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Strawberry, a globally popular crop whose fruit are known for their taste and health benefits, were used to evaluate the effects of polyethylene microplastics (PE-MPs) on plant physiology and fruit quality. Plants were grown in 2-L pots with natural soil mixed with PE-MPs at two concentrations (0.2% and 0.02%; w/w) and sizes (⌀ 35 and 125 µm). Plant physiological responses, root histochemical and anatomical analyses as well as fruit biometric and quality features were conducted. Plants subjected to ⌀ 35 µm/0.2% PE-MPs exhibited the most severe effects in terms of CO 2 assimilation due to stomatal limitations, along with the highest level of oxidative stress in roots. Though no differences were observed in plant biomass, the impact on fruit quality traits was severe in ⌀ 35 µm/0.2% MPs treatment resulting in a drop in fruit weight (-42%), soluble solid (-10%) and anthocyanin contents (-25%). The smallest sized PE-MPs, adsorbed on the root surface, impaired plant water status by damaging the radical apparatus, which finally resulted in alteration of plant physiology and fruit quality. Further research is required to determine if these alterations also occur with other MPs and to understand more deeply the MPs influence on fruit physio-chemistry., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The small-airway dysfunction (SAD), detected with impulse oscillometry (IOS) methods, has been recently better characterized in patients with asthma. However, little is known about SAD in asthmatic patients with normal spirometry (NS)., Objective: In this study, we aimed to investigate, in an unselected sample of 321 patients with physician-diagnosed asthma and NS, prevalence, clinical characterization, and impact on asthma control of IOS-defined SAD. As a secondary objective of the study, we focused on comparing the difference between IOS- and spirometry-defined SAD., Methods: Consecutive patients with a previous diagnosis of asthma but normal spirometry at the moment of the enrollment were stratified by the presence of IOS-defined SAD (difference in resistance at 5 Hz and at 20 Hz [R5-R20] greater than 0.07 kPa x s x L -1 ). We have also assessed the presence of SAD defined by spirometry, according to FEF 25-75 < 65% of the predicted. Clinical and laboratory features were collected, and univariable and multivariable analyses were used to analyze cross-sectional associations between clinical variables and outcomes (SAD)., Results: IOS-defined SAD was present in 54.1% of the cohort. In contrast, spirometry-defined SAD was present in only 10% of patients. Subjects with IOS-defined SAD showed less well-controlled asthma and a higher mean inhaled corticosteroid dosage use compared with subjects without SAD (both P < .001). Overweight (odds ratio [OR], 1.14; 95% CI, 1.05-1.23), exacerbation history (OR, 3.06; 95% CI, 1.34-6.97), asthma-related night awakenings (OR, 6.88; 95% CI, 2.13-22.23), exercise-induced asthma symptoms (OR, 33.5; 95% CI, 9.51-117.8), and controlled asthma (OR, 0.22; 95% CI, 0.06-0.84) were independently associated with SAD., Conclusions: Asthmatic patients with IOS-defined SAD showed less well-controlled asthma, more severe exacerbations and higher mean inhaled corticosteroid dosage. We confirmed exercise-induced asthma, asthma-related night awakenings, exacerbation history, and overweight as independently associated with SAD, while showing well-controlled asthma as inversely associated. SAD may be overlooked by standard spirometry., Competing Interests: Declaration of competing interest All authors have no conflicts of interest to disclose about this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Short-acting beta agonist (SABA)-only treatment is associated with poor asthma control and adverse clinical outcomes. The importance of small airway dysfunction (SAD) is increasingly recognized in asthma, but less is known in patients using SABA-only therapy. We aimed to investigate the impact of SAD on asthma control in an unselected cohort of 60 adults with physician-diagnosed intermittent asthma treated with as-needed SABA monotherapy., Methods: All patients underwent standard spirometry and impulse oscillometry (IOS) at the first visit and were stratified by the presence of SAD defined by IOS (fall in resistance 5-20 Hz [R5-R20]>0.07 kPa × s*L -1 ). Univariable and multivariable analyses were used to analyze cross-sectional relationships between clinical variables and SAD., Results: SAD was present in 73% of the cohort. Compared with patients without SAD, adults with SAD had a higher number of severe exacerbations (65.9% versus 25.0%, p < 0.05), higher use of annual SABA canisters (median (IQR), 3 (1.75-3) versus 1 (1-2), p < 0.001), and significantly less well-controlled asthma (11.7% versus 75.0%, p < 0.001). Spirometry parameters were similar between patients with IOS-defined SAD and those without SAD. The multivariable logistic regression analysis showed that exercise-induced bronchoconstriction symptoms (EIB, odds ratio [OR] 31.18; 95%CI:4.85-365.00) and night awakenings due to asthma (OR 30.30; 95%CI:2.61-1141.00) were independent predictors of SAD, with a high predictive power of the model incorporating these baseline predictors (AUC 0.92)., Conclusions: EIB and nocturnal symptoms are strong predictors of SAD in asthmatic patients using as-needed SABA-monotherapy, helping to distinguish subjects with SAD among patients with asthma when IOS cannot be performed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Streetlamp illumination disturbs the natural physiological processes and circadian rhythms of living organisms, including photosynthesizing "citizens". The light-emitting diode (LED) technology has replaced high-pressure sodium lamps. Therefore, the effects of LED streetlamps on urban trees need to be elucidated as these new lamps have a different light spectrum (with a peak in the blue and red regions of the spectrum, i.e., highly efficient wavebands for photosynthesis) compared to older technologies. To address the above-mentioned issue, two widely utilised tree species in the urban environment, including Platanus × acerifolia (P) and Tilia platyphyllos (T), were grown with or without the effect of LED streetlamps using two realistic illumination intensities (300 and 700 μmol m -2 s -1 ). Gas exchanges and biochemical features (starch, soluble sugar, and chlorophyll content) of illuminated vs non-illuminated trees were compared during the whole vegetative season. Our results showed that both tree species were strongly influenced by LED streetlamps at physiological and biochemical levels. Specifically, the mature leaves of P and T streetlamp-illuminated trees had a lower CO 2 assimilation rate at dawn and had higher chlorophyll content, with lower starch content than controls. Our results showed that the differences between the effects of the two selected light intensities on the physiochemical attributes of P and T trees were not statistically significant, suggesting the absence of a dose-dependent effect. The most significant difference between T and P trees concerning the LED-triggered species-specific effect was that the delay in winter dormancy occurred only in P individuals. This study provided insights into the extent of LED streetlamp disturbance on trees. Our findings might raise awareness of the necessity to provide less impacting solutions to improve the wellness of trees in the urban environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Trees play a pivotal role in the urban environment alleviating the negative impacts of urbanization, and for this reason, local governments have promoted strongly tree planting policies. However, poor soil quality and neglect tree maintenance (e.g., irrigation and fertilization) can seriously mine the plant health status during the tree establishment phase. The use of biochar to provide long-lasting C to the soil and, at the same time, improving soil properties (e.g., improved water holding capacity), soil enzymes activities and NPK concentrations, is a promising research field. Therefore, with a two-step experiment, the study aimed to assay the physiological responses of a commonly used urban tree species (Tilia × europaea L.) to 1.5 % (w/w) biochar amendment (B), and secondly, to assess the ability of trees, grown in biochar amended soil, to tolerate a period of drought. Biochar amendment increased P and K availability in the soil, resulting in higher P and K concentrations in B than control leaves, according to the leaf stage. This induced B trees, higher values in both total biomass than controls (+22 %) in well-watered plants. Moreover, the higher water availability in soil amended with biochar helped B trees to tolerate water stress, with better leaf photosynthetic performances and a faster recovery than stressed controls after the re-watering. This study highlights the dual function of the biochar, improving CO 2 sequestration and soil properties, and at the same time, enhancing plant physiological responses to environmental constraints. The use of biochar at the tree planting, especially in an urban environment, is a feasible and environmentally sustainable strategy to improve the success during the tree establishment phase., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Metalloid contamination in the environment is one of the serious concerns posing threat to our ecosystems. Excess of metalloid concentrations (including antimony, arsenic, boron, selenium etc.) in soil results in their over accumulation in plant tissues, which ultimately causes phytotoxicity and their bio-magnification. So, it is very important to find some ecofriendly approaches to counter negative impacts of above mentioned metalloids on plant system. Brassinosteroids (BRs) belong to family of plant steroidal hormones, and are considered as one of the ecofriendly way to counter metalloid phytotoxicity. This phytohormone regulates the plant biology in presence of metalloids by modulating various key biological processes like cell signaling, primary and secondary metabolism, bio-molecule crosstalk and redox homeostasis. The present review explains the in-depth mechanisms of BR regulated plant responses in presence of metalloids, and provides some biotechnological aspects towards ecofriendly management of metalloid contamination., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: Ataxia-Telangiectasia Mutated (ATM) has been implicated in the risk of several cancers, but establishing a causal relationship is often challenging. Although ATM single-nucleotide polymorphisms have been linked to melanoma, few functional alleles have been identified. Therefore, ATM impact on melanoma predisposition is unclear., Methods: From 22 American, Australian, and European sites, we collected 2,104 familial, multiple primary (MPM), and sporadic melanoma cases who underwent ATM genotyping via panel, exome, or genome sequencing, and compared the allele frequency (AF) of selected ATM variants classified as loss-of-function (LOF) and variants of uncertain significance (VUS) between this cohort and the gnomAD non-Finnish European (NFE) data set., Results: LOF variants were more represented in our study cohort than in gnomAD NFE, both in all (AF = 0.005 and 0.002, OR = 2.6, 95% CI = 1.56-4.11, p < 0.01), and familial + MPM cases (AF = 0.0054 and 0.002, OR = 2.97, p < 0.01). Similarly, VUS were enriched in all (AF = 0.046 and 0.033, OR = 1.41, 95% CI = 1.6-5.09, p < 0.01) and familial + MPM cases (AF = 0.053 and 0.033, OR = 1.63, p < 0.01). In a case-control comparison of two centers that provided 1,446 controls, LOF and VUS were enriched in familial + MPM cases (p = 0.027, p = 0.018)., Conclusion: This study, describing the largest multicenter melanoma cohort investigated for ATM germline variants, supports the role of ATM as a melanoma predisposition gene, with LOF variants suggesting a moderate-risk., (© 2021. The Author(s).)

