Regeneration-associated high level expression of apolipoprotein D mRNA in endoneurial fibroblasts of peripheral nerve.
A cDNA clone containing the entire coding region of rat apolipoprotein D (Apo D) was isolated from a cDNA library of regenerating sciatic nerve by differential hybridization. Only small amounts of Apo D mRNA were detected in noninjured mature nerve. Moderately increased levels of Apo D transcripts were found in transected nerves, which were prevented from regeneration by ligation. In contrast, in regenerating crushed nerve, the steady-state level of Apo D mRNA transiently increased at least 40-fold above control levels at the time when axons from the proximal stump grow into the distal nerve segment. Using transverse sections and primary cell cultures from regenerating nerve, Apo D transcripts could be localized by in situ hybridization in endoneurial fibroblasts but not in Schwann cells, macrophages or perineurial and epineurial cells. Apo D protein (Mr 32.8 kd) was secreted and accumulated in the endoneurial extracellular space where it could be detected in lipoprotein fractions by immunoblotting using established antibodies to human Apo D. High level expression of Apo D mRNA seems to be a novel regeneration-associated molecular event of endoneurial fibroblasts indicating a function for Apo D and fibroblasts in nerve repair.


A substrain mouse serologically classified in ddN strain and its behavioral characteristics.
A special substrain mouse in ddN strain was classified by cross agglutination reaction of the red blood cells with anti-ddN mice red blood cells rabbit immune serume. The agglutination reactivity in the full-grown substrain mouse was as high as in an infant ddN mouse. Incidence of the substrain mouse in ddN strain aged older than 9 weeks was about 10%. The full-grown substrain mouse revealed a form of excitation after long-term administration of methamphetamine while other mice in the same strain were depressed. The behavioral and serological properties of histocompatible strain mice such as C57Bl and C3/ were studied to compare with those of the ddN substrain mouse.


TRIACCESS Study: Randomized Comparison Between Radial, Femoral, and Pedal Access for Percutaneous Femoro-popliteal Artery Angioplasty.
The aim of this randomized study was to compare the success and complication rates of different access sites for the treatment of superficial artery stenosis. A total of 180 consecutive patients were randomized in a prospective study to treat symptomatic superficial femoral artery stenosis via radial (RA), femoral (FA), or pedal artery (PA) access. Technical success was achieved in 96.7%, 100%, and 100% of the patients in the RA, FA, and PA groups, respectively (p=0.33). Secondary access sites were used in 30%, 3.3%, and 30% of the patients in the RA, FA, and PA access groups, respectively (p=0.0002). Recanalization for chronic total occlusion was performed in 34/36 (94.4%), 30/30 (100%), and 46/46 (100%) patients in the RA, FA, and PA groups, respectively (p=0.17). The X-ray dose was significantly lower in the PA group than that in the RA and FA access groups (63.1 vs 162 vs 153 Dyn, p=0.0004). The cumulative rates of access site complications in the RA, FA, and PA groups were 3.3% (0% major and 3.3% minor), 16.7% (3.3% major and 13.3% minor), and 3.3% (3.3% major and 0% minor) (p=0.0085), respectively. The cumulative incidence of MACEs at 6 months in the RA, FA, and PA groups was 5%, 6.7%, and 1.7%, respectively. The cumulative incidence of MALEs at 6 months in the RA, FA, and PA groups was 20%, 16.7%, and 9.2%, respectively (p=0.54). Femoral artery intervention can be safely and effectively performed using radial, femoral, and pedal access, but radial and pedal access is associated with a lower access site complication rate and hospitalization. Pedal access is associated with a lower X-ray dose than that with radial and femoral access.


[Effects of equol on proliferation of colorectal cancer HCT-15 cell].
To investigate the effect of racemic equol and equol enantiomers on the proliferation of colorectal cancer HCT-15 cell and the potential mechanism. 3-( 4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide( MTT) assay was used to detect the effect of different concentrations of racemic equol and equol enantiomers( 0, 0. 5, 1, 5 and 10 μmol/L) on the proliferation of colorectal cancer HCT-15 cell. Western blot was used to detect the expression of estrogen receptor( ER)and nuclear factor 2 related factor 2( Nrf2). Racemic equol and( R) equol inhibited the proliferation of HCT-15 cell in a dose-dependent manner, whereas( S) equol had no effect on the proliferation of HCT-15 cell. Racemic equol increased the expression of ERβ and Nrf2, while( R) equol increased the expression of Nrf2. Racemic equol can inhibit the proliferation of HCT-15 cell through estrogenic and antioxidative activity. R equol can inhibit the proliferation of HCT-15 cell through antioxidative activity, while( S) equol has no effect on the proliferation of HCT-15 cell.


EPR spectroscopic analysis of binding sites of a cancerostatic agent on erythrocyte membranes.
A biologically highly active antitumor agent, chloroethyl-nitrosourea-piperidine-N-oxyl, was found to bind covalently to sulfhydryl groups of membrane proteins of erythrocytes. The agent penetrates the erythrocyte membrane very easily within three minutes. Mainly two different binding sites are distinguishable with rather high rotational mobility of the NO-moiety and high polarity of their environment. The lowered broadening of bound label suggests pocket-like binding sites with a limited accessibility for paramagnetic ions. Besides common concepts that antitumor agents often bind to DNA and inhibit cell proliferation, further targets on plasma membranes are taken into consideration for antitumor agents.


Novel hypoxia-targeting Pt(iv) prodrugs.
Novel Pt(iv) prodrugs targeting hypoxia inducible factor HIF-1α were prepared for evaluating their antitumor activity on hypoxic cancer cells for the first time. The resulting Pt(iv) prodrug exhibited effective inhibition on tumor growth in the HCT-116 xenograft mouse model with low toxicity in vivo.


Integrative Review on the Use of Newman Praxis Relationship in Chronic Illness.
Over the past 20 years, many Newman scholars across the globe have investigated health as expanding consciousness with persons living with chronic illness. This integrative review examines the use of the concept, relationship, and its seven dimensions-health, caring, consciousness, mutual process, patterning, presence, and meaning with persons with chronic illness when engaged in health as expanding consciousness praxis. A regular and sustained pattern of publication of studies that included the seven dimensions was found. Relationships among the dimensions of a Newman praxis relationship, chronic illness, and health as expanding consciousness are discussed.


Demethoxycurcumin inhibited human epithelia ovarian cancer cells' growth via up-regulating miR-551a.
Curcumin is a natural agent that has ability to dampen tumor cells' growth. However, the natural form of curcumin is prone to degrade and unstable in vitro. Here, we demonstrated that demethoxycurcumin (a curcumin-related demethoxy compound) could inhibit cell proliferation and induce apoptosis of ovarian cancer cells. Moreover, IRS2/PI3K/Akt axis was inactivated in cells treated with demethoxycurcumin. Quantitative real-time reverse transcription polymerase chain reaction demonstrated that miR-551a was down-regulated in ovarian cancer tissues and ovarian cancer cell lines. Over-expression of miR-551a inhibited cell proliferation and induced apoptosis of ovarian cancer cells, whereas down-regulation of miR-551a exerted the opposite function. Luciferase assays confirmed that there was a binding site of miR-551a in IRS2, and we found that miR-551a exerted tumor-suppressive function by targeting IRS2 in ovarian cancer cells. Remarkably, miR-551a was up-regulated in the cells treated with demethoxycurcumin, and demethoxycurcumin suppressed IRS2 by restoration of miR-551a. In conclusion, demethoxycurcumin hindered ovarian cancer cells' malignant progress via up-regulating miR-551a.


Video-understanding framework for automatic behavior recognition.
We propose an activity-monitoring framework based on a platform called VSIP, enabling behavior recognition in different environments. To allow end-users to actively participate in the development of a new application, VSIP separates algorithms from a priori knowledge. To describe how VSIP works, we present a full description of a system developed with this platform for recognizing behaviors, involving either isolated individuals, groups of people, or crowds, in the context of visual monitoring of metro scenes, using multiple cameras. In this work, we also illustrate the capability of the framework to easily combine and tune various recognition methods dedicated to the visual analysis of specific situations (e.g., mono-/multiactors' activities, numerical/symbolic actions, or temporal scenarios). We also present other applications, using this framework, in the context of behavior recognition. VSIP has shown a good performance on human behavior recognition for different problems and configurations, being suitable to fulfill a large variety of requirements.


Kinetic theory and hydrodynamics of dense, reacting fluids far from equilibrium.
The kinetic theory for a fluid of hard spheres which undergo endothermic and/or exothermic reactions with mass transfer is developed. The exact balance equations for concentration, density, velocity, and temperature are derived. The Enskog approximation is discussed and used as the basis for the derivation, via the Chapman-Enskog procedure, of the Navier-Stokes reaction equations under various assumptions about the speed of the chemical reactions. It is shown that the phenomenological description consisting of a reaction-diffusion equation with a convective coupling to the Navier-Stokes equations is of limited applicability.


Effects of exercise-based cardiac rehabilitation in patients after percutaneous coronary intervention: A meta-analysis of randomized controlled trials.
In this study, we assessed the effect of rehabilitation exercise after percutaneous coronary intervention (PCI) in patients with coronary heart disease (CHD). We performed a meta-analysis to determine the effects of exercise in patients after PCI. The Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, the Embase database, China National Knowledge Internet (CNKI), China Biology Medicine (CBM), and the Wanfang Database were searched for randomized controlled trials (RCTs). The key words used for the searches were PCI, exercise, walking, jogging, Tai Chi, and yoga. Six studies with 682 patients met our inclusion criteria; we chose the primary endpoint events of cardiac death, recurrence of myocardial infarction (MI), repeated PCI, coronary artery bypass grafting (CABG), and restenosis, and the secondary endpoint measures included recurrent angina, treadmill exercise (total exercise time, ST-segment decline, angina, and maximum exercise tolerance). The results showed that exercise was not clearly associated with reductions in cardiac death, recurrence of MI, repeated PCI, CABG, or restenosis. However, the exercise group exhibited greater improvements in recurrent angina, total exercise time, ST-segment decline, angina, and maximum exercise tolerance than did the control group. Future studies need to expand the sample size and improve the quality of reporting of RCTs.


