with tongue-tie release (frenotomy) in young infants. Randomized trial. A Pediatric Craniofacial Clinic. Forty-two infants who were referred for frenotomy were randomly allocated to receive the topical anesthetic gel 2% tetracaine or 20% benzocaine applied prior to frenotomy. Frenotomies were videotaped. The primary outcome measure was the Neonatal Facial Coding System (NFCS) score. Secondary outcome measures included cry duration and a visual analog scale (VAS) assessed by the parents. The two groups were comparable with regard to weight, age, gender, previous painful experience, and last feeding time. Median NFCS scores prior to frenotomy in the tetracaine and the benzocaine groups were 4.5 (IQR: 0.75–10.2) and 3.5 (IQR: 0–9.5), respectively (P = 0.89, 95% CI −3 to 4). During frenotomy, median NFCS score increased to 28 (IQR: 24.5–30.25) in the tetracaine group (P < 0.0001, median difference −22, 95% CI −24.5 to −19), and to 28 (IQR: 26–30) in the benzocaine group (P < 0.0001, median difference −23, 95% CI −27 to −17). Mean cry durations in the tetracaine and the benzocaine groups were 69.4 seconds and 63.9 seconds, respectively (P = 0.32, 95% CI −47 to 15), and mean VAS scores were 57.2 and 58.2, respectively (P = 0.89, 95% CI −15.2 to 13.4). These topical anesthetics seem ineffective in controlling the pain associated with frenotomy. Clinicians should continue to search for an effective treatment for this procedure.


Hyperopia correction by noncontact holmium:YAG laser thermal keratoplasty. Clinical study with two-year follow-up.
Thermal keratoplasty to correct hyperopia has been attempted with nonlaser and laser devices. Problems have included long-term regression and irregular induced astigmatism. The present clinical study was performed to investigate the safety, efficacy, and stability of a noncontact mode of holmium: YAG laser energy delivery and a modified laser thermal keratoplasty treatment procedure for correction of low hyperopia. Seventeen patients underwent noncontact holmium: YAG laser thermal keratoplasty in their nondominant eyes for correction of hyperopia of up to 3.00 diopters. Treatment parameters included simultaneous delivery of eight holmium: YAG laser spots in a symmetrical octagonal array with a centerline diameter of 6mm, 10 pulses of laser light at 5-Hz pulse repetition frequency, and pulse energies of 159 to 199mJ. Follow-up was 2 years in 15 of 17 patients. In the 15 eyes examined at 2 years after surgery, mean uncorrected distance Snellen visual acuity improved from 20/125-1 to 20/50-2. The mean change in spherical equivalent of subjective manifest refraction was -0.79 diopter. Eleven of these 15 eyes (73%) had a mean refractive correction of -1.1 diopters (range, -0.38 to -2.63 diopters); regression between 14 days and 2 years was 0.2 diopter. Four eyes (27%) had no persistent refractive correction (within +/- 0.25 diopter). Mean induced refractive astigmatism was 0.18 diopter. None of the eyes lost two or more lines of spectacle-corrected distance vision. The amount of refractive correction at 2 years after surgery was correlated to the treatment pulse energy and the volume of the opacified corneal tissue observed immediately after treatment. This technique of noncontact laser thermal keratoplasty produced safe, effective, and persistent corrections of low hyperopia in the majority of treated eyes.


Antiinflammatory drug effects on bone repair and remodeling in rabbits.
Ketorolac and methylprednisolone effects on bone repair were studied. Demineralized bone matrix was used to graft the defects of rabbits' ulnae. Twenty-seven rabbits were divided into 4 groups: Group A (control group; no drug treatment), Group B (treated with ketorolac 2 mg/kg body weight daily), Group C (treated with ketorolac 4 mg/kg body weight daily), and Group D (treated with methylprednisolone 1 mg/kg body weight weekly). Drug treatment was continued for 6 weeks. The biomechanical results indicated methylprednisolone significantly deteriorated the mechanical properties of the grafted ulnae and the contralateral intact ulnae, although the effects were more pronounced in the grafted side. In Group B, there was minimum effect of ketorolac on the bone properties. In Group C, ketorolac significantly decreased the torsional stiffness and energy absorption of the grafted ulnae and also decreased the maximum torque in the intact and the grafted bones. It was concluded that the inhibitory effect of ketorolac on bone repair was dose dependent. In comparing the effects of ketorolac and methylprednisolone, the latter is more pronounced on torsional stiffness, but the effects on maximum torque and energy absorption were similar to ketorolac. The mechanism of the effects of ketorolac needs additional investigation.


The evolution of relative trait size and shape: insights from the genitalia of dung beetles.
Insects show relatively little genital variation within species compared to extraordinary and often rapid diversification among species. It has been suggested that selection for reproductive isolation through differences in genital shape might explain this phenomenon. This hypothesis predicts that populations diverge faster in genital shape than in genital size. We tested this prediction in males from 10 dung beetle species with known phylogenetic relationships from the genus Onthophagus (Coleoptera: Scarabaeidae), including four species for which we were able to sample multiple populations. Specifically, we compared intra- and interspecific differentiation in shape and relative sizes of genitalia and calculated their respective evolutionary rates. We compared these rates to two similarly sized non-genital traits, the head and the fore-tibia. We found significant intraspecific variation in genital shape in all four species for which multiple populations were sampled, but for three of them we also identified significant relative size variation. We also found that genital shape evolved at higher rates than relative genital size. Genital shape evolved faster than head shape, but not fore-tibia shape. However, shapes of all measured structures evolved faster than their relative size. We discuss the functional constraints that may bias the developmental evolution of relative size and shape of genitalia and other morphological traits.


Lesions akin to transmissible spongiform encephalopathy in the brains of rats inoculated with immature cerebellum. Their significance in the aetiology of these diseases.
Fourteen BD IX rats were inoculated intracerebrally with a homogenate prepared from the immature cerebellar cortex of 10-day-old rats, when synaptogenesis is at its peak in this species. Eight controls were inoculated with mature cerebellar cortex. Transient ultrastructural changes were observed between 2 and 23 weeks' incubation in those animals which had received an inoculum of immature cerebellum. These changes pointed to a re-activation of embryonic or neo-natal growth mechanisms and were identical to those occurring in kuru-inoculated spider monkeys. With longer incubation histopathological lesions such as intracytoplasmic vacuolation, chromatolysis and neuronophagia appeared in neurons of the brain stem reticular formation. Such features are common in all the spongiform encephalopathies. All controls were negative. It is suggested that the transmissible agent in these diseases might be the factor which influences the various stages of normal neuronal maturation. A hypothesis is developed which would reconcile the "infectious" character of these diseases with a genetic factor and explain the "unconventional" behaviour of the agent as well as the mode of its transmission.


