text
stringlengths
10
10.1k
source
stringclasses
1 value
we T0 the use of the fitzhughnagumo fhn MM for capturing neural spiking the fhn MM is a widely used approximation of the hodgkinhuxley MM that has significant limitations in particular it cannot produce the key spiking SMB of bursting we illustrate that by allowing timevarying parameters for the fhn model these limitations can be overcome while retaining its loworder complexity this extension has applications in modeling neural spiking behaviors in the thalamus and the respiratory center we demonstrate the use of the fhn MM from an estimation perspective by presenting a novel parameter estimation method that exploits its multiple timescale properties and compare the performance of this method with the D2 kalman filter in several illustrative examples we demonstrate that the dynamics of the spiking threshold can be recovered even in the absence of complete specifications for the system
MEDAL
oxytocin ot is a nonapeptide hormone mainly synthesized in the magnocellular neurons of the paraventricular and supraoptic nucleus of the hypothalamus in the extrahypothalamic brain areas ot acts like neurotransmitters and modulators the physiological functions of ot are multiple ot participates to the coordination and control of gonadal OD and reproduction ot appears also as an important regulator of social behaviors such as affiliative parental and romantic behaviors recent evidence suggests other roles for ot such as potent effects on cardiometabolic functions or involvement in stressrelated disorders the growing interest around the clinical role of ot raised the question of the measurement of ot levels and performances of assays
MEDAL
this paper presents a reliable braincomputer interface bci based on a SSVEP ssevp method using online recursive ICA orica with denoising the proposed system includes a visual stimulator a frontend data acquisition module an orica module a power spectrum density psdbased noise channel detection module a denoising module and an eeg reconstruction module and a detection module using canonical correlation analysis cca the system with the proposed psdbased denoising mechanism is simulated using test patterns of hz and hz ssevpbased eeg raw data stream with an second sliding window length with a second step size under the condition of hz sampling rate the accuracy of the PCD is approximately and hit rate for hz and hz test patterns respectively
MEDAL
purpose to report a case of unilateral ON following measlesmumpsrubella mmr vaccination methods a yearold female developed unilateral optic neuritis five days after a measlesmumpsrubella mmr booster vaccination the patient displayed unilateral involvement with severe visual loss however VA improved significantly after four days of intravenous steroid therapy with mgday of methylprednisolone conclusions optic neuritis is one of the rare complications associated with the mumps measles and rubella vaccine it may be a toxic reaction to the nonviral component of the vaccine but the exact etiology is unknown postvaccination neuritis is generally BL and usually affects children in adults unilateral optic neuritis is usually correlated with multiple sclerosis ms
MEDAL
this article describes a novel labonachip protocol generating two electrophoretic peaks for a single analyte based on the coupling of two different precolumn enzymatic reactions of the same substrate followed by electrophoretic separation of the MRP such operation is illustrated for the measurement of gl in connection to the corresponding gl oxidase gox and gl dehydrogenase gdh reactions the precolumn enzymatic reactions generate hydrogen peroxide and nadh species that are separated based on their different charges and detected at the endcolumn amperometric detector the peak current ratio can be used for confirming the peak identity estimating the peak purity addressing comigrating interferences and deviations from linearity a driving voltage of v results in peroxide and nadh migration times of and s respectively factors influencing the unique dual gl response are examined and optimized the concept can be D2 to different target analytes based on the coupling of two precolumn reactions with electrophoretic separation of the MRP
MEDAL
psychophysical results suggest that the primate visual system is equally CS to both the onset and offset of shortwavelength light and that these responses are carried by separate pathways however physiological studies of cells in the retina and lateral geniculate nucleus find far fewer offcenter than oncenter cells whose receptivefield centers are driven by shortwavelengthsensitive s cones to determine whether s cones contact on and off midget bipolar cells as well as on bluecone bipolar cells mariani we examined contiguous cone terminals and their BCs in electron micrographs of serial sections from macaque foveal retina five widely spaced cone terminals do not contact on midget BCs these five cone terminals contact the dendrites of bluecone BCs instead showing that they are the terminals of s cones these scone terminals are smaller and contain more SR than other terminals like neighboring cones each s cone contacts its own off midget bipolar cell via triadassociated flat synaptic contacts moreover each scone off midget BP cell has a synaptic terminal in the outer half of the IPL where it contacts an off midget GCL
MEDAL
assessment of the skinfold thickness in obese patients by means of a caliper makes it possible to determine the percentage of total body fat and provides information on the distribution of subcutaneous body fat and thus to characterize the type of obesity in more severe obesity it is not possible to differentiate reliably by means of classical calipers larger skinfolds in particular the subscapular and abdominal skinfold which thus makes these anthropometric examinations useless a newly developed modification of the best caliper makes it possible to measure reliably the majority of SSF in obese subjects as the arm of the caliper can be shifted to a range as high as mm bests caliper provides in contrary to others the possibility to set a constant pressure when measuring the skinfold in the discussion the authors draw attention to some methodological problems and the clinical importance of examining obese subjects by means of a caliper
MEDAL
the occurrence and distribution of calcitonin generelated peptide cgrp immunoreactivity in the rat RT were investigated by means of immunocytochemistry and radioimmunoassay using antibodies raised in rabbits to synthetic rat cgrp substantial amounts of cgrp immunoreactivity range pmolg were detected in all parts of the RT the highest being in the stem bronchus GFC of extractable cgrp immunoreactivity revealed one single peak eluting at the position of synthetic rat cgrp cgrp immunoreactivity was localized both in mucosal endocrine cells and nerve MF from the larynx down to the peripheral lung cgrpimmunoreactive endocrine cells were found singly in tr and stem bronchi and in CG in intrapulmonary airways they appeared at a late stage of gestation days reached a maximum number near term and decreased T3 birth to maintain a population similar to that of the adult animals by PN day similarly CGRP-IR nerve MF were first identified by day of the gestation period and reached the adult distribution by postnatal day cgrpimmunoreactive nerve MF were localized among smooth muscle seromucous glands beneath and within the epithelium of the airways and around blood vessels cgrp was also found in sensory ganglia and in motor end plates of the larynx musculature neonatal pretreatment with capsaicin caused a marked reduction in cgrp immunoreactivity of nerve MF in the respiratory tracts as well as a less marked decrease in the population of cgrpcontaining endocrine cells of the lung no change was seen in motor end plates immunostaining vagal ligation experiments revealed that cgrpimmunoreactive nerve MF travelling in the vagus originate mainly from SN located in the jugular ganglion infranodosal RA vagal ligation induced a marked loss in cgrpimmunoreactive SN of the trachea and of the ipsilateral stem bronchus but no changes were observed in peripheral lung by contrast infranodosal left side vagal ligation caused a decrease in cgrpimmunoreactive nerves of the ipsilateral lung and bronchus without affecting the peptide content in the trachea left vagal ligation also induced a marked increase in both the intensity of staining and number of CGRP-IR endocrine cells in the lung we conclude that cgrp immunoreactivity is localized in both nerve MF and endocrine cells and is associated principally with the afferent sensory innervation of the respiratory tractabstract truncated at words
MEDAL
the effect of acth and electric foot shock stress on dopac content were determined in the frontal cortex and nucleus accumbens twenty min of AS enhanced dopac levels in the frontal cortex and in the nucleus accumbens by about and respectively on the other hand a single dose of acth failed to NC dopac concentration in the above brain areas the present results show that the activation of mesolimbic and mesocortical dopaminergic systems is not mediated by acth secretion
MEDAL
previous research has shown that low voltage fast activity lvfa in the neocortex and rhythmical slow activity rsa in the hippocampus can result from activity in either of two ascending pathways activity in SN in the basal forebrain may produce atropinesensitive presumably ACh lvfa and rsa during both type behavior eg head movement walking and type SMB eg waking immobility facewashing tremor activity in an aminergic pathway may produce atropineresistant lvfa and rsa during type SMB only the role of hydroxytryptamine ht in this pathway was studied in rats treated with pchlorophenylalanine pcpa mgkgday x ip amine levels were measured by OHP liquid chromatography with electrochemical detection BB slow wave and multiunit activity was assessed by inspection and by a procedure of filtering and integration pcpa treatment CT had little effect on lvfa or rsa but following pcpa and atropine mgkg together both lvfa and rsa were att or eliminated thus atropineresistant lvfa and rsa may be dependent on ht transmission a combination of pcpa and atropine produced a very severe deficit in performance in a simple WM rats treated with this drug combination may provide an animal MM of human global PSD
MEDAL
distal renal tubular acidosis is a disorder of acidbase regulation caused by PET failure of αintercalated cells in the distal nephron the recessive form of the disease which is usually associated with sensorineural deafness is attributable to mutations in atpvb or atpva which encode the tissuerestricted b and a subunits of the renal apical hatpase atpvb lies adjacent to the gene encoding the homeobox domain protein vax at p to date no human phenotype has been associated with vax mutations
MEDAL
knowledge about the optical properties μaμs and g of human blood plays an important role for many diagnostic and therapeutic applications in laser medicine and medical diagnostics they strongly depend on physiological parameters such as oxygen saturation osmolarity flow conditions PCV etc the integrating sphere technique and inverse MC simulations were applied to measure μaμs and g of circulating human blood at nm the optical properties of human blood with a haematocrit of and an oxygen saturation of were found to be ± mm for μa± mm for μs and ± for the g factor an increase of the haematocrit up to lead to a linear increase of absorption and reduced scattering variations in osmolarity and wall shear rate led to changes of all three parameters while variations in the oxygen saturation only led to a significant NC of the absorption coefficient a spectrum of all three parameters was measured in the wavelength range nm for oxygenated and deoxygenated blood showing that blood absorption followed the absorption SMB of haemoglobin and water the scattering coefficient decreased for wavelengths above nm with approximately λ the g factor was higher than over the whole wavelength range © society of photooptical instrumentation engineers
MEDAL
azathioprine aza pharmacogenetics are complex and much studied genetic polymorphism in tpmt is known to influence treatment outcome xanthine oxidasedehydrogenase xdh and aldehyde oxidase ao compete with tpmt to inactivate aza
MEDAL
the SAM a small domeshaped structure at the shoot apex is responsible for the initiation of all postembryonic shoot organs CFU-S stem cells within the meristem replenish themselves and provide daughter cells that become incorporated into lateral organ primordia around the meristem periphery we have identified three novel regulators of shoot apical meristem activity in arabidopsis thaliana that encode related ailplt transcription AF aintegumenta ant aintegumentalike ailplethora plt and aintegumentalike ailplethora plt loss of these genes results in plants that initiate only a few leaves prior to termination of shoot apical meristem activity in dayold ant ail ail seedlings we observed reduced cell division in the meristem region differentiation of meristematic cells and altered expression of the meristem regulators wuschel wus clavata clv and shoot meristemless stm genetic experiments suggest that these three ail genes do not act specifically in either the wusclv or stm pathway regulating meristem CF furthermore these studies indicate that ant ail and ail have distinct functions within the meristem rather than acting in a strictly redundant manner our T0 thus identifies three new genes whose distinct functions are together required for continuous shoot apical meristem function
MEDAL
the aim of this T0 was to evaluate interdental caries incidence and progression in relation to the effect of antibacterial varnish treatments in schoolchildren anticipated at caries risk T3 a screening procedure HC years with moderate and high counts of salivary mutans streptococci ms were invited to join a year longitudinal study at baseline ms were enumerated at all mesial interdental CS of the first permanent molars with a chairside technique the children were then treated times within weeks by interdental spot applications with a chlorhexidinethymolcontaining varnish cervitec followup samples of saliva and plaque were collected and months after ON of treat caries prevalence incidence and progression of the selected approximal surfaces were scored from bitewing radiographs exposed at baseline and T3 years sixtythree children of the same age formed a nonvarnishtreated RG reduction of caries incidence and progression was dearly dependent on the outcome of the antibacterial treatment a significantly p higher progression score was found among children who exhibited a less marked suppression of interdental ms C2 compared with those with high suppression and the children of the reference group the results suggest that a suppression of ms in interdental PI may be an important event to prevent and arrest approximal caries OD in schoolchildren at risk monitoring the effect of antibacterial agents in a sitespecific way could therefore be advocated
MEDAL