Light spectra significantly influence plant metabolism, growth and development. Here, we review the effects of monochromatic blue, red and green light compared to those of multispectral light sources on the morpho-anatomical, photosynthetic and molecular traits of herbaceous plants. Emphasis is given to the effect of light spectra on the accumulation of secondary metabolites, which are important bioactive phytochemicals that determine the nutritional quality of vegetables. Overall, blue light may promote the accumulation of phenylpropanoid-based compounds without substantially affecting plant morpho-anatomical traits compared to the effects of white light. Red light, conversely, strongly alters plant morphology and physiology compared to that under white light without showing a consistent positive effect on secondary metabolism. Due to species-specific effects and the small shifts in the spectral band within the same color that can substantially affect plant growth and metabolism, it is conceivable that monochromatic light significantly affects not only plant photosynthetic performance but also the "quality" of plants by modulating the biosynthesis of photoprotective compounds., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Iminosugars are known glycosidase inhibitors which are the subject of drug development efforts against several diseases. The access to structurally-related families of iminosugars is of primary importance for running structure-activity relationship studies. In this work, the double reductive amination (aminocyclization) reaction of a dicarbonyl derivative of the l-arabino series, in turn obtained from lactose, is reported. Different ratios of 1,6-di-deoxy-d-galacto and 1,6-di-deoxy-l-altro nojirimycin derivatives were obtained depending on the amine employed in this transformation which provided an insight into the effects of their structure on the outcome of the reaction. Of particular interest were the results obtained when two enantiomeric amino acids (d-Phe-OMe and l-Phe-OMe) were used, which resulted in the inversion of the reaction stereoselectivity., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