Effects of a fast-track area on emergency department performance.
To determine if a fast-track area (FTA) would improve Emergency Department (ED) performance, a historical cohort study was performed in the ED of a tertiary care adult hospital in the United States. Two 1-year consecutive periods, pre fast track area (FTA) opening-from February 1, 2001 to January 31, 2002 and after FTA opening-from February 1, 2002 to January 31, 2003 were studied. Daily values of the following variables were obtained from the ED patient tracking system: 1) To assess ED effectiveness: waiting time to be seen (WT), length of stay (LOS); 2) To assess ED care quality: rate of patients left without being seen (LWBS), mortality, and revisits; 3) To assess determinants of patient homogeneity between periods: daily census, age, acuity index, admission rate and emergent patient rate. For comparisons, the Wilcoxon test and the Student's t-test were used to analyze the data. Results showed that despite an increase in the daily census (difference [diff] 8.71, 95% confidence interval [CI] 6 to 11.41), FTA was associated with a decrease in WT (diff -51 min, 95% CI [-56 to -46]), LOS (diff -28 min, 95% CI [-31 to -23]) and LWBS (diff -4.06, 95% CI [-4.48 to -3.46]), without change in the rates of mortality or revisits. In conclusion, the opening of a FTA improved ED effectiveness, measured by decreased WT and LOS, without deterioration in the quality of care provided, measured by rates of mortality and revisits.


Oxoquinoline derivatives: identification and structure-activity relationship (SAR) analysis of new anti-HSV-1 agents.
Herpes simplex virus is an important human pathogen responsible for a range of diseases from mild uncomplicated mucocutaneous infections to life-threatening ones. Currently, the emergence of Herpes simplex virus resistant strains increased the need for more effective and less cytotoxic drugs for Herpes treatment. In this work, we synthesized a series of oxoquinoline derivatives and experimentally evaluated the antiviral activity against acyclovir resistant HSV-1 strain as well as their cytotoxity profile. The most active compound (3b), named here as Fluoroxaq-3b, showed a promising profile with a better cytotoxicity profile than acyclovir. The theoretical analysis of the structure-activity relationship of these compounds revealed some stereoelectronic properties such as lower LUMO energy and lipophilicity, besides a higher polar surface area and number of hydrogen bond acceptor groups as important parameters for the antiviral activity. Fluoroxaq-3b showed a good oral theoretical bioavailability, according to Lipinski rule of five, with a promising profile for further in vivo analysis.


Chronic activation of ERK and neurodegenerative diseases.
The extracellular-signal regulated kinases 1/2 (ERK or ERKs) are involved in the regulation of important neuronal functions, including neuronal plasticity in normal and pathological conditions. We present findings that support the notion that the kinetics and localization of ERK are intrinsically linked, in that the duration of ERK activation dictates its subcellular compartmentalization and/or trafficking. The latter, in turn, dictates whether ERK-expressing cells would enter a program of cell death, survival or differentiation. We summarize experimental data showing that chronic activation of ERK plays a role in the mechanisms that trigger neurodegeneration. We also discuss how MKPs, members of the subclass of dual specificity phosphatases, might be the link between ERK kinetics and its subcellular localization.


Effect of hoof trimmer intervention in moderately lame cows on lameness progression and milk yield.
The objective of this study was to evaluate the effect of hoof trimmer intervention (HTI) in moderately lame cows on lameness progression and milk yield. Two freestall Holstein herds were enrolled. Cows were milked 2 (herd A: 2,374 cows) or 3 (herd B: 2,800 cows) times a day. Within each dairy, moderately lame cows [locomotion score (LS) = 3 on a 5-point scale] were randomly assigned to control group (CON; herd A = 66, herd B = 84) or treatment group (HTI; evaluated and treated by the hoof trimmer under researchers' supervision; herd A = 73; herd B = 75). Enrollment criteria were <350 d in milk, <180 d pregnant, >10 kg/d of milk yield, not selected for therapeutic trimming 2 mo before enrollment, and >14 observations of daily milk yield during the study period. Biweekly lameness scoring (LS ≤2, LS = 3, LS ≥4) was conducted up to 6 wk post-intervention. Lesion type and severity records were collected at intervention from HTI cows and up to 6 wk post-intervention from all enrolled cows identified as lame by farm employees. Daily milk yield data were collected from -1 to 6 wk relative to intervention using Afifarm (Afimilk Ltd., Kibbutz Afikim, Israel) records. No treatment effect was detected on the predicted probability of locomotion score, but the predicted probability of LS ≥3 decreased over time in herd B, whereas in herd A, it initially decreased but later increased. A tendency for a treatment by time interaction was observed in herd A; at 2 wk post-intervention, the predicted probability for LS ≥3 was higher for HTI (0.69) than for CON (0.43), but similar at 4 wk (0.41 HTI, 0.49 CON) and 6 wk (0.77 HTI, 0.73 CON). At intervention, most study cows had no lesions (41.2%), sole hemorrhages (28.4%), thin soles (8.8%), or vertical fissure (6.8%). During the 6 wk following intervention, a similar proportion of cows were identified as lame in CON (8.7%) and HTI (6.7%) groups. In herd A, milk yield (least squares means ± standard error) was similar for CON (42.0 ± 0.77 kg/d) and HTI (42.3 ± 0.75 kg/d) cows, whereas in herd B, it tended to be lower for HTI (43.7 ± 0.61 kg/d) than for CON (45.2 ± 0.59 kg/d) cows. A significant effect of time was detected on both dairies, with milk yield decreasing over the study period. In our study, implementing HTI on moderately lame cows resulted in no improvement in gait or milk yield. The low presence of severe lesions amenable to therapy may partially explain our findings.