MCT mtc occurs usually in sporadic form but about a quarter of the cases are hereditary and appear as part of one of the multiple endocrine neoplasia type men syndromes mutations in the ret protooncogene are known to be the cause of the mena and familial MCT fmtc syndromes in the majority of the families direct dna testing allows prophylactic thyroidectomy to be offered to individuals carrying a mutation in the above codons and in mutationnegative cases it reduces the yearly screeningrelated burden on family members at risk of the disease by dna sequencing and pcrrestriction fragment length polymorphisms mtc probands were examined for mutations in residues of exon and in residues of exons and respectively of the ret protooncogene in our study mutations in the above codons were detected in all of the clinically mena and fmtc families one of these mutations tgc tcc has not been reported previously of the probands with the mutation relatives also had the identified mutation and relatives proved to be noncarriers among the probands with clinically sporadic mtc none was found to carry a mutation in the above positions even if indirect signs of mtc pheochromocytoma or hyperparathyroidism could be detected in some families the frequency e mitogenic action of TNF is primarily a direct effect of the cytokine and only to a minor extent mediated by a secondary production of il in the DU explant our findings indicate that tnfalpha and il may participate in the regulation of cell proliferation in the human small intestinal epithelium
MEDAL
the t chromosomal translocation seen in blastic crisis of chronic ML and secondary leukemias results in a formation of a chimeric protein amlevi which suppresses wildtype aml function loss of aml CF causes expansion of hematopoietic progenitor cells whereas it is not sufficient for the OD of one to identify essential mechanisms through which amlevi exerts full leukemogenic potential we introduced amlevi and its mutants in murine bone marrow cells and evaluated their transforming MICs by colony replating assays the transforming activity of amlevi was lost when any of the known PET domains of evi was deleted from the chimeric protein and forced expression of evi did not transform the amldeleted bone marrow cells unlike the mllenl and amleto leukemiarelated chimeric proteins amlevi could transform only the hematopoietic stem cell fraction moreover amlevitransformed cells show a cellmarker profile distinct from that of the cells transformed by amleto which also suppresses aml function thus leukemogenic activity of amlevi may be due to activation of molecular mechanisms distinct from those activated by mllenl or amleto in the hematopoietic stem cell fractions
MEDAL
we collected canadian retail pork chops and pork livers routinely usually weekly from april to march using the canadian integrated program for antimicrobial resistance surveillance cipars retail sampling platform samples were assayed using validated realtime q reverse transcriptase PCR reaction rtpcr and nested CP rtpcr for the detection of SH e virus hev porcine enteric calicivirus pec and RV rv the presence of escherichia coli salmonella spp and campylobacter spp was measured on a subset of our samples exact LR models were fitted for predictors for hev detection for each assay for both assays sample type pork chop versus liver was a significant predictor for hev rna detection for nested CP rtpcr but not qrtpcr region of sample collection was a significant predictor p of hev PCD odds of hev detection were greatest in spring relative to other seasons e coli was a significant predictor for hev rna detection using the qrtpcr p overall the prevalence of e coli salmonella spp and campylobacter spp was significantly greater than hev pec or rv on our retail pork samples our sparse data set for the detection of pec and rv precluded modelling of risk AF for the detection of these viruses
MEDAL
because no information exists on the prevalence of chemical sensitivity syndromes such as multiple chemical sensitivities a questionnaire for use in population studies was developed and tested to assess the presence or absence of chemical sensitivity seven hundred five individuals attending clinics answered a questionnaire asking whether each of common substances caused symptoms results showed that patients with multiple chemical sensitivities and asthma had average total scores that were significantly different from each other and from those of each of the other diagnostic categories higher total scores were also reported by female patients the instrument described here may facilitate meaningful prevalence studies of multiple chemical sensitivities it will also allow study of chemically induced PS in other conditions such as asthma
MEDAL
end diastolic flow velocity just beneath the aortic isthmus was measured within hours of cardiac catheterisation by pulsed doppler echocardiography in controls and patients with aortic regurgitation the end diastolic flow velocity was determined at the peak r wave on a simultaneously recorded electrocardiogram in all controls there was no reverse flow at the end diastole beneath the aortic isthmus in patients with aortic regurgitation the end diastolic flow velocity correlated well with the angiographic grade of regurgitation r and RF r the mean sd values were and cms for patients with RF of less than between and between and and greater than respectively an end diastolic flow velocity of greater than cms predicted a regurgitant fraction of greater than or equal to with a sensitivity of and a specificity of the T0 suggests that the pulsed doppler derived end diastolic flow velocity is a useful index in the routine noninvasive assessment of the severity of aortic regurgitation
MEDAL
the solar watersplitting protein complex photosystem ii catalyzes one of the most energetically demanding reactions in nature by using light energy to drive water oxidation the fourelectron water oxidation reaction occurs at the tetranuclear manganesecalciumoxo cluster that is present in the oxygenevolving complex of photosystem ii the tetranuclear manganesecalciumoxo cluster is comprised of mixedvalence mniii and mniv ions in the grounium channels that have been previously reported to cause severe dystoniclike symptoms in wildtype mice our findings collectively suggest that altered communication between ACh interneurons and medium spiny neurons is responsible for the ltd deficit and that this synaptic STDP modification may be involved in the striatal motor control abnormalities in our mouse MM of dyt dystonia
MEDAL
one hundred twentyeight SS samples collected from infants transfused at the neonatal ECU of kyushu university hospital fukuoka japan were tested for the presence of antibody to human tcell lymphotropic virus type i htlvi by the ELISA assay and the indirect immunofluorescence test three of were positive for antihtlvi antibody the three seropositive patients had received and ml of transfused blood these patients did not receive any transfusion thereafter in addition no antihtlvi antibodies were detected in the sera of their mothers and siblings these data suggested that htlvi infection is one of the transfusionassociated complications in neonates
MEDAL
collateral V1 arteries from the descending aorta to the pulmonary arteries are uncommon T3 ASO here we report the case of a baby girl treated with coil embolization for abnormal blood flow from the descending aorta to the pulmonary arteries T3 arterial switch operation a baby girl weighing g was delivered at weeks days of gestation and she had dtransposition of the great arteries and a VVI septal defect she underwent nitrogen inhalation to reduce pulmonary blood flow before arterial switch operation T3 the T0 she presented with left HF due to the presence of abnormal blood flow from the descending aorta to the pulmonary arteries and she was successfully treated with coil embolization after the treatment her condition improved dramatically and she was discharged without any complications
MEDAL
idiopathic achalasia is a primary esophageal motor disorder characterized by esophageal aperistalsis and abnormal LES les relaxation in response to deglutition it is a rare disease with an annual incidence of approximately and a prevalence rate of the disease can occur at any age with a similar rate in men and women but is usually diagnosed between and years it is characterized predominantly by dysphagia to solids and liquids bland regurgitation and chest pain weight loss usually between to kg is present in most but not in all patients heartburn occurs in of achalasia patients etiology is unknown some familial cases have been reported but the rarity of familial occurrence does not support the hypothesis that genetic inheritance is a significant etiologic factor association of achalasia with viral infections and autoantibodies against MP has been reported but the causal relationship remains unclear the diagnosis is based on history of the disease radiography barium esophagogram and esophageal motility testing esophageal manometry endoscopic examination is important to rule out malignancy as the cause of achalasia treatment is strictly palliative current medical and surgical therapeutic options PD surgical myotomy and pharmacologic agents aimed at reducing the les pressure and facilitating esophageal emptying by gravity and HP of retained food and liquids although it cannot be permanently cured excellent palliation is available in over of patients
MEDAL
the therapeutic efficacy of standard CA treatments such as chemotherapy may be improved if they are combined with genetherapy less than of patients with glioblastoma multiforme respond to adjuvant chemotherapy actively dividing cells are generally more CS to chemotherapy than are nondividing cells to determine whether forced cellcycle progression selectively sensitizes tumor cells to alkylating agents we examined the effects of overexpressing the ef protein a positive regulator of cellcycle progression on the sensitivity of two malignant human glioma cell lines u mg and d mg to bcnu and temozolomide treating these cells with microm bcnu or microm TMZ resulted in growth inhibition ic within or days respectively by contrast cells that were first induced to overexpress ef protein by infection with an adenoviral vector had ics that were lower conversely transferring the cyclindependent kinase inhibitors p and p to the cells also by adenoviral infection produced to fold increases in chemoresistance cellcycle analyses showed that the combination of ef overexpression and treatment with bcnu or temozolomide increased the proportion of cells in s phase but the combination of p or p overexpression and drug treatment reduced the proportion of cells in s phase these observations suggest that overexpression of genes that positively control cellcyclnoxic archean earth the Ox partner was probably iron as oxidized iron is markedly less soluble and mobile than organic carbon differential transport in the archaean biosphere would have had an effect just the opposite of that in the modern biosphere the Ox partner would have settled downward more rapidly than the reduced partner resulting in the accumulation of excess oxidant in sediments and stagnant pools an equivalent excess of the more volatile reduced compounds would have been left behind in ocean and atmosphere in the form of DOC and gaseous hydrocarbons on average therefore the archean biosphere may have been oxidizing at the bottom and reducing on top
MEDAL
the choice of primary treatment for patients with chronic myeloid leukaemia diagnosed in CP has become exceedingly difficult there is little doubt that allogeneic stem cell transplantation allosct can eradicate the leukaemia and that a graftversusleukaemia effect makes a major contribution to this result conversely only a minority of patients are eligible for transplant which still carries an appreciable risk of mortality or protracted morbidity for the majority of patients interferonalpha prolongs life to some degree in comparison with HU but is associated with considerable toxicity the newly introduced IMT kinase inhibitor imatinib mesylate imatinib glivec induces CR haematologic remission in almost all cases and is associated with a very high incidence of cytogenetic response its capacity to prolong life in comparison with interferonalpha is not yet established here we review some factors that predict survival after nontransplant therapy and T3 allografting for cml in chronic phase we consider two contrasting options for managing the newly diagnosed patient and conclude that for the present allo-SCT soon after diagnosis should continue to be offered as an option for selected patients further experience with the use of imatinib as a single agent or in combination with other antileukemic agents may alter the picture in the near future
MEDAL
cytosols prepared from adrenal PG of ovine fetuses days of gestation and of P0 lambs days postpartum were analysed for their protein kinase activities two major peaks of CS kinase MICs and two L1 peaks of histone kinase activities were observed in all cytosols of both fetal and neonatal adrenal glands they were characterized as campindependent casein kinases of type a and type g and as campdependent histone kinase isoenzymes of type i and type ii the specific activity of each enzyme increased fold between days of gestation and days postpartum casein kinase of the g type was fold higher than casein kinase of the a type in contrast the mean ratio of type ii to type i histone kinase activity varied between and fold infusion of acth microgramsday for days to to dayold ovine fetuses in utero increased their plasma corticosteroid levels and the responsiveness of their adrenal cells to stimulation by acth in vitro in addition such treatment doubled the specific activity of CK a and g but had no significant effect on campdependent histone kinase MICs in relation to current concepts of the role of protein kinases in adult adrenal cells the present results suggest that casein kinase activities are involved in cell multiplication and differentiation in the fetal adrenal gland in addition they show that neither cytosolic histone kinase of type i nor that of type ii is likely ratelimiting in the steroidogenic response to acth of ovine fetal adrenal cells
MEDAL
biosonar gain control mechanisms in a bottlenose dolphin were investigated by measuring the AEP steadystate response assr to an external tone while the animal echolocated the dolphin performed an echo changedetection task that utilized electronically synthesized echoes with echo delays corresponding to and m target range during the task amplitude modulated tones with carrier frequencies from to khz were continuously presented and the instantaneous electroencephalogram stored for later analysis assrs were extracted from the electroencephalogram by synchronously averaging time epochs temporally aligned with the ON of the external tone modulation cycle nearest to each of the dolphins echolocation clicks results showed an overall suppression of the assr amplitude for tones with frequencies near the click center frequencies a larger temporary suppression of the assr amplitude was also measured at frequencies above khz while a temporary enhancement was observed at lower frequencies temporal patterns for assr enhancement or suppression were frequency level and rangedependent with recovery to preclick values occurring within the twoway travel time suppressive effects fit the patterns expected from forward masking by the emitted biosonar PP while the TPS mechanisms responsible for the frequencydependent enhancement are unknown
MEDAL
