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one hundred and twentynine dogs with pituitarydependent hyperadrenocorticism were treated according to a protocol aimed at the complete destruction of the adrenal cortices by the administration of opddd mitotane at a daily dose of to mgkg bodyweight for days on the third day glucocorticoid and mineralocorticoid supplementation was begun for the induced HPA insufficiency the first followup examination after completion of the day course and the subsequent twiceyearly followup examinations included PE and measurements of plasma concentrations of sodium and potassium to optimise substitution therapy in dogs the full course of days treatment could not be completed of the dogs which received the full course of treatment the administration had to be stopped temporarily in because of sideeffects such as anorexia and vomiting the actual dose of opddd administered was not significantly different in the dogs with and without these sideeffects clinical remission occurred in dogs per cent of which per cent had a relapse the estimated oneyear diseasefree fraction was per cent per cent confidence interval ci to per cent the estimated oneyear survival fraction was per cent per cent ci to per cent the twoyear survival was per cent per cent ci to per cent and the threeyear survival was per cent per cent ci to per cent the bodyweight and age of the dog and vomiting occurring during the period of treatment were positively correlated with the length of the diseasefree period whereas weakness during the treatment and resistance to dexamethasone suppression of the urinary corticoidcreatinine ratios at the start of the treatment were associated with a relatively short survival time
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antibodies to anaplasma marginale were detected by the indirect fluorescent antibody test ifa in six of serum samples of whitetailed deer odocoileus virginianus from louisiana none of the SS samples were positive using the a marginale modified rapid CATT of the six ifa positive sera retested by the complement fixation test four sera gave anticomplementary and two gave SP reactions the low a marginale reactor rate in this whitetailed deer population was probably a reflection of the lack of cohabitation between cattle and deer and the fact that the primary arthropod vectors in louisiana are tabanids the validity of the indirect FAT for a marginale antibodies in whitetailed deer should be evaluated
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to investigate the feasibility of dynamic contrastenhanced magnetic resonance imaging dcemri for perfusion quantification of gastric cancers and to correlate the dcemri parameters with the pathological prognostic factors
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the tulobuterol TD therapeutic system tts is the worlds first commercially available TD preparation of tulobuterol a beta stimulant that can maintain effective blood tulobuterol levels for hours when applied once daily in the present study a total of adult patients with mildly persistent step or moderately persistent step bronchial asthma who were using inhalational steroids and who were not used tulobuterol tts for one year and underwent measurement of peak expiratory flow pef once daily IP eosinophil count serum eosinophil cationic protein ecp level and airway responsiveness dmin were evaluated at months and year T3 the start of the T0 pef exhibited significant improvements at months and year in patients treated with or without inhalational CS while SS ecp was improved significantly only in the patients on inhalational CS patients not using inhalational steroids exhibited no significant exacerbation of dmin at either months or year oneyear treatment with tulobuterol tts did not appear to cause tachyphylaxis the significant improvements in dmin at months and year in the patients using inhalational CS suggested that inhalational CS offer beneficial effects in controlling airway inflammation tulobuterol tts is considered quite beneficial in improving SQ of life qol in patients with bronchial asthma because its incidence of adverse effects including palpitations and shivering is significantly lower than those of oral preparations because of its remarkable improvement of pulmonary CF and symptoms of AO without increasing airway responsiveness even after repeated use and because it is simple to use and offers excellent clinical efficacy
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the earliest step in establishing the complex neuronal networks in the vertebrate BB is the formation of a scaffold of axon tracts how the formation of the early axon scaffold is controlled at the molecular level is unclear forming part of the scaffold neurons located at the ventral midbrainforebrain border mfb give rise to the medial longitudinal fascicle mlf and the posterior commissure pc we demonstrate that the homeobox genes sax six emx and pax are expressed in distinct domains in this area suggesting that the specification of mlf and pc SN might be controlled by the combinatorial activity of these transcription factors we have tested this hypothesis by analysing the CF of sax in the embryonic chick brain gainoffunction experiments with sax result in alterations to the early axon scaffold most prominently an enlargement of the mlf at the expense of the pc ectopic expression of sax also affects the expression of other ventral homeobox genes particularly six and emx our results indicate that the specification of neurons forming the early axon scaffold is governed by a homeobox code thus resembling the mechanism of neuronal specification in the spinal cord
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gatifloxacin tequin kyorin pharmaceutical co ltd is a new fluoroquinolone with a broad spectrum of activity for pathogens implicated in CA respiratory tract infections including grampositive negative and atypical bacteria excellent oral BA a halflife allowing oncedaily administration and excellent penetration into respiratory tissues are desirable pharmacokinetic characteristics of gatifloxacin monte carlo simulation of gatifloxacin in streptococcus pneumoniae infection demonstrates that adequate C2 of pharmacokineticpharmacodynamic parameters are obtained with gatifloxacin in almost all instances in RCT and a C1 openlabel communitybased study gatifloxacin has shown excellent clinical and bacteriological efficacy in ABS acute exacerbations of CB and CA pneumonia current guidelines recommend the initial empiric use of gatifloxacin along with the other new fluoroquinolones for CA respiratory tract infection in patients who have increased likelihood of infection with resistant pathogens another group of patients where this agent is recommended for initial antimicrobial therapy are those who because of underlying disease andor comorbid conditions need an antibiotic with high antimicrobial tau to achieve optimal outcomes
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modulations of the inotropic and chronotropic effects of ouabain and protein kinase c pkc stimulation with phorbol esters in rat RA atria were examined cumulative administration of ouabain microm caused a PIE in a concentrationdependent manner but did not produce a chronotropic effect a single administration of ouabain microm also had similar effects n p in the CF and n p in the sinus rate addition of phorbol esters reinforced the ouabainevoked PIE n p with microm betaphorboldibutyrate pdb and n p with microm otetradecanoylphorbolacetate tpa simultaneously the mixture of ouabain and phorbol ester raised the resting tension phorbol esters CT caused a positive inotropic effect by about nonpkc activating PDBu alphaphorboldidecanoate pdd microm did not have any effect i.c.v. with the ST microm significantly decreased the ouabaininduced positive inotropic effect and caused a negative chronotropic effect but h isoquinolinylsulphonylmethylpiperazine dihydrochloride microm had no effect these results suggest that pkc stimulation may be involved in the ouabainevoked responses in the RA atria of rat as seen by increased cellular ca concentration and casensitivity thus the positive inotropic effect may not be due only to modulation of nak pump activity
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primary sclerosing cholangitis is an enigmatic disease affecting the bile ducts eventually leading to liver failure necessitating liver transplantation in many cases there is currently no therapy that has proven to halt PD one of the reasons for this is the lack of proper endpoints to measure the effect of medical MI on the course of the disease relevant clinical endpoints such as death or liver transplantation occur too infrequently in this orphan disease to be used as endpoints in phase or trials it is therefore of utmost importance to identify AGA surrogate endpoints that are reasonably likely to measure true clinical benefit this article will discuss a number of surrogate endpoints that are likely candidates to serve this role this article is part of a special issue entitled cholangiocytes in health and diseaseedited by jesus banales marco marzioni nicholas larusso and peter jansen
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the intracellular ca concentration ca was monitored in single magnocellular neurones freshly isolated from rat supraoptic nucleus application of nm vasopressin increased ca two types of ca responses were observed i a transient response displayed by of the vasopressinsensitive neurones and ii a sustained response displayed by of the vasopressinsensitive neurones among responding neurones were vasopressin CS were oxytocin sensitive and were sensitive to both peptides responses to vasopressin were dose dependent showed a progressive desensitization after successive applications were specifically blocked by the va vasopressin receptor antagonist sr and were unaffected by the oxytocin receptor antagonist dchovt vasopressin responses were completely suppressed by the removal of external ca the intracellular ca mobilizers caffeine and tbubhq did not affect resting or vasopressininduced ca changes thapsigargin nm on its own evoked an increase in ca and reduced the ca increase evoked by vasopressin by suggesting that thapsigarginsensitive ca stores are partially involved in the vasopressin response immunocytochemical identification revealed that vasopressinresponding neurones synthesize vasopressin whereas oxytocinresponding neurones synthesize oxytocin in conclusion vasopressin partially external ca dependent and oxytocin totally external ca independentinduced ca changes are mediated by TPS receptors in addition vasopressin and oxytocin neurones are specifically autoregulated by their own peptides
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modified vaccinia ankara mva is an attenuated virus mva induces the production of ifn and fltl fl which results in the expansion of dendritic cells dc and enhanced resistance against viral infections we report on the interplay among ifn fl and dc in the resistance against heterologous virus after injection of neonatal mice with mva the induction of serum fl was tested on day and the expansion of dc was tested wk T3 treatment with mva at this time point the resistance against infection with rat virus was also determined T3 mva treatment SS fl was enhanced and dc including plasmacytoid cells in SP alpha TNF production and their potential relationship with bacterial products of enteric origin in alcoholic cirrhosis
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inhibin has been suggested to play a role in gonadal feedback regulation of folliclestimulating hormone fsh secretion however neither the halflife nor the time course of action of recombinant inhibin has been reported in any primate species we sought to determine the disappearance halflife of circulating endogenous inhibin following castration in adult male monkeys macaca fascicularis and to determine the halflife of administered recombinant human inhibin a and its effect on bioactive fsh and luteinizing hormone lh levels in castrate monkeys endogenous inhibin fell from ul mean sem n prior to castration to ul at hours and ul at day p at hours vs day PCD limit of assay ul the early phase halflife of endogenous inhibin was minutes between and T2 and a later phase halflife of minutes was observed between and hours following castration recombinant inhibin exhibited a minute early phase halflife between and T2 following the micrograms intravenous iv recombinant inhibin dose and a later phase halflife of T2 between and hours in castrate monkeys n serum inhibin levels were maintained within or above the precastration range for T2 single dose recombinant inhibin micrograms subcutaneous sc or IM im administered to castrate monkeys n achieved and maintained normal serum inhibin C2 for hoursabstract truncated at words
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epidemiological clinical and laboratory studies have provided definitive evidence that physical activity is able to improve fitness and reduce cardiovascular morbidity and mortality moreover physical exercise also seems to significantly reduce the risk of developing other chronic diseases such as obesity osteoporosis diabetes tumours and depression promoting PCS activity in the GP is therefore one of the primary objectives of our healthcare institutions although the benefits of an AS lifestyle have been demonstrated by numerous scientific data only a few numbers of italians and europeans take up regular PE to promote physical activity both in the GP and in subjects affected by cardiovascular diseases the italian federation of sports medicine the italian society of sports cardiology the italian association of hospital cardiologists the italian society of cardiology the italian association of outofhospital cardiologists and the italian group of cardiac rehabilitation have promoted the constitution of a task force made up of experts in the fields of sports cardiology the document produced by the task force is intended for healthcare professionals and deals with the role of physical activity in the prevention and treatment of cardiovascular diseases it examines the beneficial effects of physical activity on the cardiovascular system while analysing the possible risks involved and how they can be avoided the rational principles underlying the prescription of PCS activity in the cardiologic setting are described as are the modalities for prescribing such activity
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a fragment of the cdna encoding the third intracellular loop of the rat m muscarinic receptor was cloned and the dna was expressed in escherichia coli as a FP the FP was purified and utilized as an antigen to raise a polyclonal AS in rabbits chinese hamster ovary cells stably transfected with the cdna encoding each of the five known subtypes of muscarinic receptor were used as tissue sources to test the AS the AS was found to quantitatively immunoprecipitate m M2 while not precipitating m m m or m receptors this selective AS was utilized to quantify the density of m M2 in seven selected Az of the rat brain thus SC was found to contain approximately pmolmg of membrane protein which represents of the total density of muscarinic receptors similarly hippocampus pmolmg striatum pmolmg and olfactory tubercule pmolmg are rich in m receptors in contrast thalamushypothalamus contained only pmolmg representing approximately of the total density of M2 whereas ponsmedulla pmolmg and cerebellum less than pmolmg had very low levels of expression of m receptors the OD of a selective antiserum has provided a means for the quantification of a TPS subtype of muscarinic receptor in tissues such as the BB that express multiple subtypes this methodology will be applicable not only to the other subtypes of muscarinic receptor but also to the subtypes of several other neurotransmitter receptors that lack selective drugs with which to T0 them