Dolphin foraging sounds suppress calling and elevate stress hormone levels in a prey species, the Gulf toadfish.
The passive listening hypothesis proposes that dolphins and whales detect acoustic signals emitted by prey, including sound-producing (soniferous) fishes. Previous work showed that bottlenose dolphins (Tursiops truncatus) behaviorally orient toward the sounds of prey, including the advertisement calls of male Gulf toadfish (Opsanus beta). In addition, soniferous fishes constitute over 80% of Tursiops diet, and toadfishes alone account for approximately 13% of the stomach contents of adult bottlenose dolphins. Here, we used both behavioral (vocalizations) and physiological (plasma cortisol levels) parameters to determine if male Gulf toadfish can, in turn, detect the acoustic signals of bottlenose dolphins. Using underwater playbacks to toadfish in their natural environment, we found that low-frequency dolphin sounds (;pops') within the toadfish's range of hearing dramatically reduce toadfish calling rates by 50%. High frequency dolphin sounds (whistles) and low-frequency snapping shrimp pops (ambient control sounds) each had no effect on toadfish calling rates. Predator sound playbacks also had consequences for circulating stress hormones, as cortisol levels were significantly elevated in male toadfish exposed to dolphin pops compared with snapping shrimp pops. These findings lend strong support to the hypothesis that individuals of a prey species modulate communication behavior in the presence of a predator, and also suggest that short-term glucocorticoid elevation is associated with anti-predator behavior.


Mesenchymal cells contribute to the synthesis and deposition of the laminin-5 gamma2 chain in the invasive front of oral squamous cell carcinoma.
Tumour progression in oral squamous cell carcinoma (OSCC) is associated with a reorganisation of extracellular matrix. Laminin-5 (Ln-5) plays an important role for tumour migration and shows an increased expression in areas of direct tumour/stroma interactions. We have previously shown stromal spot like Ln-5/gamma2 chain deposits distant from the basement membrane region. In this study we have analysed which cell type is responsible for Ln-5/gamma2 chain synthesis in situ. Furthermore, we studied its spatial relation to TGF-beta1 as well as the Ln-5 modulating enzymes matrix metalloproteinase (MMP) 2, membrane type-1 (MT1-) MMP and bone morphogenetic protein (BMP-) 1 by different techniques including triple immunofluorescence labelling and in situ hybridisation in OSCC. We found that the stromal spot-like Ln-5 deposits occurred in the invasive front in the vicinity of mesenchymal cells and vessel structures. In particular, not only carcinoma cells but also mesenchymal cells were shown to express the Ln-5/gamma2 chain mRNA. Moreover, stromal Ln-5 deposits showed a spatial association with TGF-beta1 as well as with MT1-MMP and BMP-1. Based on these findings we suggest that mesenchymal cells contribute to the promotion of tumour cell migration as well as vessel formation in OSCC by providing and organising promigratory Ln-5 fragments.


Model assessment of additional contamination of water bodies as a result of wildfires in the Chernobyl exclusion zone.
Forest fires and wild fires are recognized as a possible cause of resuspension and redistribution of radioactive substances when occurring on lands contaminated with such materials, and as such are a matter of concern within the regions of Belarus and the Ukraine which were contaminated by the Chernobyl accident in 1986. Modelling the effects of such fires on radioactive contaminants is a complex matter given the number of variables involved. In this paper, a probabilistic model was developed using empirical data drawn from the Polessie State Radiation-Ecological Reserve (PSRER), Belarus, and the Maximum Entropy Method. Using the model, it was possible to derive estimates of the contribution of fire events to overall variability in the levels of (137)Cs and (239,240)Pu in ground air as well as estimates of the deposition of these radionuclides to specific water bodies within the contaminated areas of Belarus. Results indicate that fire events are potentially significant redistributors of radioactive contaminants within the study area and may result in additional contamination being introduced to water bodies.


Chemical properties of bile acids. V. Interaction with concentrated sulfuric acid.
The reaction between concentrated sulfuric acid and steroid hydroxy compounds, previously studied for a series of sterols, was used to develop an analytical method for bile acids. The reaction generates species absorbing in the wavelength ranges 300-320 and 370-390 nm, corresponding to isomeric allylic and dienylic carbocations. Eleven bile acids were examined and influence of time, temperature and sulfuric acid concentration on the chromogenic reaction was studied. The linear dependence of absorbance on concentration of individual bile acids demonstrates that the method can be used to measure spectrophotometrically micromolar concentrations of bile acids.


Energy, environmental and operation aspects of a SRF-fired fluidized bed waste-to-energy plant.
A methodology based on the ISO 14031:2013 guideline has been developed and applied to a full-scale fluidized bed waste to energy plant (WtE) burning solid recovered fuel (SRF). With reference to 3years of operation, the data on energy and environmental performance, on raw materials consumptions such as sand and diesel fuel, accidental reasons of plant shutdown, have been acquired and analyzed. The obtained results have allowed to quantify the energy and environmental performance of the WtE plant under investigation by varying the amount and mixings of the inlet waste, available in form of thickened and fluff (similar to coriander) SRF. In terms of the energy performance, the fluidized bed technology applied to the SRF was able to guarantee an adequate production of electricity (satisfying the market demands), showing a relative flexibility with respect to the inlet waste. In terms of net energy production efficiency, the plant showed values in the range of 13.8-14.9% in line with similar installations. In terms of the environmental performance, the adoption of a cleaning system based on SNCR (Selective Non Catalitic Reduction)+semi-dry scrubbing+Fabric filter generated emissions usually well below the limits set by the EU Directive 2000/76/EC as well as the Italian Law 46/2014 (more restrictive) with reference to all the key parameters. In terms of the plant shutdown, the majority of problems focused on the combustion chamber and boiler due to the erosion of the refractory material of the furnace as well as to the breaking of the superheaters of the boiler. In contrast, the mechanical and electrical causes, along with those related to the control and instrumentation system, were of secondary importance. The sand bed de-fluidization was also among the leading causes of a frequent plant shutdown. In particular, results showed how although the SRF presents standard characteristics, the use of different mixtures may affect the number of plant shutdowns. The full-scale data highlighted how the lower the rate of fluff in the mixture was, the greater the number of plant shutdown due to sand bed de-fluidization was. Finally, the aspects in terms of the energy, environmental protection and raw material consumption have been discussed with reference to similar WtE plants such as Robbins (Chicago, USA), Lidköping (Sweden), Toshima (Tokyo, Japan), Madrid (Spain), Dundee (Scotland, UK) and Valene (Mantes la Jolie, France).