There is a lack of knowledge about the possibility that plants facing abiotic stressors, such as drought, have an altered perception of a pulse of O 3 and incur in alterations of their signalling network. This poses some concerns as to whether defensive strategy to cope episodic O 3 peaks in healthy plants may fail under stress. In this study, a set of saplings of two Mediterranean deciduous species, Quercus cerris and Q. pubescens, was subjected to water withholding (20% of daily evapotranspiration for 15 days) while another set was kept well-watered. Saplings were then subjected to a pulse of O 3 (200 nl l -1 for 5 h) or maintained in filtered air. Q. pubescens had a more severe decline of photosynthesis and leaf PDΨ w (about -65% and 5-fold lower than in well-watered ones) and events of cell death were observed under drought when compared to Q. cerris, which is supportive for a higher sensitivity to drought exhibited by this species. When O 3 was applied after drought, patterns of signalling compounds were altered in both species. Only in Q. pubescens, the typical O 3 -induced accumulation of apoplastic reactive oxygen species, which is the first necessary step for the activation of signalling cascade, was completely lost. In Q. cerris the most frequent changes encompassed the weakening of peaks of key signalling molecules (ethylene and salicylic acid), whereas in Q. pubescens both delayed (salicylic and jasmonic acid) or weakened (ethylene and salicylic acid) peaks were observed. This is translated to a higher ability of Q. cerris to maintain a prompt activation of defensive reaction to counteract oxidative damage due to the pollutant. Our results reveal the complexity of the signalling network in plants facing multiple stresses and highlight the need to further investigate possible alteration of defensive mechanism of tree species to predict their behavior., (Copyright © 2018. Published by Elsevier B.V.)

During the last decades research all over the world has highlighted the deleterious effects of outdoor and indoor pollution on respiratory health of adults and children. The World Health Organization (WHO) "Air quality guidelines for Europe" played a fundamental role in providing information and guidance to authorities involved in the air pollution field and they are considered the key source on which the European Commission's directive on air quality is based. Children appear to be most vulnerable to the harmful effects of outdoor pollutants, which can cause both acute exacerbations, as well as chronic respiratory symptoms and diseases. Possible mechanisms include the induction of oxidative stress, and/or allergic sensitization, as well as increased susceptibility to infections. Cigarette smoke is one of the environmental pollutant influencing morbidity and death rate in childhood as responsible for adverse health effects in both prenatal and postnatal. There is growing epidemiological evidence that indoor allergen exposure may contribute to the development of allergic respiratory symptoms. In Italy the housing and social situation, with regard to the aspects related to exposure to secondhand smoke or the presence of fungal spores, moisture linked to household vapor and poor ventilation of the rooms are problems still not completely resolved. From a medical point of view the field of pediatrics has certainly made great strides in promoting the health of children and pediatricians to have a central role for pursuing this objective., (© 2013.)