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the understanding of genome rearrangements is an important endeavor in comparative genomics a L1 computational problem in this field is finding a shortest CS of genome rearrangements that transforms or sorts one genome into another in this paper we focus on sorting a multichromosomal genome by translocations we reveal new relationships between this problem and the well studied problem of sorting by reversals based on these relationships we develop two new algorithms for sorting by reciprocal translocations which mimic known algorithms for sorting by reversals a scorebased method building on bergerons algorithm and a recursive procedure similar to the bermanhannenhalli method though their proofs are more involved our procedures for reciprocal translocations match the complexities of the original ones for reversals
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we recorded cerebral evoked potentials back and forward averaged from the emg onset of the responding muscle in three reaction time tasks each requiring an MZ motor response to an MZ stimulus but differing in the nature of the sensory discrimination required two types of stimuli were presented a rare one to which the subject responded with fingerextension and a frequent one to which no response was required we found a close but VL relationship between the cerebral events associated with performance of a task and the timing of the motor response as completion of the discrimination process was delayed relative to stimulus occurrence emg activity began later relative to the cerebral potentials moreover we were able to record these CBF events only from the response to the rare unexpected CS- and not when subjects were required to respond to the frequent stimulus suggesting that the sensory discrimination in these experiments is an event that occurred only in the processing of the unexpected stimud mechanically ventilated new zealand white rabbits in rabbits breaths of aerosolized histamine were delivered in increasing concentrations ranging from to mgml eleven of rabbits were rechallenged with histamine on additional occasions over a week period in the remaining rabbits doses of distilled ho were aerosolized to determine the degree of spontaneous R2 in measurements of lung resistance rl and dynamic CL cdyn we defined an increase in rl of greater than of baseline tdrl and a decrease in cdyn of greater than of baseline tdcdyn as being significant based on observations in these rabbits these limits exceeded the percentile of spontaneous variability in rl and cdyn pulmonary responsiveness to histamine varied widely with a greater than fold range in tdrl and a fold range in tdcdyn between the most and least sensitive rabbits the variability of this responsiveness was lognormally distributed it was not correlated with age sex or baseline rl and cdyn in contrast withinrabbit responses to histamine challenge were quite reproducible five of rabbits were killed at the conclusion of their histamine challenges for pathologic examination of their lungs no evidence of airway inflammation was foundabstract truncated at words
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to test the hypothesis that the ON of MB is stimulated by estrogen we examined the effects of medial POA area mpoa or VMH vmh implants of the antiestrogen hydroxytamoxifen ohtam on pre and PP MB and on postpartum estrus in rats on day of pregnancy animals were implanted bilaterally with ohtam or cholesterol cannulae into mpoa or vmh unilateral cannulae of ohtam were also placed into mpoa females were tested with P0 pups for the ON of immediate retrieval prepartum at noon on day at midnight of the day and day following parturition which occurred on day on the evening of parturition implanted animals were tested with stimulus males for the occurrence of postpartum estrus in order to examine the influence of estrogen on MB in the absence of parturitional experience antiestrogenimplanted animals were delivered surgically cesarean section and were observed for the display of MB at various times T3 surgery at noon of day only a few animals in any group retrieved pups however h later females that received BL ohtam implants into mpoa remained nonresponsive while over animals in other groups retrieved and gathered pups the antiestrogen did not disrupt the display of postpartum maternal behavior in those females that were allowed to undergo normal parturition but it significantly reduced the number of cesareandelivered animals showing maternal SMB BL implants of ohtam into vmh but not into mpoa effectively blocked PP estrus the mpoa implants of ohtam resulted in a significant reduction in cytoplasmic estrogen receptor C2 and an increase in nuclear estrogen receptor concentrations the results of these experiments lend support to the current hypothesis that estrogen acts most effectively in the mpoa to stimulate maternal behavior and in the vmh to facilitate sexual receptivity
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the in vivo effect of the radiochemoprotectant amifostine on the therapeutic tau of marrow ablative treatment with cyclophosphamide cp and TB irradiation tbi followed by bone marrow transplantation bmt was studied in normal rats as well as in the brown norway rat acute myelocytic leukaemia bnml model in normal rats when the dose of tbi was escalated and the cp dose was kept constant pretreatment with amifostine yielded a positive dose modification factor of no significant improvement was found after AMI i.c.v. when the tbi dose was kept constant and cp dose escalated when leukaemic rats received cp as the only antileukaemia treatment AMI i.c.v. did not lead to a reduction in the antileukaemic efficacy of cp although protection against treatmentrelated mortality was observed in the cp only groups out of animals died of treatmentrelated toxicity compared with none of the animals in the amifostine i.c.v. CG when applying the maximum tolerated treatment of cp and tbi in various combinations to leukaemic rats out of rats died from treatmentrelated toxicity whilst i.c.v. with amifostine reduced this to out of p of those animals which survived the cp tbi conditioning treatment out of in the amifostine pretreatment group were cured versus in the cp tbi only control group p in conclusion incorporation of amifostine as a radiochemoprotectant in a marrowablative conditioning regimen allows the use of escalated doses of chemoradiotherapy without reducing the antileukaemic efficacy
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HD lipoprotein hdl is important for defense against sepsis but becomes dysfunctional dyshdl during inflammation we hypothesize that dyshdl correlates with organ dysfunction sequential organ failure assessment sofa score early sepsis
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safe and efficient vector systems for delivering antigens or immunomodulatory molecules to dendritic cells dcs t lymphocytes or both are considered ERP means of eliciting adaptive immune responses and modulating their type extent and duration as a possible tool toward this end we have developed a selfinactivating vector derived from feline immunodeficiency virus fiv showing performance characteristics similar to human immunodeficiency virusderived vectors but devoid of the safety concerns these vectors have raised
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there are several treatment options available for patients who have mild persistent asthma T3 being shown a typical case study and three possible treatment options three respiratory specialists each selected a different option the options were using a combination beclometasonealbuterol inhaler on an PRN basis daily treatment with an oral leukotriene receptor antagonist together with asneeded use of a shortacting betaagonist saba inhaler and using a combination inhaled corticosteroidlongacting betaagonist inhaler oncedaily together with asneeded saba the evidence for each option is reviewed in the CS of recent research
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tetraphenylethylene tpebased glycoconjugates were easily synthesized by coppericatalyzed click reactions between propargylattached tpe and azidofunctionalized sugars the tpe compound bearing lactosyl moieties lactpe was found to be a fluorescence turnon sensor for cholera toxin by virtue of aggregationinduced emission characteristics of the tpe motif owing to the specific interaction of lactose with the CTB subunit whilst a cellobiosefunctionalized tpe derivative did not show any response to the toxin therefore lactpe shows promising applications in the detection of cholera toxin as well as in the investigation of carbohydrateprotein interaction
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nitric oxide synthesized from the semiessential amino acid larginine by nitric oxide synthase is a remarkable RII molecule and plays an important role in physiological functions however the physiological role of nitric oxide in cardiovascular regulation by the central nervous system is not well understood in this T0 we investigated the cardiovascular effects of nitric oxide in the lateral IVT nucleus tractus solitarii AP and rostral ventrolateral medulla in urethaneanesthetized SD rats microinjection of ngmonomethyllarginine a nitric oxide synthase inhibitor into the cerebral IVT of rats elicited a dosedependent increase in blood pressure and HR rate this suggests that nitric oxide may be involved in CE cardiovascular regulation unilateral microinjection nl of larginine to nmol into the nucleus tractus solitarii and rostral ventrolateral medulla produced prominent doserelated depressor and bradycardic effects and reduced RNA however larginine had no significant cardiovascular effects in the area postrema in addition to hours after i.v. of bacterial LPS mgkg there was a timerelated potentiation of the larginineinduced depressor and bradycardic effects in the nucleus tractus solitarii these results indicate that nitric oxide is involved in CE cardiovascular regulation the depressor effect of nitric oxide in the nucleus tractus solitarii and rostral ventrolateral medulla may be through inhibition of RNA
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the food and drug administration fda is revoking the final guideline patient package inserts for classes of drugs and is withdrawing the draft guideline patient package inserts for other classes of drugs elsewhere in this issue of the federal register the agency is revoking the regulations that established general requirements for the preparation and distribution of patient package inserts for prescription drug products those regulations had established a pilot program that would have been applied to classes of drugs for years this notice revokes the draft and final guidelines which described how manufactures might comply with the regulations with respect to affected classes of drug
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fibrodysplasia ossificans progressiva fop a disabling disorder of progressive heterotopic ossification heo is caused by heterozygous gainof CF mutations in activin receptor a type i acvr also known as alk a bone morphogenetic protein bmp type i receptor presently symptomatic management is possible but no definitive treatments are available although extensive guidelines for symptomatic management are widely used regional preferences exist in order to understand if there was worldwide consensus among clinicians treating fop patients an expert panel of physicians directly involved in fop patient care was convened using a modified delphi method broad international consensus was reached on four main topics diagnosis prevention of flareups patient and FCC and GA clinical management issues this study of physician preferences provides a basis for standardization of clinical management for fop
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we aimed to assess associations between dietary intake of fats saturated and monounsaturated fats and cholesterol and certain food CG butter margarine and nuts with the prevalence incidence and progression of AHL we also aimed to investigate the link between serum lipids and cholesterollowering medication statins and hearing loss the blue mountains hearing study is a populationbased survey of agerelated hearing loss hearing loss was measured in participants aged ≥ y and was defined as the puretone average pta of frequencies and khz HL pta khz dietary data were collected using a semiquantitative ffq T3 multivariable adjustment the likelihood of prevalent hearing loss increased from the lowest reference to the highest quartile of dietary cholesterol intake ptrend among persons selfreporting statin use n a reduced odds of prevalent hearing loss was observed T3 multivariable adjustment or ci participants in the second and rd quartiles of dietary monounsaturated fat NI compared with those in the first quartile REF had a significantly reduced risk of hearing loss progression y later multivariableadjusted or ci and or ci respectively our results suggest that a diet high in cholesterol could have adverse influences on hearing whereas treatment with statins and consumption of monounsaturated fats may have a beneficial influence
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early somite mouse embryos were explanted and then maintained in SC for or h intervals various types of media were tested and it was determined that RS supported normal growth over a period of h based on total protein analysis and histological comparisons with in vivo specimens other media including fetal CS and fetal CS and waymouths supported some growth but did not equal the success of using rat SS alone during the h culture period in rat serum embryos developed to stages indistinguishable from embryos maintained for a weeks in awake rats caused persistent cardioacceleration but barely increased systolic pressure subsequent postmortem examination showed extensive fibrosis at sites of electrode implantation in both stimulated and unstimulated rats because folkow and rubinstein had succeeded in elevating blood pressure progressively by stimulating the Thy defence area chronic stimulation was repeated following their stereotaxic coordinates SP rose but the elevation was significant only on weeks and to maintain behavioral effects during chronic stimulation current strengths had to be increased periodically and stimulated rats gained weight more rapidly than unstimulated controls both these findings indicated that electrical stimulation had damaged the BB but since local fibrosis made histologic verification difficult additional experiments were done to determine if PET deficits could be detected upon further HS electrical thresholds were higher and pressor and sympathetic nerve responses were smaller in rats that had been stimulated chronically than in those that had not although our results do not disprove the hypothesis that centrallyinduced sympathetic hyperactivity initiates hypertension they show that blood pressure cannot be elevated by HS alone when the brain has been injured