Cerebral cavernous angiomas in critical areas. Reports of three cases in children.
Cerebral cavernous angiomas are congenital malformations usually presenting with symptomatic hemorrhages or seizures. The advent of MRI has allowed to detect asymptomatic, "cryptic" brain cavernomas. They can occur in a sporadic, isolated form and in a familial form characterized by multiple lesions. Surgical treatment is recommended by most authors in symptomatic cases when the lesion is isolated and readily accessible. Treatment is more controversial when the vascular malformation is located in critical brain region. On the other hand the increased risk of rebleeding after a prior hemorrhage and the decreased effectiveness of lesionectomy in patients with a long seizure history could lead to perform an early surgical excision also for cavernous angiomas located in those areas. We report three cases of symptomatic cerebral cavernomas located in critical areas, in children. In all cases the surgical removal of the lesions was successfully performed. The two cases presented with seizures are seizure-free in spite of the interruption of the antiepileptic therapy. The patient presented with neurological deficit due to intraparenchymal hemorrhage progressively recovered his motor function. Our experience seems to confirm the value of surgical removal regardless of where the cavernoma is located.


[Does acute graft rejection modify subsequent function of a transplanted liver?].
While in kidney, heart and pancreas transplantation the impairment of graft function associated with acute rejection is only partially reversible upon successful antirejection therapy, little is known about the effect of acute rejection on late graft function after liver transplantation. Our data however gives similar findings in regards to conventional and quantitative liver function tests in patients with or without acute rejection more than 12 months after liver transplantation. This may most likely be attributable to the unique regeneration potential of the adult human liver.


Misincorporation of (TP during transcription of poly dAT-dAT and poly dABU-dABU.
The synthetic DNA alternating copolymers poly dAT-dAT and dABU-dABU have been transcribed with E. coli RNA polymerase to measure the level of BrdU-induced misincorporation of guanine during transcription. GTP is found to be misincorporated into both copolymers at a frequency of 1 per 1000-2000 nucleotides polymerized. Using alpha-32P-GTP, the nearest neighbors to GMP are found to be UMP (approximately 63%), GMP (approximately 25%) and AMP (approximately 17%), with no apparent difference between the two templates. These results suggest that BrdU-substitution in DNA does not necessarily increase the potential for base mispairing during transcription, and hence, promote the production of faulty RNA molecules.


Metasurface Polarization Optics: Independent Phase Control of Arbitrary Orthogonal States of Polarization.
We present a method allowing for the imposition of two independent and arbitrary phase profiles on any pair of orthogonal states of polarization-linear, circular, or elliptical-relying only on simple, linearly birefringent wave plate elements arranged into metasurfaces. This stands in contrast to previous designs which could only address orthogonal linear, and to a limited extent, circular polarizations. Using this approach, we demonstrate chiral holograms characterized by fully independent far fields for each circular polarization and elliptical polarization beam splitters, both in the visible. This approach significantly expands the scope of metasurface polarization optics.


[The functional change in the 5-HT1A receptor induced by stress and the role of the 5-HT1A receptor in neuroprotection].
Mice exposed to various stresses, especially restrained-stress, revealed the anxiogenic effect detected by the light-dark test. Under this condition, a remarkable decrease in [35S]GTPgammaS binding to membranes from the prefrontal cortex, amygdala and hypothalamus of restrained-stress mice stimulated by the selective 5-HT1A receptor agonist 5-carboxamidotriptamine (5-CT) was clearly observed, whereas a significant increase in [35S]GTPgammaS binding stimulated by the 5-HT1A receptor agonist was clearly observed in the dorsal raphe nuclei (DRN) of restrained-stress mice. The immunohistochemical study showed a drastic reduction in phosphorylated-CREB-like immunoreactivity in the DRN of restrained-stress mice. Furthermore, we found a drastic reduction in myelin-associated glycoprotein (MAG)-like immunoreactivity (MAG-IR) in the DRN, amygdala and hypothalamus, indicating the direct suppression of synaptic transmission in these regions. It has been accepted that GSK3beta in the Wnt signal pathway plays an important role in various neuronal functions including apoptosis, clustering of synapsin I and early growth and axonal remodeling. In the present study, the increase in protein levels of GSK3beta and phosphorylated-GSK3beta to cytosol fractions of the amygdala was noted in restrained-stress mice. Taken together, these results suggest that restrained stress may directly affect the 5-HT1A receptor-regulated synaptic transmission in the brain, leading to the expression of the anxiogenic effect in mice. It is well known that various stresses induce intracellular oxidative stress. The present study was then undertaken to investigate the effect of the stimulation of 5-HT1A receptors on oxidative stress. Treatment with H2O2 caused the activation of caspase-3-positive cells and the reduction in levels of MAG-IR in the limbic neuron/glia cocultures as compared to medium alone. The stimulation of 5-HT1A receptor by 5-CT produced a dramatic protection against H2O2-triggered activation of caspase-3 and reduction in levels of MAG-IR. These results suggest that 5-HT1A receptors were involved in the modulation of anxiety and the understanding of molecular mechanisms of 5-HT1A receptor-related cascades may pave the way for new therapeutic strategies for affective disorders.


The moral lens of population control: condoms and controversies in southern Malawi.
The study presents an investigation of stories about condoms in southern Malawi. Malawians' concerns about coercive population control imposed by a national government or international cabal provide a moral lens through which condoms and other health promotions are viewed, with unknown but probably negative impact on the use of condoms. The focus of the study is on the long shadow cast by population control because it is underresearched and, in fact, virtually unmentioned in most studies of health promotion, yet appears to be common if not ubiquitous. Moreover, this long shadow poses a distinct challenge to HIV-prevention and intervention efforts. The data for the study were gathered by six Malawian research assistants in Balaka district, in southern Malawi, who kept journals over a period of three years in which they recorded conversations and everyday chats that they observed. These journals demonstrate that condoms do not arrive in communities as neutral, value-free objects; rather they enter a social setting permeated with ideas about health, self-protection, and danger. The lens of population control has proved to be both durable and flexible, providing a moral context in which both commodities and actors can be understood. Disentangling condoms from the symbolic nexus in which they are fused with disease, population control, and malevolence will be an ongoing challenge in the struggle to prevent the spread of HIV/AIDS in Malawi.


Altered Sexual Behavior in Dopamine Transporter (DAT) Knockout Male Rats: A Behavioral, Neurochemical and Intracerebral Microdialysis Study.
Central dopamine plays a key role in sexual behavior. Recently, a Dopamine Transporter knockout (DAT KO) rat has been developed, which displays several behavioral dysfunctions that have been related to increased extracellular dopamine levels and altered dopamine turnover secondary to DAT gene silencing. This prompted us to characterize the sexual behavior of these DAT KO rats and their heterozygote (HET) and wild type (WT) counterparts in classical copulatory tests with a sexually receptive female rat and to verify if and how the acquisition of sexual experience changes along five copulatory tests in these rat lines. Extracellular dopamine and glutamic acid concentrations were also measured in the dialysate obtained by intracerebral microdialysis from the nucleus accumbens (Acb) shell of DAT KO, HET and WT rats, which underwent five copulatory tests, when put in the presence of an inaccessible sexually receptive female rat and when copulation was allowed. Markers of neurotropism (BDNF, trkB), neural activation (Δ-FosB), functional (Arc and PSA-NCAM) and structural synaptic plasticity (synaptophysin, syntaxin-3, PSD-95) were also measured in the ventral tegmental area (VTA), Acb (shell and core) and medial prefrontal cortex (mPFC) by Western Blot assays. The results indicate that the sexual behavior of DAT KO vs. HET and WT rats shows peculiar differences, mainly due to a more rapid acquisition of stable sexual activity levels and to higher levels of sexual motivation and activity. These differences occurred with differential changes in dopamine and glutamic acid concentrations in Acb dialysates during sexual behavior, with lower increases of dopamine and glutamic acid in DAT KO vs. WT and HET rats, and a lower expression of the markers investigated, mainly in the mPFC, in DAT KO vs. WT rats. Together these findings confirm a key role of dopamine in sexual behavior and provide evidence that the permanently high levels of dopamine triggered by DAT gene silencing cause alterations in both the frontocortical glutamatergic neurons projecting to the Acb and VTA and in the mesolimbic dopaminergic neurons, leading to specific brain regional changes in trophic support and neuroplastic processes, which may have a role in the sexual behavior differences found among the three rat genotypes.


[Self-Medication, Health and Online Orders: An Online Survey].
Background: The intensive use of Internet as health guide is proved by a current representative survey. Online orders of OTC pharmaceuticals and prescription medicine represent a special way of utillisation. Intention: The aim of the following study is to investigate motives and backgrounds of self-medication in coherency of health and ordering of OTC pharmaceuticals via Internet. Method: With an online questionnaire developed in particular for this thesis N=104 internet users (mean age M=32,7; SD=11,1 consisting of 73 female and 31 male participants) were questioned concerning the relevant topics. Furthermore, the subjects were interviewed with regard to identification of their quality of life (with the German version of the EUROHIS-QOL 8 item index), their well-being (by using the German version of the WHO-5 well-being index, version II). Results: The wish for (especially temporal) independence from a physicians treatment and the idea of a faster convalescence or prevention of worse ailment could be identified as motives for self-medication. The most frequently selected advantages of ordering drugs via internet were the lower price, organisational aspects such as direct home delivery or saving time without a consultation. In contrast, the lack of advice was often mentioned as a possible disadvantage, just like the risk of undetected and undiagnosed diseases. Compared to participants who did not do any Internet orders, participants who ordered their non-prescription drugs on the Internet were less aware of possible risks and they also used painkillers available without prescription more frequently. However, there were no differences in the total amount of applied OTC medications, which made a drug abuse less likely. Overall, self-medication of the users of Internet forums interviewed within this thesis seemed to be quantitatively and qualitatively appropriate. Conclusion: Self-medication by Internet users in this study seems to be reasonable in a quantitative and qualitative way.


[Attitude of the chronically ill towards psychiatric hospitals].
Three hundred chronic mental patients participated in a survey to evaluate their attitudes towards the 2,000 beds hospital where they were staying. The mean duration of the actual hospitalization was 12.1 years and most patients (77.9%) suffered from schizophrenia or other psychoses. On the whole, results show a relatively high level of patients' satisfaction. Single, non psychotic and self-sufficient patients who have not been hospitalized many times and do not want to leave the institution are more inclined to be positive towards the psychiatric milieu. The authors report that participation of chronic mental patients in a survey can be reliable and give helpful suggestions in relation with the evaluation of psychiatric care and the improvement of the quality of life in state hospitals. They conclude that it will always be difficult to discharge satisfied patients without offering the same support and community services that they find in a state hospital.