Intraoperative CO2 insufflation can decrease the risk of surgical site infection.
Surgical wound infections may ruin otherwise successful operations, and are associated with extended hospital stay, extra costs, and high mortality rates. In open surgery the wound's exposure to ambient air increases the risk of wound infection via several independent factors. The open surgical wound is subjected to airborne bacterial contamination, desiccation, and heat loss that increase the bacterial load, cause superficial necrosis, and impair tissue oxygenation and cellular immune functions, respectively. The present hypothesis is that topically applied carbon dioxide in the open surgical wound can be used intraoperatively to avoid these risks, and thus help to prevent postoperative wound infection. We also criticize existing methods and describe the theoretical background and supporting evidence for our suggested method. If the hypothesis would prove to be correct in a clinical trial, the new method may be an effective complement, or even an alternative, to antibiotics in preventing surgical site infection.


Key issues in the photochemistry and signalling-state formation of photosensor proteins.
Four families of photosensors (i.e., rhodopsins, phytochromes, xanthopsins and cryptochromes) exist, which vary widely in the degree to which we understand the molecular basis of their activity. Some of their members are ideal model systems for studying the structure-function relation of proteins, and the role of dynamics therein. The photochemistry of photosensor activation is based upon the cis <--> trans isomerization of the chromophore. This configurational transition leads to the formation of a signalling state of sufficient stability to communicate the presence of photons to a downstream signal-transduction partner. In the xanthopsins it has been demonstrated that the exact nature of this signalling state is strongly dependent on the mesoscopic context of the sensor protein. The cryptochromes appear to challenge the photoisomerization rule.


Freedom of movement vs. exclusion: a reinterpretation of the "insider"-"outsider" divide in the European Union.
"This article argues that the question of free movement vs. exclusion within the European Union (EU) can be addressed satisfactorily only if we move away from the narrow state-centrism inherent in the current debate. What is required is to 'open' the state concept and examine the implications of state-society relations for EU policy making. Once this is done, it can be seen that the exclusionist stance of the immigration policy and the essentially intergovernmental nature of the policy making are due to an implicit contract between states and constituents implied by the concepts of nationality and citizenship. According to this perspective, the focus on the state or the political elite alone is too one-sided and misses the more complex factors bearing upon EU policy making in this area."


Activation and detoxification of bromobenzene in extrahepatic tissues.
Bromobenzene causes hepatic and extrahepatic toxicity in rats. Toxicity is related to the presence of covalently bound material in these tissues. A major bromobenzene metabolite, p-bromophenol, has been shown to give rise to covalently bound material in liver, lung and kidney in vivo, but is not toxic. p-Bromophenol is formed from bromobenzene in liver, lung and kidney microsomes and is subsequently metabolized to 4-bromocatechol and covalently bound material. Bromobenzene-3,4-oxide generated in situ by liver microsomes, is detoxified by kidney, liver and lung cytosol. The results suggest that the kidney toxicity caused by bromobenzene is probably not mediated by either bromobenzene-3,4-oxide or the reactive metabolites of p-bromophenol. In contrast, bromobenzene-3, 4-oxide may play a role in the lung toxicity observed after bromobenzene administration. However, the covalently bound material found in extrahepatic tissues may be derived from both bromobenzene-3,4-oxide or the reactive metabolites of p-bromophenol, which may be formed directly by these tissues or transported there from the liver.


Renal vein thrombosis in a newborn: a case report with emphasis on pathological and radiological features.
A case of renal vein thrombosis in a newborn is presented. Trauma during pregnancy is suggested as an etiological factor. In contradistinction to most cases reported the newborn showed no signs of acute illness except for a palpable abdominal mass. Therefore, surgical intervention was delayed for 10 months but this did not impair the infant's growth and well-being.


Copper corroles are inherently saddled.
X-ray crystallographic analyses of two sterically unhindered copper meso-triarylcorroles, Cu[5,15-P(2)-10-(4-MeOP)C] and Cu[5,15-(4-CF(3)P)(2)-10-(4-MeOP)C] (P = phenyl and C = corrole), revealed substantially saddled corrole rings. These results are in marked contrast to those on highly sterically hindered cobalt(III) and iridium(III) corroles, which exhibit planar corrole macrocycles. The solution to this conundrum is that copper corroles are inherently saddled, as a result of a specific copper(d)-corrole(pi) orbital interaction. This orbital interaction results in a noninnocent corrole ligand, and the overall electronic structure may thus be described as Cu(II)-corrole(*2-). While many specific metal(d)-macrocycle(pi) orbital interactions are known for nonplanar metalloporphyrins, this work provides a rare example of such an orbital interaction providing the actual driving force for a significant nonplanar distortion. Our findings on copper corroles, along with those of others on cobalt and iridium corroles, thus constitute an intriguing and somewhat counterintuitive chapter in the structural chemistry of metallocorroles.


Cutting edge: endotoxin tolerance in mouse peritoneal macrophages correlates with down-regulation of surface toll-like receptor 4 expression.
Monocytes/macrophages exposed to LPS show reduced responses to second stimulation with LPS, which is termed LPS tolerance. In this study, we investigated molecular mechanism of LPS tolerance in macrophages. Mouse peritoneal macrophages pre-exposed to LPS exhibited reduced production of inflammatory cytokines in a time- and dose-dependent manner. Activation of neither IL-1 receptor-associated kinase nor NF-kappaB was observed in macrophages that became tolerant by LPS pretreatment, indicating that the proximal event in Toll-like receptor 4 (TLR4)-MyD88-dependent signaling is affected in tolerant macrophages. Although TLR4 mRNA expression significantly decreased within a few hours of LPS pretreatment and returned to the original level at 24 h, the surface TLR4 expression began to decrease within 1 h, with a gradual decrease after that, and remained suppressed over 24 h. A decrease in inflammatory cytokine production in tolerant macrophages well correlates with down-regulation of the surface TLR4 expression, which may explain one of the mechanisms for LPS tolerance.


Where's the orange? Geometric and extra-geometric influences on English children's descriptions of spatial locations.
The effect of both geometric and extra-geometric factors on children's production of in is reported (free-response paradigm). Eighty children across four age groups (means 4;1, 5;5, 6;1, and 7;1) were shown video scenes of puppets placing real objects in various positions with reference to a bowl and a plate. Located objects were placed at three heights on top of piles of other objects in the scene. The extrageometric factor of location control of the located object was manipulated by comparing static scenes to dynamic scenes in which the located object was depicted as either moving independently of, or together with, the reference object. Additionally, the located object was placed on other objects that were either the same or different (e.g. an apple on apples or on oranges). The results indicate that even the youngest children altered the way they talked according to not only geometric but also extra-geometric factors.