inbred fisher and outbred harlanwistar rats were compared in the elevated plus maze the blackandwhite box the social interaction test and a modified openfield test to assess the contribution of genetic AF to aversionmotivated SMB all animals used were born and raised under identical conditions compared to the WR the fischer rats displayed a more pronounced fearful SMB in all tests in a separate MD study the relationship between behavioral variations to biochemical differences was assessed with serotonin ht release in the VP hippocampus being measured during the elevated plusmaze test SE to the elevated plusmaze induced an increase in hippocampal ht in the more anxious fischer rats but not in the less anxious WR the results confirm the influence of genetic AF on emotionality in rats and demonstrate a close although not simple relationship between the serotonergic system and anxietyrelated SMB
MEDAL
a series of consecutive osteoarthritic patients was randomised to undergo total knee replacement using a millergalante ii prosthesis with or without a cemented polyethylene patellar component knee function was evaluated using the american knee society score western ontario and mcmaster university OA index specific patellofemoralrelated questions and radiographic DUE until the fourth postoperative year then via questionnaire until ten years postoperatively a tenpoint difference in or placebo h before induction of anesthesia followed by oral nimodipine mg or PL hourly for hours postoperatively SA was induced with hyperbaric BUP ml and fluids and ephedrine were given at the discretion of the anesthesiologist morphine patientcontrolled analgesia pca bolus mg lockout min was given for postoperative analgesia primary outcome measures were visual analog pain scores at rest and on moving sitting forward and pca morphine consumption morphine consumption was significantly larger in nimodipine patients at h versus p h versus p and h versus p there were no significant differences in pain scores at rest or moving or in time to first use of morphine analgesia this study has demonstrated increased morphine consumption after h in postoperative patients receiving nimodipine suggesting that in patients undergoing knee replacement surgery it has no adjunctive analgesic effect and may actually inhibit the analgesic effect of morphine
MEDAL
members of the california serogroup of orthobunyaviruses particularly la crosse lac and tahyna tah viruses are significant human pathogens in Az where their mosquito vectors are endemic previous studies using wildtype lac and tah a highly neurovirulent CS with low neuroinvasiveness janssen r gonzalezscarano f nathanson n mechanisms of bunyavirus virulence comparative pathogenesis of a virulent CS of la crosse and an avirulent CS of tahyna virus lab invest have demonstrated that the neuroinvasive phenotype maps to the m segment the segment that encodes the two viral glycoproteins gn g and gc g as well as a nonstructural protein nsm to further define the role of gn and gc in F0 and entry we prepared a panel of recombinant m segment constructs using lac tah and vf a monoclonalresistant variant of lac with deficient F0 function these m segment constructs were then tested in two surrogate assays for virus entry a celltocell F0 CA based on tluciferase expression and a pseudotype transduction CA based on the incorporation of the bunyavirus glycoproteins on an mlv backbone both assays demonstrated that gc is the principal determinant of virus F0 and cell entry and furthermore that the region delineated by amino acids corresponding to the membrane PT twothirds of gc is key to these processes these results coupled with structural modeling suggesting homologies between the carboxy region of gc and sindbis virus e suggest that the lac gc functions as a type ii F0 protein
MEDAL
a case of severe colitis requiring subtotal colectomy following administration of mg solganal b for intractable ICA is described abdominal pain and watery diarrhea developed six weeks T3 the last dose of gold colonoscopy revealed mucosal edema and ulceration of the entire colon supportive measures failed and the patient required STC review of the literature revealed cases ranging in severity from limited ileal involvement to fulminant panenteritis most of the patients responded to intravenous fluids steroids and antibiotics but four required surgery the case described is notable for the delay in appearance of abdominal PS following the cessation of gold therapy the mechanism of injury is unknown abdominal complaints in a patient who has received gold therapy especially parenteral merit strict attention even if occurring several weeks T3 the final dose and the diagnosis of gold colitis should be entertained
MEDAL
damage to the microvascular networks constitutes one of the most important components of ionizing radiation damage to normal tissue previously we have reported the early and days postirradiation effects of IR on the structure and function of T/N microvascular networks here we report on the late effects of IR on the structural and functional changes in microvascular networks in locally irradiated single gy dose hamster cremaster muscles observed and days postirradiation agematched animals were used as controls as in the previous study intravital microscopy was used to measure structural and functional parameters in complete microvascular networks in vivo a factorial design was used to examine the effects of radiation status time postirradiation and network vessel type on the structure and CF of microvascular networks our results indicate that the progression of radiationinduced microvascular damage continues during the late times but that there is partial REC from radiation damage within months postirradiation red blood cell flux red blood cell velocity and capillary blood flow in irradiated networks at PI were significantly greater than control levels as at the early times all vessel types were not damaged equally by radiation at every time
MEDAL
the epithelia from the crypts of the intestine are exquisitely sensitive to metabolic perturbation and undergo cell death with the CP morphology of apoptosis administration of mgkg fluorouracil fu to bdf p mice resulted in an increase in p protein at cell positions in the crypts that were also those subjected to an apoptotic cell death in p mice apoptosis was almost CR absent even T3 hr fu is a pyrimidine antimetabolite cytotoxin with multiple mechanisms of action including inhibition of thymidylate synthase ts which gives rise to dna damage and incorporation into rna the inhibition of ts can be increased by coadministration of folinic acid and can be abrogated by administration of thymidine the incorporation of fu into rna is inhibited by administration of uridine pdependent cell death induced by fu was only inhibited by administration of UR uridine had no effect on the apoptosis initiated by gy of gammaradiation although thymidine abrogated apoptosis induced by the pure ts inhibitor tomudex it had no effect on fuinduced apoptosis and coadministration of folinic acid did not increase apoptosis the data show that fuinduced cell death of intestinal epithelial cells is pdependent and suggests that changes in rna metabolism initiate events culminating in the expression of p
MEDAL
recent imaging studies have suggested that MP is decreased centrally in macular telangiectasia type mt the uptake of xanthophyll pigment into the macula is thought to be facilitated by a xanthophyllbinding protein xbp the pi isoform of glutathione stransferase gstp represents one such xbp with high IB affinity this casecontrol study aimed to determine whether two common singlenucleotide polymorphisms snps of gstp were associated with mt dna samples from cases and controls were collected two polymorphic sites of ileval and alaval in exons and respectively of the gstp gene were analysed comparison of alleles and genotypes between cases and controls indicated that there were no statistically significant differences for either the ileval snp p or the alaval snp p or for any combinations however the homozygous atrisk genotype gg of the ileval snp was present in of cases but absent in controls this T0 found no statistically significant association between two common gstp snps and mt however a trend towards a greater frequency of the gg genotype of the ileval snp in cases is of great interest the biological plausibility of disturbed macular pigment uptake in mt makes gstp an excellent candidate gene further investigation is warranted in future studies of mt
MEDAL
this T0 aims to define functioning C2 of patients with schizophrenia by using a method of interpretable clustering based on a specific functioning scale the PET remission of general schizophrenia frogs scale and to test their validity regarding clinical and neuroimaging characterization in this observational study patients with schizophrenia have been classified using a hierarchical topdown method called clustering using unsupervised binary trees cubt sociodemographic clinical and neuroimaging spect perfusion data were compared between the different clusters to ensure their clinical relevance a total of patients were analyzed a fourgroup SF-36 level structure has been identified are classified as minimal as low as moderate and atients with arterial hypertension ah chronic kidney disease ckd cardiovascular disease cvd or metabolic syndrome hyperuricemia is not confirmed as a causative factor of these disorders the aim is to point to the latest studies of the importance of urate as a possible cardiorenal risk factor the literature published in and was searched for the possible impact of urate level on the OD of cardiorenal diseases the pubmed cochrane medline and uptodate databases were searched for the literature published between november and october using the following key words urate hyperuricemia cardiovascular disease and chronic kidney disease causative correlation of hyperuricemia is confirmed only in disorders where deposits of monosodium urate crystals are present results of recent studies do not justify routine use of xanthine oxidase inhibitors in asymptomatic hyperuricemia some studies with small numbers of patients and short follow up report on EC CF improvement on therapy with xanthine oxidase inhibitors nonpharmacological MI by changing unhealthy lifestyle is preferred treatment of asymptomatic hyperuricemia in ckd is still debated and additional studies are necessary to demonstrate the benefit of lowering urate level in ckd family doctors general practitioners should be familiar with the recommended approach to patients with asymptomatic hyperuricemia evidence based medicine still does not recommend target determination of SS urate level for identifying cvd and ckd risk AF recent studies suggest the possible effect of uric acid in cardiorenal diseases and that treatment of asymptomatic hyperuricemia with xanthine oxidase inhibitors may also be useful in cvd prevention additional studies are needed to prove this statement
MEDAL
ticks are bloodfeeding parasites that secrete a number of immunomodulatory factors to evade the host immune response saliva isolated from different species of ticks has recently been shown to contain chemokine NT activity to characterize this activity we constructed a cdna library from the SGs of the common brown dog tick rhipicephalus sanguineus pools of cdna clones from the library were transfected into hek cells and the CS media from the transfected cells were tested for chemokine binding activity by chemical crosslinking to radiolabeled ccl followed by sdspage by deconvolution of a single positive pool of clones we identified a FL cdna encoding a protein of amino acids which T3 signal peptide cleavage was predicted to yield a mature protein of amino acids that we called evasin recombinant evasin was produced in hek cells and in insect cells using SPR we were able to show that evasin was exquisitely selective for cc chemokines ccl and ccl and the closely related chemokine ccl with kd values of and nm respectively the affinities for ccl and ccl were confirmed in competition receptor binding assays analysis by size exclusion chromatography demonstrated that evasin was monomeric and formed a complex with ccl thus unlike the other chemokinebinding proteins identified to date from viruses and from the parasitic worm Sm evasin is highly specific for a subgroup of cc chemokines which may reflect a TPS role for these chemokines in host defense against parasites
MEDAL
the effect of cholecystokinin octapeptide cck and pentagastrin on periodic pancreatic secretion was studied in fasting conscious dogs both cck and pentagastrin in small doses prolonged the interval of periodic pancreatic secretion periodicity was disrupted by C1 doses of cck and PG cck at the dose which did not disrupt the cycle raised the peak and the valleytovalley means but not the valley mean of protein secretion in one cycle except at large doses pentagastrin failed to increase the peak and valley mean but increased mean valleytovalley protein secretion large doses of both PG and cck increased protein secretion at the valley the peak of periodic pancreatic protein secretion was about half the observed maximum protein response to cck atropine reduced pancreatic fluid and protein responses to small doses of cck to the levels of valleys at large doses however both responses were augmented by atropine hexamethonium reduced the responses to any dose of cck to valley C2 or less volume and protein responses to PG following atropine or hexamethonium were of similar magnitude to those at valleys it is concluded that cck and pentagastrin stimulate pancreatic enzyme secretion directly by acting on acinar cells and indirectly by modifying ACh ganglionic activities which control periodic secretion in conscious dogs
MEDAL
the term CEH ceh describes a syndrome originating from the cervical spine there are a variety of therapeutic approaches used for the management of ceh but scientific evidence of their effectiveness is scarce no medication drug has proven to be effective the evidence for greater occipital nerve blocks C2 nerve blockades facet joint i.v. and surgical procedures is limited several PT interventions are proposed for ceh with spinal manipulation and soft tissue interventions being the most commonly used however the lack of solid evidence of positive effects and risks of serious complications for spinal manipulation should be considered in favor of other physical therapy interventions associated with less risk the inconsistent results in the literature can be related to the fact that maybe not all therapeutic interventions are appropriate for all patients with ceh or maybe not all patients with ceh will benefit from particular interventions
MEDAL
human mucin muc b mRNA in human airway epithelium was studied in both tissue sections and cultures of tracheobronchial epithelial tbe cells in situ hybridization demonstrated that mucb message was expressed mainly in the mucous cells of SM glands of normal human airway tissues nevertheless an elevated mucb message level could be seen in surface goblet cells from patients with airway diseases and inflammation regardless of the airway tissue sources mucb message was regulated by alltransretinoic acid ra and SC conditions in both primary and passage cultures of tbe cells mucb message to a lesser extent was also found in the immortalized epithelial cell line hbe but not in beasb cells to elucidate the molecular mechanism of mucb gene expression a genomic clone was obtained and sequenced for the amino terminal and the flanking region of mucb gene a luciferase reporter construct containing base pairs of the flanking region of mucb gene demonstrated a cell typespecific basal promoter activity in transfection studies both ra and the airliquid interface culture condition further enhanced this promoter activity these results suggest that the flanking region of mucb gene contains ciselements that are potentially involved in the regulation of mucb gene expression
