Search

STUDY QUESTION Is there a possible etiologic link between cervical stiffness and adenomyosis? SUMMARY ANSWER Women with adenomyosis have a stiffer internal cervical os than those without adenomyosis. WHAT IS KNOWN ALREADY An increased myometrial contractility during menses, leading to breaches in the endometrial basal lamina and subsequent infiltration of endometrial cells into the myometrium, has been proposed as a possible pathogenic mechanism for adenomyosis. Intense menstrual pain has already been shown to be associated with an increased stiffness, at elastography, of the internal cervical os. STUDY DESIGN, SIZE, DURATION A cross-sectional study on 275 women was performed between 1 February and 31 July 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS Among the participants, 103 were and 172 women were not affected by adenomyosis as evaluated by ultrasonography. General and clinical characteristics of the patients were collected. Strain elastography was used to document tissue stiffness at different regions of interest of the cervix, i.e. the internal cervical os, the middle cervical canal, the anterior and the posterior cervical compartment. Tissue stiffness was expressed as a colour score from 0.1 = blue/violet (high stiffness) to 3.0 = red (low stiffness). Simple and multiple logistic regression analyses were used to evaluate the relation between the presence of adenomyosis, as the dependent variable, and independent factors. MAIN RESULTS AND THE ROLE OF CHANCE Women with adenomyosis had a higher prevalence (P = 0.0001) and intensity (P = 0.0001) of pain during menses, between menses and at intercourse compared to control. The internal cervical os colour score was lower (higher stiffness) in women with adenomyosis (0.55 ± 0.29 versus 0.67 ± 0.26; P = 0.001) and the middle cervical canal/internal cervical os colour score ratio was greater (3.32 ± 4.36 versus 2.59 ± 4.99; P = 0.008), compared to controls. Upon logistic regression modelling (R2 = 0.077), the internal cervical os stiffness was an independent factor related to adenomyosis (odds ratio (OR) 0.220, 95% CI 0.077, 0.627; P = 0.005) along with age (P = 0.005) and the use of gonadal steroid therapies (P = 0.002). We obtained the same results using a different logistic regression model (R2 = 0.069), by substituting the internal cervical os stiffness with the ratio of the middle cervical canal/internal cervical os stiffness (OR 1.157, 95% CI 1.024, 1.309; P = 0.019). LIMITATIONS, REASONS FOR CAUTION Women did not undergo surgery therefore we have no histological confirmation of the adenomyosis diagnosis. Strain elastography is a semiquantitative analysis and can be conditioned by the force applied by the operator during the analysis. The data were obtained mainly in White women in a single centre. WIDER IMPLICATIONS OF THE FINDINGS To the best of our knowledge, this is the first study indicating that women with adenomyosis have an increased stiffness of the internal cervical os. The results indicate that a stiff internal cervical os, as determined by elastography, is a possible contributor to the development of adenomyosis. These findings may have clinical significance and should prompt further investigation. STUDY FUNDING/COMPETING INTEREST(S) None. TRIAL REGISTRATION NUMBER N/A.

Currently there are no potential curative therapies that can improve the central nervous system (CNS) regeneration after traumatic injuries or diseases. Indeed, the regeneration of CNS is greatly impaired by limited drug penetration across the blood brain barrier (BBB), poor drug targeting, deficient progenitor neural cells and limited proliferation of mature neural cells. To overcome these limitations, bioengineered injectable hydrogels in combination with drug and cell therapy have been proposed to mimic the complexity of the CNS microenvironment and architecture. Additionally, to enhance relevant CNS regeneration, proper biophysical and biochemical cues are needed. Recently, great efforts have been devoted to tailor stimuli-responsive hydrogels as novel carrier systems which are able to guide neural tissue regeneration. This review provides an extensive overview on the most promising injectable hydrogels for neural tissue engineering. A special emphasis is made to highlight the ability of these hydrogels to deliver bioactive compounds/cells upon the exposure to internal and external stimuli.; Bioactive injectable hydrogels have a broad application in central nervous system's (CNS) regeneration. This review gives an overview of the latest pioneering approaches in CNS recovery using stimuli-responsive hydrogels for several neurodegenerative disorders. STATEMENT OF SIGNIFICANCE: : This review summarizes the latest innovations on bioactive injectable hydrogels, focusing on tailoring internal/external stimuli-responsive hydrogels for the new injectable systems design, able to guide neural tissue response. The purpose is to highlight the advantages and the limitations of thermo-responsive, photo responsive, magnetic responsive, electric responsive, ultrasound responsive and enzymes-triggered injectable hydrogels in developing customizable neurotherapies. We believe that this comprehensive review will help in identifying the strengths and gaps in the existing literature and to further support the use of injectable hydrogels in stimulating CNS regeneration.