Expression of rotavirus VP6 protein: a comparison amongst Escherichia coli, Pichia pastoris and Hansenula polymorpha.
During this study. we successfully expressed a codon-optimized gene for rotavirus VP6 protein intracellularly in two methylotrophic yeasts, Pichia pastoris and Hansenula polymorpha, during methanol induction. Expressions were performed in shake flasks and subsequently scaled-up to 1.3 L bioreactors. The yields obtained in the yeasts were compared with that observed in Escherichia coli. Despite producing the lowest biomass levels of all the expression systems in shake flasks, the highest VP6 concentration was obtained with E. coli. In shake flasks, P. pastoris yielded higher volumetric levels of VP6 than H. polymorpha, but specific production of VP6 was approximately similar in both yeasts. In the controlled environment of bioreactors, yeast strains attained typical high cell densities, but also increased VP6 production compared to all shake flask cultures. Unlike in shake flask expressions, H. polymorpha outperformed both P. pastoris as well as E. coli during bioreactor cultivation. VP6 production was in all three expression systems growth-associated. In contrast to yeast expressions, bacterial expressed VP6 protein was found to be insoluble upon analysis. This is the first report of VP6 expressed in methylotrophic yeast and holds the promise for the inexpensive production of VP6 as a possible vaccine candidate or drug delivery mechanism.


A randomized blind study comparing standard heparin and a new low molecular weight heparinoid in cardiopulmonary bypass surgery in dogs.
Postoperative hemorrhage remains a serious complication in cardiopulmonary bypass (CPB) surgery. In our study, alternative anticoagulation with a new low molecular weight (LMW) heparinoid (Org 10172) was compared with a standardized heparin regimen. A preliminary dose-finding study indicated the minimal effective heparinoid dose to be 260 anti-Xa U/kg body weight, which was comparable to the standardized heparin regime, as revealed by similar plasma anti-Xa values. The following randomized open pilot study in 12 mongrel dogs undergoing CPB showed the heparinoid to be as effective as heparin, with an additional advantageous decrease in postoperative blood loss in the Org 10172 group. Our randomized blind study in 16 mongrel dogs undergoing CPB was performed to confirm previous results. Both antithrombotic agents were effective in the prevention of clot formation within the extracorporeal circuit. Hematocrit values and erythrocyte and platelet counts showed no significant intergroup differences. Post-CPB leukocyte counts revealed a significantly more rapid increase in the group given heparinoid (P less than 0.05). In the group given heparin, the expected prolongations of both the thrombin time (TT) and activated partial thromboplastin time (APTT) were noted, whereas in the group given heparinoid, only a transient peak prolongation of the TT after dose administration was revealed, and no significant prolongation of the APTT. Mean anti-Xa plasma levels were similar during CPB, showing a rapid decrease in the group given heparin on protamine administration, as did the APTT. Assessment of the operating field indicated an elevated intraoperative blood loss in the group given heparin. Postoperative blood loss measured over a period of 2.5 hours after closure of the thorax was significantly lower in the group given heparinoid than in the heparinized animals (625 +/- 100.0 ml, mean +/- SD, and 806 +/- 178.2 ml, respectively; P less than 0.05). Our observations suggest that the LMW heparinoid Org 10172 has an increased benefit/risk ratio over standard heparin and is effective in CPB in dogs. Additional investigations in humans should verify the possibility of use of this substance as an alternative means of anticoagulation during CPB in patients in whom heparin is relatively contraindicated.


Predictors of pain control in patients undergoing flexible bronchoscopy.
The purpose of this study was to assess the extent to which patients undergoing flexible bronchoscopy (FOB) experience pain and to identify patient factors and process of care factors that are associated with pain. We conducted a prospective cohort study on 481 patients undergoing FOB. Overall control of pain during FOB was the primary outcome. The mean age of the patients was 48 yr, 50% were male, and 32% required supplemental oxygen prior to FOB. Pain control was excellent in 36% of patients, but 10% considered it to be fair or poor. Patient factors associated with excellent pain control were excellent health (versus poor health, OR = 6.25 [95% CI, 2.28-16.67]), more education (college education versus high school education, OR = 1.72 [95% CI, 1.05-2.86]), and not having asthma (OR = 2.86 [95% CI, 1.09-7.14]). Process of care factors associated with excellent pain control were not being bothered by scope insertion (versus bothered, OR = 3.65 [95% CI, 1.99-6.98]), no memory of FOB (versus some memory, OR = 2.33 [95% CI, 1.24-4.44]), and higher ratings of information about the procedure (per 1-point increase on a 12-point scale, OR = 1.57 [95% CI, 1.41-1.78]). This is the first large-scale, prospective study to evaluate patient and process of care factors that influence pain control during FOB. It demonstrated that there are patient characteristics and process of care factors that need to be considered when evaluating pain during bronchoscopy. Improved preparation of patients with lower education, inferior health status, and asthma may lead to decreased pain during FOB. Bronchoscopists may be able to reduce pain during FOB by identifying methods to decrease pain on scope insertion, by improving the information provided to patients, and by achieving greater levels of amnesia during FOB.


Incidence of ambulatory care visits after needlestick and sharps injuries among healthcare workers in Taiwan: a nationwide population-based study.
Healthcare professionals have a high risk of needlestick and sharps injuries (NSIs), which have a high potential for disease transmission. Ambulatory care follow up is essential, but is usually overlooked. This study aimed to investigate the annual and cumulative (age-, sex-, and subtype-specific) incidences of ambulatory care visits after NSIs. This study was also designed to evaluate the incidences of blood-borne diseases associated with NSIs among Taiwanese health professionals in Taiwan between 2004 and 2010. Data were obtained from the National Health Insurance Research Database, which contains anonymized records representing approximately 99% of the Taiwan population. A total of 4443 nurse healthcare workers (NHCWs) and 3138 non-nurse healthcare workers (NNHCWs), including physicians, medical technologists, and other health professionals were included in this longitudinal study. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The Mantel-Haenszel method was used to adjust for sex, age, and type of affiliation. Results showed that the annual incidence of ambulatory care visits of NHCWs increased from 0.7% in 2004 to 1.9% in 2010; this incidence was significantly higher than that of NNHCWs (from 0.3% in 2004 to 0.5% in 2010) in any yearly comparison (p < 0.05). The sex-adjusted 7-year cumulative incidence rate was 3.23 (95% CI = 1.23-8.45) in males and 3.92 (95% CI = 2.70-5.69) in females (p < 0.05). The age-adjusted 7-year cumulative incidence rate was 2.74 (95% CI = 1.99-3.77) and 2.14 (95% CI = 1.49-3.07) in subjects ≤ 30 and ≥31 years old, respectively (p < 0.0005). The affiliation-adjusted 7-year cumulative incidence rate was 1.89 (95% CI = 1.21-2.94) in medical centers and 3.33 (95% CI = 2.51-4.41) in nonmedical centers (p < 0.01). In conclusion, NSIs increased steadily from 2004 to 2010 in Taiwan with NHCWs having higher NSIs incidences than NNHCWs. A routine ambulatory care visit after NSIs can prevent blood-borne transmission, especially for NHCWs. Educational programs may be helpful for reducing the incidence of NSIs and increasing ambulatory care visit ratios after NSIs.