Background: Some patients diagnosed with early-stage lung cancer and treated according to standard care survive for only a short period of time, while others survive for years for reasons that are not well understood. Associations between markers of inflammation and survival from lung cancer have been observed., Materials and Methods: Here, we investigate whether circulating levels of 77 inflammatory markers are associated with long versus short survival in stage I and II lung cancer. Patients who had survived either <79 weeks (~1.5 years) (short survivors, SS) or >156 weeks (3 years) (long survivors, LS) were selected from a retrospective population-based study. Logistic regression was used to calculate adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs). The false discovery rate was calculated to adjust for multiple testing., Results: A total of 157 LS and 84 SS were included in this analysis. Thirteen markers had adjusted OR on the order of 2- to 5-fold when comparing the upper and lower quartiles with regard to the odds of short survival versus long. Chemokine CCL15 [chemokine (C-C motif) ligand 15] was the most significant marker associated with increased odds of short survival (ORs = 4.93; 95% CI 1.90-12.8; q-value: 0.042). Smoking and chronic obstructive pulmonary disease were not associated with marker levels., Conclusions: Our results provide some evidence that deregulation of inflammatory responses may play a role in the survival of early-stage lung cancer. These findings will require confirmation in future studies.

Reclamation and reuse of wastewater is one of the most effective ways to alleviate water resource scarcity. In many countries very stringent limit for chlorination by-products such as trihalomethanes has been set for wastewater reuse. Accordingly, the use of alternative oxidation/disinfection systems should be evaluated as possible alternative to chlorine. Recently ultrasound (US) was found to be effective as pre-treatment for wastewater disinfection by UV irradiation. The aim of this work is to investigate the wastewater advanced treatment by simultaneous combination of UV and US in terms of bacteria inactivation (Total coliform and Escherichia coli) at pilot-scale. The pilot plant was composed of two reactors: US-UV reactor and UV reactor. The influence of different reaction times, respective US and UV dose and synergistic effect was tested and discussed for two different kinds of municipal wastewater. An important enhancement of UV disinfection ability has been observed in presence of US, especially with wastewater characterized by low transmittance. In particular the inactivation was greater for T. coliform than for E. coli. Furthermore, the results obtained showed also that the fouling formation on the lamps was slower in US-UV reactor than in UV reactor both with and without solar radiation.

Background: Mild hypothermia confers a myocardial protective effect that may make it a useful adjunct to reperfusion therapy for myocardial infarction (MI). The effect of temperature on the extent and distribution of myocardial reperfusion injury in a collateral deficient ovine model was studied., Methods: Topical cooling maintained left atrial temperature at 39.5 degrees C (n = 8), 38.5 degrees C (n = 5), 37.5 degrees C (n = 6), 36.5 degrees C (n = 6), or 35.5 degrees C (n = 5) in sheep prior to 1 hour of coronary occlusion to produce an anteroapical myocardial risk area (AR) followed by 3 hours of reperfusion. A dual staining and planimetry technique was used to assess infarct size as a percentage of the AR in 3 myocardial short axis slices that included the entire AR (slice 1= most apical; slice 3= most basal). The subendocardial, midmyocardial, and subepicardial extent in short axis of the infarct was also assessed in each slice. Microspheres assessed transmural blood flow., Results: At 39.5 degrees C there was a long-axis gradient in myocardial injury that was most severe at the apex and lessened toward the base. The midmyocardial region was most susceptible to injury at all long axis levels. Temperature reduction (as little as 1 degrees C) was associated with improved salvage that was most pronounced in the apical subendocardium and least in the basilar midmyocardium. Reperfusion at 39.5 degrees C resulted in severe transmural microvascular injury (no-reflow) that was completely obviated at temperatures below 38.5 degrees C., Conclusions: Myocardial reperfusion injury varies over the long and short LV axes. Mild hypothermia preferentially improves myocardial salvage at the LV apex. Small temperature changes can dramatically affect microvascular integrity.

Background: Mild hypothermia (< 4 degrees C) improves myocardial salvage after infarct reperfusion in animals and in early clinical studies. In this experiment the effect of mild hypothermia during ischemia and early reperfusion on long-term postinfarction left ventricular (LV) remodeling was assessed in an ovine infarct model., Methods: In the initial phase of the experiment the effect of progressive degrees of hypothermia on infarct size was quantified. Thirty-eight male sheep were subjected to 1 hour of ischemia using a standardized anteroapical infarct followed by 3 hours of reperfusion. Temperature was maintained at either 39.5 degrees C (n = 11), 38.5 degrees C (n = 7), 37.5 degrees C (n = 7), 36.5 degrees C (n = 7), or 35.5 degrees C (n = 6) for the entire period of ischemia and reperfusion. The area at risk (AR) and infarct size as a percentage of AR (I/AR) were determined with a double staining and planimetry technique. In the second phase of the study, chronic post-infarction remodeling was assessed in animals with nonreperfused infarcts (n = 6), 1 hour of ischemia followed by reperfusion at 39.5 degrees C (n = 6) and 1 hour of ischemia followed by reperfusion at 37.5 degrees C (n = 6). Remodeling was determined at 8 weeks after infarction using echocardiography., Results: The I/AR in the 39.5 degrees C, 38.5 degrees C, 37.5 degrees C, 36.5 degrees C, and the 35.5 degrees C groups was 71.8 +/- 3.0%, 63.1 +/- 1.9%, 49.4 +/- 1.4%, 38.7 +/- 1.4%, and 21.7 +/- 2.2%, respectively (p < 0.05 between all groups). In the chronic study LV end systolic volume at 8 weeks after infarction was 81 +/- 8 mL in the nonreperfused group, 57 +/- 4 mL in the 39.5 degrees C reperfusion group, and 41 +/- 3 mL in the 37.5 degrees C reperfusion group (p < 0.05 for between group differences)., Conclusions: Subtle degrees of hypothermia can significantly improve immediate myocardial salvage and long-term LV remodeling after infarct reperfusion.