In this paper, we present a novel finite element model to simulate alkali-silica reaction in a realistic concrete meso-structure. Application of the internal ASR loading leads to the evolution of multiple deviated cracks and corresponding macroscopic expansion. A particular crack-extension algorithm and a solution scheme provide numerical stability and allow to model complicated crack patterns while preserving the physics. The predictive validity of the model is demonstrated by matching an analytical solution of a loaded penny-shaped crack. The model is applied to the experimental dataset comprising the time-evolving X-ray tomograms of the ASR-affected concrete. Similar to the tomography data, the model results in an expanded concrete sample with a developed crack network. Two hypotheses on the crack loading and extension mechanisms are tested by comparing the crack statistics. Simulations with varying number of ASR sites and application of the uniaxial loading bring interesting insights. The latter concerns the role of the ASR-sites number, the individual loading amplitude and the difference in crack patterns., Cement and Concrete Research, 162, ISSN:0008-8846

International audience; Dense ceramics of MnSO4 composition have been successfully densified at 400 °C in only 5 min under a uniaxial pressure of 400 MPa, using Spark Plasma Sintering technique. Since the stable form of MnSO4 in ambient atmosphere is its hydrate MnSO4·H2O, crystallizing in a different space group, dehydration is required to reach a purely anhydrous phase. In situ dehydration during Spark Plasma Sintering allows to lower both sintering temperature and time. Applied pressure strongly influences dehydration step and therefore is a key parameter to tune densification, so far as to obtain a dense MnSO4·H2O ceramic. The presence of a reversible phase transition to a β-MnSO4 high temperature form seems to influence the dehydration temperature under pressure, and likely drives the sintering mechanisms. The high densification obtained, beyond 95% of theoretical density, added to the preservation of the structural and physical properties of MnSO4 after sintering allowed to perform reliable and reproducible measurements showing a dielectric anomaly associated to the magnetic transition, and the hysteretic behaviour of capacitance versus magnetic field, which is a clue for an intrinsic magnetoelectric coupling in MnSO4.

Studies in Oregon, California, Pennsylvania and Italy evaluated the relative performance of the Ajar trap compared with several other traps for the capture of Grapholita molesta (Busck), in pome and stone fruit orchards treated with sex pheromone dispensers for mating disruption. The Ajar is a delta-shaped trap with a screened jar filled with an aqueous terpinyl acetate plus brown sugar bait solution (TAS) that opens inside the trap and is surrounded by a sticky liner. The TAS-baited Ajar trap was evaluated with and without the addition of a sex pheromone lure and compared with a delta trap baited with a sex pheromone lure and a bucket trap filled with the TAS bait. Although the Ajar trap had a 90% lower evaporation of the TAS bait than the bucket trap, both of them caught similar numbers in the majority of the field tests of both sexes of G. molesta. The addition of the sex pheromone lure did not increase moth catches by the TAS-baited Ajar trap. The TAS-baited Ajar trap caught significantly greater numbers of moths than the sex pheromone-baited delta trap in 18 of the 20 orchards. Few hymenopterans were caught in orange TAS-baited Ajar traps, but the catch of flies and other moths relative to the target pest remained high. Flight tunnel and field tests evaluated the effect of several screen designs on the catches of G. molesta and non-target species. All exclusion devices significantly reduced the catch of larger moths. However, designs that did not reduce the catch of male G. molesta did not reduce the catch of muscid flies. Exclusion devices with openings