Single molecule/particle tracking analysis program SMTracker 2.0 reveals different dynamics of proteins within the RNA degradosome complex in Bacillus subtilis.
Single-molecule (particle) tracking is a powerful method to study dynamic processes in cells at highest possible spatial and temporal resolution. We have developed SMTracker, a graphical user interface for automatic quantifying, visualizing and managing of data. Version 2.0 determines distributions of positional displacements in x- and y-direction using multi-state diffusion models, discriminates between Brownian, sub- or superdiffusive behaviour, and locates slow or fast diffusing populations in a standardized cell. Using SMTracker, we show that the Bacillus subtilis RNA degradosome consists of a highly dynamic complex of RNase Y and binding partners. We found similar changes in molecule dynamics for RNase Y, CshA, PNPase and enolase, but not for phosphofructokinase, RNase J1 and J2, to inhibition of transcription. However, the absence of PfkA or of RNase J2 affected molecule dynamics of RNase Y-mVenus, indicating that these two proteins are indeed part of the degradosome. Molecule counting suggests that RNase Y is present as a dimer in cells, at an average copy number of about 500, of which 46% are present in a slow-diffusive state and thus likely engaged within degradosomes. Thus, RNase Y, CshA, PNPase and enolase likely play central roles, and RNase J1, J2 and PfkA more peripheral roles, in degradosome architecture.


Ultrastructure of the pineal gland in the adult rat.
The ultrastructure of the rat pineal gland was studied from 75 days until 10 months of age. Type I pinealocytes of young adults showed nuclei with dispersed chromatin, numerous infoldings of the nuclear envelope and well developed nucleoli. The cytoplasm displayed many mitochondria and clusters of smooth endoplasmic reticulum. With increasing age, there was a clear increase in the number of dense bodies or lysosomes in the Type I pinealocyte. The changes in the Type II pinealocytes with age were mainly in nuclear shape and in the appearance of lipofuscin granules.


Applications of additive semivarying coefficient models: monthly suicide data from Hong Kong.
A semivarying coefficient model for the monthly numbers of suicides in Hong Kong is developed and a new estimation procedure for estimating the parametric component is proposed. The estimators are examined in a small simulation study and fitted to monthly suicide data to estimate a nonparametric long-term trend and parametric seasonal and socioeconomic effects. Fitting the model detected interpretable structure in the data that is consistent with that driving public health policy. While exploratory, the analysis motivates the collection of more detailed data and the development of more sophisticated models to help determine target groups and strategies to reduce the suicide rate in Hong Kong.


Real-Time Data Collection Using Text Messaging in a Primary Care Clinic.
The use of text messaging is nearly ubiquitous and represents a promising method of collecting data from diverse populations. The purpose of this study was to assess the feasibility and acceptability of text message surveys in a clinical setting and to describe key lessons to minimize attrition. We obtained a convenience sample of individuals who entered the waiting room of a low-income, primary care clinic. Participants were asked to answer between 17 and 30 survey questions on a variety of health-related topics, including both open- and closed-ended questions. Descriptive statistics were used to characterize the participants and determine the response rates. Bivariate analyses were used to identify predictors of incomplete surveys. Our convenience sample consisted of 461 individuals. Of those who attempted the survey, 80% (370/461) completed it in full. The mean age of respondents was 35.4 years (standard deviation = 12.4). Respondents were predominantly non-Hispanic black (42%) or non-Hispanic white (41%), female (75%), and with at least some college education (70%). Of those who completed the survey, 84% (312/370) reported willingness to do another text message survey. Those with incomplete surveys answered a median of nine questions before stopping. Smartphone users were less likely to leave the survey incomplete compared with non-smartphone users (p = 0.004). Text-message surveys are a feasible and acceptable method to collect real-time data among low-income, clinic-based populations. Offering participants a setting for immediate survey completion, minimizing survey length, simplifying questions, and allowing "free text" responses for all questions may optimize response rates.


Rapid and irreversible cystic change of pulmonary tuberculosis in an immunocompetent adult.
This case report illustrates rapid and irreversible cystic change associated with disseminated pulmonary tuberculosis in an immunocompetent adult. In this patient, cystic lesions persisted after successful treatment of Mycobacterium tuberculosis and resulted in spontaneous pneumothorax with persistent air leak.


Molecular and cellular responses of the pathogenic fungus Lomentospora prolificans to the antifungal drug voriconazole.
The filamentous fungus Lomentospora (Scedosporium) prolificans is an emerging opportunistic pathogen associated with fatal infections in patients with disturbed immune function. Unfortunately, conventional therapies are hardly of any use against this fungus due to its intrinsic resistance. Therefore, we performed an integrated study of the L. prolificans responses to the first option to treat these mycoses, namely voriconazole, with the aim of unveiling mechanisms involved in the resistance to this compound. To do that, we used a wide range of techniques, including fluorescence and electron microscopy to study morphological alterations, ion chromatography to measure changes in cell-wall carbohydrate composition, and proteomics-based techniques to identify the proteins differentially expressed under the presence of the drug. Significantly, we showed drastic changes occurring in cell shape after voriconazole exposure, L. prolificans hyphae being shorter and wider than under control conditions. Interestingly, we proved that the architecture and carbohydrate composition of the cell wall had been modified in the presence of the drug. Specifically, L. prolificans constructed a more complex organelle with a higher presence of glucans and mannans. In addition to this, we identified several differentially expressed proteins, including Srp1 and heat shock protein 70 (Hsp70), as the most overexpressed under voriconazole-induced stress conditions. The mechanisms described in this study, which may be directly related to L. prolificans antifungal resistance or tolerance, could be used as targets to improve existing therapies or to develop new ones in order to successfully eliminate these mycoses.


Zellweger's Syndrome With PEX6 Gene Mutation in Mixteco Neonates Due to Possible Founder Effect.
Zellweger spectrum disorder (ZSD) is a group of autosomal recessive peroxisomal disorders caused by PEX gene mutations that commonly present with symptoms of severe hypotonia, epileptic seizures, failure to thrive, hepatomegaly, craniofacial dysmorphisms, and sensorineural hearing loss. This article highlights three patients born with ZSD in Central California. All three patients were born to Mixteco mothers. Patients were genetically analyzed, which revealed mutations that correspond to ZSD. They presented with hypotonia at birth, abnormal hepatic panels, and increased fatty acid levels, findings consistent with Zellweger syndrome (ZS). However, only two of three patients displayed sensorineural hearing loss. Two of the patients failed to survive more than one year of age, which reflects the average life expectancy of an infant presenting with ZS. Observed and recorded cases of ZS in the Mixteco population have been postulated to be related to consanguinity and/or a founder effect. Studies have shown that autosomal recessive diseases are more prevalent in consanguineous populations. Consanguinity has been denied by patient 1 and is unknown for patients 2 and 3. Founder mutations have been implicated in areas with high rates of autosomal recessive diseases. All three of our Mixteco patients share a distinct lineage as well as a mutation at PEX6, leading us to believe that they suffered from an inherited founder mutation. The Mixteco population is not studied well enough to come to a definitive conclusion; however, the recognition of the relationship between ZS and Mixteco background is important, as it allows parents to plan accordingly and increases awareness in the community.


Physiology and genetics of the dimorphic fungus Yarrowia lipolytica.
The ascomycetous yeast Yarrowia lipolytica (formerly Candida, Endomycopsis, or Saccharomyces lipolytica) is one of the more intensively studied 'non-conventional' yeast species. This yeast is quite different from the well-studied yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe with respect to its phylogenetic evolution, physiology, genetics, and molecular biology. However, Y. lipolytica is not only of interest for fundamental research, but also for biotechnological applications. It secretes several metabolites in large amounts (i.e. organic acids, extracellular proteins) and the tools are available for overproduction and secretion of foreign proteins. This review presents a comprehensive overview on the available data on physiology, cell biology, molecular biology and genetics of Y. lipolytica.


Assessment of ventilation and respiratory rate by healthy subjects.
Ability to judge ventilation (VI) and respiratory rate (RR) was examined in healthy subjects using the standard psychophysical technique of magnitude production. The relationships between objective and subjective magnitudes of VI could be adequately described by power function with the mean exponent 1.9. The mean deviation from the regression line was 3.0%. The requested levels of VI were produced either by changing tidal volume (VT) or RR. Changes in VT resulted in higher exponents of VI judgment. When requesting the subjects to keep VI constant by matching either VT with the imposed changes in RR or vice versa, the lesser acuity was found in adjusting RR to VT than in matching VT with RR. The results indicate that VI is judged on the basis of either VT or RR and is not treated as a concept in its own power. The 'RR' experiments consisted of assessment of RR and breath duration. The relationships between objective and subjective magnitudes of these two parameters were characterized by power functions with the exponents 1.0 and 1.2 respectively and mean deviation from the regression line of 13%. It is speculated that difficulties in adjusting RR to VT depended on a lesser precision in RR judgment.


Highly π-extended copolymers with diketopyrrolopyrrole moieties for high-performance field-effect transistors.
Two donor-acceptor (D-A) copolymer PDVTs based on diketopyrrolopyrole and (E)-2-(2-(thiophen-2-yl)vinyl)thiophene (TVT) units are synthesized for solution-processed field-effect transistors (FETs). The highly π-extended TVT units strengthen the coplanarity of the polymer backbone. FETs based on PDVTs show high mobilities above 2.0 cm(2) V(-1) s(-1) with a current on/off ratio of 10(5)-10(7) , high shelf storage, and operation stability.


Differential production of chemokines by phagocytosing rat neutrophils and macrophages.
In this study, rat neutrophils and macrophages produced cytokine-induced neutrophil chemoattractants (CINCs) and rat macrophage inflammatory protein-1 alpha (MIP-1 alpha) in different patterns during phagocytosis of heat-killed yeast cells in vitro. The cultured supernatants of the phagocytosing rat neutrophils and macrophages had chemotactic activities toward neutrophils, and the chemotactic potencies were markedly inhibited by anti-CINCs IgGs or/and anti-MIP-1 alpha IgG, suggesting that CINCs and MIP-1 alpha are major neutrophil chemoattractants produced by the phagocytosing neutrophils and macrophages. Dexamethasone suppressed the production of CINCs and MIP-1 alpha by the phagocytosing cells in a dose-dependent manner. Our results demonstrate significant differences in the production of CINCs and MIP-1 alpha by neutrophils and macrophages during phagocytosis of yeast cells and thus may suggest the different contribution of each chemokine to neutrophil recruitment in the processes of inflammation in rats.


1,2-Bis(methylsulfanyl)-1,2-dicarba-closo-dodecaborane(12).
In the title compound, 1,2-(SCH3)2-1,2-closo-C2B10H10 or C4H16B10S2, the methylsulfanyl groups are bonded to the C atoms of the 1,2-dicarba-closo-dodecaborane cage. The Ccage-Ccage distance is 1.8033 (18) A and the S-Ccage-Ccage-S torsion angle is 1.07 (13) degrees. The Ccage-Ccage distance is compared with those in other 1,2-dicarba-closo-dodecaborane derivatives.