MEDAL
to describe our technique of roboticassisted laparoscopic radical cystectomy and IA formation of an orthotopic neobladder hautmann for treatment of transitional cell carcinoma of the bladder
MEDAL
fifty consecutive patients were studied to assess the utility of fineneedle aspiration cytology for the diagnosis of hypofunctioning thyroid nodules in two patients cysts were evacuated and did not recur thirtythree patients underwent excisional biopsy the aspiration biopsy result was not a criterion for surgery satisfactory aspiration specimens were obtained in patients the diagnosis in nine aspiration specimens was malignant of these seven were correct and there was one falsepositive and one occult carcinoma unrelated to the clinically detected nodule five aspirations showed suspected malignancy of these two were carcinoma one was an occult carcinoma and two were benign eighteen aspirations were interpreted as benign of these were correct and the one falsenegative diagments in all mucosal structures the lesions are demonstrated to depend on nonspecific AF on the one hand and on genetically foreigh tissue on the other hand in every exp group the earliest changes occur in MCB disorders in vessel and blood flow tone lymphotasis and interstitial edema result in disturbances of capillaryepithelial interrelations and metabolic processes destructive changes are followed by tissue neutrophilosis activation of macrophages and plasmocytic cells degranulation of eosinophil enterochromaffin and mast cells profound mucin excretion unlike autoperfusion alloperfusion is characterized by massive neutrophillic degranulation and more severe lesions of mucosal structures at allotransplantation PMNL cell reaction nonspecific by its nature is supposed to be the earliest and primary in the course of establishing transplantation immunity at xenotransplantation intestinal destruction developing and rapidly progressing is connected with the influence of NK antibodies
MEDAL
in the sheep it has been shown that the pars tuberalis of the PIT may mediate the photoperiodic control of seasonal changes in prolactin secretion high concentrations of melatonin receptors are present on the ovine pars tuberalis and melatonin is known to inhibit forskolinstimulated cAMP production in this tissue other hormonal inputs to the ovine pars tuberalis have not yet been identified in the rat mrna for the igfi receptor has been identified in the pars tuberalis using in situ hybridization in order to define whether igfi may influence the CF of the ovine PT the presence of receptors for igfi has been investigated using in vitro autoradiography specific iigfi binding was found in high concentrations over the ovine PT particularly associated with certain of the capillaries homogenate receptor assays showed saturable specific binding of iigfi with a mean KB kd of nm n competition studies revealed a rank order of potency of igfi igfii insulin in displacing iigfi binding indicative of a mixed population of igfi and igfiimannosephosphate receptors and IGFBPs igfbps crosslinking of iigfi to pars tuberalis membrane homogenates and analysis by sdspage under reducing conditions confirmed the presence of both igfi receptors and binding proteins autophosphorylation of a kda ATP compatible with the betasubunit of the igfi receptor was increased in the presence of igfi indicating the existence of functional igfi receptors on the ovine pars tuberalis in contrast in the rat iigfi binding was restricted to the ME region of the BB and was not detectable over the pars tuberalis
MEDAL
pancreatic ductal adenocarcinoma pdac is the most lethal human malignant tumor because of the early ON of local invasion and distant metastasis PNI is a prominent characteristic of pancreatic adenocarcinoma which is a multifactorial process that involves various signaling molecules from different signaling pathways the glial cell linederived neurotrophic factor family of ligands was reported to be involved in perineural invasion in pancreatic CA artemin is one member of the glial cell linederived neurotrophic factor family of ligands although artemin has previously been demonstrated to promote invasiveness of pancreatic CA the mechanisms remain poorly understood in this T0 we performed an analysis to determine the effects of artemin on modulating tumor cell M1 potential and invasion activity and explored its mechanisms in pancreatic cancer we indicated that artemin and X4 were overexpressed in cancer tissues and widely expressed in pancreatic CA cell lines we observed that activation of erk and akt in artemintreated cells led to enhanced nuclear accumulation of nfκb which then induced cxcr expression through regulation of the expression of cxcr artemin functionally promoted the migration and invasion in pancreatic cancer cells the present T0 indicated that artemin induced X4 expression by activating akt and erk nfκb signaling thereby modulating tumor cell M1 potential and invasion activity in pancreatic CA by regulating sdfαcxcr axis artemin might be an effective and potent therapeutic target for pancreatic CA metastasis especially in perineural invasion
MEDAL
a yearold woman was brought by ambulance due to abrupt anal bleeding elastic hard and solid mass was found in rectal examination the pathological diagnosis of the tumor revealed adenocarcinoma the M1 × mm CL RT was also found at ct scan acute bleeding with hemoglobin level of gdl necessitated an urgent arterial embolization of bilateral internal iliac i.a. and superior rectal artery T3 REC from the SVR condition radical operation was performed comprising abdominoperineal resection of the rectum with extended lymph node dissection involving paraaortic area followed by synchronous LR arterial infusion of fu g in total via proper hepatic artery was added postoperatively she was followed for over years and no recurrence was observed
MEDAL
the effects of IGT and obesity in isolation and in combination on basal postabsorptive intermediary metabolism were examined in four CG of subjects n for each matched for age and gender group nonobese HCs with NGT g group nonobese subjects with impaired glucose tolerance group morbidly obese subjects with NGT group mo subjects with IGT while there was no significant difference in fasting blood glucose concentrations between the four groups plasma IRI concentrations were elevated p or less in the obese subjects relative to the nonobese subjects within each category of glucose tolerance basal immunoreactive insulin concentrations in nonobese subjects with impaired gl tolerance were also elevated p relative to the nonobese healthy controls concentrations of glycerol p nonesterified fatty acids p and total ketone HB p were significantly higher in the obesenormal gl tolerance and obeseimpaired glucose tolerance groups relative to their matched nonobese counterparts compared with the subjects with normal gl tolerance only lactate p and Pyr p concentrations were elevated in the nonobeseimpaired glucose tolerance and obeseimpaired glucose tolerance groups respectively in conclusion in addition to fasting hyperinsulinaemia the regulation of lipolysis and ketone body metabolism is abnormal in the basal state in mo by contrast despite normal fasting blood glucose concentrations impaired gl tolerance is associated with disturbances of other aspects of basal carbohydrate metabolism
MEDAL
the solution xray scattering technique has been applied to examine the conformations of the proteolytic fragment f asplys of calmodulin in the absence of both ca and mastoparan in the presence of ca only and in the presence of both ca and MP the radius of gyration and the molecular weight for the f fragment increased by a and respectively upon IB of both mol of camol to the f fragment and MP to form the tertiary complex a smaller NC was found for the casaturated f fragment in the absence of mastoparan a without any NC of the molecular weight the analysis based on the smallangle scattering data showed that the f fragment in the presence of ca CT preserved the tertiary structure of the globular domain in the crystal to a great extent further analyses based on a twodomain model showed that the centertocenter distance between f and MP is about a if the structure of the f fragment in the presence of MP resembles that in the absence of MP and if mastoparan in the complex retains an alphahelical conformation the modeling studies using their crystal structure coordinates have been made on the basis of the solution xray scattering data the combined results support a MM proposed by persechini and kretsinger persechini a kretsinger r h j cardiovasc pharmacol suppl ss although the centertocenter distance between MP and the f fragment is shorter by about a than that in their modelabstract truncated at words
MEDAL
evidence on the effectiveness of workplace MH promotion for people with disabilities is limited this study aimed to evaluate the effectiveness of a brief MH promotion intervention in social enterprises it had a nonblinded cluster randomized controlled trial design with followup one and four months T3 the intervention in total employees agreed to participate intervention and control empowerment was the main outcome secondary outcomes were resilience palliative behavior determinants of four coping strategies of mental health SQ of life and life satisfaction a brief participant satisfaction survey was conducted after the MI no significant intervention effect on empowerment was found however at one month followup significant favorable effects were found on perceived SS for coping strategies for MH and on palliative behavior at four months followup favorable MI effects were found on SQ of life but unfavorable effects were found on unjustified worrying in addition the MI was well received by the employees this brief intervention might be a promising first step to improve MH in people with disabilities working in social enterprises nevertheless additional monitoring by professionals and managers working in the organizations might be needed to maintain these effects
MEDAL
for chronic repeated cardiovascular studies in trained conscious dogs we describe a technique for implantation of an arterial vascular access catheter in the aorta in comparison to previous techniques our technique enables arterial catheter implantation without interrupting the systemic circulation or compromising peripheral arterial flow requires only a single penetration of the aortic wall and results in a catheter facing downstream in the aorta the catheter is usable for both arterial blood sampling and intraarterial i.t. of pharmacologic agents
MEDAL
in this T0 patients received piroxicam po orally or sublingually T3 undergoing removal of symmetrically positioned lower third molars during two separate appointments this study used a randomized blind crossover protocol objective and subjective parameters were recorded for comparison of postoperative results for days T3 surgery patients treated with oral or sublingual piroxicam reported low postoperative pain scores the patients who received piroxicam orally took a similar average amount of analgesic rescue medication compared with patients who received piroxicam sublingually p patients exhibited similar values for mouth opening measured just before surgery and immediately following suture removal days later p and showed no significant differences between routes of piroxicam administration for swelling control during the second or seventh postoperative days p in summary pain trismus and swelling after lower third molar extraction independent of surgical difficulty could be controlled by piroxicam mg po orally or sublingually and no significant differences were observed between the route of delivery used in this study
MEDAL
the catastrophic antiphospholipid syndrome caps is a rare disease that affects of cases with antiphospholipid syndrome aps caps can mimic or overlap with different thrombotic diseases many patients present with a microthrombotic storm or thrombotic microangiopathic HA tmha thus the differential diagnosis of caps includes thrombotic TP ttp typical and atypical HUS hus systemic infections HM pregnancyrelated disorders malignant hypertension heparininduced thrombocytopenia and druginduced thrombotic microangiopathies antiphospholipid antibody apl positivity has been proposed as the clue in this differential diagnosis however apl can also occur in healthy people and in those with infections or malignancies thus the differential diagnosis of an aplpositive patient presenting with a microthrombotic storm is broad the workup should include a special attention to signs of infection and disseminated malignant disease assessing the funduscopic signs of malignant hypertension testing adamts activity and antiheparinplatelet factor hpf antibodies and searching previous exposure to certain drugs this article aims to review the main diseases included in the differential diagnosis of caps in the context of other thrombotic microangiopathies
MEDAL
two proteins of the AHG type serum globulin and tuberin and the protein of milk casein have been purified a of the other proteins and b of the inorganic electrolytes with which they exist in nature the methods that were employed are described all three proteins were found to be only very slightly soluble in water in the pure uncombined state the solubility of each was accurately measured at degrees degrees c the most probable solubility of the pseudoglobulin of SS was found to be gm in liter of tuberin gm and of CS gm the methods that were employed in their determination are described each protein investigated dissolved in water to a constant and characteristic extent when the amount of protein precipitate with which the solution was in heterogeneous equilibrium was varied within wide limits the solubility of a pure protein is therefore proposed as a fundamental physicochemical constant which may be used in identifying and in classifying proteins the concentration of protein dissolved must be the sum of the concentration of the undissociated protein molecule which is in heterogeneous equilibrium with the protein precipitate and of the concentration of the dissociated protein ions the dissociated ions of the dissolved protein give a hydrogen ion concentration to water that is also a characteristic of each protein
MEDAL
two studies were performed to determine the best medium for the isolation of anaerobes from vaginal secretions in the first three different medium bases brucella centers for disease control cdc and schaedler were compared semiquantitatively for ability to support the growth of GN anaerobes from vaginal fluid media were supplemented with laked sheep blood kanamycin and vancomycin the brucella base agar formulation supported the growth of anaerobic gramnegative bacilli better than either the cdc or schaedler base agar formulation in a second study nonselective brucella and cdc base SBA were compared for ability to support the growth of anaerobic GPC anaerobic GP cocci grew in higher concentrations on cdc base agar than on brucella base agar on the basis of these observations we recommend that a cdc base sheep blood agar be used for the nonselective plate and a brucella base plate supplemented with laked sheep blood kanamycin and vancomycin be used for isolation of gramnegative bacilli in studies of the anaerobic flora of the female genital tract