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increased cardiovascular mortality has been associated with rheumatoid ICA ra there are reports indicating that TN factor tnf blockers may exert favorable but transient effects on the lipid profile flowmediated vasodilatation fmd of the brachial artery and the common CIMT ccimt in ra we evaluated ra patients females and five males with a mean age of ± years who were unresponsive to tnf blockers the patients received one or more courses of two RTX rtx mg infusions SLEDAI was evaluated at each visit investigatiience of the students
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structured information provided by manual annotation of proteins with gene ontology concepts represents a highquality reliable data source for the research community however a limited scope of proteins is annotated due to the amount of human resources required to fully annotate each individual gene product from the literature we introduce a novel method for automatic ID of go terms in natural language text the method takes into consideration several features the evidence for a go term given by the words occurring in text the proximity between the words and the specificity of the go terms based on their information content the method has been evaluated on the biocreative corpus and has been compared to current state of the art methods the precision reached at a recall of for the identified terms at rank in our analysis we observe that the identification of go terms in the cellular component subbranch of go is more accurate than for terms from the other two subbranches this observation is explained by the average number of words forming the terminology over the different subbranches
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no current patientcentred SF-36 captures all dimensions of physical activity in chronic obstructive pulmonary disease copd our objective was item reduction and initial validation of two instruments to measure PCS activity in copdphysical activity was assessed in a week randomised twoway crossover multicentre study using proactive draft questionnaires daily and clinical visit versions and two activity monitors item reduction followed an iterative process including classical and rasch model analyses and input from patients and clinical experts copd patients from five european centres were included results indicated the concept of PCS activity in copd had two domains labelled amount and difficulty T3 item reduction the daily proactive SF-36 comprised nine items and the clinical visit contained both demonstrated good MM fit person separation index confirmatory factor analysis supported the bidimensional structure both instruments had good internal consistency cronbachs α testretest reliability ICC coefficient ≥ and exhibited moderatetohigh correlations r with related constructs and very low correlations r with unrelated constructs providing evidence for construct validitydaily and clinical visit proactive physical activity in copd instruments are hybrid tools combining a short patientreported outcome questionnaire and two SAM variables which provide simple valid and reliable measures of physical activity in copd patients
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we present a complex case of the buddchiari syndrome due to thrombosis of the hepatic veins in the presence of stenosis of the left hepatic vein and membranous one of the VPI vena cava the acute thrombosis occurred after laparoscopic surgical removal of the GB because we strongly suspected the buddchiari syndrome hepatic venography was performed the hepatic A-V outflow one was relieved by angioplasty and TT with use of local infusions of urokinase into the clot we propose that angiography be performed in patients in whom the buddchiari syndrome is suspected and that angioplasty and thrombolytic therapy be initiated early
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more than years have passed since the original demonstration that proteins such as chromogranin a and dopaminebetahydroxylase which are costored together with noradrenaline in C1 dense cored LDV in adrenergic SN are releaseand infertility current methodologies for detecting and identifying m bovis are time consuming and difficult tests which rely on antigen or antibody detection have poor sensitivity and specificity in this paper associated protocols for the OD of a hybridization probe and pcr are described a genomic library sauiiia digested was prepared from m bovis dna colindale reference CS nc and cloned into puc colony hybridization using a probe preparation made from purified m bovis dna was used to identify colonies of interest m bovis dna fragments were retrieved from recombinant plasmids by digestion with ecori and hindiii this dna was used to prepare randomly primed probes for dot blot hybridization analysis with immobilized dna from m bovis two strains m dispar m agalactiae m bovigenitalium two strains m ovipneumoniae a group CS m arginini and bacteria belonging to different genera four probes were found to hybridize only with m bovis and m ovipneumoniae dna whereas one probe reacted with genomic dna from only one of the two m bovis strains the level of sensitivity of the DBH CA was cfu colony forming unitsml to enhance the sensitivity further an m bovisspecific pcr CA was developed the primers were designed using sequences obtained from the probe dna which discriminated m bovis from all other mycoplasma dna tested the minimum amount of target dna that could be detected by the pcr CA was that isolated from cfuml the pcr CA was therefore times more CS than dot blot hybridization
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the receptors that couple to the g protein gz in vivo are still relatively unknown in this T0 we investigated the effects of various dopamine receptor agonists in a mouse deficient in the alpha S1 of gz the dopamine dlike IL-1ra skf stimulated comparable locomotor activity in both wildtype mice and mice lacking galphaz in contrast the dopamine dlike receptor agonist quinpirole suppressed locomotor activity in both groups of mice but this suppression was significantly smaller in galphaz knockout mice consistent with these behavioural observations quinpirole inhibition of dopamine release in the forebrain nucleus accumbens evoked by electrical stimulation of dopamine axons was significantly attenuated in mice lacking galphaz in addition hypothermia and adrenocorticotropic hormone release resulting from activation of dopamine dlike receptors were also significantly reduced in galphaz KO mice however ACTH secretion induced by corticotrophin releasing hormone and the serotonin a 8-OH-DPAT were similar between wildtype and galphaz KO western blot analysis showed that the expression C2 of galphai galphao galphas galphaq and gbeta were the same in the brains of mice of both genotypes overall our data suggest that gz proteins are functionally coupled to dopamine dlike receptors in vivo
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nc subunits were purified from gel filtration pools of acidextracted collagenasedigested human glomerular basement membranes hgbm this methodology which enriches kda monomers m in the total digest allowed purification of these monomers and kda m and kda m monomers free from dimers CR of these subunits with GP autoantibodies using immunoblotting of sodium dodecyl sulfatepolyacrylamide gel electrophoresis and 2DE nonequilibrium ph gradient electrophoresis gels showed strong reactivity with the purified m subunits inhibition ELISA assay used to quantitate the reactivity of the purified nc subunits indicated that m had a greater than fold increase in ability to inhibit IB to nc than nc itself comparison of hgbm nc components were made with those obtained from collagenase digests of salt and acidextracted bovine and sheep gbm and englebrethholmswarm tumor similarly purified by GF and reversephase high performance liquid chromatography 2DE gel analysis of these nc isolates revealed absence of the very cationic m monomers reactivity with antibodies eluted from diseased kidneys of sheep immunized with hgbm steblay nephritis was compared with GP autoantibody CR by immunoblotting 2DE gels of hgbm nc we conclude that a very cationic m monomer m found only in hgbm is the probable target in GP syndrome that the epitope is present on most nc components from extracted and unextracted hgbm and is exposed by urea denaturation which is enhanced by acid treatment a weakly cationic m monomer m is present in gbm from other species and is the probable target in steblay nephritis differential recognition of the two m components by these antibodies points to different genetic origins or possibly distinct posttranslational modifications for these components this is supported by their presence or absence in different species and tissues as well as PSA differences from the m monomers which presumably are derived from alpha iv and alpha iv collagen chains
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multiple system atrophy msa is a sporadic AO neurodegenerative disorder clinically characterized by a VL combination of dysautonomia levodopaunresponsive parkinsonian and cerebellar symptoms neurodegeneration in msa occurs in the substantia nigra putamen inferior olive pontine and BS nuclei as well as IML of the spinal cord msa is recognized as a synucleinopathy due to the accumulation of insoluble alphasynuclein in oligodendroglial cytoplasmic inclusions several animal models have been developed in order to reproduce various clinical and pathological features of msa using double toxindouble lesion or single toxindouble lesion neurotoxinbased models were designed in rats mice and nonhuman primates to reproduce the neuropathology of msa in the nigrostriatal system while genebased models were developed in mice to reproduce the accumulation of insoluble alphasynuclein in oligodendrocytes both approaches have then been merged to create optimized dualhit models this review describes the different animal models of msa their respective advantages and limitations and their usefulness to decipher the pathophysiology of msa then to define efficient symptomatic and diseasemodifying therapies this article is part of a special issue entitled neuroscience disease models
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a stress analysis of the primate mandible suggests that vertically deep jaws in the molar region are usually an adaptation to counter increased sagittal bending stress about the balancingside mandibular corpus during unilateral mastication this increased bending stress about the balancing side is caused by an increase in the amount of balancingside muscle force furthermore this increased muscle force will also cause an increase in dorsoventral shear stress along the mandibular symphysis since increased symphyseal stress can be countered by symphyseal F0 and as increased bending AS can be countered by a deeper jaw deep jaws and symphyseal F0 are often part of the same PET DP in some primates eg cercocebus albigena deep jaws are an adaptation to counter bending in the sagittal plane during powerful incisor biting rather than during unilateral mastication the AS analysis of the primate mandible also suggests that jaws which are transversely thick in the molar region are an adaptation to counter increased torsion about the long axis of the workingside mandibular corpus during unilateral mastication increased torsion of the mandibular corpus can be caused by an increase in masticatory muscle force an increase in the transverse component of the postcanine bite force andor an increase in premolar use during mastication patterns of masticatory muscle force were estimated for galagos and macaques demonstrating that the ratio of workingside muscle force to balancingside muscle force is approximately in macaques and in galagos during unilateral isometric molar biting these data support the hypothesis that mandibular symphyseal fusion is an adaptative response to maximize unilateral molar MBF by utilizing a greater percentage of balancingside muscle force
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over half of young SCA victims show no prior warning signs or PS and survival depends on secondary prevention notably prompt initiation of CPR cpr and the use of an automated external defibrillator aed for outofhospital arrests there is increasing public interest in and uptake of PAD programs in communities and schools our purpose was to review recent data on sudden cardiac arrest in children and its outcome to identify ways to improve the current low survival rate of youth who experience sudden CA
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otamixaban under OD by sanofiaventis is a directly activated FX fxa inhibitor that is currently in phase iib PCTs for acute coronary syndrome and myocardial infarction preclinical studies with otamixaban demonstrated high selectivity of the compound for fxa otamixaban effectively inhibited TG without interfering with existing thrombin activity intravenously administered otamixaban was well tolerated in both male and female patients independent of age otamixaban exhibited a welldescribed doseexposure relationship a low interpatient R2 in plasma exposure and was both rapidly distributed in the plasma and quickly eliminated the rapid decrease in otamixaban PC following the termination of an infusion is an advantage over other fxa inhibitors that have longer halflives otamixaban exhibited an improved pharmacodynamic profile over conventional AC therapies such as heparin during clinical trials with otamixaban no major drug interactions were observed with agents that were likely to be used in ACT otamixaban is a promising agent that merits further consideration for clinical trials in patients with coronary thrombosis
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despite the commercial availability of numerous computerpointing devices many severely disabled individuals still rely on customized equipment to operate computers this T0 presents a novel integrated pointing device apparatus ipda that integrates numerous commercial pointing devices the novel ipda which complies with a standard usb interface is compatible with most tested computerpointing devices and flexibly integrates commercial computer devices tailoring them to suit individual needs by using simple integrated circuit design and lowcost electronic components this lowcost apparatus is easily maintained the feasibility of the ipda was evaluated by four subjects with highlevel cervical c spinal cord injury sci participants performed normal moveandclick and draganddrop tasks typically performed by computer pointing devices each participant not able to use a traditional computer mouse or trackball were able to operate a computer adequately with the ipda and three including one operating a trackball with his chin operated computers easily and smoothly this feasibility study showed that the ipda effectively integrates commercial pointing devices thereby providing the possibility for some people with sci to obtain computer operability this T0 demonstrated the advantages of flexibility low cost and acceptable efficiency of the novel ipda