[Diagnosis of health conditions in a pan-mining community in the Tapajós River Basin, Itaituba, Par , Brazil, 1992].
The purpose of this article is to describe health conditions in a pan-mining community, in particular the interaction of mercury contamination with other health problems. This study was carried out in a panning mine located on Rato Creek, a tributary of the Tapajó s River Basin in the municipality of Itaituba, State of Par The study population consisted of 223 individuals. An epidemiological questionnaire was applied, medical treatment was given, and biological specimens were collected. Testing of fecal samples showed that 96.1% of the individuals had parasites and 66.4% were anemic. Prevalence of hepatitis B virus was 85.0%, and 11 individuals (6.0%) were virus carriers (HBsAg positive). Of 186 patients tested for malaria, 65 individuals (35.0%) had the infection, of whom 34 (52.3%) were asymptomatic. Prevalence of syphillis was 41.6%. Urine mercury levels were measured in 173 individuals. Some 16 (9.2%) of those tested had mercury levels between 10 and 19 ug/l, while 9 patients (5.2%) had levels above 20 ug/l. An overview of general health conditions showed a combination of problems in individuals, who lacked adequate diagnosis, in addition to a high level of self-medication, given the absence of health facilities. In addition, these individuals are threatened by critical levels of mercury contamination. In conclusion, this article gives a general overview of health conditions in these pan-mining communities, demonstrating the multicausal nature of health conditions in the Amazon region, a fact which should be considered when planning appropriate strategies for clinical treatment.


Cell proliferation and STAT6 pathways are negatively regulated in T cells by STAT1 and suppressors of cytokine signaling.
Suppressor of cytokine signaling (SOCS) proteins have emerged as important regulators of cytokine signals in lymphocytes. In this study, we have investigated regulation of SOCS expression and their role in Th cell growth and differentiation. We show that SOCS genes are constitutively expressed in naive Th cells, albeit at low levels, and are differentially induced by Ag and Th-polarizing cytokines. Whereas cytokines up-regulate expression of SOCS1, SOCS2, SOCS3, and cytokine-induced Src homology 2 protein, Ags induce down-regulation of SOCS3 within 48 h of Th cell activation and concomitantly up-regulate SOCS1, SOCS2, and cytokine-induced Src homology 2 protein expression. We further show that STAT1 signals play major roles in inducing SOCS expression in Th cells and that induction of SOCS expression by IL-4, IL-12, or IFN-gamma is compromised in STAT1-deficient primary Th cells. Surprisingly, IL-4 is a potent inducer of STAT1 activation in Th2 but not Th1 cells, and SOCS1 or SOCS3 expression is dramatically reduced in STAT1(-/-) Th2 cells. To our knowledge, this is the first report of IL-4-induced STAT1 activation in Th cells, and suggests that its induction of SOCS, may in part, regulate IL-4 functions in Th2 cells. In fact, overexpression of SOCS1 in Th2 cells represses STAT6 activation and profoundly inhibits IL-4-induced proliferation, while depletion of SOCS1 by an anti-sense SOCS1 cDNA construct enhances cell proliferation and induces constitutive activation of STAT6 in Th2 cells. These results are consistent with a model where IL-4 has dual effects on differentiating T cells: it simulates proliferation/differentiation through STAT6 and autoregulates its effects on Th2 growth and effector functions via STAT1-dependent up-regulation of SOCS proteins.


Intelligent diagnosis and prescription for a customized physical fitness and healthcare system.
With the advent of the era of global high-tech industry and commerce and its associated sedentary lifestyle, opportunities for physical activity are reduced. People's physical fitness and health is deteriorating. Therefore, it is necessary to develop a system that can enhance people's physical fitness and health. However, it is difficult for general physical fitness and healthcare systems to meet individualized needs. The main purpose of this research is to develop a method of intelligent diagnosis and prescription for a customized physical fitness and healthcare system. The proposed system records all processes of the physical fitness and healthcare system via a wireless sensor network and the results of the diagnosis and prescription will be generated by fuzzy logic inference. It will improve individualized physical fitness and healthcare. Finally, we demonstrate the advantages of intelligent diagnosis and prescription for a customized physical fitness and healthcare system.


Transplantation of Embryonic Spinal Cord Derived Cells Helps to Prevent Muscle Atrophy after Peripheral Nerve Injury.
Injuries to peripheral nerves are frequent in serious traumas and spinal cord injuries. In addition to surgical approaches, other interventions, such as cell transplantation, should be considered to keep the muscles in good condition until the axons regenerate. In this study, E14.5 rat embryonic spinal cord fetal cells and cultured neural progenitor cells from different spinal cord segments were injected into transected musculocutaneous nerve of 200-300 g female Sprague Dawley (SD) rats, and atrophy in biceps brachii was assessed. Both kinds of cells were able to survive, extend their axons towards the muscle and form neuromuscular junctions that were functional in electromyographic studies. As a result, muscle endplates were preserved and atrophy was reduced. Furthermore, we observed that the fetal cells had a better effect in reducing the muscle atrophy compared to the pure neural progenitor cells, whereas lumbar cells were more beneficial compared to thoracic and cervical cells. In addition, fetal lumbar cells were used to supplement six weeks delayed surgical repair after the nerve transection. Cell transplantation helped to preserve the muscle endplates, which in turn lead to earlier functional recovery seen in behavioral test and electromyography. In conclusion, we were able to show that embryonic spinal cord derived cells, especially the lumbar fetal cells, are beneficial in the treatment of peripheral nerve injuries due to their ability to prevent the muscle atrophy.


A recombinant antibody-interleukin 2 fusion protein suppresses growth of hepatic human neuroblastoma metastases in severe combined immunodeficiency mice.
A genetically engineered fusion protein consisting of a human/mouse chimeric anti-ganglioside GD2 antibody (ch14.18) and recombinant human interleukin 2 (rhIL-2) was tested for its ability to target rhIL-2 to tumor sites and stimulate immune effector cells sufficiently to achieve effective tumor cell lysis in vivo. The ch14.18-IL-2 fusion protein proved more effective than equivalent doses of rhIL-2 in suppressing dissemination and growth of human neuroblastoma in an experimental hepatic metastases model of scid (severe combined immunodeficiency) mice reconstituted with human lymphokine-activated killer cells. The ch14.18-IL-2 fusion protein was also more proficient than equivalent doses of rhIL-2 in prolonging the life-span of these animals. This recombinant antibody-cytokine fusion protein may prove useful for future treatment of GD2-expressing human tumors in an adjuvant setting.


Closed tendon rupture as a result of Kienböck disease.
Closed tendon rupture is a well-known complication of Kienböck disease, but only 11 cases have been reported. We reviewed six cases of Kienböck disease with subcutaneous rupture of a tendon. There were five cases of 4th extensor tendons and one case of the flexor digitorum profundus tendons of the ring finger and little finger. Radiographs showed protrusion of the segmented lunate or the deformed lunate in all cases. Intraoperative findings confirmed rupture of the wrist joint capsule by these lunate lesions. We then reviewed 11 reported cases in English and 48 cases in Japanese and confirmed that all cases had similar clinical characteristics and radiological features to our own, except the involved digits of flexor tendon rupture. Our case was unique in that the ulnar side tendons were ruptured, while in the reported cases the radial flexor tendons were more susceptible to rupture than the ulnar ones. Closed rupture of tendons should be recognised as a complication in patients over middle age with stage IIIb or IV asymptomatic or less symptomatic Kienböck disease.


Different epithelial cleavage planes produced by various epikeratomes in epithelial laser in situ keratomileusis.
To determine the anatomic cleavage planes produced by various epikeratomes in epithelial laser in situ keratomileusis (epi-LASIK). Department of Ophthalmology, IIsan Paik Hospital, Goyang, Korea. Sixteen eyes (8 patients) were included in this study. Three epikeratomes, the Moria Epi-K, Centurion SES, and Amadeus II, were used to collect 4 epithelial flaps from 2 patients in the epi-LASIK procedure. Four epithelial flaps from 2 patients were also obtained by laser-assisted subepithelial keratectomy (LASEK). Immunohistochemical staining using monoclonal antibodies against integrin beta1, integrin beta4, laminin 5, and collagen type VII was performed. Immunohistochemical staining showed expression of integrin beta1 and integrin beta4 in all epithelial flaps. In epi-LASIK, the expression of laminin 5 and collagen type VII had a linear or dotted pattern that differed based on the epikeratome used. In the epithelial flaps obtained using LASEK, the expression of laminin 5 and collagen type VII had a dotted pattern. Each epikeratome yielded reproducible but different cleavage planes of corneal epithelium. The results suggest that further study is needed to elucidate the wound-healing process after epi-LASIK because different cleavage planes produced by different epikeratomes may influence the process.


Bone scan alterations in aromatase inhibitor-treated patients.
We report bone scan changes in 3 patients receiving aromatase inhibitors as adjuvant treatment for postmenopausal hormone receptor-positive breast cancer. Compared with bone scans before treatment, repeated scans after at least 10 months of aromatase inhibitor treatment showed increased activity in the peripheral skeleton and the skull. In 2 patients, these alterations could be correlated with increased markers of bone turnover. They probably result from high bone turnover induced by estrogen depletion caused by aromatase inhibitors. This effect should be taken into account in the differential diagnosis of a bone scan pattern suggestive of hyperparathyroidism, which was ruled out.


Teaching student nurses to be culturally safe: can it be done?
From the perspective of a third-year student nurse about to graduate in New Zealand, this article discusses the complexities of teaching and learning the concept of cultural safety for educators and student nurses. The background of the implementation of cultural safety content into New Zealand nursing curriculum is briefly discussed, and the evolution of cultural safety and its diverse meanings that has led to some confusion among student nurses. How is cultural safety taught and what are the surrounding barriers? Also, where does the student nurse fit into this process? Recommendations are then made to improve the teaching of cultural safety in the New Zealand nursing curriculum.