MEDAL
thymidylate synthase ec is a key enzyme for the de novo synthesis of dna and as such a target for anticancer drug development there is a need to develop noninvasive methods for assessing thymidylate synthase inhibition in tumors the aim of this study was to assess the potential of deoxyffluorothymidine fflt positron emission tomography pet for early measurement of thymidylate synthase inhibition and to elucidate the cellular mechanisms involved radiationinduced fibrosarcoma tumorbearing mice were injected with a single ip dose of the thymidylate synthase inhibitor fluorouracil fu mgkg and imaged by ffltpet at to hours T3 treatment deoxyuridine thymidine kinase cytoplasmic thymidine kinase ec and atp levels in excised PT were measured cellular assays for membrane transport were also done there was a fold increase in the minute fflt tumorheart radioactivity ratio in drugtreated mice compared with VH controls p plasma and RT deoxyuridine levels increased significantly but thymidine kinase and atp levels were unchanged wholecell assays implicated a low level PET role for the type equilibrative nucleoside transporter ent there was an increase in type entbinding sites per cell from in UT cells to p in cells treated with microgml fu for hours without a change in transporter affinity p we conclude that ffltpet can be used to measure thymidylate synthase inhibition as early as to hours T3 treatment with fu by a mechanism involving RD of nucleoside transporters to the BPM
MEDAL
as previously shown in vivo NE and glutamatergic neurons can regulate the denervation supersensitivity of d dopaminergic da receptors in the rat prefrontal cortex and striatum respectively therefore the effects of methoxamine an alpha adrenergic agonist and glu on the resensitization of d da receptors were investigated in cultured cortical and striatal neurons from the embryonic rat in the presence of sulpiride and propranolol da stimulated the d da receptormediated conversion of hadenine into hcamp in both intact cortical and striatal cells and these responses were markedly desensitized in cells preexposed for min to da microm the CR REC of the d da response was more rapid in striatal min than in cortical min SN methoxamine accelerated the resensitization of the d response in cortical but not in striatal SN the effect of the alpha adrenergic agonist in cortical neurons was blocked by prazosin and CEC in contrast glu accelerated the resensitization of the d response in striatal but not in cortical neurons and the effect observed in striatal SN was totally blocked by aminophosphonovaleric acid an nmda receptor antagonist protein kinase c was shown to be involved in the alpha adrenergicinduced resensitization of the cortical d response but not in the glutamateevoked resensitization of the striatal d response finally for comparison similar experiments were performed on betaadrenergic receptors using isoproterenol microm as an agonist methoxamine did not modify the resensitization of the betaadrenergic response in cortical neurons but glutamate accelerated the resensitization of this response in striatal neurons
MEDAL
our principled trauma have not yet been fully elucidated in an attempt to shed more light on the matter we investigated the endothelialmediated dilations in the rat middle CBF i.a. mca following severe traumatic BB injury tbi rats were subjected to severe controlled cortical impact injury cci ms ms duration mm deformation over the right parietal SC at h postinjury ipsilateral segments of mca and corresponding CL segments were isolated mounted in a vessel chamber and pressurized the responses to methylthioatp mesatp a selective agonist for the py purinoceptors L-NA lname an no synthase inhibitor and snitrosonacetylpenicillamine snap an exogenous no donor were determined mesatp elicited concentration dependent dilations in all mcas studied ipsilateral mcas harvested following tbi or shamtbi showed similar maximum dilations to mesatp n and n respectively however tbi reduced the concentration of mesatp necessary to elicit onehalf of the maximum dilation ec from to nm p inhibition of no synthase with m lname abolished the dilation to mesatp in both tbi and shamtbi mcas the constriction to lname was significantly reduced in tbi mcas compared to sham vessels dilations to snap an no donor were not altered by tbi indicating that the mechanisms of dilation involving no in the V1 smooth muscle were not affected unlike other pathological conditions which often diminish endothelialmediated responses severe tbi enhanced the sensitivity to mesatp without altering the maximum response
MEDAL
the general shortage of evidence regarding benefits and harms of medical devices has been highlighted following the serious safety concerns with metalonmetal hip replacements and silicone breast implants and was again pointed out in a recent survey of european health technology assessment institutions in this context the new european medical device regulation will enforce postmarketing surveillance of existing and new implants the usefulness of registry data as a source of information for medical device realworld clinical performance and safety has been demonstrated however these data might be underused by researchers and policy makers one reason for this is the insufficient awareness of their existence the aim of this review is to provide information to relevant stakeholders on the extent and breadth of the data currently collected in EU joint replacement registries we identified registries most of them of national coverage total numbers of primary total hip and knee replacements included were over and million records respectively the current focus of these registries is on wholelifespan implant surveillance via revision rate monitoring QA of surgical and perioperative care and hospital performance assessment more recently national and international comparison and benchmarking have increasingly become part of their endeavors
MEDAL
tissue factor tfinduced coagulation was compared in contact pathway suppressed human blood from normal factor viiideficient and factor xideficient donors the progress of the reaction was analyzed in quenched samples by immunoassay and immunoblotting for fibrinopeptide a fpa thrombinantithrombin tat FV activation and osteonectin in hemophilia a blood factor viiic treated with pmoll tf clotting was significantly delayed versus normal whereas replacement with recombinant factor viii uml restored the clot time near normal values fibrinopeptide a release was slower over the course of the experiment than in normal blood or hemophilic blood with factor viii replaced but significant PR was observed by the end of the experiment FV activation was significantly impaired with both the heavy and CS chains presenting more slowly than in the normal or replacement cases differences in platelet activation osteonectin PR between normal and factor viiideficient blood were small with the midpoint of the profiles observed within minute of each other TG during the propagation phase subsequent to clotting was greatly impaired in factor viii deficiency being depressed to less than nmol tatlmin the rate in normal blood nmol tatlmin replacement with rFVIII normalized the rate of tat generation thus coagulation in hemophilia a blood at pmoll tf is impaired with significantly slower TG than normal during the propagation phase this reduced thrombin appears to affect fpa production and factor v activation more profoundly than PLT activation at the same level of tf in factor xideficient blood xic only minor differences in clotting or product formation fpa osteonectin and factor va were observed using reduced levels of initiator pmoll tf the reaction was more strongly influenced by factor xi deficiency clot formation was delayed from to minutes which shortened to minutes with factor xi replacement the maximum thrombin generation rate observed approximately nmol tatlmin was approximately one third that for normal nmoll tatmin or with factor xi replacement nmol tatlmin fpa PR factor v activation and PR of platelet osteonectin were slower in factor xideficient blood than in normal blood the data demonstrate that factor xi deficiency results in significantly delayed clot formation only at sufficiently low tf concentrations however even at these low tf concentrations significant thrombin is generated in the propagation phase after formation of the initial clot in hemophilia c blood
MEDAL
a best evidence topic in cardiac surgery was written according to a structured protocol the question addressed was which patient undergoing mitral valve surgery should also have the tricuspid repair altogether papers were found using the reported search of which represented the best evidence to answer the clinical question the authors journal date and country of publication patient group studied T0 type relevant outcomes and results of these papers are tabulated while a GA agreement exists for TV tv repair in cases of severe regurgitation and concomitant multivalvular disease requiring surgical intervention current guidelines provide more vague indications for patients with less severe TR tr since this condition has a lower eventfree survival rate and the prognosis after PS OD is dismal a lower threshold and a more aggressive strategy for MI is needed in rheumatic valve disease mitral valve involvement and disease spreading to tv may be responsible for further regurgitation although patients with pulmonary hypertension ph may benefit from mitral valve replacement mvr or balloon valvotomy many studies found that preoperative ph does not predict late tr however patients with high pulmonary pressure have a lower occurrence of late tr tricuspid annular dilatexpensive here we report new findings that suggest pharmaceutical formulations such as rifapentine in combination with clarithromycin or moxifloxacin that have shown promising results in mice footpad trials moreover alternative treatment options such as heat therapy nitric oxide cremes and french clay show bactericidal effects the genotyping of m ulcerans also promises new ways of finding drug targets and vaccines trachoma induced by the bacterium chlamydia trachomatis is the primary infectious cause of blindness worldwide recurrent infections lead to chronic inflammation of the upper tarsal conjunctiva as a consequence scarring and distortion of the eye lids occur eventually resulting in blindness firstline medications for trachoma treatment are bacteriostatic agents such as topically applied tetracylines and systematically administered azithromycin surgery environmental improvements and personal hygiene are further crucial AF in controlling trachoma moreover efforts are being undertaken towards the development of vaccine systems with the L1 outer membrane protein and the polymorphic membrane protein acting as attractive candidates
MEDAL
from to burned patients with ARF arf were treated by venovenous continuous renal replacement therapy crrt at the burn unit of hôteldieu de montréal their mean sd age was years and the mean burned surface covered of total body surface area all patients were MV and presented evidence of sepsis the mean delay before occurrence of arf was days and arf was mainly related to sepsis and SH main reasons for crrt initiation were azotemia and fluid overload a total of crrt modalities were applied continuous venovenous HDF cvvhdf two continuous venovenous hemofiltration cvvh and one continuous venovenous hemodialysis cvvhd over days for crrt nine patients received heparin and three were not anticoagulated mean values for dialysate and reinjection PFR were mlh and mlh respectively admission weight was kg with a mean WG before crrt initiation of kg and a mean weight loss during crrt of kg nine patients received EN plus parenteral nutrition and three parenteral nutrition only the total caloric NI was kcalkgday and protein NI gkgday the normalized protein catabolic rate npcr was evaluated at gkgday during crrt the mortality rate was the six survivors all recovered normal renal CF with four of them requiring IHD for short periods in conclusion venovenous crrt is particularly well suited for this selected population allowing smooth fluid removal and aggressive NS
MEDAL
the effects of anabolicandrogenic steroid aas abuse on the onset of puberty in female adolescents are largely unknown this study assessed the acute effects of one aas stanozolol on pubertal ON in the female rat a single i.t. of stanozolol mgkg on postnatal day pn advanced VO but did not alter the ON of vaginal estrus higher doses of ST treatment and mgkg also advanced vaginal opening but had no effect on vaginal estrus the advancement of vaginal opening by stanozolol mgkg was prevented by the concomitant administration of the pure antiestrogen ici mgkg on pn administration of the androgen receptor antagonist flutamide mgkg twice daily on pn had no effect on the advancement of VO by stanozolol stanozolol treatment also T3 vaginal opening in OVX perivaginal i.v. of a low dose of stanozolol mg on pn and pn also T3 VO these results suggest that ST is acting directly at estrogen receptors in the vaginal epithelium to advance VO and that prepubertal ST treatment does not induce true precocious puberty
MEDAL
supplemental education is desirable for neurosurgical training and the use of human cadaver specimen and VR models is routine an in vivo porcine training model for cranial neurosurgery was introduced in and our recent experience with this unique model is outlined here for the first time porcine anatomy is illustrated with particular respect to neurosurgical procedures the pros and cons of this model are described the aim of the course was to set up a laboratory scenery imitating an almost realistic operating room in which anatomy of the BB and neurosurgical techniques in a mentored environment free from time constraints could be trained learning objectives of the course were to learn about the microsurgical techniques in cranial neurosurgery and the management of complications participants were asked to evaluate the SQ and utility of the programme via standardized questionnaires by a grading scale from a best to e worst in total residents have been trained on the porcine model to date none of the participants regarded his own residency programme as structured the bleeding and complication management the realistic laboratory setup and the working environment were favoured by the vast majority of trainees and confirmed our previous findings T3 finishing the course the participants graded that their skills in bone drilling dissecting the BB and preserving cerebral vessels under microscopic magnification had improved to level a and b in vivo handson courses fully equipped with microsurgical instruments offer an outstanding training opportunity in which one management on a pulsating vital brain represents a unique training RPA our results have shown that education programmes still lack practical training facilities in which in vivo models may act as a cDNA approach in surgical training
MEDAL