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imaging studies in PTS disorder ptsd have shown differing neural network patterns between hypoarouseddissociative and hyperaroused subtypes since dissociative identity disorder did involves different emotional states this study tests whether did fits aspects of the differing brainactivation patterns in ptsd while BB activation was monitored using positron emission tomography did individuals n and matched didsimulating HCs n underwent an autobiographic scriptdriven imagery paradigm in a hypoaroused and a hyperaroused identity state results were consistent with those previouslophilic iodine atoms and chloride anions in hochcn solvent mixtures the rotaxane host exhibits strong binding affinity and selectivity for chloride bromide and iodide over a range of oxoanions
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we have advocated the use of highpressure freezing hpf in TPS types of correlative CS electron microscopy clem experiments because the intracellular components such as the cytoskeleton and membrane tubules can only be adequately preserved via cryofixation to allow fast transfer from the LM into a cryofixation device we have developed the rapid transfer system rts for the empact highpressure freezer in this chapter we will describe how to prepare and perform a clem experiment using this device and will highlight the latest changes made to the original system to optimize the workflow
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TN factor tnf increases STG in rats by increasing de novo hepatic HFA synthesis and very LD lipoprotein production we have recently shown that several other cytokines increase hepatic fatty acid synthesis in the mouse we now explore the mechanism by which these cytokines increase de novo lipogenesis and the interactions between cytokines in fed mice tnf administration results in increased hepatic levels of citrate the primary ae detection techniques in patients T0 no i coronary angiograms were taken in MZ angiographic projections before control and immediately following several at average subsequent diagnostic dye i.v. administered over a period of about min the ionic UCA diatrizoate induced a coronary dilation of mean sd p less than n the nonionic agent iopromide increased the coronary i.a. diameters by only p less than n in another patients T0 no ii coronary angiograms were obtained using the nonionic contrast medium iopamidol at and min T3 the control acquisition this protocol was repeated in the same patients with diatrizoate with iopamidol coronary diameter changes were not significant at any time with diatrizoate however coronary dilation was measured at min p less than and at min p less than in a third study it was tested whether standardization of coronary vasomotor tone eg in coronary angiographic followup studies is possible by the induction of a reproducible maximum coronary dilation with nitrocompounds in patients the mean diameters of angiographically normal coronary segments were analyzed before and at various times T3 iv administration over min of mg sinkg bodyweight coronary dilation was maximal at or min T3 the ON of the sininfusion p less than mg nitroglycerin given sl at min did not further dilate the coronary arteries one hour T3 sin coronary dilation still amounted to an average of p less than and became maximal again when mg nitroglycerin was again po sublingually p less than in conclusion ST R2 of coronary vasomotor tone induced by ionic RCM can be eliminated by the use of nonionic contrast agents and observation of i.t. intervals of at least min in quantitative coronary angiographic followup studies as well as during acute interventions eg ptca identical baseline vasomotor tone can be achieved by induction of the maximal coronary dilation using nitrocompounds
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we show how to numerically calculate several quantities that characterize topological order starting from a microscopic fractional quantum hall hamiltonian to find the set of degenerate ground states we employ the infinite density matrix renormalization group method based on the matrixproduct state representation of fractional quantum hall states on an infinite cylinder to T0 localized quasiparticles of a chosen topological charge we use pairs of degenerate ground states as boundary conditions for the infinite density matrix renormalization group we then show that the wave function obtained on the infinite cylinder geometry can be adapted to a torus of arbitrary modular parameter which allows us to explicitly calculate the nonabelian berry connection associated with the modular t transformation as a result the quantum dimensions topological spins quasiparticle charges chiral central charge and hall viscosity of the phase can be obtained using data contained entirely in the entanglement spectrum of an infinite cylinder
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children with end stage renal failure and anaemia have an increased cardiac index and often gross ventricular hypertrophy the contribution of anaemia to these abnormalities is uncertain eleven children with end stage renal failure and anaemia haemoglobin concentration gl were enrolled into a single blind PL controlled crossover study to assess the cardiovascular effects of reversing anaemia using subcutaneous human recombinant erythropoietin rhuepo each limb lasted weeks seven children completed both limbs of the study haemoglobin increased with rhuepo remaining above gl for a mean of weeks cardiac index fell as a result of a reduction in both left VVI stroke volume and HR rate left VVI end diastolic diameter also decreased in five children left VVI wall thickness and left ventricular mass decreased with rhuepo but this failed to reach significance for the whole group blood pressure did not change in six normotensive children completing an rhuepo limb the decrease in cardiac index was therefore balanced by an increase in peripheral vascular resistance three children were taking antihypertensive treatment at the start of the study one required an increase and one a decrease in treatment during the rhuepo limb short term treatment with rhuepo reduces cardiac index a longer T0 is needed to determine whether this will in time result in a significant reduction in left VVI hypertrophy
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complexes of the composition wocll and worl r me et l bidentate lewis base ligand have been prepared and are fully characterized including an exemplary xray crystal structure of woclditertbutylbipyridine this latter compound crystallizes in the orthorhombic space group p with a a b a c a and z the title complexes are applied as catalysts in olefin epoxidation catalysis with tertbutyl hydroperoxide tbhp as the oxidizing agent the wvi complexes display only moderate turnover frequencies but can be reused several times without loss of catalytic activity the highest activity can be achieved at reaction temperatures of ca degrees c chloro derivatives are somewhat more AS than alkyl complexes and sterically less crowded complexes show also higher activities than their congeners with bulky ligands l kinetic examinations show that the catalyst formation is the rate determining step and it is observed that tertbutyl alcohol the byproduct of the epoxidation reaction acts as a competitor for tbhp thus lowering the reaction velocity during the course of the reaction but not irreversibly destroying the catalyst
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the aim of this T0 was to investigate the salinity uptake by NK zeolite when used as an ingredient during the composting process the amounts of and of natural zeolite were applied to PL as volume and compared with the compost made with no amendment the resutrinsic nature of the genes being targeted these properties make reliable hit selection in the rnai screen a difficult task the use of robust methods based on median and median absolute deviation mad has been suggested to improve hit selection in such cases but mean and sigma sdbased methods are still predominantly used in many rnai hts in an experimental RPA to compare these methods a genomescale small interfering rna sirna screen was performed in which the identification of novel targets increasing the therapeutic index of the chemotherapeutic agent MMC c mmc was sought mad values were resistant to the presence of outliers and the hits selected by the madbased method included all the hits that would be selected by sdbased method as well as a significant number of additional hits when retested in triplicate a similar percentage of these sirnas were shown to genuinely sensitize cells to mmc compared with the hits shared between sd and madbased methods confirmed hits were EC with the genes involved in the dna damage response and Tc regulation validating the overall hit selection strategy finally computer simulations showed the superiority and generality of the madbased method in various rnai hts data models in conclusion the authors demonstrate that the madbased hit selection method rescued physiologically relevant false negatives that would have been missed in the sdbased method and they believe it to be the desirable stchoice hit selection method for rnai screen results
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internationally adopted adolescents are at increased risk for MH problems however little is known about problematic alcohol and drug use which are important indicators of maladjustment the aim of this T0 was to examine the level of problematic alcohol and drug use in internationally adopted adolescents compared to their nonadopted peers the study is based on data from the youthhordalandsurvey which was conducted in hordaland county norway in the spring of all adolescents born from to residing in hordaland at the time of the T0 were invited to participate information on adoption was obtained from the CE adoption registry and linked to selfreport data from the youthhordalandsurvey among participants were identified as internationally adopted no significant differences were found between international adoptees and their peers regarding whether or not they had tried alcohol or illicit drugs or their patterns of drinking behavior however adopted adolescents had a higher mean score on a measure of problematic alcohol and drug use compared to their nonadopted peers the difference was attenuated and no longer significant when adjusting for measures of depression and attentiondeficithyperactivity disorder results from a structural equation model indicated a full mediation effect of mental health problems on the association between adoption status and problematic alcohol and drug use our findings indicate that internationally adopted adolescents experience more problematic alcohol and drug use than their nonadopted peers and the difference can largely be explained by mental health problems psycinfo DB record
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in the preceding paper we described the responses of cells in the cats lateral suprasylvian visual area ls to largefield optic flow and texture movies to assess response properties such as DS cells were also tested with moving bar stimuli we expected that there would be good PA between response properties elicited with optic flow movies and those revealed with bar stimuli we first asked how well bar response properties predicted responsiveness to optic flow movies there was no rho between responsiveness to movies and the degree of endstopping length summation or preference for bars that accelerated and expanded we then considered only the cells that responded to both bars and optic flow or texture movies and asked how well the strength of their response to movies could be predicted from the directiontuning curves generated with bar stimuli onethird of these cells responded much more strongly to movies than could be predicted from their directiontuning curves generally such cells were rather well tuned for the direction of bar motion and preferred a direction substantially different from what they saw in optic flow movies optic flow movies shown in the forward direction were the most effective variety of movie for twothirds of these cells to see whether this outcome stemmed from differential direction tuning for bars and C1 multielement displays in a second series of experiments we compared direction tuning for bars and largefield texture movies many cells showed substantially different direction tuning for the two kinds of stimulus almost of cells had TCs that overlapped each other by but only a small number of cells responded much better to texture movies than to bars in the predominant direction of image motion in optic flow movies this result like that reported in the preceding paper suggests that cells in ls respond differently to optic flow than to texture displays lacking optic flow motion cues
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in a search for chemical lures to manage the cosmopolitan crop pest western flower thrips wft frankliniella occidentalis a ytube olfactometer was used to screen compounds including pyridyl compounds comparison of ytube results for new zealand flower thrips nzft thrips obscuratus with field trapping data for ethyl nicotinate and ethyl isonicotinate suggested that the minimum attractive dose mad of an odor compound where significantly p more than of thrips walked up the odorladen arm provided a measure for selecting EDC to evaluate for potential lure efficacy in the field eighteen synthetic pyridyl EDC were tested on female wft in a ytube olfactometer and four pyridyl carbonyl EDC had mads lower than the known wft attractants panisaldehyde mad microl and EN microl methyl isonicotinate microl ethylchloropyridinecarboxylate microl ethyl isonicotinate microl and methyl pyridyl ketone microl the suitability of mad for selecting compounds for further DUE of practical lure tau is discussed comparisons of activities within rat series of esters and ketones showed that attractant activity decreased with chain length formyl pyridine was an attractant at a dose of microl but was repellent at higher doses degrees microl
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the OD of an arteriovenous fistula avf is a rare complication of cardiac catheterization we report a rare case with a FA avf following cardiac catheterization originating from the RA deep FA artery and eventually draining into the RA superficial FV through the subcutaneous vein