The regulatory mechanism of Hsp90alpha secretion from endothelial cells and its role in angiogenesis during wound healing.
Heat shock protein 90alpha (Hsp90alpha) is a ubiquitously expressed molecular chaperone, which is essential for the maintenance of eukaryote homeostasis. Hsp90alpha can also be secreted extracellularly and is associated with several physiological and pathological processes including wound healing, cancer, infectious diseases and diabetes. Angiogenesis, defined as the sprouting of new blood vessels from pre-existing capillaries via endothelial cell proliferation and migration, commonly occurs in and contributes to the above mentioned processes. However, the secretion of Hsp90alpha from endothelial cells and also its function in angiogenesis are still unclear. Here we investigated the role of extracellular Hsp90alpha in angiogenesis using dermal endothelial cells in vitro and a wound healing model in vivo. We find that the secretion of Hsp90alpha but not Hsp90beta is increased in activated endothelial cells with the induction of angiogenic factors and matrix proteins. Secreted Hsp90alpha localizes on the leading edge of endothelial cells and promotes their angiogenic activities, whereas Hsp90alpha neutralizing antibodies reverse the effect. Furthermore, using a mouse skin wound healing model in vivo, we demonstrate that extracellular Hsp90alpha localizes on blood vessels in granulation tissues of wounded skin and promotes angiogenesis during wound healing. Taken together, our study reveals that Hsp90alpha can be secreted by activated endothelial cells and is a positive regulator of angiogenesis, suggesting the potential application of Hsp90alpha as a stimulator for wound repair.


Topical delivery of nonsteroidal anti-inflammatory drugs for osteoarthritis.
Osteoarthritis (OA) is one of the most commonly reported chronic pain syndromes experienced in the United States. Treatment guidelines for OA recommend acetaminophen for first-line pharmacotherapy for these patients; however, this strategy is rarely effective as monotherapy. Nonsteroidal anti-inflammatory drugs (NSAIDs) are considered the next step in therapy and have accumulated a large body of data to support their efficacy for OA. Unfortunately, this class of agents is not without the potential for significant adverse effects. In an effort to capture the efficacy of NSAIDs while decreasing their side effect burden, many clinicians are turning to the topical administration of these agents. Localized pain and smaller, superficial joints may be especially amenable to the topical administration of NSAIDs. Numerous commercially available topical NSAID formulations have been shown to be efficacious in patients with OA. This review focuses on the topical delivery of NSAIDs for the treatment of OA.


Control of adrenocorticotropin secretion and adrenocortical sensitivity in neurohypophysectomized conscious dogs: effects of acute and chronic vasopressin replacement.
We examined the effect of neurohypophysectomy with and without vasopressin replacement on the ACTH response to hypotension and ovine CRF infusion and on the adrenocortical response to ACTH and angiotensin II infusion in conscious dogs. Nitroprusside hypotension (decrease in mean arterial pressure of 25 mm Hg) in the intact state resulted in large increases in plasma arginine vasopressin (pAVP; from 2.6 +/- 0.3 to 296 +/- 63 pg/ml) and ACTH (from 35 +/- 6 to 395 +/- 92 pg/ml). Neurohypophysectomy resulted in greatly attenuated pAVP (8.4 +/- 1.6 pg/ml) and ACTH (80 +/- 10 pg/ml) responses to hypotension which were not normalized by physiological low dose vasopressin replacement (6-18 pg/kg.min continuously, iv, for 2 weeks). However, acute administration of vasopressin (4-6 ng/kg.min) simultaneously with hypotension in the neurohypophysectomized (neurohypox) dog, which produced pAVP levels equivalent to the hypotensive response to intact dogs, almost completely normalized the ACTH response to hypotension (to 248 +/- 74 pg/ml). The ACTH response to 20 ng/kg.min ovine CRF, iv (from 43 +/- 8 to 268 +/- 77 pg/ml), was not attenuated by neurohypophysectomy. The cortisol responses to infusion of 0.5 and 2 ng/kg.min ACTH-(1-24), iv, were essentially normal in neurohypox dogs. However, the ACTH and aldosterone responses to 5 ng/kg.min angiotensin II infusion iv were attenuated in neurohypox dogs off AVP replacement. Histological examination revealed normal adrenal glands and anterior pituitaries in neurohypox dogs. Immunocytochemical staining for vasopressin and neurophysin revealed normal cell bodies in the paraventricular and supraoptic nuclei of the hypothalami from neurohypox dogs. However, median eminence staining for AVP and neurophysin was greatly diminished in neurohypox dogs. In summary, neurohypophysectomy 1) attenuated the ACTH response to hypotension and angiotensin II, but not to CRF, and 2) attenuated the aldosterone response to high dose angiotensin II. Furthermore, the deficit in ACTH secretion was almost completely normalized by increasing plasma AVP levels to those observed in the intact dogs. We conclude that an action of circulating pAVP increases ACTH secretion by a direct effect at the pituitary and by activating afferent input to the hypothalamus.


Poly(ethylene glycol) Crowding as Critical Factor To Determine pDNA Packaging Scheme into Polyplex Micelles for Enhanced Gene Expression.
A critical role of polyethylene glycol (PEG) crowding in the packaging of plasmid DNA (pDNA) into polyplex micelles (PMs) was investigated using a series of PEG-b-poly(l-lysine) (PEG-PLys) block copolymers with varying molecular weights of both PEG and PLys segments. Rod-shaped PMs preferentially formed when the tethered PEG chains covering pDNA in a precondensed state were dense enough to overlap one another (reduced tethering density (RTD) > 1), whereas globular PMs were obtained when they were not overlapped (RTD < 1). These results submitted a scheme that steric repulsive effect of PEG regulated packaging pathways of pDNA either through folding into rod-shape or collapsing into globular depending on whether the PEG chains are overlapped or not. The rod-shaped PMs gave significantly higher gene expression efficacies in a cell-free system compared to the globular PMs, demonstrating the practical relevance of regulating packaging structure of pDNA for developing efficient gene delivery systems.