Effect of Diet on the Vitamin B Profile of Bovine Milk-Based Protein Ingredients.
The influence of diet on the water-soluble vitamin composition of skim milk powder and whey protein ingredients produced from the milk of cows fed pasture or concentrate-based diets was examined. Fifty-one Holstein-Friesian cows were randomly assigned into three diets (n=17) consisting of outdoor grazing of perennial ryegrass (GRS), perennial ryegrass/white clover (CLV), or indoor feeding of total mixed ration (TMR) for an entire lactation. Raw mid-lactation milk from each group was processed into skim milk powder and further processed to yield micellar casein whey and acid whey. Sweet whey was also produced by renneting of pasteurised whole milk from each system. The water-soluble vitamin profile of each sample was analysed using a combination of direct injection mass spectrometry and reverse-phase liquid chromatography-mass spectrometry. Vitamin B3 and B3-amide concentrations were significantly higher (p < 0.05) in TMR-derived samples than in those from CLV and GRS, respectively. Vitamin B1, B2, and B7 concentrations were significantly higher in GRS and CLV-derived samples than those from TMR. Significant differences in vitamins B1, B2, and B3-amide were also observed between protein ingredient types. This study indicates that bovine feeding systems have a significant effect on B vitamin composition across a range of protein ingredient types.


A decline in the occurrence of extended-spectrum β-lactamase-producing Escherichia coli in retail chicken meat in the UK between 2013 and 2018.
The aim of this study was to report on the occurrence of antimicrobial resistant (AMR) Escherichia coli from retail chicken meat samples in the UK, with particular focus on AmpC and extended spectrum beta-lactamase (ESBL) production and carbapenem resistance. Methods from EU protocols were used for selective isolation of AmpC-/ESBL-producing E. coli, carbapenem-resistant E. coli and for performing minimum inhibitory concentrations. Additional work not part of EU protocols included viable counts, detection by PCR of blaCTX-M , blaOXA, blaSHV and blaTEM genes in ESBL-phenotype E. coli and screening for mcr plasmid-mediated colistin resistance. From the 313/309 retail chicken meat samples tested in 2016/2018, carbapenem or mcr plasmid-mediated colistin-resistant E. coli were not detected. For 2016/2018 chicken samples, 141/42 (45·0%/13·6%), 90/23 (28·8%/7·4%), 48/16 (15·3%/5·2%) and 3/3 (1·0%/1·0%) were positive for ESBL- and/or AmpC-, ESBL- alone AmpC- alone and AmpC+ESBL-phenotype E. coli respectively. ESBL-producing E. coli were predominantly blaCTX-M-1 . All AmpC and/or ESBL-phenotype E. coli were sensitive to colistin, ertapenem, imipenem, meropenem, temocillin and tigecycline, applying epidemiological cut-off values. A previous study in 2013/14 showed that 65·4% of retail chicken meat samples tested in the UK were positive for ESBL-producing (mainly CTX-M) E. coli. Since then the proportion of samples positive in the UK has dropped significantly to 7·4% in 2018. Significant reductions in antimicrobials used in the UK poultry meat sector between 2012 and 2016 may be linked to significant reductions in AmpC/ESBL-phenotype E. coli in retail chicken between 2013/14 and 2018.


Synthesis, Characterization, and NH3-SCR Catalytic Performance of Fe-Modified MCM-36 Intercalated with Various Pillars.
Two series of MCM-36 zeolites intercalated with various pillars and modified with iron were synthesized, analyzed with respect to their physicochemical properties, and tested as catalysts for the NH3-SCR process. It was found that the characteristic MWW morphology of MCM-36 can be obtained successfully using silica, alumina, and iron oxide as pillars. Additionally, one-pot synthesis of the material with iron resulted in the incorporation of monomeric Fe3+ species into the framework positions. The results of catalytic tests revealed that the one-pot synthesized sample intercalated with silica and alumina was the most efficient catalyst of NO reduction, exhibiting ca. 100% activity at 250 °C. The outstanding performance of the material was attributed to the abundance of Lewis acid sites and the beneficial influence of alumina on the distribution of iron species in the zeolite. In contrast, the active centers originating from the Fe2O3 pillars improved the NO conversion in the high-temperature range. Nevertheless, the aggregated particles of the metal oxide limited the access of the reacting molecules to the inner structure of the catalyst, which affected the overall activity and promoted the formation of N2O above 300 °C.


NADPH oxidase biology and the regulation of tyrosine kinase receptor signaling and cancer drug cytotoxicity.
The outdated idea that reactive oxygen species (ROS) are only dangerous products of cellular metabolism, causing toxic and mutagenic effects on cellular components, is being replaced by the view that ROS have several important functions in cell signaling. In aerobic organisms, ROS can be generated from different sources, including the mitochondrial electron transport chain, xanthine oxidase, myeloperoxidase, and lipoxygenase, but the only enzyme family that produces ROS as its main product is the NADPH oxidase family (NOX enzymes). These transfer electrons from NADPH (converting it to NADP-) to oxygen to make O(2)•-. Due to their stability, the products of NADPH oxidase, hydrogen peroxide, and superoxide are considered the most favorable ROS to act as signaling molecules. Transcription factors that regulate gene expression involved in carcinogenesis are modulated by NADPH oxidase, and it has emerged as a promising target for cancer therapies. The present review discusses the mechanisms by which NADPH oxidase regulates signal transduction pathways in view of tyrosine kinase receptors, which are pivotal to regulating the hallmarks of cancer, and how ROS mediate the cytotoxicity of several cancer drugs employed in clinical practice.


Skin diseases affecting a population occupationally exposed to terrestrial fauna and flora in Brittany over a 15-year period.
Brittany is the leading agricultural production region of France where many workers are exposed to the local flora and fauna. The aim of the study is to describe the different skin diseases found among the workers occupationally exposed to the terrestrial fauna and flora in Brittany, and to assess the possible over-representation of some work environments. This was a retrospective, descriptive study carried out between 1 October 2002 - 30 April 2017, based on the coding of files from a multi-disciplinary occupational dermatology clinic at the Brest University Hospital. The study population of 84 patients was drawn from a total 788 patients seen during this period. Allergic contact dermatitis was the most frequently coded diagnosis with 35 cases (42%). There were 13 cases of irritant contact dermatitis (15%). Infectious diseases were poorly represented with only 5 cases (6%).The 6 most frequently represented occupations were packers in the agri-food industry (12.0%), cattle farmers and tomato greenhouse workers (both 10.7%), maintenance workers of parks and gardens (9.5%), agri-food factory cleaning operatives (8.3%) and pig farmers (7.1%). There was a marked incidence of allergic contact dermatitis and irritative contact dermatitis, mostly occupational in origin. While no specific diseases were found among these workers, some of the allergens and irritants identified may be specific to certain work environments. Overall, there did not seem to be a major risk of occupational dermatoses among workers exposed to Brittany's terrestrial fauna and flora in this population, compared with other professional sectors, such as hairdressing or care work. The incidence rate of the cases of occupational skin diseases in this population is assessed from 3 - 5 cases per 100,000 workers.


Novel classes of mouse repeated DNAs.
Mouse DNA cleaved with Eco R11 (bst NI) displays two prominent restriction bands of 1.5 and 1.7 kb in agarose gels stained with ethidium bromide. These constitute novel subsets of repeated DNA in the mouse. Sequential Hoechst 33258-CsCl gradient fractionation of mouse DNA, yielding more GC rich main band DNA, and AT rich satellite DNA, revealed that both these fragments copurified with GC rich main band DNA. They were not detected in purified satellite preparations. Together these restriction bands constituted larger than or equal to 0.2% of main band DNAs. Hybridization of 32p labelled satellite DNA to blots of Eco R11 restricted mouse DNA showed positive hybridization only to smaller satellite restriction fragments, indicating satellite DNA had little or no homology with either the 1.5 or 1.7 kb fragments. The 1.5 and 1.7 kb fragments were isolated from gels and labelled with 32p by nick translation. Using a series of restriction endonucleases each of these two fragments showed different cleavage patterns. Filter hybridization confirmed that these two fragments were distinct subsets as they did not cross hybridize with each other. They also did not hybridize to other more minor repeated non-satellite DNA bands noted in ethidium bromide stained gels. Neither of them could be assigned to ribosomal genes as they did not hybridize to 32p kinase labelled 18S and 28S RNA. Isolation of DNA from male and female mice showed comparable amounts of both the 1.5 and 1.7 kb fragments. Thus neither was Y chromosome specific. From restriction patterns, and preliminary chromosome hybridization studies, these fragments are thought to represent "interspersed" repeated sequences rather than very long tandem (satellite like) centromeric arrays. The relationship between these repeated sequence subsets, their evolution and detailed organization, and their representation in different mouse species, remain to be determined.


Tissue and molecular events in human conjunctival scarring in ocular cicatricial pemphigoid.
Detailed histomorphometric analysis of human conjunctival biopsy specimens has convincingly demonstrated that tissue remodeling of the extracellular matrix (ECM) is an essential and dynamic process associated with conjunctival scarring in ocular cicatricial pemphigoid (OCP). The conjunctival scarring often eventually results in impaired vision and/or blindness. The molecular mechanisms of conjunctival scarring are not completely understood. Accumulating evidence indicates that the early phase of conjunctival fibrosis is linked with an immuno-inflammatory process mediated by cytokines released by activated conjunctival cells and/or by infiltrating cells. Fibrogenic cytokines secreted by inflammatory cells and fibroblasts might actively be involved in remodeling of the matrix within the conjunctival stroma, possibly by regulating the altered metabolism of matrix proteins.


[Insulated arm pilomatrixoma: A rare localization. A case report].
Pilomatrixoma also known as calcified epithelioma of Malherbe, is a rare benign cutaneous tumor. It is most commonly seen in the head and neck areas, during the first two decades of life. We report a 30-year-old female patient with a rare localisation of pilomatrixoma in the right arm. The pilomatrixoma was excised and at one year follow-up there has been no evidence of recurrence.


Subacute necrotizing encephalomyelopathy. Its relationship to central pontine myelinolysis.
Clinical and neuropathological features of a case of subacute necrotizing encephalomyelopathy are discussed and compared with the features of central pontine myelinolysis. A hypothesis is offered relating the two diseases to a common aetiological factor.


Expression of CHPF modulates cell proliferation and invasion in lung cancer.
Lung cancer is the most common malignancy worldwide and is characterized by rapid progression, aggressive behavior, frequent recurrence, and poor prognosis. The TCGA database indicates that chondroitin polymerizing factor (CHPF) is overexpressed in human lung cancer tissues compared with normal tissues and this overexpression corresponds to shorter overall survival in lung cancer patients. In this study, to investigate the function of CHPF in lung cancer, lentiviral vectors expressing CHPF shRNA were stably transduced into A549 and H1299 cells. Compared to shCtrl cells, CHPF knockdown cells had significantly reduced proliferation. Furthermore, the silencing of CHPF in A549 and H1299 cells resulted in apoptotic induction, which led to decreased colony formation. Wound healing and transwell invasion assays revealed that CHPF could positively regulate the migration of lung cancer cells. The tumorigenic role of CHPF was also validated in nude mouse xenograft models. Affymetrix gene chip analysis indicated that CHPF regulated the proliferation and invasion of lung cancer cells through CDH1, RRM2, MKI67, and TNFRSF10B. We thus highlight CHPF as a novel target for lung cancer treatment.