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a baseline study to evaluate the prevalence of schistosoma mansoni infection as well as the diagnostic tau of serodiagnostic tests was performed in kabaganga village kome island lake victoria tanzania a total of individuals were examined parasitologically and clinically egg excretion was demonstrated by onesample katokatz test specific igg and igg antibodies against s mansoni AD worm sawa and egg sea antigens as well as circulating anodic antigen caa were determined in SS samples from of these subjects as a control population individuals from a nonendemic area were examined parasitologically clinically and serologically in the parasitologically examined kabaganga population were excreting eggs the DP of egg excretion was typical for an endemic area with a peak in the age group years sixtyfive percent of the serologically tested villagers were positive in the caa test a total of were positive in either of the two tests indicating an active infection in of these individuals the C2 of isotype specific antibodies were increased the prevalence of caa positivity corresponded fairly well with that of katokatz results in the age groups years but in the younger age CG a considerably greater number of individuals were positive in the caa test than in the katokatz test the results obtained indicate that virtually all of the kabaganga villagers regardless of age had an ongoing AS infection or had previously been INF with s mansoni this population therefore may be useful for evaluation of the diagnostic efficacy of various antibody tests the highest degree of discrimination between the endemic and the nonendemic village populations was noted for antiegg igg antibodies it is concluded that the combined determination of parasite eggs in faeces and caa in SS provides high sensitivity as regards active infection increased levels of isotypespecific antibodies particularly of the igg subclass is a sensitive indicator of past or present infection and the prevalence of individuals with such increased C2 may be a simple and reliable indicator of the frequency of schistosomiasis in a community
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in Sp etd is a positive regulator of the septation initiation network sin a conserved gtpaseregulated kinase cascade that triggers cytokinesis here we show that a mutation in the pab gene which encodes the bregulatory S1 of the protein phosphatase a ppa suppresses mutations in the etd gene etd is required for the function of the gtpase spg a key regulator of sin signaling interestingly the loss of pab function restored the activity of spg in etddeficient cells this result suggests that ppapabmediated dephosphorylation inhibits spg thus antagonizing etd CF the loss of pab function also rescues the lethality of mutants of other genes in the sin cascade such as mob sid and cdc twohybrid assays indicate that pab physically interacts with mob sid sid and cdc suggesting that the phosphatase a bsubunit is a component of the sin complex together our results indicate that ppapab plays a novel role in cytokinesis regulating sin activity at different C2 pab is also required to activate polarized cell growth thus ppapab may be involved in coordinating polar growth and cytokinesis
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the present study examined the effects of the hydroxytryptaminergic htc agonist dimethoxyiodophenylaminopropane doi on periventricularhypophysial dopaminergic da neuronal activity and the secretion of alphamelanocytestimulating hormone alpha msh for comparison the effects of doi on tuberoinfundibular da neuronal activity and the secretion of prolactin were also examined periventricular hypophysial and tuberoinfundibular da neuronal activities were estimated by measuring the concentrations of dihydroxyphenylacetic acid dopac in the terminal regions of these neurons ie in the intermediate lobe of the PIT and ME respectively acute administration of doi produced dose and timerelated decreases in intermediate lobe dopac concentrations and corresponding increases in plasma alpha msh concentrations pretreatment of animals with either the htc antagonist ritanserin or the selective ht antagonist alphaphenylphenylethylpiperidine methanol mdl blocked the doiinduced decrease in IL dopac concentrations and increase in plasma alpha msh concentrations acute administration of doi produced dose and timerelated increases in plasma prolactin concentrations but did not alter dopac concentrations in the ME furthermore the doiinduced increase in plasma prolactin concentrations was blocked by ritanserin but not mdl i.c.v. taken together these data suggest that doi inhibits periventricular hypophysial da neuronal activity and increases the secretion of alpha msh by activating ht receptors whereas the doiinduced prolactin secretion is independent of a decrease in TI da neuronal activity and is most likely mediated by htc receptor activation
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in this T0 we report the relationship between fasting plasma insulin creactive protein adiponectin C2 and the components of metabolic syndrome
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we report an unusual case of a popliteal aneurysm complicating a distal FA osteochondroma caused by the repeated massages of a traditional medicine practitioner sinseh management was by excision of the exostosis and reconstruction of the damaged arterial segment by a reversed long saphenous vein graft we advice against massage over an osteochondroma on the distal medial aspect of the femur and suggest prophylactic removal of such lesions because of this potential complication
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gstm glutathione stransferase mu and gstt glutathione stransferase theta are critical enzymes for detoxification of endogenous and environmental carcinogens constitutive gst gene polymorphisms may be associated with increased risk for cancer development we made an explorative T0 of a brazilian population with malignant glioma to determine whether gstm and gstt genetic polymorphisms influence the response to intranasal administration of perillyl alcohol and the survival rate patients were stratified into groups according to clinical presentation tumor classification and RT location circulating dna was extracted from BP or SS and genotypes were detected by multiplex pcr the cohort included patients with recurrent malignant glioma included in a phase iii clinical trial with perillyl alcohol and matched healthy control subjects gstm frequency was similar in patients with glioma and healthy controls but gstt deletion was found in patients contrasting with in controls a longer survival rate was associated with a lack of gstm deletion weeks and a deletion for gstt weeks a poor survival rate was associated with gstm deletion weeks and with a lack of a gstt deletion weeks a significantly lower frequency of gstt deletion in glioma patients compared to HCs indicates that gstt deletion may exert a protective role against gliomagenesis influence therapeutic response to intranasal POH treatment and increase overall survival especially considering RT topography
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PTN is an kda secreted polypeptide growth factor with direct proangiogenic and tumorigenic properties pleiotrophin is a ATP for proteolytic enzymes such as PL leading to proteolytic fragments with distinct MICs on endothelial cell activation in vitro or angiogenesis in vivo aprotinin is a naturally occurring broad spectrum KPI used widely in CS due to its ability to inhibit PL and reduce perioperative bleeding since we have seen that aprotinin inhibits proteolysis of pleiotrophin by plasmin the aim of the present study was to evaluate the possible role of pleiotrophin in the effects of aprotinin on angiogenesis and human EC cell migration our data demonstrate that aprotinin in a concentrationdependent manner is angiogenic in the CE chorioallantoic membrane CA in vivo and induces human endothelial cell migration in vitro aprotinin inhibits PTN proteolysis and induces expression and secretion of PTN through an apdependent transcriptional activation of the PTN gene and pleiotrophin seems to mediate the stimulatory effects of aprotinin on cell migration through its receptor protein tyrosine phosphatase betazeta the stimulatory effect of aprotinin on PTN expression and cell migration may explain at least partly the problems observed with the clinical use of aprotinin
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maternal obesity programmes offspring OD we addressed maternal obesity effects induced by highfat diets on maternal mammary gland mg structure and CF and offspring BB liver and fat outcomes mothers were fed control c n or obesogenic mo n diet from the time they were weaned through pregnancy beginning at d through lactation at F1 PN day pnd milk OB and nutrients were determined at the end of lactation maternal liver and mg fatty acid profile were measured desaturase δd and δd and elongase elovl and elovl protein was measured by immunohistochemistry and western blotting wb in the liver and wb in the mg in mothers liver mg and MF content were higher in mo than in c liver AA aa and epa and mg epa were lower in mo than in c CL desaturases were higher in mo the mg was heavier in mo than in c with decreased δd expression in mo desaturases and elongases were immunolocalised in PC cells of both CG milk yield water cain basal lamina and EC cells methoxyxo thioflavins or e were used to visualize aβ accumulation in living mice or in fixed BB tissues positioning of reactive iba microglia and gfap astrocytes at the vasculature was rendered using confocal microscopy plateletderived growth factor receptor beta pdgfrβ IF was used to visualize perivascular PCs in vivo photon microscopy revealed methoxyxo amyloid perivascular deposits on leptomeningeal and penetrating cortical vessels in xfad mice typical of CAA caa amyloid deposits were visible in vivo at m and aggravated over time progressive microvascular damage was concomitant to parenchymal aβ plaque accumulation in xfad mice microvascular inflammation in xfad mice presented with sporadic fitcalbumin leakages at m becoming more prevalent at m and m d colocalization showed inflammatory iba microglia PT to microvascular fitcalbumin leaks the number of perivascular pdgfrβ PCs was significantly decreased at m in the frontoparietal cortices with a trend decrease observed in the other structures at mm pdgfrβ PCs displayed hypertrophic perivascular ramifications contiguous to reactive microglia cerebral amyloid angiopathy and microvascular inflammation occur in xfad mice concomitantly to PC plaque deposition the prospect of cerebrovascular pharmacology in ad is discussed
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anticancer vaccination is a promising RPA to increase the tau of cytotoxic t lymphocyteassociated protein ctla and programmed death ligand pdl checkpoint blockade therapies however the landmark fda registration trial for antictla therapy ipilimumab revealed a CR lack of benefit of adding vaccination with gp peptide formulated in incomplete freunds adjuvant ifa here using a mouse model of melanoma we found that gp vaccination induced gpspecific effector t cells teffs which dominantly forced trafficking of antictlainduced nongpspecific teffs away from the RT reducing RT control the inflamed vaccination site subsequently also sequestered and destroyed antictlainduced teffs with specificities for tumor antigens other than gp reducing the antitumor efficacy of antictla therapy mechanistically teffs at the vaccination site recruited inflammatory monocytes which in turn attracted additional teffs in a vicious cycle mediated by ifnγ X4 icam and ccl dependent on ifa formulation in contrast nonpersistent vaccine formulations based on dendritic cells viral vectors or watersoluble MMP potently synergized with checkpoint blockade of both ctla and pdl and induced complete RT regression including in settings of primary resistance to dual checkpoint blockade we conclude that cancer vaccine formulation can dominantly determine synergy or lack thereof with ctla and pdl checkpoint blockade therapy for cancer
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CG of cba mice IS with antithymocyte serum ats treatment were xenotransplanted with either hela human cervical carcinoma cells or GM cells expressing the human TN factoralpha tnf gene all cells both cell lines were highly resistant to the cytotoxic effects of tnf if x tumor celine from a prochiral ketone ATP was a more reactive amino donor the yield could be increased dramatically by removing pyruvate which is a more GABA product than salphamethylbenzylamine salphamba when acetophenone and lalanine are used as an amino acceptor and donor respectively the removal of Pyr was carried out by incorporating lactate dehydrogenase ldh in CF extract or by using whole cells the whole cell reaction yielded a much better result when mm benzylacetone and mm acetophenone were used as an amino acceptor with mm lalanine and of the reaction yields after day were obtained with whole cells respectively enantiomeric excesses of both salphamba and smethylphenylpropylamine smppa were all above
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antiaromatase agents inhibit the cytochrome p component of the aromatase enzyme complex responsible for the final step of estrogen biosynthesis in IP tissues these drugs can be classified into firstgeneration eg aminoglutethimide secondgeneration eg formestane and fadrazole and thirdgeneration eg anastrozole letrozole and exemestane agents antiaromatase agents can also be divided into type i and type ii inhibitors type i inhibitors have a steroidal structure similar to androgens and inactivate the enzyme irreversibly by blocking the substratebinding site and are therefore known as aromatase inactivators type ii inhibitors are nonsteroidal and their action is reversible this article reviews the recent evidence regarding the role of thirdgeneration aromatase inhibitors in the management of breast cancer relevant pubmed listed articles and presentations at recent international symposia were reviewed there is a growing body of evidence supporting the role of thirdgeneration aromatase inhibitors anastrozole letrozole and exemestane as firstline and secondline therapy for estrogen receptor er andor progesterone receptor pgrpositive ABC in PM women and as a neoadjuvant therapy in postmenopausal women with hormone receptorpositive invasive breast cancer unsuitable for breastconserving surgery furthermore the preliminary results of the atac arimidex tamoxifen CT and in combination study have shown that adjuvant anastrozole is superior to tamoxifen in terms of diseasefree survival dfs adverse effects and prevention of CL breast CA in postmenopausal women with early erpositive breast cancer however longer followup is required to assess the longterm effects of these agents on bone mineral density cognitive CF and overall survival prior to considering their routine use in the adjuvant setting instead of tamoxifen the potential role of these drugs in the management of ductal carcinoma in situ dcis premenopausal breast CA and breast CA prevention is worth investigating
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following thiopental i.t. to rabbits in doses of mg kg intravenously iv the sleeping time lasted longer after injection by bolus than T3 administration made more slowly over or s respectively peak concentration in the blood of the animals after bolus i.t. was about four time higher than T3 slow i.t. the determination of protein IB showed that the unbound fraction of thiopental at the high concentration following bolus i.t. is almost doubled compared with the unbound concentration following the slow i.v. therefore it is concluded that this contributes to an increased concentration of thiopental in the BB during the initial phase of CSD thus extending the sleeping time the results from experiments using a distribution MM give additional evidence supporting this conception