Metabotropic glutamate receptors (mGluR) can control neuronal excitability by modulating several ionic channels. In hippocampal pyramidal cells, groups I/II mGluR are located extrasynaptically, suggesting that their endogenous activation is dependent on the glutamate clearance rate and therefore on excitatory amino-acid transporters (EAAT) efficiency. Deficiency of glutamate uptake can generate seizures in rodents and has been suggested as a mechanism of seizure generation in some human epileptic syndromes. However, the cellular mechanisms linking EAAT dysfunction and pathological cortical activities remain elusive. Here, we investigate the possible role of mGluR on paroxysmal burst of multiple unit activities (MUA) generated in the CA1 region of developing hippocampal slices using an EAAT inhibitor, TBOA. These bursts are generated by a synaptic release of glutamate and involve extrasynaptic NMDA receptors (NMDAR) activated by transmitter spillover. Here, we show that postsynaptic mGluR (groups I/II) are tonically activated by the rise in ambient glutamate concentration after EAAT inhibition and strongly contribute to paroxysmal burst genesis. The inhibition of mGluR with broad spectrum antagonists or addition of a glutamate scavenger strongly reduced the occurrence of paroxysmal burst and the frequency/number of MUA during the burst. Moreover, this endogenous activation of groups I/II mGluR leads to (i) the reduction of the slow afterhyperpolarization current (I(sAHP)), increasing the firing pattern of pyramidal cells, and (ii) the potentiation of extrasynaptic NMDAR-mediated responses, enabling glutamate spillover to generate a suprathreshold depolarization for several seconds. Our data show that an insufficient buffering of extracellular glutamate enables a cross talk between groups I/II mGluR and NMDAR, which, combined with a decrease of I(sAHP), leads to the hyperexcitability of the hippocampal network, facilitating the genesis of epileptical-like activity in response to glutamate release. These findings highlight the importance of the control exerted by EAAT on mGluR.

Aim: To ferment buttermilk, a low-cost by-product of the manufacture of butter, with a proteolytic strain of Lactobacillus helveticus, to enhance its value by the production of a functional peptide-enriched powder. Methods and Results: Buttermilk was fermented with Lact. helveticus 209, a strain chosen for its high proteolytic activity. To enhance the release of peptidic fractions, during fermentation pH was kept at 6 by using NaOH, Ca(CO)3 or Ca(OH)2. Cell-free supernatant was recovered by centrifugation, supplemented or not with maltodextrin and spray-dried. The profile of peptidic fractions released was studied by RP-HPLC. The lactose, Na and Ca content was also determined. The powder obtained was administered to BALB/c mice for 5 or 7 consecutive days, resulting in the proliferation of IgA-producing cells in the small intestine mucosa of the animals. Conclusions: Buttermilk is a suitable substrate for the fermentation with Lact. helveticus 209 and the release of peptide fractions able to be spray-dried and to modulate the gut mucosa in vivo. Significance and Impact of the Study: A powder enriched with peptides released from buttermilk proteins, with potential applications as a functional food additive, was obtained by spray-drying. A novel use of buttermilk as substrate for lactic fermentation is reported.

The growth capacity of probiotic Lactobacillus paracasei A13, Bifidobacterium bifidum A1 and L. acidophilus A3 in a probiotic fresh cheese commercialized in Argentina since 1999 was studied during its manufacture and refrigerated storage at 5 °C and 12 °C for 60 days. Additionally, viable cell counts for probiotic bacteria in the commercial product are reported for batch productions over the last 9 years. L. paracasei A13 grew a half log order at 43 °C during the manufacturing process of probiotic cheese and another half log order during the first 15 days of storage at 5 °C, without negative effects on sensorial properties of the product. However, a negative impact on sensorial characteristics was observed when cheeses were stored at 12 °C for 60 days. Colony counts in the commercial product showed variations from batch to batch over the last 9 years. However, colony counts for each probiotic bacterium were always above the minimum suggested. Growth capacity of L. paracasei A13 in cheese during manufacturing and storage, mainly at temperatures commonly found in retail display cabinets in supermarkets (12 °C or more), would make it necessary to re-evaluate its role as possible probiotic starter and the consequences on food sensorial characteristics if storage temperature during commercial shelf life is not tightly controlled. Fil: Vinderola, Celso Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; Argentina Fil: Prosello, W.. Sucesores de Alfredo Williner S.A; Argentina Fil: Molinari, F... Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; Argentina Fil: Ghiberto, D.. Sucesores de Alfredo Williner S.A; Argentina Fil: Reinheimer, Jorge Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; Argentina

Purpose: To describe a case of primary open angle glaucoma (POAG) and to illustrate a new principle in detecting and managing the disease using intraocular pressure (IOP) corneal hysteresis as a clinical guide. Method: A case report is reviewed of a white 87-year-old male who was detected with ocular hypertension (OHTN) with bilateral asymmetrical corneal stiffness and POAG. Conclusion: A new indicator and alternative approach to determine and manage POAG is presented using evidence-based technology for clinical care and facilitating positive outcomes for one of the leading causes of blindness in the world.