Incidence of status epilepticus in French-speaking Switzerland: (EPISTAR).
To determine the incidence, risk factors, and case fatality rate of status epilepticus (SE) in the French-speaking part of Switzerland. Between October 1, 1997 and September 30, 1998 all cases of SE referred to all the hospitals in the six cantons of the French-speaking part of Switzerland were identified by physicians working in emergency rooms, intensive care units, and electroencephalography departments; neurologists; and pediatricians from all hospitals in the area. Each case was validated and classified according to seizure type and etiology. Over 1 year, 172 cases were identified, of whom 74 had a history of epilepsy (42.4%). The crude and standardized annual incidence rate were 9.9/100,000 (95% CI, 8.4 to 11.4) and 10.3/100,000 (95% CI, 8.7 to 11.9). The incidence rate was higher among children < 1 year of age and adults > 65 years, and among men than women. There were 108 cases of acute symptomatic SE (incidence: 6.2 per 1000), 49 cases of remote symptomatic SE, and 15 cases of unknown etiology. Case fatality rate was 7.6%. The standardized incidence rate of SE in the French-speaking part of Switzerland was lower than that reported in Rochester, MN (18.3/100,000) and in the white population of Richmond, VA (20/100,000). The discrepancy may stem from the lack of a homogeneous, rigorous, and pragmatic definition of SE and the efficient management of acute repetitive seizures in this area.


Amniotic band syndrome with significant orofacial clefts and disruptions and distortions of craniofacial structures.
Amniotic band syndrome (ABS) is a rare disorder in which bands of mesoderm that emanate from the chorionic side of the amnion and insert on the fetal body can generate a wide variety of disfiguring and disabling malformations. It usually is sporadic, and the incidence is approximately 1 in 15,000 live births, and affected children typically require involvement of several pediatric surgical subspecialties. The authors describe a case of ABS with extensive craniofacial anomalies.


Feasibility study of the positronium imaging with the J-PET tomograph.
A detection system of the conventional PET tomograph is set-up to record data from [Formula: see text] annihilation into two photons with energy of 511 keV, and it gives information on the density distribution of a radiopharmaceutical in the body of the object. In this paper we explore the possibility of performing the three gamma photons imaging based on ortho-positronium annihilation, as well as the possibility of positronium mean lifetime imaging with the J-PET tomograph constructed from plastic scintillators. For this purposes simulations of the ortho-positronium formation and its annihilation into three photons were performed taking into account distributions of photons' momenta as predicted by the theory of quantum electrodynamics and the response of the J-PET tomograph. In order to test the proposed ortho-positronium lifetime image reconstruction method, we concentrate on the decay of the ortho-positronium into three photons and applications of radiopharmaceuticals labeled with isotopes emitting a prompt gamma. The proposed method of imaging is based on the determination of hit-times and hit-positions of registered photons which enables the reconstruction of the time and position of the annihilation point as well as the lifetime of the ortho-positronium on an event-by-event basis. We have simulated the production of the positronium in point-like sources and in a cylindrical phantom composed of a set of different materials in which the ortho-positronium lifetime varied from 2.0 ns to 3.0 ns, as expected for ortho-positronium created in the human body. The presented reconstruction method for total-body J-PET like detector allows to achieve a mean lifetime resolution of ∼40 ps. Recent positron annihilation lifetime spectroscopy measurements of cancerous and healthy uterine tissues show that this sensitivity may allow to study the morphological changes in cell structures.


Revision of failed flatfoot surgery.
Revision of failed flatfoot surgery presents a unique and challenging dilemma for the foot and ankle surgeon. Revision surgery is focused on establishing a plantigrade foot with correction of the hindfoot valgus, midfoot abduction, and forefoot varus. Successful reconstruction of failed flatfoot surgery begins with a proper evaluation. No treatment algorithm exists for the management of the malaligned flatfoot. Patient complaints, an understanding of the initial deformity and biomechanical problems, and surgeon experience play a role in correction of failed flatfoot surgery.


Cognitive stimulation for Portuguese older adults with cognitive impairment: a randomized controlled trial of efficacy, comparative duration, feasibility, and experiential relevance.
Although some studies point to cognitive stimulation as a beneficial therapy for older adults with cognitive impairments, this area of research and practice is still lacking dissemination and is underrepresented in many countries. Moreover, the comparative effects of different intervention durations remain to be established and, besides cognitive effects, pragmatic parameters, such as cost-effectiveness and experiential relevance to participants, are seldom explored. In this work, we present a randomized controlled wait-list trial evaluating 2 different intervention durations (standard = 17 vs brief = 11 sessions) of a cognitive stimulation program developed for older adults with cognitive impairments with or without dementia. 20 participants were randomly assigned to the standard duration intervention program (17 sessions, 1.5 months) or to a wait-list group. At postintervention of the standard intervention group, the wait-list group crossed over to receive the brief intervention program (11 sessions, 1 month). Changes in neuropsychological, functionality, quality of life, and caregiver outcomes were evaluated. Experience during intervention and costs and feasibility were also evaluated. The current cognitive stimulation programs (ie, standard and brief) showed high values of experiential relevance for both intervention durations. High adherence, completion rates, and reasonable costs were found for both formats. Further studies are needed to definitively establish the potential efficacy, optimal duration, cost-effectiveness, and experiential relevance for participants of cognitive intervention approaches.


Teacher approval and disapproval in Hongkong secondary school classrooms.
OPTIC (Observation of Pupils and Teachers in Classrooms) was used to study Hongkong secondary school teachers' use of approval and disapproval and pupils' on-task behaviour. Despite great individual differences, the sample of teachers was found overall to focus upon pupils' academic behaviour and to emphasise the use of approval. However, disapproval was emphasised as a means of responding to pupils' social behaviour. Positive correlations were found between approval (particularly to academic behaviour) and on-task behaviour. Negative correlations were found between disapproval (particularly to social behaviour) and on-task behaviour. In these respects the findings were similar to those of a recent UK study.