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preimplantation diagnosis provides couples at high genetic risk the possibility of avoiding genetic disease without the need for prenatal diagnosis and selective abortion of the affected pregnancy following extensive BG work on the reliability of genetic diagnosis in a single cell we offered on a research basis preimplantation diagnosis to five couples at risk for F1 with the deltaf mutation the major mutation causing cystic fibrosis there was no detrimental effect from polar body removal on either fertilization or preimplantation development genetic analysis undertaken in polar HB and corresponding blastomeres identified embryos of which ten were transferred
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obesity is a concern in the LT management of patients following liver transplantation yet the risk of obesity and the factors that influence its OD have not been well defined we evaluated posttransplantation weight NC among a cohort of adults who had their height and weight recorded before liver transplantation at three L1 centers obesity was defined as a body mass index bmi of at least kgm weight at transplantation was adjusted by the amount of ascites removed mean bmi increased from kgm pretransplantation to kgm in the first posttransplantation year to kgm in the second year and very little with subsequent observation among patients who were not obese before transplantation became obese within years after transplantation on evaluation of numerous potential donor and pretransplantation risk factors greater recipient bmi greater donor bmi and being married were found to be predictors of subsequent obesity p posttransplantation predictors of obesity included absence of ACR higher cumulative prednisone dose in the second year and cyclosporinebased immunosuppression although only AAR and prednisone dose remained predictors on MVA despite the marked WG Tx prevalence of obesity at years was only slightly greater than in the GA us population obesity occurred commonly after liver transplantation sometimes with a striking gain in weight in addition to bmi at transplantation donor bmi marital status occurrence of AR and prednisone dose affected the incidence of obesity
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many essential functions in eukaryotic cells like phagocytosis division and motility rely on the dynamical properties of the actin CSK a central player in the actin system is the arp complex its activity is controlled by members of the wasp wiskottaldrich BLM family in this work we investigated the effect of the carbazole derivative wiskostatin a recently identified nwasp inhibitor on actindriven processes in motile cells of the social ameba dictyostelium discoideum drugtreated cells exhibited an altered morphology and strongly reduced pseudopod formation however tirf microscopy images revealed that the overall cortical network structure remained IN we probed the mechanical stability of wiskostatintreated cells using a microfluidic device while the total amount of factin in the cells remained constant their stiffness was strongly reduced furthermore wiskostatin treatment enhanced the resistance to fluid shear stress while spontaneous motility as well as chemotactic motion in gradients of camp were reduced our results suggest that wiskostatin affects the mechanical integrity of the actin SC so that its rigidity is reduced and actindriven force generation is impaired
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a yearold man presented with acute RA ventricular infarction a percutaneous coronary MI was undertaken but he developed shock and required extracorporeal membrane oxygenator support PD bypass was performed and a abiomed bvs was implanted as a right VVI assist device circulation gradually stabilized and the device was removed after days there no sign of HF or infection at months postsurgery
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in previous research rats subjected to prolonged sleep ED have shown disturbances of thermoregulation hormonal and metabolic changes in apparent response to the thermoregulatory problems lesions on the tail and paws and eventual death to search for alterations of PET activity in BB the expression of the IE1 gene egr was examined by immunocytochemistry and RNA blotting in rats subjected to total sleep deprivation tsd for days controls included yoked stimuluscontrol tsc rats surgically implanted but otherwise undisturbed control rats and unoperated control rats photographs of immunoreacted coronal sections from four sets of rats were ranked blindly for BB regions tsd rats showed tendencies for regionally specific increases in egrlike immunoreactivity in dorsal raphe lateral habenula superior colliculus and VP PAG however most regions showed no differences in egrlike immunoreactivity between tsd and control rats neither was there a difference in whole brain egr mrna by northern blot in two additional sets of rats thus this study like previous studies of BB histology amines adrenoceptors and glucose utilization does not provide positive support for the hypothesis that sleep protects the CNS system against massive global damage fatigue or dysfunction
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this review summarizes the various forms of behavioral treatment of migraine which could demonstrate empirical efficacy the main unimodal kinds of treatment are thermal and electromyography emg biofeedback training and progressive muscle relaxation the various relaxation techniques do not differ in their efficacy in treating migraine on average a reduction in migraine frequency of is achieved the mean ESs es of various biofeedback techniques are between and CBT is applied as a multimodal treatment and on average achieves an improvement in migraine activity by and an es of all behavioral procedures can be used in combination or as an alternative to drug prophylaxis with comparable success a combination of pharmacological and behavioral treatment can achieve additional success there is strong evidence for the clinically significant efficacy of all forms of behavioral treatment in childhood and adolescence there are no signs of differential indications
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CIN enables RT development enabled in part by aberrant expression of the mitotic checkpoint protein mad here we identify a novel regulatory mechanism for mad expression involving mirpmediated inhibition of mad translation and we demonstrate that this mechanism is triggered by inactivation of the RT suppressor vhl the most common event in clear cell renal cell carcinoma ccrcc in vhlpositive CA cells enhanced expression of mirp diminished mad C2 and promoted checkpoint weakness and chromosomal instability conversely in checkpointdeficient vhlnegative renal carcinoma cells inhibition of mirp CF restored mad C2 MI checkpoint proficiency and chromosomal stability notably chromosome missegregation errors and aneuploidy that were produced in a mouse MM of acute renal injury as a result of kidneyspecific ablation of pvhl CF were reverted in vivo also by genetic inhibition of mirp finally bioinformatic analyses in human ccrcc associated loss of vhl with increased mirp expression and CIN together our results defined mirp as a critical regulator of mad translation and MI checkpoint CF by identifying a potential mediator of chromosomal instability in vhlassociated cancers our work also suggests a novel micrornabased therapeutic strategy to target aneuploid cells in vhlassociated cancers
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congenital cystic adenomatoid malformation ccam is a developmental lung abnormality characterized by abnormal proliferation of mesenchymal elements and failure of bronchiolar structures to mature ultimately resulting in the compression of normal pulmonary tissue and mediastinal shift with rapid expansion of cysts although various clinical and pathologic studies of ccam in humans exist ccam has yet to be reported in animals even in nonhuman primates in the present study histopathologic analyses of a neonatal cynomolgus monkey that died days T3 birth revealed that normal lung architecture was replaced by disorganized overgrowths of cysts lined with simple cuboidal epitheely broad ATP specificity makes hhec a promising tool for biocatalytic applications we have designed large quantum chemical models of the hhec active site and used DFT to study the reaction mechanism of the hheccatalyzed ringopening of rstyrene oxide with the nucleophiles cn and n both the cyanolysis and the azidolysis reactions are shown to take place in a single concerted step the results support the suggested role of the putative sertyrarg catalytic triad where tyr acts as a general acid donating a proton to the ATP and arg interacts with tyr and facilitates proton abstraction while ser positions the ATP and reduces the barrier for epoxide opening through interaction with the emerging oxyanion of the ATP we have also studied the regioselectivity of rstyrene oxide opening for both the cyanolysis and the azidolysis reactions the employed AS site model was shown to be able to reproduce the experimentally observed betaregioselectivity of hhec in silico mutations of various CG in the hhec active site model were performed to elucidate the important factors governing the regioselectivity
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achalasia is a rare esophageal motility disorder much of the literature is based on the AD population in adults guidance of therapeutic approach by manometric findings has led to improvement in patient outcome promising results have been achieved with novel therapies such as peroral endoscopic myotomy poem areas covered in this review we provide an overview of the novel diagnostic and therapeutic tools for achalasia management and in what way they will relate to the future management of pediatric achalasia we performed a pubmed and embase search of english literature on achalasia using the keywords children achalasia pneumatic dilation myotomy and poem cohort studies cases and studies describing patients ≥ years were excluded data regarding patient characteristics treatment outcome and AEs were extracted and presented descriptively or pooled when possible expert commentary available data report that PD and laparoscopic hellers myotomy are effective in children with certain studies suggesting lower success rates in pneumatic dilation poem is increasingly used in the pediatric setting with promising shortterm results GE reflux disease gerd may occur postachalasia intervention due to disruption of the les and therefore requires diligent followup especially in children treated with poem
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the pharmacokinetic pk similarity between pf a proposed trastuzumab biosimilar trastuzumab sourced from european union trastuzumabeu or from united states trastuzumabus was evaluated safety and immunogenicity were also assessed
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excessive ethanol consumption causes adverse effects and contributes to organ dysfunction ethanol metabolism triggers oxidative stress altered immune CF and gut dysbiosis the gut microbiome is known to contribute to the maintenance of intestinal homeostasis and disturbances are associated with pathology a consequence of gut dysbiosis is also alterations in its metabolic and fermentation byproducts the gut microbiota ferments undigested dietary polysaccharides to yield shortchain fatty acids predominantly acetate propionate and butyrate butyrate has many biological mechanisms of action including antiinflammatory and immunoprotective effects and its SD is associated with intestinal injury we previously showed that butyrate protects gutliver injury during ethanol SE while the intestine is the largest immune organ in the body little is known regarding the effects of ethanol on intestinal immune function this work is aimed at investigating the effects of butyrate supplementation in the form of the structured triglyceride tributyrin on intestinal innate immune responses and oxidative stress following chronicbinge ethanol exposure in mice our work suggests that tributyrin supplementation preserved immune responses and reduced oxidative AS in the PT colon during chronicbinge ethanol exposure our results also indicate a possible involvement of tributyrin in maintaining the integrity of intestinal villi vasculature disrupted by chronicbinge ethanol exposure
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previous studies have suggested that obstructive SA osa may be a risk factor for stroke in this study we assessed that osa is an independent risk factor of silent cerebral infarction sci in the GA population and in a nonobese population this T0 recruited a total of participants men and women aged years as part of the korean genome and epidemiology T0 koges they underwent polysomnography BB magnetic resonance imaging and health screening examinations sci was assessed by subtypes and brain regions and LI represented lesions mm in size in the penetrating arteries moderatesevere osa was determined by apneahypopnea index ≥ the results indicated that had moderatesevere osa of participants had sci and had LI moderatesevere osa was associated positively with sci odds ratio or confidence interval ci and lacunar infarction or ci in the age ≥year group compared with those with nonosa additionally in the basal ganglia osa was associated with an increase in the odds for sci and lacunar infarction in all age CG and especially in the ≥year age group in the nonobese participants osa was also associated positively with sci in the ≥year age group LI in all age CG and especially in the ≥year age group there was also a positive association with the BG moderatesevere osa was associated positively with sci and lacunar infarction in elderly participants treatment of osa may reduce new firsttime cerebrovascular events and recurrences
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physical inactivity may an important outcome in the prognosis of breast CA physical activity C2 decrease significantly for breast cancer patients following the treatment and remain low T3 oncology treatment is completed the aim of this study was to determine PCS activity C2 and to examine associations among PCS activity comorbidity PET capacity IP muscle strength and psychosocial status in breast cancer patients forty breast cancer survivors were included in this study demographic and clinical characteristics were recorded PCS activity was assessed with a short form of the international PCS activity questionnaire ipaq we defined comorbid diseases according to the charlson comorbidity index cci PET capacity was evaluated with a sixminute walk test mwt IP muscle strength was measured for QF muscle with a handheld dynamometer psychosocial status was measured with the hospital anxiety depression scale hads forty percent of patients were inactive the ipaq total score was significantly related with quadriceps muscle strength r p and hads depression score r p marked correlations were also observed between ipaq walking score and quadriceps muscle strength r p hads depression score r p and cci r p the cci score was also markedly associated with quadriceps muscle strength r p mwt distance was not significantly correlated with any of the parameters regression analyses revealed that psychosocial status and IP muscle strength were significant predictors of physical activity estimated with the ipaq short form and when combined they explained of the variance comorbidities peripheral muscle strength and psychosocial status partially explain the variability of PAL in breast cancer survivors these results suggest that PCS inactivity contributes to worsening health in breast cancer survivors