Background: Hypothermia during ischemia has been shown to reduce myocardial reperfusion injury. We sought to establish the cardioprotective effect of very mild total-body hypothermia (

Background: Reperfusion therapy for myocardial infarction is currently the most effective means for limiting early and late mortality. We sought to elucidate how reperfusion influences remodeling strains in the infarct, borderzone, and remote myocardial regions. Understanding the effects of reperfusion on regional remodeling will help to evaluate and optimize emerging treatments for patients who do not achieve effective reperfusion after myocardial infarction., Methods: An ovine infarct model (n = 13) was used to assess the effect of 1 hour of ischemia followed by reperfusion on regional and global myocardial geometry, function, and perfusion using sonomicrometry, echocardiography, and microspheres. Thirteen additional animals were assessed chronically (8 weeks) with echocardiography and postmortem analysis after either reperfusion (n = 5) or untreated infarction (n = 8)., Results: During ischemia the area at risk thinned, stretched, and became dyskinetic. The normally perfused borderzone also stretched, and contraction decreased by 40% during ischemia. Reperfusion increased area at risk wall thickness and reduced area at risk stretching but did not restore contractile function. Borderzone stretching was reduced and contractile function improved by reperfusion. Contractile function of remote regions was also improved with reperfusion. Ventricular dilatation after ischemia was reversed within 180 minutes of reperfusion. Chronically, reperfusion significantly improved global remodeling when compared with nonreperfused controls. Reperfused animals had thicker infarcts and akinetic rather than dyskinetic apical segments., Conclusions: Reperfusion acutely increases area at risk wall thickness, reduces area at risk and borderzone stretching, and improves borderzone and remote function. Reperfusion increases mature scar thickness and improves chronic global remodeling. These beneficial effects of reperfusion result primarily from reduced infarct expansion (stretching).

Background: Ischemic mitral regurgitation results from a variable combination of annular dilatation and remodeling of the subvalvular apparatus. Current surgical techniques effectively treat annular dilatation, but methods for addressing subvalvular remodeling have not been standardized. An effective technique for determining the extent of subvalvular remodeling could improve surgical results by identifying patients who are unlikely to benefit from annuloplasty alone., Methods: A well-characterized ovine model of ischemic mitral regurgitation was used. Real-time three-dimensional echocardiography was performed on each animal at baseline and at 1 hour and 8 weeks after infarction. Multiple valvular geometric measurements were calculated at each time point., Results: Immediate and long-term changes in mitral valvular geometry were observed. Annular height-to-commissural width ratio decreased from 20.0% +/- 1.6% to 11.2% +/- 0.9% 1 hour after infarction (p < 0.001) and to 9.4% +/- 0.4% 8 weeks after infarction (p < 0.001), whereas mitral annular area increased from 8.1 +/- 0.3 cm2 to 9.2 +/- 0.4 cm2 (p < 0.05) and then to 10.5 +/- 0.6 cm2 (p < 0.05). Maximum mitral valve tenting area increased from 49.7 +/- 5.1 mm2 to 58.6 +/- 4.2 mm2 (p < 0.05) and then to 106.4 +/- 3.9 mm2 (p < 0.001), whereas mitral valve tenting volume increased from 679.0 +/- 75.5 mm3 to 828.6 +/- 102.4 mm3 (p = 0.050) and then to 1530.5 +/- 97.8 mm3 (p < 0.001). The mitral valve tenting index increased from 0.83 +/- 0.08 mm to 0.88 +/- 0.08 mm (p > 0.05) and then to 1.46 +/- 0.08 mm (p < 0.001)., Conclusions: We have described a technique that uses real-time three-dimensional echocardiography to perform a comprehensive assessment of leaflet tethering on the entire mitral valve. Our methodology is not influenced by viewing plane selection, regional tenting asymmetry, or annular dilatation and therefore represents a potentially useful, clinically relevant, and consistent measure of subvalvular remodeling.

Background: The mammalian mitral annulus is saddle shaped. Experimental studies have shown that loss of saddle shape occurs in ischemic mitral regurgitation. However, neither the temporal pattern of global annular remodeling nor the geometric pattern of regional annular remodeling has been described. We sought to characterize these changes using real-time three-dimensional echocardiography in an ovine model., Methods: Ten sheep underwent real-time three-dimensional echocardiography at baseline and 1 hour and 8 weeks after posterobasal myocardial infarction. Multiple mitral annular geometric indexes were measured at each time point to assess regional and global annular remodeling., Results: One hour after infarction, global annular height decreased from 5.8 +/- 0.5 mm to 4.0 +/- 0.4 mm (p < 0.001) while intercommissural width increased from 29.0 +/- 1.3 mm to 35.7 +/- 1.7 mm (p = 0.023), resulting in a decrease in the global annular height to commissural width ratio from 20.0% +/- 1.6% to 11.2% +/- 0.9% (p < 0.001). Eight weeks after infarction, global annular height decreased to 3.9 +/- 0.2 mm (p < 0.05) while intercommissural width increased to 40.7 +/- 1.5 mm (p < 0.001), resulting in an additional decrease in the global annular height to commissural width ratio to 9.4% +/- 0.4% (p < 0.001). Although annular remodeling involved the entire mitral annulus, there was regional heterogeneity in its extent., Conclusions: Significant global annular flattening and dilatation occur during the development of ischemic mitral regurgitation in an ovine model. Regional annular remodeling is heterogeneous and is not limited the posterior commissure or the posterior annulus.