Cerium(IV) Pyrasal Complexes: A pH-Dependent 8- to 10-Coordinate Cerium Chelate Switch.
In this work, five cerium(IV) complexes were synthesized, three of which were structural isomorphs from the same pyrasal ligand with the solid-state result identified by structural analysis dependent on the initial pH of the reaction solution and the temperature at which the reaction is performed. The ligands explored here are pyrasal ligands, which are Schiff-base ligands formed by the condensation of 2,3-diaminopyrazine and a salicylaldehyde derivative. Pyrasal ligands have weaker binding than other salophen-type ligands due to the electron-withdrawing effect of the nitrogen atoms contained within the pyrazine ring. The weaker binding leaves the ligand more susceptible to the changes in pH and temperature that alternate the chelating environment from 8- to 10-coordinate. This electron-withdrawing effect of the pyrazine backbone also deactivates the second amine after the first condensation addition of salicylaldehyde. Without a metal to template the complex formation reaction, even with extended reaction times and the addition of a large excess of ligand, the result is the addition of only one salicylaldehyde.


Apelin (APLN) regulates progesterone secretion and oocyte maturation in bovine ovarian cells.
APLN and its G-protein coupled receptor APLNR are expressed in the bovine ovary. However their role in granulosa cells and oocytes is unknown. Here, we studied their expression in bovine ovarian cells and investigated their regulation in cultured luteinizing granulosa cells in response to IGF1 and FSH. We determined the effect and the molecular mechanism of APLN (isoforms 17 and 13) on bovine granulosa cell progesterone secretion and on oocyte maturation. By RT-qPCR and immunoblot, we showed that the expression of both APLN and APLNR in granulosa and oocytes significantly increased with ovarian follicles size whereas it was similar in theca interstitial cells. In vitro, in unstimulated luteinizing bovine granulosa cells and in response to IGF1 (10-8 M) but not to FSH (10-8 M), we observed that APLN (-17 and -13) (10-9 M) increased progesterone production; this was abolished in response to the APLNR antagonist ML221. These latter effects were dependent on the MAPK ERK1/2 kinase. Furthermore, we showed that APLN (-17 and -13) (10-9 M) increased cell proliferation through AKT signaling. Conversely, the addition of APLN-13 and APLN-17 to in vitro maturation medium containing IGF1 (10-8 M) but not FSH (10-8 M) arrested most oocytes at the germinal vesicle stage, which was associated with a decrease in progesterone secretion, an inhibition in MAPK ERK1/2 phosphorylation and an increase in PRKA phosphorylation in oocytes. Thus, APLN can increase progesterone secretion and cell proliferation in bovine luteinizing granulosa cells in vitro, while it blocks meiotic progression at the germinal vesicle stage during bovine oocyte in vitro maturation.


[Chronological age estimation based on dental panoramic radiography].
Determination of the dental age is a valuable tool in planning of orthodontic treatment and could be used to estimate the chronological age of unidentified human beings. Among the various age estimation methods one of the most accepted one is the Demirjian method, which has already been modified to selected Hungarian population. In this study we have evaluated the association between the dental age determined by panoramic radiography and the chronological age. 199 panoramic radiographs taken from persons between the ages of 2,8 and 20,3 years were selected to the study. The dental ages of persons were estimated either with the Demirjian or the modified Demirjian method adapted to Hungarian population and the results were compared to the chronological ages in selected age groups. Furthermore the angle of the mandible was registered on both sides with an image analysing software. Statistical analysis of data was performed using SPSS software. Our results show that mean values of mandibular angles exhibited a decreasing trend with age. The two age determination methods resulted in different values. Between 3 and 9 years and the age group between 15 and 17,3 years the adapted Hungarian method proved to be more accurate than the Demirjian method. We have established a mathematical function between the two methods. We could conclude that the panoramic radiography based dental age calculation is a reliable method to estimate the chronological age, but the utility of gonial angle has not been proved.


Eliminating Concentration Polarization with Cationic Covalent Organic Polymer to Promote Effective Overpotential of Nitrogen Fixation.
Electrocatalytic nitrogen reduction reaction offers a sustainable alternative to the conventional Haber-Bosch process. However, it is currently restricted by low effective overpotential due to the concentration polarization, which arises from accumulated products, ammonium, at the reaction interface. Here, a novel covalent organic polymer with ordered periodic cationic sites is proposed to tackle this challenge. The whole network exhibits strong positive charge and effectively repels the positively charged ammonium, enabling an ultra-low interfacial product concentration, and successfully driving the reaction equilibrium to the forward direction. With the given potential unchanged, the suppressed overpotential can be much liberated, ultimately leading to a continuous high-level reaction rate. As expected, when this tailored microenvironment is coupled with a transition metal-based catalyst, a 24-fold improvement is generated in the Faradaic efficiency (73.74 %) as compared with the bare one. The proposed strategy underscores the importance of optimizing dynamic processes as a means of improving overall performance in electrochemical syntheses.


Motor deficits in homozygous and heterozygous p/q-type calcium channel mutants.
P/Q-type voltage-dependent Ca(2+) channels (VDCCs) are highly expressed in the cerebellum, and mutations of these channels are associated with disrupted motor function. Several allelic variants of the alpha1A pore-forming subunit of P/Q-type VDCCs have been described, and mice homozygous for these mutations exhibit gait ataxia, as do alpha1A knockout mice. Here we report that heterozygous alpha1A mutants also have a motor phenotype. Mice heterozygous for the leaner and alpha1A knockout mutations exhibit impaired motor learning in the vestibulo-ocular reflex (VOR), suggesting that subtle disruption of P/Q Ca(2+) currents is sufficient to disrupt motor function. Basal VOR and optokinetic reflex performance were normal in the heterozygotes but severely impaired in the leaner and alpha1A knockout homozygotes.


Amygdala activity can be modulated by unexpected chord functions during music listening.
Numerous earlier studies have investigated the cognitive processing of musical syntax with regular and irregular chord sequences. However, irregular sequences may also be perceived as unexpected, and therefore have a different emotional valence than regular sequences. We provide behavioral data showing that irregular chord functions presented in chord sequence paradigms are perceived as less pleasant than regular sequences. A reanalysis of functional MRI data showed increased blood oxygen level-dependent signal changes bilaterally in the amygdala in response to music-syntactically irregular (compared with regular) chord functions. The combined data indicate that music-syntactically irregular events elicit brain activity related to emotional processes, and that, in addition to intensely pleasurable music or highly unpleasant music, single chord functions can also modulate amygdala activity.


Genetic mapping of mutations in a highly radiation-resistant mutant of Salmonella typhimurium LT2.
The genes involved in the high radiation resistance of mutant R68 of Salmonella typhimurium LT2 were mapped by conjugation. It was observed that the high radiation resistance involved genes localized in two regions of the chromosome, which have been designated as garA and garB for high gamma resistance. The garA gene mapped near gal and uvrB at about 18 map units, and the garB gene mapped near purC at about 49 map units. The resistance of R68 was reduced to the wild-type level by the acquisition of the two wild-type alleles, garA+ and garB+. Recombinants carrying the garA or garB gene repaired single-strand breaks in their DNA faster than did the wild-type strain. However, only those with the garA mutation showed a marked increase in UV irradiation resistance above the wild-type level, whereas those with garB mutation exhibited an increased rate of spontaneous degradation of DNA beyond the level observed in recA cells.


Tobacco rattle virus genome alterations in the Hosta hybrid 'Green Fountain' and other plants: reassortments, recombinations and deletions.
Tobacco rattle virus from a Hosta hybrid contained one RNA1 (Ho-1) and two RNA2 species (Ho-2a, Ho-2b). Whereas Ho-1 resembles TRV Al RNA1 from Alstroemerias, Ho-2a and Ho-2b resemble TRV TpO1 RNA2 from a potato field. Ho-2a has a complete RNA2-specific sequence, whereas that of Ho2-b carries a large deletion. The short RNA1-related 3' end of Ho-2a is distinct from that of Ho-1, whereas the longer one of Ho-2b is identical to that of Ho-1. TRV RNA2 molecules may apparently become associated with different TRV RNA1 molecules, from which they can acquire 3'ends of various lengths while often losing large portions of their RNA2-specific sequences.


Assessing the impact of in-utero exposures: potential effects of paracetamol on male reproductive development.
Human male reproductive disorders (cryptorchidism, hypospadias, testicular cancer and low sperm counts) are common and some may be increasing in incidence worldwide. These associated disorders can arise from subnormal testosterone production during fetal life. This has resulted in a focus on in-utero environmental influences that may result in reproductive effects on the offspring in later life. Over recent years, there has been a dramatic increase in the scientific literature describing associations between in-utero environmental exposures (eg, industrial chemicals and pharmaceuticals) and subsequent reproductive outcomes in male offspring. This includes studies investigating a potential role for in-utero analgesic exposure(s) on the fetal testis; however, providing definitive evidence of such effects presents numerous challenges. In this review, we describe an approach to assessing the potential clinical relevance of in-utero (and postnatal) environmental exposures on subsequent male reproductive function using exposure to the analgesic paracetamol as an example.


Vitamin U prevents valproic acid-induced liver injury through supporting enzymatic antioxidant system and increasing hepatocyte proliferation triggered by inflammation and apoptosis.
The aim of this study was to investigate the cellular mechanisms that cause valproic acid (VPA)-induced liver damage and the therapeutic effect of Vitamin U (Vit U) on these mechanisms. Female Sprague Dawley rats were randomly divided into four groups: intact control animals, animals that received Vit U (50 mg/kg/day), animals given VPA (500 mg/kg/day), and animals given both VPA and Vit U. The rats in the Vit U + VPA group were administered Vit U by gavage an hour before VPA administration every day for 15 days. Liver tissues were evaluated through histopathological, biochemical, immunohistochemical, and Western blotting techniques. Administration of Vit U with VPA resulted in (i) prevention of histopathological changes caused by VPA; (ii) blockage of the decrease in catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), and superoxide dismutase (SOD) activities; prevention of the elevation in gamma-glutamyl transferase (GGT) activity and advanced oxidation protein products (AOPP) level; (iii) increased in the levels of interleukin-1 beta (IL-1β), active caspase-3, and cytoplasmic cytochrome c; (iv) increase in cleaved poly (ADP-ribose) polymerase (PARP) level and decrease in LC3B (II/I) ratio; (v) increase in the number of proliferating cells nuclear antigen (PCNA) positive hepatocytes. These findings show that Vit U prevents liver damage caused by VPA through increasing the antioxidant enzyme capacity and hepatocyte proliferation by triggering inflammation and apoptosis. These findings suggest that Vit U provides its protective effects against VPA-induced liver damage by stimulating homeostasis and regeneration.