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the incidence and mortality of malignant melanoma mm has markedly increased in the federal republic of germany the data available show a doubling of incidence in the past years and a doubling of mortality in the past years germany holds a middle range in the incidence list of mm compared to worldwide data mm were registered per inhabitants and year in germany during the mid eighties whereas x higher incidences where reported from australia and the southern states of the usa incidences higher than where found in the scandinavian countries while sun SE is regarded as the most important risk factor in the international epidemiology of mm a relationship between sun exposure and increasing risk of mm could not be clearly established for the german population in contrast the total number of MN mcn and the occurrence of dysplastic nevi where found to be significant markers of an increased relative risk for developing mm in the german population the increase of the relative risk was x for persons with greater than mcn compared to individuals with greater than or equal to mcn and there was an additional x increase of the relative risk for persons with greater than or equal to dysplastic nevus the course of the disease is lethal in most cases of metastatic malignant melanoma of all patients in the federal republic of germany however were first diagnosed in clinical stage i primary RT CT and the average years survival rate was in the time period since multivariate SRA revealed that the most important prognostic AF in stage i mm were tumor thickness and sex this finding should be taken into consideration for a prognostic classification of stage i mm
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a yearold woman had morning glory syndrome of the fundus of the RA eye the finding was related to chronic simple glaucoma and without pulsation of the staphyloma the clinical PS and echographic pattern during the endocular hypertensive phase with normal intraocular pressure was studied after AGA medication this associated disease is attributed to the presence of a congenital malformation of the anterior chamber angl
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giving an opinion on disputable paternity concerning monozygotic twins in practice at the department of forensic medicine silesian academy of medicine katowice demonstrated their ideal agreement according to examined genetic markers possible even the mutation which was revealed using the rflpvntr method was the same for both twin sisters in the case of DZ a firm differentiation of paternity index and probability of paternity was proved this was the consequence of independent features segregation in first reductive meiotic division while the rare outladder allele at the csfpo locus was transmitted to both twins a daughter and a son by the putative father
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patients with thin breslow thickness or mm melanoma have a good prognosis year survival consequently the added benefit of lymphatic mapping and sentinel LA lmsl in these patients is controversial we hypothesize that lmsl with a focused examination of the sentinel node sn will detect a significant number of sn metastases in patients with thin melanoma and that certain clinical or histopathologic AF may serve as predictors of sn tumor involvement
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growing evidence supports the view that in AD stem cells the defining SC features of potency and selfrenewal are associated with the quiescent state thus uncovering the molecular logic of this reversibly arrested state underlies not only a fundamental understanding of adult tissue dynamics but also hopes for therapeutic regeneration and rejuvenation of damaged or aging tissue a key question concerns how adult stem cells use G0 to establish or reinforce the property of selfrenewal since selfrenewal is largely studied by assays that measure proliferation the concept of selfrenewal programs imposed during nonproliferating conditions is counterintuitive however there is increasing evidence generated by deconstructing the G0 that highlights how programs characteristic of this particular cell cycle exit may enhance SC capabilities through both cellintrinsic and extrinsic programstoward this end SC models that recapitulate key aspects of stem cell quiescence are useful for molecular analysis to explore attributes and regulation of the quiescent state in this chapter we review the different methods used to generate homogeneous populations of quiescent muscle cells largely by manipulating SC conditions that feed into core signaling programs that regulate the cell cycle we also provide detailed protocols developed or refined in our lab over the past two decades
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to evaluate the opinions of regional education advisers academics and other consultants about features of the curriculum vitae we undertook a small attitude survey the response rate was which provided data from a total of influential anaesthetists the respondents attitude to each feature of the CV was reported using a linear visual analogue scale the three groups had similar attitude scores to most features but not to research time training time higher degrees and abstracts of papers presented to the anaesthetic research society publications in the main anaesthesia journals time in other L1 medical specialties research and the possession of a higher degree were scored highly by all respondents papers in nonpeerreviewed journals letters unsubmitted papers and time in training for general practice attracted lower scores the free text comments of many respondents indicated a considerable disillusionment about the whole appointments process
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in order to analyze peripheral circulation in coronary disease cd patients with tachysystolic atrial fibrillation taf as many as patients were examined based on the magnitudes of the cardiac index and the pressure of LV filling the patients were distributed into CG depending on the variant hypovolemic hypokinetic hypervolemic normokinetic and hyperkinetic of the taf dynamics twentytwo cd patients with sinus tachycardia and persons without any cardiovascular pathology were also examined all the examinees were exposed to longitudinal BP rheovasography rvg of the legs the most pronounced changes in the blood flow in the lower limbs manifested by the lowest magnitudes of the pulse blood content circulation intensity velocity of the systolic inflow and the highest tone of the peripheral arteries were recorded in patients with the hypovolemic and hypokinetic patterns of the taf hemodynamics the peripheral circulatory disorders correlated well with the degree of circulatory failure and with the incidence of the clinical manifestations of microcirculatory CA at the same time the rvg readings in patients with the hyperkinetic normokinetic and hypervolemic variants of the hemodynamics and in those with ST appeared to be similar the relationship was also established between the time of PP wave spreading and the degree of circulatory failure atherosclerosis of the IP arteries and the degree of the reduction in stroke volumes because of variations in the duration of cardiac cycles antiarrhythmic treatment favoured the improvement of the rvg readings both in cases where the rhythm became rarer and where the sinus rhythm got recoveredabstract truncated at words
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gl one of the proposed chemopreventive drugs was used to inhibit NAT1 nat activity in klebsiella pneumoniae both in cytosol and intact bacteria the nat activity was measured by using highperformance liquid chromatography to assay the amounts of acetylaminofluorene and remaining aminofluorene the nat activity in k pneumoniae was inhibited by glycyrrhizic acid in a dosedependent manner the cytosol nat MICs were nmol min mg protein for the acetylation of aminofluorene without glycyrrhizic acid and nmol min mg protein with mm gl the nat activities measured from intact bacteria were nmol min colony forming units for the acetylation of aminofluorene without gl and nmol min colony forming units in the presence of mm gl the inhibition of nat activity by gl was demonstrated to remain for at least h the apparent km and vmax values calculated from cytosol nat were mm and nmol min mg protein respectively for aminofluorene in the presence of mm gl the apparent km and vmax values were mm and nmol min mg protein respectively for aminofluorene in intact bacteria the apparent km and vmax values were mm and nmol min colony forming units respectively for aminofluorene however in the presence of mm gl the apparent km and vmax values were mm and nmol min colony forming units respectively for aminofluorene taking these results together the nat activity in k pneumoniae was inhibited by gl both in cytosol and IN bacteria this study provides the first evidence to demonstrate that gl inhibits bacterial nat activity
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choreaacanthocytosis chac is an AR hereditary disease characterized by neurodegeneration in the striatum and acanthocytosis caused by lossoffunction mutations in the vacuolar protein sorting homolog a vpsa gene which encodes chorein we previously produced a chacmodel mouse with a homozygous deletion of exons in vpsa which corresponded to the human disease mutation we found that male chacmodel mice exhibited CR infertility as a result of severely diminished sperm motility ICC T0 revealed that choreinlike immunoreactivity is abundant only in the midpiece MR region of the sperm of wild type mice they showed no significant differences from wild types in terms of the adenosine triphosphate atp concentration of their sperm sperm count or sexual activity electron microscopy revealed abnormal ultrastructural morphology of the mitochondria in the midpiece of sperm from chacmodel mice these results suggest that chorein is essential in mouse sperm for the maintenance of ultrastructural mitochondrial morphology and sperm motility
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we reported previously that the herpes simplex virus type hsv thymidine kinase reporter gene tk was expressed in the testes of transgenic mice when coupled to the promoter of a liverspecific mouse L1 urinary protein mup gene here we show that hsv tk is also expressed in the testis when coupled to a mup pseudogene promoter to a truncated mup promoter that is not active in the CL and to the promoter of the bovine thyroglobulin gene furthermore hsv tk itself was expressed in the testis although its normal expression had been disabled by removing an upstream regulator of transcription in every case the same multiple transcripts were observed with their ends located downstream of the normal hsv tk translation initiation codon we conclude that the transcription of hsv tk in the testis is directed by a cryptic tata boxindependent promoter located in the coding region of the gene the longest hsv thymidine kinase tk polypeptides synthesized in the testis were shorter than fulllength tk and probably result from translational initiation at met and met the second and third atg codons of the tk reading frame male mice of most transgenic lines were sterile and the severity of the lesion in spermatogenesis was directly related to the level of tk expression in the most highly expressing lines sperm counts were low and morphologically defective sperm were common in other sterile lines tk was expressed at a lower level and sperm counts were normal but sperm motility was greatly reduced lines with the lowest C2 of hsv tk expression were fertile hsv tk was expressed in germ L1 cells mainly in the haploid spermatids however lowlevel hsv tk activity was found in the testis before the first germ cells entered meiosis showing that if expression is confined to the germ cells it also occurs in spermatogonia
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neural bases of human olfactory SM are poorly understood very few studies have examined neural substrates associated with correct odor recognition and none has tackled neural networks associated with incorrect odor recognition we investigated the neural basis of task performance during a yesno odor recognition memory paradigm in young and elderly subjects using eventrelated functional magnetic resonance imaging we explored four response categories correct hit and incorrect false alarm fa recognition as well as correct cr and incorrect miss rejection and we characterized corresponding BB responses using MVA and linear SRA we hypothesized that Az of the medial temporal lobe were differentially involved depending on the accuracy of odor recognition in young adults we found that significant activity in the hippocampus and the PHG was associated with correct true recognition of odors whereas the perirhinal cortex was associated with fas and misses these findings are consistent with literature regarding hypothetical functional organization for memory processing we also found that for correct recognition and AAR responses the involvement of the hippocampus decreased when SM performances improved in contrast to young individuals elderly subjects were more prone to false memories and exhibited less TPS activation patterns for the four response categories activation in the hippocampus and the parahippocampal gyrus was positively correlated with response bias scores for true and false recognition demonstrating that conservative subjects produced an additional search effort leading to more activation of these two medial temporal lobe regions these findings demonstrate that correct and incorrect recognition and rejection induce distinct neural signatures
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gold NPs modified with antimouse igg have been used to trace oligonucleotides carrying a cmyc peptide two strategies a dotblot format as well as ICP mass spectrometry icpms have been used to detect the nanoparticle tracer for both cases oligonucleotidepeptide conjugates were first applied to a nitrocellulose membrane using a manifold attached to a suction device T3 immobilization of the oligonucleotide by uv radiation the samples were incubated with an anticmyc monoclonal antibody in the case of the dotblot format strategy it was followed by incubation with a secondary antibody conjugated to horseradish peroxidase and OD with luminol as chemiluminescent ATP in the case of icpms strategy it was followed by incubation with the secondary antibody antimouse igg conjugated to gold NPs and their icpms PCD after dissolving the nonspecific adsorptions were found to be around zero the limit of PCD for peptidemodified dna was pmol the method may have significant potential as an important icpmsbased nonradioactive dna PCD method for the simultaneous determination of various sequences by labeling different kinds of inorganic NPs