A new preparation of D-xylo-hexos-4-ulose (1) and of its 3-m-chlorobenzoate (2) has been devised using the epoxidation of 3-deoxy-1,2:5,6-di-O-isopropylidene-D-erythro-hex-3-enofuranose (6) as the key step. The epoxidation of 6 in CH2Cl2 furnished with high yield 1,2:5,6-di-O-isopropylidene-3-O-m-chlorobenzoyl-4-C-hydroxy-D-xylo-hexos-4-ulo-1,4-furanose as a mixture of C-4 hemiacetal anomers (7a,b), which, on acid hydrolysis, gave a tautomeric mixture of 3-O-m-chlorobenzoyl-D-xylo-hexos-4-ulose (2) with an overall 60% yield from 6. The formation of 4-C-methoxy-diacetone-D-glucose derivatives (11a,b) through epoxidation-methanolysis of 6, took place with reduced yield because of the competition between m-chlorobenzoic acid (MCBA) and methanol to the opening by attack at C-4 of the intermediate epoxide and the formation of acyclic products arising from the alternative nucleophilic attack at C-1. Acid hydrolysis of derivatives 11 gave D-xylo-hexos-4-ulose (1) with a 35% overall yield from 6. NMR analysis showed that 2 is composed, in CD3CN, mainly by a 7:3 mixture of 4-keto-alpha- and beta-pyranose forms, while 1, in D2O, is present as a more complex mixture constituted mainly by 4-keto-alpha- and beta-pyranoses and their respective hydrates in a 17:15:34:34 ratio.

The synthesis and biological evaluation of some new glycose esters bearing the 1,2-O-isopropylidene-d-hexofuranose functionality and belonging to the 3-O-acyl-d-allose and 6-O-acyl-d-glucose series are reported. When the results concerning cell growth inhibition are compared, it appears that the 6-O-acyl-d-glucose derivatives are more active than the 3-O-acyl-d-allose compounds. Within both 6-O-acyl-d-glucose and 3-O-acyl-d-allose derivatives, butyric esters displayed the highest inhibitory effects. Inhibition of cell growth is not associated with high induction levels of erythroid differentiation, despite the fact that pivaloates induce erythroid differentiation to an extent similar to that exhibited by previously reported molecules [Bioorg. Med. Chem. Lett.1999, 9, 3153-3158].

Background: Regional myocardial geometry, function, and perfusion status are critical variables for understanding infarction-induced left ventricle (LV) remodeling. Three-dimensional contrast echocardiography (3DCE) is uniquely suited to measure these parameters. We evaluate the ability of 3DCE to assess geometric changes in the normally perfused but hypocontractile borderzone myocardium (BZM) immediately after a myocardial infarction (MI) in an ovine model, and we compare 3DCE with two-dimensional contrast echocardiography (2DCE) in the long and short axis., Methods: Four sheep were studied with 3DCE and 4 were studied using 2DCE, before and 30 minutes after an anteroapical MI. Each 3DCE data set was acquired over 18 consecutive cardiac cycles. The LV geometry was reconstructed and perfusion data spatially correlated, thereby constituting a 3D model of ventricular geometry and perfusion. The borderzone was defined as the contrast-perfused myocardium adjacent to the infarct., Results: The 2DCE short-axis analysis demonstrated decreased curvature and decreased wall thickness in the borderzone after MI. These findings are consistent with increased BZM wall stress. However, the long-axis 2DCE analysis demonstrated increased BZM wall thickness and a surprising change in BZM concavity acutely after infarction. The 3DCE analysis confirmed these findings and added additional information regarding regional variability in BZM geometry that was not evident in the two orthogonal 2D views., Conclusions: This study provides evidence that regional changes in BZM geometry are more complex than previously believed and are not necessarily indicative of increased regional stress. The superiority of 3DCE over 2DCE for assessing these changes is strongly supported.