Myostatin and mechano-growth factor (MGF), an isoform of insulin-like growth factor-I (IGF-I), are two important regulators of muscle hypertrophy. The aim of the present study was to investigate the effects of recombinant human growth hormone (rhGH) and/or testosterone on muscle MGF/IGF-IEa/myostatin expression in intact and hypophysectomized rats treated for 15 d with 1) saline or rhGH, 2) sesame oil or testosterone, 3) saline+sesame oil, or rhGH+testosterone (first experiment) or for 7 d with saline or rhGH (second experiment). Animals were killed by decapitation 24 h or 4 d after the last injection (first or second experiment, respectively). Muscle expressions of MGF, IGF-IEa, and myostatin were determined by RT-PCR. A significant increase in the weight of gastrocnemius muscle was observed only in hypophysectomized rats treated with rhGH alone or in combination with testosterone. Administration of rhGH to hypophysectomized rats caused a marked increase in both MGF and IGF-IEa muscle mRNA levels (without any change in the muscle expression of myostatin), an effect that was abolished when testosterone was combined with rhGH. Conversely, in intact rats rhGH increased myostatin muscle mRNA levels without affecting those of MGF and IGF-IEa. Testosterone, alone or combined with rhGH, induced an inhibition of myostatin expression in the muscle of intact rats, but did not change muscle paradigms of hypophysectomized rats. In conclusion, rhGH and/or testosterone anabolic effects in the muscle are mediated by a different expression of MGF/IGF-IEa/myostatin, which is related to the pituitary function.

The growth of six probiotic commercial strains of lactobacilli was assessed in reconstituted dried whey and buttermilk supplemented with yeast extract, meat peptone, soy peptone, tryptone or casein acid hydrolysate at 0.3%, 0.6% or 1%. The addition of 1% glucose was also tested. Growth and acidification kinetics were determined at 37°C using MRS broth and a commercial culture medium as references. The suitability of whey and buttermilk as cryoprotectants at –20°C and –70°C was also assessed. Whey and buttermilk with 0.3% yeast extract were chosen for the growth of probiotic lactobacilli, since no satisfactory growth was observed without an external nitrogen source, whereas glucose did not improve the growth of any of the strains assayed. In general, buttermilk performed as satisfactorily as the reference media. The effectiveness of these media as cryoprotectants was strain dependent: skimmed milk and whey were the most suitable ones, especially for long-term storage at –20°C. However, at –70°C, no significant differences were observed between the culture media assessed. The use of whey or buttermilk as culture media for the production of probiotic lactic acid bacteria and for their cryopreservation implies a novel use of these low-cost products, offering an alternative way of utilizing the by-products of the dairy industry, helping to minimize their negative impact on the environment.

Undoubtedly, the most exciting development in stroke treatment in many years is the potential application of fibrinolytic drugs to the first few hours after the onset of acute cerebral ischemia. Given in the window of opportunity between the abrupt loss of function (functio laessa), concomitant with the biochemical and metabolic disorder (inadequate blood supply), and the onset of irreversible anatomical changes (tumor, dolor, calor, rubor, etc.), nicely visualized today by a number of transcranial imaging methods, rt-PA and other proven fibrinolytic agents offer the best chance yet for the secondary prevention of thromboembolic strokes, that is, the prevention of permanent functional impairment from an extant disease state that began long before the patient sought medical intervention. Early reports of scientific feasibility in animal models (1,2) and recent reports of open-label (3,4) and controlled clinical trials are encouraging (5). Reports of hemorrhagic complications of these drugs, both in heart patients (6,7) and in those with strokes (3-5,8), are worrisome. Although struggling to prove the efficacy of tPA in acute completed stroke, simultaneously taking into account the natural history of strokes due to thrombosis, cerebral embolism, transient ischemic attacks (TlAs) and stroke-in-evolution, we must also evaluate the spontaneous hemorrhagic complication rates in each of these events, in order to establish a true risk/ benefit ratio of early fibrinolysis. Therefore, a number of controlled clinical trials are in progress. These studies exclude most of the patients who present with known risk factors for spontaneous hemorrhages and