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shortterm aldosterone m h induces in ac cell epithelia an increase in na transport which is due to the in situ activation of the apical na channel and presumably the basolateral na pump nakatpase we have now directly measured the effect of aldosterone on the transport activity of endogenous na pumps and hybrid na pumps containing an exogenous alpha S1 by measuring the pump current ip across epithelia apically permeabilized with amphotericin b aldosterone h had no significant early effect on the maximal ip nor on the na concentration required for halfmaximal activation in contrast it increased the ip at physiological intracellular na concentrations fold at mm na this effect was blocked by the protein synthesis inhibitor cycloheximide hybrid pumps containing the transfected cardiotonic steroidresistant alpha subunit of bufo marinus were also stimulated by aldosterone h a long aldosterone treatment days increased the maximal ip produced by the endogenous pumps to fold in conclusion aldosterone acts on na pumps containing an alpha S1 in two ways during its early phase of action it stimulates their transport activity by increasing their apparent na affinity at physiological intracellular na concentrations in the long term it produces an increase in the maximal transport capacity which corresponds to the known increase in the number of na pumps
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we present a case of laryngeal cleft in a yearold man to illustrate the cooccurrence of laryngeal cleft and TE fistula we advocate the use of the modified barium swallow study in the diagnosis of laryngeal cleft we also review the advantages and limitations of the various diagnostic methods as well as the potential for known TE fistula to mask laryngeal cleft finally we discuss the importance of early identification of laryngeal cleft in the context of its potentially serious health implications
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as obligate parasites mycoplasma species are continuously exposed to oxidative damage due to hostgenerated peroxides and ROS species ros in addition the production of endogenous oxidants is believed to be a primary virulence mechanism of several mollicute species indicating that oxidative AS resistance is crucial to survival of these bacteria in the host milieu despite the abundance of oxidants at the site of infection enzymes responsible for the detoxification of ros have never been characterized in mycoplasmas here we characterize a homolog of the ohr organic hydroperoxide resistance family from mycoplasma gallisepticum encoding mga unlike previously characterized ohr genes the mga gene is not upregulated in response to oxidative stress but displays a novel pattern of expression both organic and inorganic peroxides can act as substrates for mga but they are degraded with various efficiencies furthermore cumene hydroperoxide an aromatic peroxide metabolized with high efficiency by other ohr proteins was shown to rapidly inactivate mga accounting for the sensitivity of m gallisepticum cells to this compound comparative modeling of the mga quaternary structure revealed that the active site of this molecule has a relatively wide conformation these data indicate that the NK substrate for mga differs from that for previously characterized ohr proteins triton x partitioning demonstrated that mga is located in both cytosol and MF suggesting that in vivo this molecule plays a role in the detoxification of both endogenous and exogenous peroxides a MM describing how mga is likely to be oriented in the cell membrane is presented
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retrospective T0 in patients undergoing cataract surgery by facoemulsification in order to evaluate the incidence of regional peribulbar anaesthesia compared with mac monitored anesthesia care
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when a CDSS cdss or other ancillary system detects an abnormal or problematic condition healthcare providers must be notified in a timely manner so that AGA corrective action can be taken delivery of clinical alerts to the appropriate providers is the role of a notification system the content generating system must therefore communicate to the notification system the content to be delivered and any additional directives regarding the resulting notifications this work is sanctioned by the health level seven inc CDS technical committee cds tc and is based on previous proposals to the cds tc the proposed message MM is presented as an xml schema
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acute RD syndrome is a manifestation of acute injury to the lung commonly resulting from sepsis trauma and severe pulmonary infections clinically it is characterized by dyspnea profound hypoxemia decreased CL and diffuse bilateral infiltrates on CXR provision of supplemental oxygen lung rest and supportive care are the fundamentals of therapy the management of acute RD syndrome frequently requires endotracheal intubation and mechanical ventilation a low tidal volume and low plateau pressure ventilator strategy is recommended to avoid ventilatorinduced injury timely correction of the inciting clinical condition is essential for preventing further injury various medications directed at key stages of the pathophysiology have not been as clinically efficacious as the preceding exp trials indicated complications such as PTX effusions and focal pneumonia should be identified and promptly treated in refractory cases advanced ventilator and novel techniques should be considered preferably in the setting of clinical trials during the past decade mortality has declined from more than percent to about to percent death usually results from multisystem organ failure rather than respiratory failure alone
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an avulsion of the posterior root attachment of the lateral meniscus or a radial tear close to the root att can lead to degenerative knee ICA although the biomechanical effects of comparable injuries involving the medial meniscus have been studied we are aware of no such T0 involving the lateral meniscus we hypothesized that in situ pullout suture repair of lateral meniscus root avulsions and of CR radial tears and mm from the root att would increase the contact area and decrease mean and peak tibiofemoral contact pressures at all knee flexion angles relative to the corresponding avulsion or tear condition
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percutaneous transluminal balloon angioplasty was attempted in seven patients with internal CAS including one patient who had two procedures all had recurssociated with differences in the allocation of hospital services
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membrane associated guanylate kinase maguk family has been extensively studied in cellular adhesion and ST at CS of cell–cell contact recently growing attention has been paid to its role in the initiation and progression of various cancers however its role in hepatocellular carcinoma hcc has been rarely investigated in this study we found that membrane palmitoylated protein mpp a member of maguk family was significantly upregulated in both high metastatic potential cell lines and clinical tissue samples of hcc and the most significant increase was observed in the PT invading the portal veins higher level of mpp correlated with poorer survival of patients with hcc forced expression of mpp significantly enhanced hcc cell migration and invasion whereas knockdown of this gene inhibited this oncogenic effect mechanismly we found that mpp promoted hcc cell migration and invasion via upregulating matrix metalloproteinase mmp these findings indicate that mpp play an important role in hcc metastasis by promoting cell migration and invasion suggesting that it may serve as a novel prognostic marker and molecular target for therapy of hcc
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a yearold man with B-ALL in second remission received an allogeneic bone marrow SPK from an hlacompatible sibling donor unfortunately cytomegalovirus cmv pneumonitis was histologically documented on day ACT with ganciclovir hydroxyhydroxymethyl ethoxymethyl guanine and highdose intravenous immunoglobulin ivig was started immediately the treatment comprised a threeweek induction course ganciclovir mgkg qh and ivig mgkg qod and a sevenweek fixeddose maintenance course ganciclovir mgkg thrice a week for doses and ivig mgkg twice a week for eight doses the pneumonia resolved gradually and he was free from PS within two weeks the only significant side effect was moderately severe myelosuppression which was reversible T3 discontinuation of ganciclovir the patient had a relapse of leukemia on day but there was no recurrence of cmv pneumonitis this result confirms that such ACT is effective in the treatment of cmv pneumonitis in a patient with a bone marrow SPK
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the male reproductive system of dolycoris baccarum linnaeus is studied morphologically and histologically using both CS and SEM microscopes sem the reproductive system of the male d baccarum consists of a pair of testis a pair of vas deferens a pair of seminal LDV accessory glands mesadenia ectadenia a bulbus ejaculatorius a pair of ectodermal sacs and a ductus ejaculatorius the number of testicular follicles varies from four to six the testicular follicles have three different development zones growth zone maturation zone differentiation zone the testes are connected to the seminal vesicles by the vas deferens VD and seminal LDV which are finelong and cylindrical the seminal vesicle is connected with bulbus ejaculatorius which is balloonshaped and surrounded with accessory glands the bulbus ejaculatorius is continuous with ductus ejaculatorius which connected to the aedeagus
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Arg can be produced in the kidney from citrulline an important source of circulating citrulline is the intestinal breakdown of glutamine consequently partial enterectomy leads to decreased plasma citrulline levels the aim of the present T0 was to investigate the effect of diminished arterial citrulline C2 on renal Arg production and totalbody free Arg pools renal amino acid metabolism was studied h after SBR in rats fasted overnight h n total fast h shamoperated n and nonoperated h and h fasted controls were studied in parallel nn during anaesthesia l harginine and paraaminohippuric acid were infused until Css subsequently arterial and renal venous blood samples were taken concentrations of paraaminohippurate and amino acids and TPS activity of Arg and citrulline were measured to calculate renal plasma flow net renal uptake or PR and unidirectional influx or efflux of Arg and citrulline as well as wholebody Arg turnover arterial citrulline was decreased in enterectomized rats compared with sham versus microm net renal citrulline uptake and arginine PR were almost stoichiometric and nmolmin g body weight respectively in shamoperated rats and were both diminished by in enterectomized versus sham in all groups net renal Arg production accounted for less than of wholebody rate of arginine appearance nmolmin g body weight in the sham group despite decreased net renal citrulline consumption and renal arginine production in enterectomized rats wholebody rate of arginine appearance as pregnancy is confirmed and before weeks gestation for women who have at deficiency the incidence of thrombosis during pregnancy is between and adjusteddose heparin throughout pregnancy is recommended followed by warfarin for at least months PP for patients who have FVL mutant factor ii or a deficiency of protein c or protein s treatment can be based on personal and family history thromboprophylaxis during late pregnancy and postpartum should be considered fetal loss may be increased for women with inherited thrombophilia the risk appears to be greatest for women with at deficiency and women with more than one thrombophilic defect for women with recurrent fetal death and inherited thrombophilia a number of case reports claim that prophylaxis with heparin during pregnancy has resulted in successful pregnancy
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we have recently shown that immobilized metal affinity chromatography imac is an effective technique for purification of herpes simplex virus type hsv gene vector engineered to display cobalt affinity tag on the envelope however the tagged hsv viruses were severely inactivated by oxidative hydroxyl FRs when crude hsv supernatant was applied on an immobilized cobalt column and eluted by a low ph buffer furthermore we have reported that virus inactivation could be prevented by inclusion of high concentration of ascorbate in chromatographic mobile phase in this paper we report that when elution of bound virus was attempted by inclusion of imidazole in elution buffer rather than lowering the ph of elution buffer similar inactivation was also observed the results also demonstrated that virus inactivation was dramatically reduced by inclusion of mm imidazole in the loading buffer electron spin resonance esr experiments suggest that imidazole prevents hydroxyl free radical generation from the cobalt complexes this is the first report describing the role of imidazole in preventing free radical formation in an imac column from a practical stand point our results imply that inclusion of appropriate amount of imidazole in the loading buffer is an effective strategy for improving the recovery yield of active products and for enhancing product SQ during imac purification
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FM in europe started to develop in the s with the introduction of obligatory specialist training slovenia is a country with a long tradition of FM specialist training but up until this was neither elaborated on nor conducted by peers in general practicefamily medicine when the countrys socialist system started to transform due to political reforms slovenia began to modify its system in order to meet the criteria of the european union one of the changes was the introduction of a new healthcare system with an influential medical chamber responsible for postgraduate training in all specialities a new MM for VT in family medicine was established in following the recommendations of the european union of GA practitioners uemo according to the new programme which lasts years trainees spend half of their training in a hospital setting and half in GP where they are supervised by a trainer in practice this article describes the legal process of introducing new forms of specialist training in slovenia and its content
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