ALP phosphatase activity has been investigated by histochemical methods in normal and diseased human C1 intestine the tissues were constantly maintained at degrees c or below specimens were either frozen in liquid nitrogen FD and embedded in glycol methacrylate for sectioning at mu or fixed in icecold formolcalcium for frozen sectioning at mu the simultaneous coupling azo dye method using the substrates sodium alphanaphthyl phosphate and naphthol asbi phosphate resulted in the demonstration of alkaline phosphatase activity in the surface epithelial cells and the middle and upper crypts of normal and transitional mucosa
MEDAL
neurons might interact via electric fields and this notion has been referred to as ephaptic interaction it has been shown that various types of SAC are distributed along the dendrites and are capable of supporting generation of dendritic spikes we hypothesized that generation of dendritic spikes play important roles in the ephaptic interactions either by amplifying the impact of electric fields or by providing current source to generate electric fields to test if dendritic activities can be modulated by EFs we developed a method to monitor local catransients in the dendrites of a neuronal population in acute rat HPC slices by applying spinningdisk confocal microscopy and multicell dye loading technique in a condition in which the dendrites of ca pyramidal neurons show spontaneous catransients due to added μm aminopyridine to the bathing medium and adjusted extracellular potassium concentration we examined the impact of sinusoidal electric fields on the catransients we have found that spontaneously occurring fastcatransients in the tufts of the apical dendrites of ca pyramidal SN can be blocked by applying μm tetrodotoxin and that the timing of the transients become entrained to subthreshold hz electric fields with an intensity as weak as mvmm applied parallel to the somatodendritic axis of the SN the extent of entrainment increases with intensity below mvmm but does not increase further over the range of mvmm these results suggest that population of pyramidal cells might be able to detect EFs with biologically relevant intensity by modulating the timing of dendritic spikes
MEDAL
outward k current of cardiac membrane has been shown to be suppressed by caesium chloride cs and enhanced by NIC a coronary vasodilator the aim of this study was to assess the effects of nicorandil on the cs induced early afterdepolarisations and associated VAs in the rabbit HR in vivo
MEDAL
recent developments in medical informatics research have afforded possibilities for great advances in health care delivery these exciting opportunities also present formidable challenges to the implementation and integration of technologies in the workplace as in most domains there is a gulf between technologic artifacts and end users since medical practice is a human endeavor there is a need for bridging disciplines to enable clinicians to benefit from rapid technologic advances this is turn necessitates a broadening of disciplinary boundaries to consider cognitive and social AF pertaining to the design and use of technology the authors argue for a place of prominence for cognitive science cognitive science provides a framework for the analysis and modeling of complex human performance and has considerable applicability to a range of issues in informatics its methods have been employed to illuminate different facets of design and implementation this RPA has also yielded insights into the mechanisms and processes involved in collaborative design cognitive scientific methods and theories are illustrated in the context of two examples that examine humancomputer interaction in medical contexts and computermediated collaborative processes the framework outlined in this paper can be used to refine the process of iterative design enduser training and productive practice
MEDAL
recent evidence suggests that OB reduces FI via actions in the BB circuitry of food reward such as the ventral tegmental area vta as leptin receptors are present in the vta and leptin i.t. in the vta reduces food NI in the hypothalamus leptininduced anorexia requires signaling via janus kinasesignal transducer and activator of transcription jakstat insulin receptor ATP irsphosphatidylinositol kinase pi kinase and rat target of rapamycin mtor in this study we determined whether leptin activates each of these signal transduction pathways in the vta and whether these signaling pathways are required for vtaleptin induced anorexia here we show that pstattyr a marker of leptin activation was induced in a midbrain region containing the vta and substantia nigra following either intracerebroventricular OB or direct administration of OB to the vta but these interventions failed to increase C2 of either paktser or phosphopskthr markers of irspi kinase and mtor signaling respectively moreover the effect of intravta leptin administration to reduce and h FI and h body weight was blocked by an inhibitor of jak at a dose that had no effect on FI or body weight by itself but not by local inhibition of either pi kinase ly or mtor rapamycin in this timeframe taken together these data support the hypothesis that OB signaling in the vta is involved in the regulation of EB but in contrast to the leptin signaling in the hypothalamus these effects are mediated predominantly via jak signaling rather than via the irspi kinase or mtor signaling pathway
MEDAL
optical imaging of bacterial infection in living animals is usually conducted with genetic reporters such as lightemitting enzymes or fluorescent proteins however there are many circumstances where genetic reporters are not applicable and there is a need for exogenous synthetic probes that can selectively target bacteria the focus of this study is a fluorescent imaging probe that is composed of a bacterial affinity group conjugated to a IR dye the affinity group is a synthetic zinc ii coordination complex that targets the anionic surfaces of bacterial cells the probe allows detection of staphylococcus aureus infection x cells in a mouse leg infection model using whole animal NIRF imaging region of interest analysis showed that the signal ratio for infected leg to uninfected leg reaches at h postinjection of the probe ex vivo imaging of the organs produced a signal ratio of for infected to uninfected leg immunohistochemical analysis confirmed that the probe targeted the bacterial cells in the INF tissue optimization of the imaging filter set lowered the background signal due to autofluorescence and substantially improved imaging contrast the T0 shows that IR molecular probes are amenable to noninvasive optical imaging of localized s aureus infection
MEDAL
aerial parts of sutherlandia frutescens r br family fabaceae are extensively used in SA traditional medicines for the treatment management andor control of an array of human ailments including childhood convulsions and epilepsy in this T0 we examined the anticonvulsant property of the plants shoot AQ extract sfe mgkg ip against pentylenetetrazole ptz picrotoxin pct and bicuculline bclinduced seizures in mice PB and diazepam were used as REF anticonvulsant drugs for comparison like the REF antiseizure drugs used s frurescens shoot AE sfe mgkg ip significantly delayed p the ON of and antagonized PTZ ptzinduced seizures the plants shoot aqueous extract sfe mgkg ip also profoundly antagonized PT pctinduced seizures but only weakly antagonized BIC bclinduced seizures although the data obtained in the present study do not provide conclusive evidence it appears that s frurescens shoot AE sfe produces its antiseizure effect directly by acting like gaba or indirectly by enhancing gabaergic neurotransmission andor action in the brain the results of this laboratory animal study suggest that the herb may be used as a natural supplementary remedy in the management control andor treatment of childhood convulsions and epilepsy in conclusion the findings of this study indicate that s frurescens shoot AE possesses anticonvulsant activity and thus lend pharmacological credence to the suggested folkloric ethnomedical uses of the herb in the management or treatment of childhood convulsions and epilepsy in some rural communities of SA
MEDAL
twenty patients with exocrine pancreatic carcinomas were studied immunohistochemically using a monoclonal antibody against pcna the percentage of tumor cells with positive staining was defined as pcna labelling index li and ranged from to pcna li was found to correlate significantly with grading and more specifically with MI activity and degree of nuclear anaplasia no rho was found with glandular differentiation or with vessel invasion lymphatic vessel invasion lymph node metastasis perineural invasion or size of RT our results indicate that MA and degree of nuclear anaplasia might be the most important parameters to take into consideration when studying the role of pcna in exocrine pancreatic carcinomas
MEDAL
organophosphates ops are commonly used as pesticides throughout the world exposures to ops cause a significant number of poisonings and deaths every year organophosphateinduced delayed polyneuropathy is a sensorymotor distal axonopathy which usually occurs T3 exposure of certain op insecticides neuropathies due to ingestion of ops have rarely been reported in the literature moreover until now there is no report of a patient developing organophosphorus injectioninduced delayed neuropathy in the literature we report a patient with serious organophosphorusinduced OPIDN due to malathion injection the patient was a yearold female who selfinjected undetermined amounts of malathion over the median nerve trace on the forearm crease in a suicide attempt which resulted in peripheral neuropathy
MEDAL
experimental autoimmune uveoretinitis eau induced by immunization of albino Le rats with a retinal soluble antigen santigen has been studied extensively by many workers an intraorchidic injection of santigen days prior to immunization of the animal with the antigen emulsified in adjuvant was found to prevent the onset of the disease orchiectomy in hr after the intraorchidic injection did not abolish the effect of treatment the SVR suppression induced by the orchidic treatment persisted at least for weeks after treatment in rats that received orchidic treatment delayedtype hypersensitivity was markedly inhibited but antisantigen antibody C2 in the SS were as high as those in immunized rats without orchidic pretreatment these results indicate that antigen challenge to the testis is a novel method to SVR activation of the IS mechanism
MEDAL
cAMP camp metabolism has been studied in rat aortic myocytes grown in primary culture to characterize this second messenger system in vascular smooth muscle cells that retain responses to vasoactive drugs for comparison camp metabolism was also studied in the aorta from donor rats adenylate cyclase activity from myocytes and from the aorta was stimulated to a similar degree by gtp naf or forskolin and the enzyme activation produced by isoproterenol or vasoactive intestinal polypeptide was observed only in the presence of gtp a camp phosphodiesterase activity was found in homogenates from cultured myocytes and aorta as well and it was similarly stimulated by calmodulin in both cases the rates of camp production and Kd were about sevenfold higher in cultured myocytes than in aorta basal levels of camp were also higher in the cultured cells than in the aorta hormones and drugs acting on adenylate cyclase or campphosphodiesterase in CF preparations altered the camp content of undisrupted cultured myocytes and aorta in the expected manner differences between cultured myocytes and aorta resided in the courses of druginduced camp increases and in the magnitude of the camp response to isoproterenol which was markedly increased in cultured myocytes compared with aorta it is concluded that despite some quantitative differences the camp system of rat aortic myocytes grown in primary SC has characteristics similar to those displayed in rat isolated aorta these cells are therefore suitable for studying the effects of drugs involving camp as a second messenger
MEDAL
microinfarcts small ischaemic foci common in ageing BB are associated with PSD and gait dysfunction we determined their relationship with dementia mobility and cerebrovascular disease in an older populationrepresentative brain donor cohort these data on microinfarcts were evaluated in relation to pathological assessments of clinically significant CBF small vessel disease svd
MEDAL
OC is a common and lethal CA affecting women globally Ber is a natural compound from the plant berberis amurensis which is used in chinese traditional medicine recent studies have shown the antitumor effects of berbamine in several types of cancers but not in ovarian CA in the present T0 we investigated the potential antitumor effects of berbamine in ovarian CA and explored the underlying molecular mechanisms berbamine suppressed the cell viability of OC cells in a concentrationdependent manner as revealed by methyl thiazolyl tetrazolium assay berbamine also suppressed the cell growth and invasion of ovarian CA cells as measured by colony formation and cell invasion assays respectively FC experiments showed that berbamine increased cell apoptotic rate and induced cell cycle arrest at gg phase in OC cells western blot analysis showed that Ber increased the protein C2 of cleaved caspase cleaved caspase bax and decreased the protein level of bcl in ovarian cancer cells quantitative RT pcr and western blot analysis demonstrated that Ber treatment inhibited the wntβcatenin signaling in OC cells the GABA effects of Ber on cell viability and invasion of OC cells can be partially reversed by lithium chloride licl treatment growth of tumors developed from skov cells was significantly suppressed in berbaminetreated group and Ber treatment enhanced ICE and cleavage and reduced βcatenin protein level in tumor tissues in summary Ber exerts its anticancer effects in vitro and in vivo via induction of apoptosis partially associated with the inhibition of wntβcatenin signaling
MEDAL
AE of flowers of butea monosperma fabaceae was evaluated at different dose C2 mgkg po for its protective efficacy against ccl mlkg ip induced acute liver injury to validate its use in traditional medicines the ccl administration altered various biochemical parameters including serum transaminases protein albumin hepatic lipid peroxidation reduced glutathione and total protein C2 which were restored towards control by therapy of b monosperma adenosine triphosphatase and glucosephosphatase activity in the liver were decreased significantly in ccl treated animals therapy of b monosperma showed its protective effect on biochemical and histopathological alterations at all the three doses in dose dependent manner b monosperma extract possess modulatory effect on drug metabolizing enzymes as it significantly decreased the hexobarbitone induced sleep time and increased excretory capacity of liver which was measured by bsp retention histological studies also supported the PSA finding and maximum improvement in the histoarchitecture was seen at higher dose of bm extract
MEDAL