Laboratory tests for anticardiolipin antibodies (aCL) and anti-β2glycoprotein I antibodies (a-β2GPI) face problems common to many autoantibody assays: the lack of a reference standard and the need for each laboratory to assess assay-specific cut-off values. The aims of the study were to evaluate the reference range upper limits (99th percentile) used for aCL and a-β2GPI in the northwest of Italy and to investigate the analytical performances of these assays with the newly obtained reference ranges. We assayed aCL and a-β2GPI in 104 serum samples from patients without a history of thrombosis, pregnancy morbidity, tumours, infections and/or autoimmune diseases (30 males and 74 non-pregnant females). We tested all the commercial assays available in our regions (i.e. Orgentec Diagnostika, Aesku Diagnostics and Inova Diagnostics ELISA; CliA Zenit-RA and EliA Phadia Laboratory Systems). A further 30 serum samples, including 10 from healthy subjects, 10 from antiphospholipid syndrome (APS) patients and 10 from septic patients were assessed to investigate the analytical performance of the obtained cut-off limits. Reference range upper limits obtained with the commercial kits differ among assays and from the values reported by the manufacturer. Moreover, normal reference ranges calculated for IgG and IgM aCL differed from the arbitrary selected laboratory classification values suggested in the guidelines of 40 GPL and MPL.

The response of Grapholita molesta (Busck) males to three-component sex pheromone blends containing a 100% ratio of the major sex pheromone component, (Z)-8-dodecenyl acetate and a 10% ratio of (Z)-8-dodecenol, but with varying ratios of (E)-8-dodecenyl acetate (0.4, 5.4, 10.4, 30.4, and 100.1% E-blends) was tested with populations in eight stone and pome fruit orchards in Europe, Asia, and North and South America. Traps baited with the 5.4% E-blend caught significantly more males than traps with any other blend with all populations. Significantly more males were caught in traps baited with the 10.4% E-blend than in traps with the remaining blends, except with the 0.4% E-blend in Turkey. Significant differences in male moth catches occurred between the other blends with the 0.4>30.4% E-blend, and the 30.4>100.1% E-blend. Male moth catches with the 100.1% E-blend only differed from the hexane control in Chile. No apparent differences were noted to these blends in populations collected from pome or stone fruits. Flight tunnel assays to synthetic blends with a subset of populations were similar to the field results, but the breadth of the most attractive E-blends was wider. Flight tunnel assays also demonstrated a high level of male-female cross-attraction among field-collected populations. Female gland extracts from field-collected populations did not show any significant variation in their three-component blends. The only exceptions in these assays were that long-term laboratory populations were less responsive and attractive, and produced different blend ratios of the two minor components than recently collected field populations. We would like to thank the financial support of MEC, Spain (AGL2010-17486) to C.G., D.B, and L.A.E., and the Chilean grant ‘Conicyt MEC 80120005’to C.G. In Girona, Spain, Cesca Alcalá with RTA conducted the field experiments and Maria Carbó obtained the research sites. In Turkey, the research assistant Bilgi Pehlevan (Uludag University, Turkey) was very helpful in these studies. In Korea the work was supported by the Basic Science Research Program through the National Research Foundation of Korea. In Italy, Matteo Anaclerio and Manuela Cigolini (Catholic University) were very helpful. Help with the studies conducted in Oregon was provided by Rick Hilton at Oregon State University, Medford, OR. Laboratory colonies from Pennsylvania were provided by Greg Krawczyk, Penn State University, Biglerville, PA, and from California by personnel at the USDA, ARS Laboratory, Parlier, CA. Jean-Claude Tournié, of Prestagro, collected insects in France and shipped them to Spain.

Establishing relationship between coronary calcium volumes from Intravascular Ultrasound (IVUS) and automated carotid intima-media thickness (cIMT) helps in understanding the genetic nature of atherosclerosis disease. In this research, we have quantified the detected calcium from IVUS video frames and associated a relationship between coronary calcium volumes computed and automated cIMT from B-mode ultrasound.Coronary calcium volume is computed from IVUS and auto cIMTs are computed using B-mode ultrasound. An automated computer based application is developed and tested on 100 patient volumes (an average of 2549 frames per volume) to calculate lesion area and normalized coronary calcium volume. We use an integrated approach for volume computation which is based on lesion area per frame. We have measured the normalized volume from the calcium detected video frames using proposed integration method. The cIMT of 100 carotids were measured with novel and dedicated automated software analysis (AtheroEdge™ from AtheroPoint™ LLC, Roseville, CA, USA).The computer-based coronary calcium volume (from IVUS) showed a correlation coefficient with respect to cIMT for left and right carotids as 9.1% and 13.9%, respectively.Coronary calcium volume computed from IVUS and auto cIMT are moderately correlated. The association between auto cIMT (right side) vs. computer-based coronary calcium volume (IVUS) is stronger than the association between auto cIMT (left side) vs. computer-based coronary calcium volume.