Dose-dependent effects of recombinant human erythropoietin on the reticulocyte population of rabbits.
The effects of repeated applications of recombinant human erythropoietin (rhEPO, epoetin beta, Recormon, CAS 122312-54-3) on the reticulocyte count and the reticulocyte maturation distribution of rabbits were investigated using the automated reticulocyte analysis system Sysmex R-1000. Therefore, 150, 300, and 600 IU rhEPO per animal were injected 3 times in intervals of 5-6 weeks. The strongest reaction was found on the second day after application of rhEPO with respect to maturation distribution characterized by the distribution quotient (DQ) and on the fourth day with respect to reticulocyte count. At this time these parameters showed a distinct dose dependence (p < 0.001). The effect of rhEPO on the erythropoietic system in the same rabbit population could be repeated. Thus, immunological neutralization of rhEPO did not take place in rabbits in response to a 3-fold application. The results indicate a potential basis for a simple bioassay in order to determine rhEPO activity in normocythemic rabbits.


Identification of candidate genes for Parkinson's disease through blood transcriptome analysis in LRRK2-G2019S carriers, idiopathic cases, and controls.
The commonest known cause of Parkinson's disease (PD) is the G2019S mutation of the LRRK2 gene, but this mutation is not sufficient for causing PD, and many carriers of the mutation never develop PD symptoms during life. Differences at the expression level of certain genes, resulting from either genetic variations or environmental interactions, might be one of the mechanisms underlying differential risks for developing both idiopathic and genetic PD. To identify the genes involved in PD pathogenesis, we compared genome-wide gene expression (RNA-seq) in peripheral blood of 20 PD patients carrying the G2019S mutation of the LRRK2 gene, 20 asymptomatic carriers of the mutation, 20 subjects with idiopathic PD, 20 controls and 7 PD patients before and after initiating dopaminergic therapy. We identified 13 common genes (ADARB2, CEACAM6, CNTNAP2, COL19A1, DEF4, DRAXIN, FCER2, HBG1, NCAPG2, PVRL2, SLC2A14, SNCA, and TCL1B) showing significant differential expression between G2019S-associated PD and asymptomatic carriers and also between idiopathic PD and controls but not between untreated and treated patients. Some of these genes are functionally involved in the processes known to be involved in PD pathogenesis, such as Akt signaling, glucose metabolism, or immunity. We consider that these genes merit further attention in future studies as potential candidate genes involved in both idiopathic and LRRK2-G2019S-associated forms of PD.


Effect of the genetic background on the reproduction of leptin-deficient obese mice.
Obesity is often associated with an impairment of the hypothalamic-pituitary-gonadal axis. The leptin-deficient ob/ob mouse model is characterized by a morbid obesity with a sterility in males and females that is corrected by continuous leptin treatment. Since ob/ob mice are maintained on the C57BL/6J inbred genetic background, we sought to determine whether their infertility can be corrected without leptin treatment but via the effect of modifier genes brought into the obese-sterile phenotype by a different genetic background. Thus, we generated via an F2 intercross ob/ob mice on a mixed C57BL/6J-BALB/cJ genetic background and assayed them for fertility by mating with wild-type C57BL/6J mice. Whereas genetically heterogeneous F2 obese females remained sterile like male and female C57BL/6J ob/ob mice, 41% of F2 C57BL/6J-BALB/cJ obese males were capable of reproducing despite a morbidly obese state. Therefore, the sterility of the original C57BL/6J ob/ob mouse model was genetically corrected independently of its obese state via the effects of modifier genes. Unlike testosterone levels, triglyceride levels, and testes weight-to-body weight ratios, which were all higher in fertile vs. sterile mice, glucose levels were similar in both groups, indicating that the underlying hyperglycemia of ob/ob mice was not an impediment to the onset of fertility. A genome-wide scan in F2 ob/ob males resulted in the localization of four modifier loci on chromosomes 1, 3, 5, and 14 with respective quantitative traits consisting of number of pregnancies, testes weights normalized to body weights, body weight at 8 weeks of age, and circulating testosterone. We conclude that the inheritance of modifier genes at the identified loci acts to promote fertility of otherwise sterile leptin-deficient obese male mice.


Temporal trends (2004-2009) of imposex in rock shells Thais clavigera collected along the Korean coast associated with tributyltin regulation in 2003 and 2008.
We investigated the temporal trend in contamination of butyltin compounds (BTs) along the Korean coast using imposex and tributyltin (TBT) burden in gastropods (Thais clavigera) as a biomonitor. Thais clavigera were collected from 26 locations with different shipping activities between 2004 and 2009 after restrictions on TBT-based antifouling paints were imposed in Korea. In the present study, imposex indices and TBT tissue concentrations significantly decreased over time from 2004 to 2009, confirming the effectiveness of TBT regulation. However, imposex in 2009 samples was still found. Significantly high imposex indices and TBT tissue residues were found in large ports containing commercial and ferry services compared with small ports and background areas. Imposex indices in background areas had decreased to zero, suggesting recovery from imposex caused by BT contamination. These results suggest that recovery from TBT contamination occurs faster in areas with very low maritime activities than areas with high maritime activities.


Leukoencephalomalacia in a horse induced by fumonisin B1 isolated from Fusarium moniliforme.
Each of two horses was dosed by stomach tube with culture material on maize of Fusarium moniliforme MRC 826. One horse developed severe hepatosis and mild oedema of the brain after 6 doses of 2.5 g of culture material/kg body mass/day in 7 days. The second horse, in a similar experiment but at a dosage rate of 1.25 g/kg/day, developed mild hepatosis and moderate oedema of the brain. In both animals the brain oedema was particularly noticeable in the medulla oblongata. The mycotoxin fumonisin B1 was extracted and purified from the culture material of F. moniliforme MRC, 826 which contained approximately 1 g/kg of this compound. A horse was injected intravenously 7 times from Day 0-Day 9 with 0.125 mg of fumonisin B1/kg body mass/day. Clinical signs of neurotoxicosis, which appeared on Day 8, included nervousness followed by apathy, a wide-based stance, trembling, ataxia, reluctance to move, paresis of the lower lip and tongue, and an inability to eat or drink. Euthanasia was performed on the horse on Day 10 while the animal was in a tetanic convulsion. The principal lesions were severe oedema of the brain and early, bilaterally symmetrical, focal necrosis in the medulla oblongata. This report provides experimental evidence that fumonisin B1, produced by F. moniliforme, causes equine leukoencephalomalacia.