Background: Early infarct expansion impairs function of normally perfused borderzone myocardium (BZM), initiates adverse remodeling, and portends a poor long-term outcome. Early ventricular restraint has been demonstrated to improve global remodeling but its effect on BZM function has not been assessed. Using an ovine model of infarct induced remodeling and MRI, we tested the hypothesis that ventricular restraint early after MI preserves BZM function and reduces remodeling., Methods: Six sheep had a large anterior infarction after ligation of all diagonal branches. One week after infarction 3 sheep had placement of a cardiac support device (CSD) to restrain infarct expansion. Global remodeling and borderzone wall thickening strain were assessed using tagged MRI before and 8 weeks after infarction., Results: Global remodeling was greatly reduced in the CSD group compared with control. The BZM systolic wall thickening was similar in both groups at baseline (13.5% +/- 2.0%, control; 12.8% +/- 2.0%, CSD, p = 0.8). After 8 weeks of infarction-induced remodeling, systolic wall thickening strain decreased significantly to 4.9% +/- 0.7% in the control group (p = 0.03). In contrast, systolic wall thickening was preserved in the CSD group at 8 weeks (11.0% +/- 1.6%, p = 0.3). In the control group all thickening occurred during isovolemic contraction, plateauing during ejection. The CSD improved late systolic borderzone wall thickening, although dynamics remained perturbed., Conclusions: Ventricular restraint early after MI improves both contractile function of the BZM and global ventricular remodeling. The dynamics of BZM wall thickening are impaired during remodeling. The CSD significantly improves but does not completely maintain baseline BZM wall thickening dynamics.

Background: A body surface area (BSA) of 1.7 m2 was considered as the lower limit to implant a CardioWest Total Artificial Heart (TAH). We reviewed our experience with the TAH in patients with a BSA of less than 1.7 m2., Methods: From April 1986 to May 2003, among 149 patients implanted with a TAH in our institution, 30 had a BSA of less than 1.7 m2 (Group I). Results were compared with the remaining 119 patients (Group II)., Results: One patient in Group I experienced a fitting problem and was left with the chest open. Otherwise, in this group, the Day 1 cardiac index averaged 3.6 +/- 0.6 liter/min/m2, which was significantly higher than the 2.8 +/- 0.36 liter/min/m2 observed in Group II. Post-implantation central venous pressure and mean arterial pressure were similar in both groups: 14.7 +/- 3.8 mm Hg vs 14.5 +/- 4 mm Hg and 87 +/- 23 mm Hg vs 88 +/- 19 mm Hg, respectively. In Group I, survival on the device dramatically increased from 9% before 1992, to 36% between 1992 and 1997 and finally reached 75% after then. In the meantime, for the same time periods, global survival to hospital discharge increased from 9% to 36% and reached 50% after 1997. In Group II, global survival to hospital discharge was 25.5% before 1992, 34.6% between 1993 and 1997, and reached 52% thereafter., Conclusion: The CardioWest TAH can be used in patients with a BSA between 1.5 m2 and 1.7 m2 with few fitting problems. In this group of patients, results are similar to those obtained in patients with a BSA greater than 1.8 m2.

Background: Early infarct expansion initiates adverse remodeling, leads to left ventricular dilatation and portends a poor long-term outcome. Early mechanical prevention of infarct expansion has been proposed as a method to improve remodeling, but the extent of ventricular restraint necessary to optimize the salutary effect is not known. We tested the hypothesis that left ventricular restraint (wrap) is superior to infarct stiffening (patch)., Methods: Infarction of 20% to 25% of the left ventricle was induced by coronary ligation in 69 sheep. Infarcts were either anteroapical (n = 33) or posterobasal (n = 36). Animals with each infarct received either no treatment (anteroapical, n = 26; posterobasal, n = 17), infarct stiffening with a localized Marlex mesh patch (posterobasal, n = 9) or left ventricular wrapping with Merseline mesh (anteroapical, n = 7; posterobasal, n = 10). End-systolic volume, end-diastolic volume, end-systolic muscle to cavity area ratio, left ventricular sphericity, ejection fraction, and degree of mitral regurgitation as determined by quantitative echocardiography were assessed before infarction and at 2, 5, and 8 weeks after infarction to evaluate the extent of left ventricular remodeling., Results: Control animals in both groups experienced adverse remodeling. Anteroapical infarct animals developed large left ventricular aneurysms and the posterobasal infarct animals developed severe mitral regurgitation. Early infarct stiffening did not significantly improve any aspect of remodeling due to the posterobasal infarct. Early left ventricular wrapping significantly improved remodeling after both types of infarctions., Conclusions: Early left ventricular wrapping attenuates infarct expansion and has a salutary effect on remodeling. Simple infarct stiffening alone is not effective.

Background: The anterior mitral annulus is considered a fixed structure. Recent data suggest otherwise. This study tested the hypothesis that the size of the anterior annulus varies with hemodynamic loading and ventricular contractility., Methods: Sonomicrometry array localization measured annular area, total annular circumference, anterior circumference, and posterior circumference in 6 sheep before and after neosynephrine increased systolic blood pressure by at least 150% during atrial pacing at 120 beats/min. In 6 additional animals the same dimensions were measured during atrial pacing (at 120 and 150 beats/min) and during isoproteronol infusions to increase heart rate to 120 and 150 beats/min., Results: Neosynephrine increased systolic total annular circumference from 99.7 +/- 5.5 mm to 106.9 +/- 9.6 mm. Anterior circumference increased from 40.8 +/- 4.0 mm to 45.3 +/- 5.7 mm whereas posterior circumference only increased from 59.0 +/- 5.5 mm to 61.6 +/- 7.0 mm. Low isoproteronol infusion decreased systolic total annular circumference from 107.5 +/- 8.3 mm to 101.9 +/- 10.6 mm. Most of this change occurred in the posterior circumference. Higher infusions of isoproteronol decreased total annular circumference from 106.8 +/- 8.3 mm to 98.3 +/- 9.7 mm. At this higher inotropic state the decrease in annular size was similar in the anterior and posterior annulus., Conclusions: In sheep, the anterior annulus is a dynamic structure that varies in size in response to changes in hemodynamic loading and ventricular contractility.