v is a kda protein consisting of three consecutive ank repeats which are believed to serve as the surface for proteinprotein interactions it is thought to have a role in neural OD for its temporal profile of expression during mu cerebellar development but its precise role remains unknown here we applied the proteomic approach to search for protein targets that interact with v the v cdna attached with a tandem affinity purification tag was expressed in the CTC and the protein complex formed within the cellerweight most of the overweight participants did not identify themselves as such no significant gender differences were observed in terms of the behavioural features of eating disorders of the men and of the women reported binge eating on at least one day per week inappropriate weight compensatory behaviours were reported by of the men vs of the women but the women had significantly higher attitudinal scores than the men our findings suggest that in patients recovering from substance abuse overweight and features of eating disorders are common in both men and women and occur in poor and minority groups
MEDAL
human endogenous retrovirus herv long terminal repeat ltr elements contain regulatory sequences that can influence the expression of adjacent cellular genes which may contribute to breakdowns of the immune CF leading to autoimmune disease RA arthritis ra is associated with particular hladrdq haplotypes that modulate the pathogenesis of this autoimmune disease we have therefore studied a solitary ltr element dqltr of the hervk family at the hladqb locus for a possible disease association among ra patients and unrelated blood donors the dqltr was significantly more frequent among patients vs or p with the majority of patients being heterozygous for the dqltr vs p hladrb positive patients did still differ for the presence of the dqltr vs or p with an increase of both dqltr homozygous and heterozygous patients when compared to drb positive controls p hladrdq genotype analysis among hladrb positive individuals revealed significantly more dqltr homozygotes among hladrbdqbi homozygous patients vs p and the number of dqltr homozygous vs and heterozygous vs individuals was also increased among hladrb heterozygous patients p the presence of the dqltr PE increased both the or and the positive predictive value for either drbdqb positivenegative individuals when compared to the presence of hladrbdqb CT in conclusion these data suggest that this dqltr enhances susceptibility to ra
MEDAL
the locations of brønsted acid sites bas in the channels of mediumpore zeolites have a significant effect on the spontaneous ionization of paraterphenyl pp insofar as spatial constraints determine the stability of transition states and chargetransfer complexes relevant to CS the ionization rates and ionization yield values demonstrate that a strong synergy exists between the h polarization energy and spatial constraints imposed by the channel topology spectroscopic and modeling results show that pp incorporation charge separation charge transfer and charge recombination differ dramatically among zeolites with respect to channel structure hfer hmfi hmor and bas density in the channel compartmentalization of ejected electrons away from the initial site of ionization decreases dramatically the propensity for CR the main mode of pp decay is hole transfer to form aloh ⋠⋠⋠pp chargetransfer complexes characterized by intense ab have indicated that ldlc concentrations can be reduced up to which suggests that more pronounced reductions can be achieved at higher intakes studies describing effects of high plant sterol intakes on serum ldlc concentrations are not consistent besides the effects of higher than advocated intakes on serum ldlc concentrations several topics will be discussed in this review first besides the wellcharacterized effect of plant sterols and stanols on serum ldlc concentrations evidence is now emerging of their effects on triacylglycerol metabolism which makes them highly attractive for interventions in metabolic syndromelike populations secondly there is an ongoing debate whether increased plant sterol concentrations are associated with an increased cardiovascular disease risk or not for this there are at least two possible explanations first the potential atherogenicity of increased plant sterol concentrations might be ascribed to the formation of plant sterol oxidation products socalled oxyphytosterols or secondly elevated serum plant sterol concentrations should only be seen as surrogate markers for characterizing subjects with high intestinal cholesterol absorption finally we discuss recent studies which suggest that plant sterols and stanols can improve endothelial dysfunction in subjects at risk although evidence is limited and more research is needed
MEDAL
homozygous familial hypercholesterolemia hofh is caused by mutations in the MDA-LDL receptor gene and is characterized by severe hypercholesterolemia from birth and ON of premature cardiovascular disease cvd during childhood the ON and progression of cvd using currently available testing methods in children with hofh have not been fully characterized a large cohort of patients with hofh referred to our subspecialty clinic was studied thirtynine patients aged or years underwent extensive cardiovascular lipid and genetic evaluation sixteen children or years without known cvd when first evaluated were followed up longitudinally for up to years cvd was clinically evident in of subjects aged years and of those or years markers of atherosclerosis correlated significantly with age at which lipidlowering treatment was initiated abnormal coronary angiogram abnormal AV using echocardiography and high calcium score using electron beam computed tomography all p abnormal carotid doppler result p twenty of children had no clinical evidence of coronary artery disease yet of these children had angiographically confirmed mild PD disease and had mild to moderate AR using echocardiography of noninvasive tests only evaluation of AV regurgitation using echocardiography predicted the presence of angiographic coronary stenosis p during followup children developed progression of coronary andor aortic valvular disease during their teenage years and required surgical interventions in conclusion in these patients aggressive lipidlowering treatment initiated in early childhood is warranted careful coronary and valvular surveillance strategies and coronary revascularization when appropriate are also warranted in this highrisk population
MEDAL
the effects of mastoparan on phosphoinositide hydrolysis and prostaglandin e pge generation were investigated in astrocytes cultured from rabbit BB mastoparan inhibited the accumulations of hinositol phosphates induced by BK microm in a time and concentrationdependent manner MP microm also released pge in a time and concentrationdependent manner mastoparaninduced PR of pge was inhibited by indomethacin a cyclooxygenase inhibitor by dexamethasone a steroidal antiinflammatory drug and by pertussis toxin an inactivator of some g proteins such as gi and go mastoparan also caused harachidonic acid liberation which was inhibited by dexamethasone or pertussis toxin in contrast indomethacin dexamethasone and pertussis toxin failed to attenuate mastoparaninduced inhibition of hinositol phosphate accumulation induced by bradykinin thus mastoparaninduced inhibition of phosphoinositide hydrolysis does not involve pertussis toxinsensitive g protein nor AA metabolites in addition to the inhibition of phospholipase c mastoparan activates phospholipase a through pertussis toxinsensitive g protein
MEDAL
investigating the cellular internalization pathways of single molecules or single nano objects is important to understanding cellmatter interactions and to applications in drug delivery and discovery imaging and tracking the motion of single molecules on cell plasma membranes require high spatial resolution in 3D fluorescence imaging along the axial dimension with nanometre resolution has been highly challenging but critical to revealing displacements in transmembrane events here utilizing a plasmonic ruler based on the sensitive distance dependence of nearinfrared fluorescence enhancement of carbon nanotubes on a gold plasmonic substrate we probe nm scale transmembrane displacements through changes in nanotube FI enabling observations of single nanotube endocytosis in 3D cellular uptake and transmembrane displacements show clear dependences to temperature and clathrin assembly on CM suggesting that the cellular entry mechanism for a nanotube molecule is via clathrindependent endocytosis through the formation of clathrincoated pits on the CM
MEDAL
obesity with associated metabolic disturbances worsens IHD outcomes and rodent studies confirm that obesity with insulinresistance impairs myocardial resistance to ischemiareperfusion ir injury however the effects of obesity per se are unclear with some evidence for paradoxic cardioprotection particularly in older subjects we tested the impact of dietary obesity on ir tolerance and reperfusion injury salvage kinase risk signalling in hearts from middleaged months old insulininsensitive rats NF from WR on either a week control cd or high carbohydrate obesogenic ob diet were assessed for ir resistance in vivo minutes left anterior descending artery occlusion and minutes reperfusion and ex vivo minutes was developed to understand the origin of the population group differencessimilarities in psychological traits between south koreans and nigerians this article summarizes the main findings based on the sktr sample to date recruitment procedures zygosity assessment measures and future plans for the sktr
MEDAL
the mode of action of two types of antiestrogens tamoxifen and progestins has been studied in the estrogen responsive cell lines mcf and td established from M1 human breast cancer non steroidal antiestrogens we present evidence indicating that tamoxifen inhibits the growth of BCCs via an interaction with the estrogen receptor re which leads to a partial activation of the receptor and a dissociated effects on gene expression at concentrations of less than microm effects of non steroidal antiestrogens are only observed when re sites are available at concentrations greater than microm an additional cytotoxic effect of tamoxifen is observed which is not mediated by the re progestins direct antiestrogenic effect of progestins r progesterone on BCCs have been demonstrated three series of responses to r are obtainedon n aldosterone excretion microgramday and in group b with insufficient suppression n aldosterone excretion microgramsday despite similarly low plasma renins rise of serum aldosterone C2 during a ii infusion was significantly higher in group b patients than in group a patients and normotensive controls rise in MAP blood pressure however brought about by graded a ii infusion was similar in both CG of hypertensives and in normotensive controls the results demonstrate an increased adrenal sensitivity to a ii in a subgroup of EHT only a similar adrenal hypersensitivity to a ii found by others in patients with hyperaldosteronism due to adrenal PH supports the hypothesis that the same mechanism underlies both disorders
MEDAL
plasma potassium concentrations were measured in four CG of unpremedicated patients in whom anesthesia was induced with thiopentone mgkg followed by tubocurarine mgkg gallamine mgkg pancuronium mgkg or ah mgkg prior to elective dental surgery there was a small but consistent decrease in PK following the i.t. of pancuronium and to a lesser extent following gallamine no changes were found during the first min following tubocurrarine with ah there was an early reduction in PK but the values returned to within normal limits by min
MEDAL
OB a CAA peptide is synthesized predominantly in the adipose tissues and plays a key role in the regulation of FI and body weight recent studies indicate that leptin receptor is expressed with high C2 in many brain regions that may regulate synaptic STDP here we show that deprivation of rapid eye movement remd sleep resulted in impairment of both cue and contextual fear memory in parallel surface expression of glur was reduced in the amygdala intraperitoneal injection of OB to the remd mice rescued SM impairment and reversed surface glur reduction using wholecell recording to evaluate the synaptic function of the thalamuslateral amygdala la pathway we found a decrease in frequency and amplitude of miniature excitatory PSCs mepscs concomitant with reduced ampanmda ratios in the remd mice by contrast pairedpulse facilitation ppf was increased the effects of remd on mepscs and ampanmda ratio could be reversed by OB treatment whereas on ppr it could not PTEN pten a dual proteinlipid phosphatase downregulates the effect of the pi kinase pathway CFC increased whereas remd led to a decrease in the phosphorylated states of pten akt and glycogen synthase kinaseβ gskβ and the effects of remd were reversed by OB these results suggest that both pre and postsynaptic functions of the thalamusla pathway were altered by fear conditioning and remd in opposite directions OB treatment reversed remdinduced memory deficits primarily by a postsynaptic action by restoring surface expression of glur without affecting ppr
MEDAL
a new virulent phage phildb of lactobacillus delbrueckii subsp bulgaricus was isolated from a chinese yogurt sample showing slow acidification it belonged to the siphoviridae family with an icosahedral CA of nm in diameter and a long tail of nm the genome of phage phildb was estimated to be approximately kbp and did not contain cohesive ends OS growth kinetics of its lytic development revealed latent and burst periods of min and min respectively with a burst size of phage particles per INF cell phage phildb was highly TPS for lactobacillus delbrueckii subsp bulgaricus the presence of calcium or magnesium ions was necessary to accelerate cell lysis and improve plaque formation phage phildb was able to survive in a ph range between and and resist ethanol and isopropanol however a treatment of degrees c for min was observed to inactive phage phildb thoroughly calcium ions ph as well as temperature did not show significant influence on phage adsorption and the adsorption kinetics were similar on viable and nonviable cells the characterization of this novel phage was helpful to establish a basis for adopting the most effective phage control strategies in industrial plants
MEDAL
campmediated pka signaling is the main known pathway involved in maintenance of the EC barrier tight regulation of pka function can be achieved by discrete compartmentalization of the enzyme via physical interaction with AKAPs akaps here we investigated the role of akaps and in EC barrier regulation analysis of human and mouse microvascular endothelial cells as well as isolated rat MES microvessels was performed using tatahxakapis peptide designed to competitively inhibit pkaakap interaction in vivo microvessel hydraulic conductivity and in vitro transendothelial ER measurements showed that this peptide destabilized EC barrier properties and dampened the campmediated EC barrier stabilization induced by forskolin and rolipram immunofluorescence analysis revealed that tatahxakapis led to both adherens junctions and actin CSK reorganization those effects were paralleled by RD of pka and rac from EC junctions and by rac inactivation similarly membrane localization of akap was also reduced in addition depletion of either akap or akap significantly impaired EC barrier function and akap was also shown to interfere with campmediated barrier enhancement furthermore immunoprecipitation analysis demonstrated that akap interacts not only with pka but also with vecadherin and ßcatenin taken together these results indicate that akapmediated pka subcellular compartmentalization is involved in EC barrier regulation more specifically akap and akap contribute to EC barrier CF and akap is required for campmediated barrier stabilization
MEDAL