Objective: To analyze the frequency, clinical characteristics, and predictors of symptomatic intracerebral hemorrhage (ICH) after intraarterial (IA) thrombolysis with recombinant pro-urokinase (r-proUK) in acute ischemic stroke. Method: The authors conducted an exploratory analysis of symptomatic ICH from a randomized, controlled clinical trial of IA thrombolysis with r-proUK for patients with angiographically documented occlusion of the middle cerebral artery within 6 hours from stroke onset. Patients (n = 180) were randomized in a ratio of 2:1 to either 9 mg IA r-proUK over 120 minutes plus IV fixed-dose heparin or IV fixed-dose heparin alone. As opposed to intention to treat, this analysis was based on “treatment received” and includes 110 patients given r-proUK and 64 who did not receive any thrombolytic agent. The remaining six patients received out-of-protocol urokinase and were excluded from analysis. The authors analyzed centrally adjudicated ICH with associated neurologic deterioration (increase in NIH Stroke Scale [NIHSS] score of ≥4 points) within 36 hours of treatment initiation. Results: Symptomatic ICH occurred in 12 of 110 patients (10.9%) treated with r-proUK and in two of 64 (3.1%) receiving heparin alone. ICH symptoms in r-proUK–treated patients occurred at a mean of 10.2 ± 7.4 hours after the start of treatment. Mortality after symptomatic ICH was 83% (10/12 patients). Only blood glucose was significantly associated with symptomatic ICH in r-proUK–treated patients based on univariate analyses of 24 variables: patients with baseline glucose >200 mg/dL experienced a 36% risk of symptomatic ICH compared with 9% for those with ≤200 mg/dL ( p = 0.022; relative risk, 4.2; 95% CI, 1.04 to 11.7). Conclusions: Symptomatic ICH after IA thrombolysis with r-proUK for acute ischemic stroke occurs early after treatment and has high mortality. The risk of symptomatic ICH may be increased in patients with a blood glucose >200 mg/dL at stroke onset.

Viene illustrato l'andamento di un Progetto PRIN (2005), riguardante le tecniche di allevamento e il controllo di qualità degli insetti entomofagi, alla data dell'11 giugno 2007. Il Progetto coinvolgeva, oltre all'Unità di Bologna (Coordinatrice), le Unità di Milano e Piacenza

We have hypothesized that antiallergic activity of inhaled heparin is molecular weight dependent and mediated by “nonanticoagulant fractions” (NAF-heparin). Therefore, we studied comparative effects of high-, medium-, and ultralow-molecular-weight (HMW, MMW, and ULMW, respectively) NAF-heparins on acute bronchoconstrictor response (ABR) and airway hyperresponsiveness (AHR) in allergic sheep. Specific lung resistance was measured in 23 allergic sheep, before and immediately after challenge with Ascaris suum antigen, without and after pretreatment with inhaled NAF-heparins. Airway responsiveness was estimated before and 2 h postantigen as the cumulative provocating dose of carbachol in breath units, which increased specific lung resistance by 400%. NAF-heparins attenuated ABR and AHR in a molecular-weight-dependent fashion. HMW NAF-heparin ( n = 8) was the least effective agent: it attenuated ABR [inhibitory dose causing 50% protection (ID50) = 4 mg/kg] but had no effect on AHR. MMW NAF-heparin ( n = 8) showed intermediate efficacy (ABR ID50= 0.8 mg/kg, AHR ID50= 1.4 mg/kg), whereas ULMW NAF-heparin ( n = 7) was the most effective agent (ABR ID50= 0.4 mg/kg, AHR ID50= 0.2 mg/kg). ULMW NAF-heparin was 3.5 times more potent in attenuating antigen-induced AHR when administered “after” antigen challenge and failed to inhibit the bronchoconstrictor response to carbachol and histamine. In 15 additional sheep, segmental antigen challenge caused a marked increase in histamine in bronchoalveolar lavage fluid that was not prevented by any of the inhaled NAF-heparins. These data indicate that antiallergic activity of inhaled heparin is independent of its anticoagulant action and resides in the

Data are being used to redefine, transform, and empower the roles of providers, payers, and patients. The empowering potential of data on these three groups, and theirchanging roles are reviewed The use of data to transform care and increase equality is not new, yet the comprehensive application ofprinciples of continuous quality improvement to the delivery processes is just beginning. The approach to the quality improvement processes employed by peer review organizations includes idea capture, development of intuitively appealing quality indicators, formulating the intervention, formalizing the research architecture, and quantifying the impact of the interventions. The multifaceted interventions for improvement are discussed. Thefuture of medicine includes a greater use of data and the quantitative sciences to inspire improvement across the health care delivery continuum.