Time-dependent optimized coupled-cluster method for multielectron dynamics. IV. Approximate consideration of the triple excitation amplitudes.
We present a cost-effective treatment of the triple excitation amplitudes in the time-dependent optimized coupled-cluster (TD-OCC) framework called TD-OCCDT(4) for studying intense laser-driven multielectron dynamics. It considers triple excitation amplitudes correct up to the fourth-order in many-body perturbation theory and achieves a computational scaling of O(N7), with N being the number of active orbital functions. This method is applied to the electron dynamics in Ne and Ar atoms exposed to an intense near-infrared laser pulse with various intensities. We benchmark our results against the TD complete-active-space self-consistent field (TD-CASSCF), TD-OCC with double and triple excitations (TD-OCCDT), TD-OCC with double excitations (TD-OCCD), and TD Hartree-Fock (TDHF) methods to understand how this approximate scheme performs in describing nonperturbatively nonlinear phenomena, such as field-induced ionization and high-harmonic generation. We find that the TD-OCCDT(4) method performs equally well as the TD-OCCDT method, almost perfectly reproducing the results of the fully correlated TD-CASSCF with a more favorable computational scaling.


Reference-based pricing: an evidence-based solution for lab services shopping.
To determine the effect of reference-based pricing (RBP) on the percentage of lab services utilized by members that were at or below the reference price. Retrospective, quasi-experimental, matched, case-control pilot evaluation of an RBP benefit for lab services. The study group included employees of a multinational grocery chain covered by a national health insurance carrier and subject to RBP for lab services; it had access to an online lab shopping tool and was informed about the RBP benefit through employer communications. The reference group was covered by the same insurance carrier but not subject to RBP. The primary end point was lab compliance, defined as the percentage of lab claims with total charges at or below the reference price. Difference-in-difference regression estimation evaluated changes in lab compliance between the 2 groups. Higher compliance per lab claim was evident for the study group compared with the reference group (69% vs 57%; P<.05). The online shopping tool was used by 7% of the matched-adjusted study group prior to obtaining lab services. Lab compliance was 76% for study group members using the online tool compared with 68% among nonusers who were subject to RBP (P<.01). RBP can promote cost-conscious selection of lab services. Access to facilities that offer services below the reference price and education about RBP improve compliance. Evaluation of the effect of RBP on higher-cost medical services, including radiology, outpatient specialty, and elective inpatient procedures, is needed.


Bone mineral density loss in clinically suspect arthralgia is associated with subclinical inflammation and progression to clinical arthritis.
Peripheral bone mineral density (BMD) may be decreased in early rheumatoid arthritis (RA) but it is unknown whether BMD loss emerges before arthritis is clinically apparent. We aimed to study whether BMD loss occurs in patients with clinically suspect arthralgia (CSA), and whether it is associated with progression to clinical arthritis and magnetic resonance imaging (MRI)-detected subclinical inflammation. Patients with CSA had arthralgia for <1 year and were at risk of progressing to RA according to their rheumatologists. At baseline, a 1.5 T MRI was performed of unilateral metacarpophalangeal, wrist, and metatarsophalangeal joints, and scored on synovitis, bone marrow oedema, and tenosynovitis;. summing these features yielded the total MRI inflammation score. Digital X-ray radiogrammetry (DXR) was used to estimate BMD on two sequential conventional hand radiographs (mean interval between radiographs 4.4 months). The change in BMD was studied; BMD loss was defined as a decrease of ≥2.5 mg/cm2/month. Patients were followed for arthritis development for a median of 18.4 months. In CSA patients (n = 108), change in BMD was negatively associated with age (β = -0.03, p = 0.007). BMD loss in CSA patients was associated with arthritis development [adjusted for age hazard ratio (HR) = 6.1, 95% confidence interval (CI) 1.7 to 21.4] and was most frequently estimated in the months before clinical arthritis development. The total MRI inflammation scores were associated with the change in BMD (adjusted for age β = -0.05, p = 0.047). The total MRI inflammation score and BMD loss were both independently associated with arthritis development (HR = 1.1, 95% CI 1.1 to 1.2, and HR = 4.6, 95% CI 1.2 to 17.2, respectively). In CSA patients, severe BMD loss is associated with MRI-detectable subclinical inflammation and with progression to clinical arthritis.


Childhood obesity and risk of cardiovascular disease: a review of the science.
Childhood obesity has been connected to hyperlipidemia, diabetes, hypertension, and atherosclerosis (Klish, 1998). Both genetic and environmental influences play a role in the development of obesity. Prevention of obesity in childhood is the best chance of instituting lifestyle change for the reduction of cardiovascular morbidity and mortality. Children at high risk for obesity-related cardiovascular disease (CVD) should receive family-based individualized treatment. Nurse practitioners practicing in the primary care setting are in an ideal position to address children and families with regard to lifestyle modification of diet and exercise.


Lipid peroxidation and antioxidant enzymes in gestational diabetics.
The exact pro-oxidant and antioxidant status in gestational diabetes is still unclear. To add new insight to the question, changes in the lipid peroxidation products (MDA) and activities of antioxidant enzymes: superoxide dismutase (SOD) and catalase in red blood cell hemolysates were evaluated in 20 women with gestational diabetes. 20 healthy pregnant women served as the control group. Statistical analysis was done using unpaired Student' t - test. Pregnant women with gestational diabetes showed an increase in lipoperoxidation products (P < 0.001) and a decrease in SOD activity (P < 0.01) as compared to normal pregnant women while no significant change was observed in catalase activity. These findings suggest increased oxidative stress and decreased detoxification or free radical scavenging capacity in pregnancy complicated by diabetes.


Does magnetic resonance imaging make a difference for patients with musculoskeletal sarcoma?
MR imaging has had an unparalleled impact on the treatment of patients with musculoskeletal sarcoma. Basically, the high accuracy of local staging has made the introduction of reconstructive and limb salvage procedures instead of amputation of disarticulation available to the majority of patients with musculoskeletal sarcoma. Pre-operative work-up with MRI is not only more accurate, but also much faster and cheaper than the conventional work-up. Staging is the single most important reason for performing MR imaging in patients with musculoskeletal tumours. The impact of MR specificity is less dramatic but the benefit to the patient is an increased safety margin. When diagnostic errors with devastating consequences are made nowadays, it is usually because the proper protocol has not been followed. A patient with a potentially malignant, or equivocal, musculoskeletal mass deserves to have a combined radiographic-MRI examination prior to invasive procedures. MRI does not currently have a major impact on chemotherapy decisions and colour Doppler ultrasound has a higher accuracy than MRI. However, selected cases, i.e. intraosseous tumours, dynamic Gd-enhanced MRI, can replace colour Doppler ultrasound.


A semiautomated journal check-in and binding system; or variations on a common theme.
The journal check-in project described here, though based on a computerized system, uses only unit-record equipment and is designed for the medium-sized library. The frequency codes used are based on the date printed on the journal rather than on the expected date of receipt, which allows for more stability in the coding scheme. The journal's volume number and issue number, which in other systems are usually predetermined by a computer, are inserted at the time of check-in. Routine claiming of overdue issues and a systematic binding schedule have also been developed as by-products.


Phenotypic sensitivity to activated protein C in healthy families: importance of genetic components and environmental factors.
The relative importance of environmental factors and genetic components other than factor V Leiden on the sensitivity to activated protein C (APC) in healthy nuclear families was determined. We studied 149 European families (298 parents and 278 biological offspring aged more than 6 years). APC response was measured and expressed as normalized APC-sensitivity ratio (n-APC-SR). Subjects were genotyped for G1691A and G20210A polymorphisms of factor V and II genes; levels of factors II, V and VIII, antithrombin, cholesterol, high-density lipoprotein cholesterol and triglycerides were measured. After identifying variables influencing the n-APC-SR by a stepwise multiple regression model, variance component analysis was used. The heritability (proportion of the overall variability of a trait due to polygenic effects) of n-APC-SR was determined after adjustment for all clinical and laboratory variables, including factor V Leiden. Heritability coefficients (mean +/- standard deviation) were different for males (0.68 +/- 0.06) and females (0.34 +/- 0.12) younger than 25 years and in subjects older than 25 years: 0.37 +/- 0.09. This analysis provides strong evidence for a polygenic component influencing n-APC-SR in addition to factor V Leiden and suggests age- and gender-specific genetic effects.


Age-, gender-, and socioeconomic status-specific incidence of Parkinson's disease and parkinsonism in northeast Scotland: the PINE study.
There have been few high quality incidence studies of Parkinson's disease (PD). We measured age-, gender- and socioeconomic-specific incidence rates for parkinsonism and PD in north-east Scotland, and compared our results with those of previous high quality studies. Incident patients were identified prospectively over three years by several overlapping methods from primary care practices (total population 311,357). Parkinsonism was diagnosed if patients had two or more cardinal motor signs. Drug-induced parkinsonism was excluded. Patients had yearly follow-up to improve diagnostic accuracy. Incidence rates using clinical diagnosis at latest follow-up were calculated for all parkinsonism and for PD by age, gender and socioeconomic status. Meta-analysis with similar studies was performed. Of 377 patients identified at baseline with possible or probable parkinsonism, 363 were confirmed as incident patients after median follow-up of 26 months (mean age 74.8 years, SD 9.8; 61% men). The crude annual incidence of parkinsonism was 28.7 per 100,000 (95% confidence interval (CI) 25.7-31.8) and PD 17.9 per 100,000 (95% CI 15.5-20.4). PD was more common in men (age-adjusted male to female ratio 1.87:1, 95% CI 1.55-2.23) but there was no difference by socioeconomic status. Meta-analysis of 12 studies showed an incidence of PD (adjusted to the 1990 Scottish population) of 14.6 per 100,000 (95% CI 12.2-17.3) with considerable heterogeneity (I(2) 95%), partially explained by population size and recruitment duration. The incidence of PD was similar to other high quality studies. The incidence of PD was not affected by socioeconomic status.