this T0 was designed to investigate the differences of histologic gastritis according to the endoscopic diagnosis and between h pylori positive and negative gastritis using the sydney system a total of patients DU ulcer chronic gastritis gastric ulcer and gastric CA underwent endoscopy with biopsies from the antrum and body among the patients were h pylori positive h pylori density of the antrum was significantly higher in DU ulcer than in chronic gastritis gastric ulcer and gastric CA the positivity of intestinal metaplasia was lowest in DU ulcer and highest in gastric cancer h pylori density as well as grade of activity inflammation and atrophy were significantly higher in the antrum than in the body in DU ulcer while in chronic gastritis gastric ulcer and gastric cancer there was no difference of h pylori density activity inflammation and atrophy between the antrum and body the grade of activity and chronic inflammation were significantly higher in h pylori positive patients than in h pylori negative patients in both the antrum and body in conclusion the gastritis of DU ulcer was mainly localized to the antrum while the gastritis of chronic gastritis gastric ulcer or GC was rather uniform in the antrum and body h pylori seemed to be related to the OD of chronic inflammation and activity
MEDAL
we developed a reproducible relatively rapid bioassay that quantitatively correlates with the osteoinductive capacity of DBM obtained from human long bones we have found that saos human osteosarcoma cells proliferate in response to incubation with demineralized bone matrix and that an index of this proliferative activity correlates with demineralized bone matrixinduced osteogenesis in vivo the bioassay saos cell proliferation had an interassay coefficient of variation of and an intraassay coefficient of cell proliferation was normalized to a standard sample of DBM with a clinically high osteoinductive capacity which was assigned a value of one the saos cell proliferation for each sample was related to the standard and assigned a value placing it into the low intermediate or high osteoinductive index group osteoinduction of human DBM was quantitated by expressing new bone formation as a CF of the total BV/TV new bone plus the demineralized bone powder the DBM was placed in pouches formed in the RA muscles of athymic rats and endochondral bone formation was assessed at days following implantation when marrow spaces in the ossicles were formed by new bone bridging the spaces between demineralized ABM particles the proliferative index correlated with the area of new bone formation in histological sections of the newly formed ossicles when the proliferative index the osteoinductive index was divided into low intermediate and high groups the correlation between it and new bone formation osteoinduction was p in samples of DBM there was no overlap in the osteoinduction stimulated between the samples with low and high osteoinductive indices we conclude that the proliferation assay is useful for the routine screening of bone allograft donors for osteoinductive potential furthermore the twodimensional area of new bone formation as it relates to total new bone area is a quantitative measure of osteoinduction
MEDAL
nonsyndromic clefts of the lip and palate clp are developmental craniofacial CA that are often associated with cognitive dysfunction this study was designed to evaluate in patients with clp the presence of a TPS midline brain anomaly enlarged cavum septi pellucidi csp that has been shown in other developmental syndromes to be related to poor cognitive function
MEDAL
the inducible iκb kinase ikkiikkε is a recently described serinethreonine ikkrelated kinase previous studies have reported the role of ikki in infectious diseases and CA however its role in the cardiac response to pressure overload remains elusive in this study we investigated the effects of ikki deficiency on the development of pathological cardiac hypertrophy using in vitro and in vivo models first we developed mouse models of pressure overload CH induced by pressure overload using aortic banding ab four weeks after ab cardiac CF was then assessed through echocardiographic and hemodynamic measurements WB realtime pcr and histological analyses were used to assess the pathological and molecular mechanisms we observed that ikkideficient mice showed significantly enhanced cardiac hypertrophy cardiac dysfunction apoptosis and fibrosis compared with wt mice furthermore we recently revealed that the ikkideficient mice spontaneously develop cardiac hypertrophy moreover in vivo experiments showed that ikki deficiencyinduced CH was associated with the activation of the akt and nfκb signaling pathway in response to ab in cultured cells ikki overexpression suppressed the activation of this pathway in conclusion we demonstrate that ikki deficiency exacerbates CH by regulating the akt and nfκb signaling pathway
MEDAL
an evaluation of human tcell lymphotropic virus type htlv infection among pregnant women in salvador bahia brazil using enzymelinked immunosorbent assay western blot analysis and polymerase chain reaction assay found a rate of infection of of women epidemiologic and obstetric data on the htlvpositive pregnant women were analyzed and compared with data on a control group of htlvnegative pregnant women the mean age of the htlvpositive women was years all were seronegative for hiv and syphilis and only reported a past history of sexually transmitted infection and more than sexual partners of the htlvpositive women were breastfed were bottle fed and did not know six women had received blood transfusions and only reported intravenous drug use fiftytwo htlvpositive women could be followed had fullterm deliveries had premature deliveries and had abortions our results indicate that the frequency of htlv infection among pregnant women is relatively high in salvador bahia brazil maternal infection was probably acquired more frequently through breastfeeding but the sexual route was certainly the second most important means of transmission htlvpositive women had a PH of eczemalike infections in childhood more frequently than the control group htlv infection did not interfere in the course of pregnancy and no associated congenital infections were observed in the htlvpositive women
MEDAL
fortyfour pathologic specimens of bladder cancer patients were analyzed IHC with d monoclonal antibody to detect overexpression of mutant p gene the findings were interpreted by correlating with patient age sex CS number and macroscopic appearance of tumour histological tumour grade muscular invasion V1 invasion necrosis and urothelial atypia or dysplasia mutant p gene was overexpressed in specimens statistically significant rho with grade vascular invasion necrosis and patient sex was found with p overexpression available followup data were insufficient to draw a conclusion about the prognostic role of p overexpression prospective studies with larger number of patients are needed to define the exact place of nuclear p overexpression in transitional cell bladder cancer
MEDAL
in this paper the reclamation and reuse of municipal secondary effluents as well as the reclamation and recycling of refinery secondary effluents are technically and economically evaluated it is shown that both practices are feasible and sustainable and that the reclamation costs depend largely on specific circumstances such as legal requirements price policy reuse application raw water composition etc the reclaimed water is reused or respectively recycled as boiler makeup therefore both reclamation plants employ T3 multibarrier systems including ultrafiltration and reverse osmosis the employed processes have shown excellent performance with regard to the removal of critical parameters such as silica for example this parameter was reduced from mgl in the raw water to μgl in the boiler makeup
MEDAL
nuclear factorkappab nfkappab binds to nucleotide sequences between and bp UP of the transcriptional start site in the interleukin il promoter and is crucial for transcription of the il gene we showed that exogenous nitric oxide in the form of a nitric oxide donor significantly reduced il mrna in cytokineactivated ecv similarly nitric oxide significantly reduced migration of polymorphonuclear neutrophils through cytokineactivated ecv monolayers an ildependent process using a luciferase reporter construct containing the nfkappab site of the il gene we showed that exposing cytokineactivated ecv to exogenous nitric oxide resulted in significant reduction of nfkappab IB followup studies using a luciferase reporter construct possessing a mutated nfkappab site confirmed that the luciferase activity observed in the nfkappab reporter resulted from nfkappab IB these studies demonstrate that nitric oxide supplied exogenously into reactions containing G1 endothelium downregulates Th1 activity such as the secretion of chemokines and PET activity such as transendothelial migration of neutrophils
MEDAL
in this T0 we have examined the effects of both volatile and iv GA anesthetics on excitatory synaptic transmission with and without recurrent inhibition to clarify whether excitatory or inhibitory synapses are the major targets of action field population spike amplitudes fpss of ca pyramidal neurons were recorded in rat HPC slices schaffercollateralcommissural fibers sch were stimulated orthodromically and the evoked fpss pssch in ca area were measured in addition the fpss psalvsch elicited by stimulation of the sch T3 antidromic stimulation of the alveus hippocampi alv to produce RI were determined it was observed that sevoflurane and ISO primarily inhibited pssch and also produced additive inhibition on the psalvsch in a concentrationdependent manner the calculated ERP concentration ec values for pssch and psalvsch were vol and vol sevoflurane and vol and vol isoflurane respectively in comparison thiopental x x moll reduced both the pssch and psalvsch in a concentrationdependent manner the calculated ec values for thiopental on pssch and psalvsch were x and x moll respectively propofol x x moll had little effect on the pssch but reduced psalvsch with a calculated ec value of x moll the effects of the iv anesthetics with RI were antagonized in the presence of the gammaaminobutyric acidareceptor antagonist bicuculline methiodide in addition all anesthetics prolonged RI from ms sevoflurane and ISO to ms propofol the results suggest that sevoflurane and isoflurane inhibit mainly on glutamatemediated orthodromic pathways whereas thiopental and propofol enhance gammaaminobutyric acidamediated recurrent GABA pathways in ca neurons thus providing further evidence that the mechanisms of general anesthetics are drug and pathwayspecific
MEDAL
we have analyzed MMP associated with six human major histocompatibility complex mhc class i allomorphs expressed by the u cell line peptides were isolated by mild acid elution or by mhc class i immunoprecipitation by using w monoclonal antibody eightyfive peptides were sequenced by mass spectrometry and their putative binding alleles were assigned using bioinformatic tools only three peptides isolated by the two approaches were identical suggesting that the approaches may yield distinct partially overlapping peptide populations mild acid treatmentderived MMP manifested overall characteristics suggestive of relatively lower affinity of binding for mhc class i interestingly a C1 proportion of putative hlabbinding peptides was evident among the mild acid treatmenteluted peptides and to a lesser degree in the affinitypurified peptide pool these results suggest that hlab may bind a potentially large pool of peptides with relatively lower affinity we suggest that lower affinity of peptide binding may be the basis for inefficient tolerance to hlabbinding selfpeptides a predisposce outcomes survey pvos instrument an additional objective was to assess for the presence of any associations between laryngeal findings concomitant medical disorders and pvos measures the method used was a retrospective chart review twenty patients are identified in the study period there were females mean age years and three males mean age years the mean pvos scores are uniformly normal for the subset of boys n mean pvos the mean pvos for the females was sd lower than that measured in healthy agematched females n who had a mean pvos of sd the difference between these two CG was not statistically significant p unpaired t test although the absolute pvos scores were affected by observed laryngeal CA asthma PH or reflux PH the absence of any of these were significantly more likely to be associated with a perfect score on the pvos the overall pvos does not show a significant decline in the selfreported vrqol several cofactors may be associated with the detectable but not significant reduction in the pvos scores for the females in this study
MEDAL
a prospective study was performed to assess the value of differential quantitative blood cultures in the diagnosis of CRS when this condition is suspected on clinical grounds and to establish a reliable discriminative value for application without removal of the inserted catheter a total of central venous catheters from patients were used for the T0 blood was obtained simultaneously through the suspected infected device and from a IP venipuncture the catheter was removed and its tip cultured semiquantitatively catheterrelated sepsis occurred in patients using as cutoff value a colony count fourfold higher in blood drawn through the catheter than in simultaneously drawn IP blood a sensitivity of specificity of and positive predictive value of were obtained a single bacterial count greater than cfuml in the quantitative culture of the catheter blood specimen in the presence of a positive qualitative IP blood culture of the same organism was also highly suggestive of catheterrelated sepsis differential quantitative blood SC is a reliable method for the diagnosis of catheterassociated sepsis without catheter removal
MEDAL
ironsulfur proteins are among the primary targets of nitric oxide in cells previous studies have shown that ironsulfur clusters hosted by cysteine residues in proteins are readily disrupted by nitric oxide forming a proteinbound dinitrosyl iron complex thiolatebridged diiron tetranitrosyl complex or octanitrosyl cluster here we report that human mitochondrial protein miner fes clusters can bind nitric oxide without disruption of the clusters miner is a member of a new cdgsh ironsulfur protein family that also includes two mitochondrial proteins the type ii diabetesrelated mitoneet and the wolfram syndrome linked miner miner contains two cdgsh motifs and each cdgsh motif hosts a fes cluster via three cysteine and one histidine residues IB of nitric oxide in the reduced miner fes clusters produces a major absorption peak at nm without releasing iron or sulfide from the clusters the epr measurements and mass spectrometry analyses further reveal that nitric oxide binds to the reduced fes clusters in miner with each cluster IB one nitric oxide although the fes cluster in purified human mitoneet and miner fails to bind nitric oxide a single mutation of asp to val in mitoneet or asp to val in miner facilitates nitric oxide binding in the fes cluster indicating that a subtle change of protein structure may switch mitoneet and miner to bind nitric oxide the results suggest that binding of nitric oxide in the cdgshtype fes clusters in mitochondrial protein miner may represent a new nitric oxide signaling mode in cells
MEDAL