Unfractionated heparin (UF-heparin) has been shown to prevent antigen-induced airway hyperresponsiveness (AHR), but it is ineffective when administered after the antigen challenge. We hypothesized that the failure of UF-heparin to modify postantigen AHR might depend on molecular weight. We therefore studied the effects of UF-heparin and three low-molecular-weight heparin fractions (medium-molecular-weight heparin [MMWH]; low-molecular-weight heparin [LMWH]; and ultralow-molecular-weight heparin [ULMWH]) on antigen-induced AHR and histamine release in bronchoalveolar lavage fluid (BALF). Specific lung resistance (SRL) was measured in 20 allergic sheep before, immediately after, and up to 2 h after challenge with Ascaris suum antigen. Airway responsiveness was expressed as the cumulative provocative dose of carbachol, in breath units, that increased SRL by 400% (PD400). PD400 was determined before and 2 h after antigen, both without and after treatment with aerosolized UF-heparin (1,000 U/kg) and various heparin fractions (0.04 mg/kg to 5 mg/kg) administered after the antigen challenge. Inhaled UF-heparin (n = 4), MMWH (n = 4), and LMWH (n = 6) failed to modify postantigen AHR when administered after the challenge. Only ULMWH (n = 6) inhibited postantigen AHR in a dose-dependent manner (percent protection ranged from 31% to 139%). In eight additional sheep, histamine in BALF was measured with a radioimmunoassay (RIA) before and after the segmental antigen challenge, without and after pretreatment with inhaled UF-heparin, LMWH, or ULMWH. Inhaled UF-heparin and LMWH inhibited antigen-induced histamine release as measured in BALF by 81% and 75%, respectively; whereas ULMWH was ineffective in this respect. We conclude that: (1) modification of antigen-induced AHR by fractionated heparins is molecular-weight dependent; and (2) only ULMWH attenuates AHR when administered after antigen challenge, via an unknown mast-cell-independent action.

This study sought to evaluate the quality of care rendered to Medicare beneficiaries with acute myocardial infarction by establishing the use patterns of well-proven therapies in this population. We analyzed the quality of care rendered to 4300 Medicare beneficiaries seen at Maryland and District of Columbia hospitals with retrospectively confirmed acute myocardial infarction by evaluating the use of proven therapies. The proportion of patients ideal for therapies ranged from 10% for reperfusion to 100% for smoking cessation counseling. For ideal patients the following therapies were implemented: aspirin (87%), reperfusion therapy (64%), beta-blockers on discharge (60%), and smoking cessation counseling (41%). A substantial proportion of Medicare patients with acute myocardial infarction has one or more relative or absolute contraindications to standard regimens and therefore are not ideal therapeutic candidates. In the group of ideal patients, those with no therapeutic contraindications, a significant proportion do not receive these treatments.

Purpose: To describe a case of steroid-induced ocular hypertension in which a clinical significant increase in intraocular pressure resulted with a corresponding corneal hysteresis decreased response. Method: A case report is presented in which a 62-year-old white male who was diagnosed with rosacea meibomitis and treated with topical antibiotic steroid combination ointment responded such. Conclusion: This case report illustrates a reverse model of the topical antiglaucoma medication studies recently described of decrease in intraocular pressure with an increase in corneal hysteresis with the application of topical prostaglandins and beta-blocker compounds. This may provide additional insight into how the biomechanical properties of the cornea and tunics of the eye respond to local applications of different ocular medications.

The purpose of this study was to evaluate whether the automated carotid intima-media thickness (CIMT) identified by using automated software could predict the SYNTAX score for coronary artery disease (CAD) patients.Three-hundred-seventy consecutive patients (males 218; median age 69±11 years) who underwent carotid-ultrasound and coronary angiography were analyzed. Two experienced interventional cardiologists calculated the SYNTAX score from the carotid angiograms. After ultrasonographic examinations were performed, the plaque score (PS) was calculated and automated carotid IMT analysis was obtained by a fully automated algorithm. Correlation and stepwise logistic regression analysis were calculated and also the receiver operating characteristics (ROC) curve analysis was computed.The mean SYNTAX score was 8.1±14.4; the PS was 7.1±14.4 and the mean CIMT was 0.86±0.23 mm (Normality rejected with a P-value of 0.001). A statistically significant correlation was found between the CIMT and SYNTAX score (r=0.323; P=0.0001) and between the PS and SYNTAX score (r=0.583; P=0.0001). The area under the ROC curve (Az) between CIMT and coronary artery disease was 0.648 (P=0.0001) and the CIMT of 1 mm or more was associated with the presence coronary artery disease with a specificity of 90.5%. Logistic regression analysis confirmed the association between CIMT and SYNTAX score (P=0.0002).Results of our study using an automated algorithm showed a statistical significant association between CIMT and SYNTAX score and indicated that CIMT may be considered a reliable parameter for prediction of SYNTAX score in coronary artery disease patient population from Japan.