Measurement of platelet aggregation during antiplatelet therapy in ischemic stroke.
Aspirin, ticlopidine and clopidogrel are used as a pharmacological means to efficiently decrease the number of reoccurrence of ischemic stroke (100-325 mg/d). This antiplatelet treatment could prevent the secondary stroke by approximately 22%. Laboratory effective platelet inhibition for the clinician, and methods for routine screening evaluation for the laboratory were studied. (1) For the standardisation of platelet aggregation technology blood samples of 150 healthy persons were studied in 5 centres. CARAT TX computerised optical aggregometer was used for measuring with collagen (2 microg/ml), epinephrine (10 microM), arachidonic acid 0.5 mM and ADP 5 microM as inductors. (2) Laboratory tests were compared in each centres performed in platelet-rich plasma of ischemic cardiovascular and stroke patients (n=823) taking 100-325 mg aspirin/d. (3) Blood samples of 555 ischemic stroke patients treated with aspirin (100-325 mg/d), 96 patients treated with ticlopidine (500 mg/d), and 67 patients treated with clopidogrel (75 mg/d) were evaluated, respectively.(1) The mean of maximal aggregation (%) - 2SD of untreated controls (n=150) were detected for collagen with 64%, epinephrine 59% and ADP 62%. (2) In 823 aspirin treated patients were found similar inhibition in different centres with same methods for standardisation. The mean inhibition level was in case of collagen 38%, epinephrine 37% and ADP 61%. (3) The distribution of ineffective platelet inhibition was detected in 17% of aspirin group (collagen and epinephrine), 4% of ticlopidine and 18% of clopidogrel group with ADP, respectively. Our findings were in the stroke cohort: effective inhibition levels: 36% in aspirin group, 73% in ticlopidine and 25% treated with clopidogrel. Platelet aggregation tests could help to find the optimal, and "custom taylored" dose of antiaggregating drugs in the secondary prevention of ischemic stroke.


Curcumin Attenuates Angiotensin II-Induced Abdominal Aortic Aneurysm by Inhibition of Inflammatory Response and ERK Signaling Pathways.
Background and Objectives. Curcumin has long been used to treat age-related diseases, such as atherosclerosis and coronary heart disease. In this study, we explored the effects of curcumin on the development of abdominal aortic aneurysm (AAA). Methods. ApoE(-/-) mice were randomly divided into 3 groups: AngII group, AngII + curcumin (AngII + Cur) group (100 mg/kg/d), and the control group. Miniosmotic pumps were implanted subcutaneously in ApoE(-/-) mice to deliver AngII for 28 days. After 4-week treatment, abdominal aortas with AAA were obtained for H&E staining, immunohistochemistry, and Western blotting. Results. The results showed that curcumin treatment significantly decreased the occurrence of AAA. The levels of macrophage infiltration, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factors-α (TNF-α) were significantly lower in AngII + Cur group than those in AngII group (all P < 0.01). The level of superoxide dismutase (SOD) was significantly higher in AngII + Cur group than those in AngII group (P < 0.01). The ERK1/2 phosphorylation in AngII + Cur group was significantly lower than that in AngII group (P < 0.01). Conclusions. These results suggested that curcumin can inhibit the AngII-induced AAA in ApoE(-/-) mice, whose mechanisms include the curcumin anti-inflammation, antioxidative stress, and downregulation of ERK signaling pathway.


Gene expression profiling of primary fibrochondrocyte cultures in traumatic and degenerative meniscus lesions.
This study aimed to investigate how fibroblastic and chondrocytic properties of human meniscal fibrochondrocytes are affected in culture conditions according to the type of meniscal pathology and localization, and to provide basic information for tissue-engineering studies. Primary fibrochondrocyte cultures were prepared from meniscus samples of patients who had either traumatic tear or degeneration due to osteoarthritis. Cultures were compared in terms of mRNA expression levels of COL1A1, COL2A1, COMP1, HIF1A, HIF2A, and SOX9 and secreted total collagen and sulfated sGAG levels according to the type of meniscal pathology, anatomical localization, and the number of subcultures. mRNA expression levels of COL1A1, COMP1, HIF1A, HIF2A, and SOX9 were found to be increased in subsequent subcultures in all specimens. COL1A1 mRNA expression levels of both lateral and medial menisci of patients with traumatic tear were significantly higher than in patients with degenerative pathology, indicating a more fibroblastic character. P1 subculture of lateral and P3 or further subculture of medial meniscus showed more fibroblastic characteristics in patients with degenerative pathology. Furthermore, in patients with degenerative pathology, the subcultures of the lateral meniscus (especially on the inner part) presented more chondrocytic characteristics than did those of medial meniscus. The mRNA expression levels of the cultures showed significant differences according to the anatomical localization and pathology of the meniscus, indicating distinct chondrocytic and fibroblastic features. This fundamental knowledge would help researchers to choose more efficient cell sources for cell-seeding of a meniscus scaffold, and to generate a construct resembling the original meniscus tissue.


Nucleotide sequence and expression of the cloned gene of bacteriophage SP6 RNA polymerase.
The coding region of the gene for bacteriophage SP6 RNA polymerase was cloned into pBR322, and its entire nucleotide sequence was deduced. The predicted amino acid sequence for the polymerase consists of 874 amino acid residues with a total molecular weight of 98,561 daltons. Comparison of the amino acid sequence with that of T7 RNA polymerase reveals that regions with partial homology are present along the sequence. The coding region of SP6 RNA polymerase was inserted into an E. coli expression vector. The polymerase gene was efficiently expressed in E. coli cells, and the enzymatic properties of the expressed polymerase were very similar to those of the enzyme synthesized in SP6 phage-infected Salmonella typhimurium cells.


[Ascaris lumbricoides: heterogeneity in ABO epithopes expression].
Ascaris lumbricoides and its hosts can present the same ABO System epithopes. The aim was to study ABO epithopes expression in A. lumbricoides by Inhibition Agglutination Test using different monoclonal antibodies and policlonal sera. We worked with 27 parasite extracts (14 extracts from A Group patients, 2 AB Group 1, B Group and 10 from unknown ABO Group patients). Inhibition Agglutination Test was made facing the extracts from A, AB and unknown ABO Group patients against monoclonal antibodies and policlonal serum of A specificity and the extracts from B, AB and unknown ABO Group patients against monoclonal antibodies and policlonal serum of B specificity. The Semiquantitative Test was made with the extracts which inhibited the agglutination of any antibody. The 50% of the parasite extracts faced against A specificity antibodies and the 46% of the parasite extracts faced against B specificity antibodies significantly inhibited the agglutination in the Semiquantitative Test. No extract inhibited the totality of the antibodies. All the antibodies reacted with some extract, except one antibody of B specificity. The ABO activity in the extracts was independent of the antibody's immunoglobulin class, titre and concentration and it only was dependent on the antibody union with the epithope at which the antibody is directed. The heterogeneity in the ABO epithopes expression of A.lumbricoides might be involved in the escape of the host's immune response. The used Inhibition Tests are sensitive, simple, rapid and economic. We conclude that the use of different antibodies alows the best definition of the antigen-antibody specificity.


Genotypic variation in spike fertility traits and ovary size as determinants of floret and grain survival rate in wheat.
Spike fertility traits are critical attributes for grain yield in wheat (Triticum aestivum L.). Here, we examine the genotypic variation in three important traits: maximum number of floret primordia, number of fertile florets, and number of grains. We determine their relationship in determining spike fertility in 30 genotypes grown under two contrasting conditions: field and greenhouse. The maximum number of floret primordia per spikelet (MFS), fertile florets per spikelet (FFS), and number of grains per spikelet (GS) not only exhibited large genotypic variation in both growth conditions and across all spikelet positions studied, but also displayed moderate levels of heritability. FFS was closely associated with floret survival and only weakly related to MFS. We also found that the post-anthesis process of grain set/abortion was important in determining genotypic variation in GS; an increase in GS was mainly associated with improved grain survival. Ovary size at anthesis was associated with both floret survival (pre-anthesis) and grain survival (post-anthesis), and was thus believed to 'connect' the two traits. In this work, proximal florets (i.e. the first three florets from the base of a spikelet: F1, F2, and F3) produced fertile florets and set grains in most cases. The ovary size of more distal florets (F4 and beyond) seemed to act as a decisive factor for grain setting and effectively reflected pre-anthesis floret development. In both growth conditions, GS positively correlated with ovary size of florets in the distal position (F4), suggesting that assimilates allocated to distal florets may play a critical role in regulating grain set.


Preparation of caffeic acid phenethyl ester-incorporated nanoparticles and their biological activity.
The aim of this study is to fabricate caffeic acid phenethyl ester (CAPE)-incorporated nanoparticles using methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) (CE) copolymer and to study their antitumor activity against pulmonary metastasis model of CT26 colon carcinoma cells. CAPE-incorporated nanoparticles showed spherical shapes having small diameters less than 300 nm and CAPE was continuously released from CE nanoparticles over 4 days. CAPE-incorporated polymeric micelles properly inhibited proliferation and induced apoptosis of CT26 cells as well as CAPE itself. Furthermore, they showed similar anti-invasive and antimigrative effect against CT26 cells at in vitro compared with CAPE itself, indicating that CAPE-incorporated nanoparticles have at least equivalent anticarcinogenic activity against CT26 cells compared with CAPE itself. At pulmonary metastasis model of CT26 cells using nude mouse, CAPE-incorporated nanoparticles have superior antimetastatic efficacy against, that is, control treatment with pulmonary metastasis model showed significant increase of lung weight because of the metastasis of tumor cells, whereas CAPE or CAPE-incorporated nanoparticles properly inhibited metastasis of tumor cells. We suggest CAPE-incorporated nanoparticles as a promising candidate for antimetastatic chemotherapeutic agent. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:144-154, 2015.


Effect of various sources of organic carbon and high nitrite and nitrate concentrations on the selection of denitrifying bacteria. I. Stationary cultures.
The effect of methanol, ethanol, acetic acid and glucose together with NaNO2 or KNO3 (1,000 mg N/l) on the intensity of denitrification and selection of denitrifying bacteria from the bottom sludge of nitrogenous wastewater reservoir was examined. Denitrification was found to be the most efficient in medium with ethanol or acetic acid. The presence of glucose facilitated the selection of Alcaligenes faecalis whereas the other carbon sources enabled the selection of bacteria of the genus Pseudomonas: methanol -- P. fluorescens, ethanol -- P. mendocina. In medium with acetic acid species selection depends on the form of nitrogen: NaNO2 -- P. fluorescens, KNO3 -- P. aeruginosa.