In this study, we used a specific tryptase inhibitor, APC-366 [N-(1-hydroxy-2-napthoyl)-L-arginyl-L- prolinamide hydrochloride] to investigate the effect of intradermally administered tryptase and tryptase released by antigen challenge on the immediate cutaneous reaction (ICR) in allergic sheep. The surface areas of cutaneous wheals produced by intradermal injections (0.05 ml) of 1 and 10 ng tryptase alone, tryptase combined with 3 U heparin (tryptase-heparin), or Ascaris suum antigen (10(-5) dilution) with or without pretreatment with APC-366 (1 mg/ml) were measured at 20 and 60 min after challenge. Intradermal injections of 1 and 10 ng tryptase alone (n = 7) produced an ICR of < or = 20% of that obtained after injection of histamine (5% wt/vol). Intradermal injection of tryptase-heparin (n = 7), however, resulted in 50 (1 ng) and 82% (10 ng) of the ICR to histamine (both, P < 0.05 vs. tryptase alone). APC-366 inhibited (P < 0.05) the ICR to 1 and 10 ng tryptase-heparin by > or = 70% at all times (n = 8) but had no effect on the histamine-induced ICR (n = 3). A combination of the histamine H1 antagonist chlorpheniramine (2 mg/kg iv) and the H2 antagonist metiamide (3 mg/kg iv) given 40 min before challenge (n = 8) inhibited the response to 1 and 10 ng tryptase-heparin by 42 and 62% at 20 min and by 96 and 86% at 60 min, respectively (all, P < 0.05). APC-366 also blocked the ICR to A. suum antigen by 68% (P < 0.05) in nine sheep. These results indicate that intradermal injection of tryptase-heparin can induce an ICR. This ICR can be inhibited by APC-366 or a combination of the histamine H1 and H2 antagonists, suggesting that the tryptase response is mediated by histamine. APC-366 also blocks the mast cell-mediated ICR to intradermally injected A. suum antigen. Collectively, these results suggest that tryptase may modulate mast cell histamine release.

The etiology and outcome of microembolisms detected by ultrasonic devices along with descriptions of personality changes and cognitive loss in postoperative open heart surgery patients give rise to hy

The aims of this study were: 1) to analyze the interobserver carotid intima-media thickness (CIMT) variability using three different measurement metrics on large multi-institutional databases; 2) to evaluate the three kinds of metrics when comparing completely automated CIMT measurement (Auto Edge CIMT) to two manually derived CIMT (manual CIMT).Two expert sonographers manually analyzed 665 carotid B-Mode ultrasound images collected from five institutions and using four different scanners. The two readers traced the lumen-intima (LI) and media-adventitia (MA) interfaces. The manual CIMT was computed from the LI/MA tracings by using three different distance measurement metrics: the Hausdorff, the PolyLine, and the Centerline distance metrics. The LI/MA tracings of a completely automated method we previously developed were then compared to manual CIMT.The average CIMT values of Readers 1 and 2 were 1.904±0.650 mm and 1.421±0.394 using Hausdorff, 0.808±0.269 mm and 0.790±0.227 mm using Polyline, and 0.762±0.266 mm and 0.782±0.228 mm using Centerline, respectively. The correlation coefficients were 0.14 (0.07-0.22) for Hausdorff, 0.77 (0.74-0.80) for Polyline, and 0.82 (0.79-0.84) for Centerline. The variation coefficients (CV) were equal to 46.4% (Hausdorff), 2.6 % (Polyline), and 14.1% (Centerline). The Auto Edge CIMT values were: 1.655±0.676 mm using Hausdorff, 0.808±0.282 mm using Polyline, and 0.776±0.275 mm using Centerline.Centerline and Polyline yield very close results and are clinically suitable distance measurement techniques for computing the CIMT from LI/MA profiles.