Background: Propofol-anaesthesia administrated via target-controlled infusion (TCI) has been proposed for cardiac surgery. Age-related changes in pharmacology explain why propofol dose requirement is reduced in elderly patients. However, the Marsh pharmacokinetic model incorporated in the Diprifusor propofol device does not take age into account as a covariable. In the absence of depth of anaesthesia monitoring, this limitation could cause adverse cardiovascular effects resulting from propofol overdose in older patients. We assessed the influence of age on effect-site propofol concentrations predicted by the Diprifusor and titrated to the bispectral index score (BIS) during cardiac anaesthesia., Methods: Forty-five patients received propofol by Diprifusor and remifentanil by software including Minto model. Propofol and remifentanil effect-site concentrations were adapted to BIS (40-60) and haemodynamic profile, respectively. The influence of age on effect-site concentrations was assessed by dividing patients into two groups: young (<65 yr) and elderly (> or =65 yr)., Results: For a similar depth of anaesthesia, effect-site propofol concentrations were significantly lower in elderly patients at the different stages of cardiac surgery. The mean dose of propofol required to perform tracheal intubation was significantly lower in elderly patients. However, the overall doses of propofol were comparable in both groups. Neither effect-site remifentanil concentrations nor overall doses of remifentanil were significantly different between the two groups., Conclusions: In cardiac anaesthesia, target concentrations of propofol must be reduced in elderly patients. Although this probably contributes to improving intraoperative haemodynamic stability, the absence of decrease in overall dose requirement of propofol suggests that this adjustment is relatively moderate.

Objective: To determine perioperative variables for predicting allogenic transfusion in adult cardiac surgery., Study Design: Prospective study., Patients: We included 335 consecutive patients undergoing cardiac surgery between February and April 2001., Methods: Perioperative variables were prospectively collected in a database. For each patient who received transfusion, hemoglobin threshold for transfusion and total number of units of red cell concentrates were collected. Univariate and multivariate analysis were performed., Results: The two strategies for blood conservation which were predominantly used were aprotinin therapy (78%) and blood salvage from the extracorporeal circuit (68%). During perioperative period, 42% of patients [95% CI: 37-47%] received allogenic transfusion. The haemoglobin threshold for transfusion was 7.4 +/- 1.1 and 8.0 +/- 0.7 g x dl(-1) in operating room and in intensive care unit, respectively. On average, 3.4 +/- 2.7 units of red cell concentrates were transfused perioperatively per patient. Using multivariate analysis, perioperative allogenic transfusion was significantly associated with the following variables: preoperative haemoglobin level < 12 g x dl(-1) (odds ratio 8.9; p = 0.001), emergency procedure (odds = 3.7, p = 0.01), reoperation (odds ratio = 3.3; p = 0.002), chronic obstructive pulmonary disease (odds ratio = 2.5; p = 0.03) and complex surgery (odds ratio = 2.4; p = 0.01). The age, the gender, and body mass index were only independent risk factors by univariate analysis., Conclusion: In despite of techniques to limit requirement of allogenic transfusion, a large proportion of cardiac surgical patients remains transfused. Independent risk factors of perioperative transfusion are haemoglobin level < 12 g x dl(-1), emergency procedure, reoperation, chronic obstructive pulmonary disease and complex surgery.

The main cause of death and long-term disability of patients undergoing carotid artery surgery is coronary artery disease. To identify the prognostic value of the status of the contralateral artery, we studied the course of 224 consecutive patients in whom one or both carotid arteries were operated on at our institution between 1985 and 1995. The 224 patients were divided into three groups: group I (n = 56) had an occluded contralateral carotid artery, in group II (n = 56) both carotids were operated on, and group III (n = 112) had a normal contralateral carotid artery. The clinical status of all patients except one was ascertained by one of us. We found that the status of the contralateral artery does not influence the long-term prognosis of patients undergoing carotid artery surgery. A periodic cardiological and vascular follow-up of these patients seems warranted to improve their survival.

Objective: To investigate whether the systemic antibody response to Helicobacter pylori heat shock protein B can be considered, in addition to anti cytotoxin-associated protein [CagA) antibody determination, a further serological marker of increased risk of gastric cancer development., Methods: A total of 98 Giemsa positive Helicobacter pylori patients (28 with gastric cancer, 30 with duodenal ulcer and 40 with nonulcer dyspepsia) were studied. Serum samples obtained from all patients were tested for IgG antibodies to CagA (116 kDa), VacA [89kDa) and heat skock protein B (54 kDa) antigens of Helicobacter pylori by the Western blot technique., Results: 26/28 patients [(92.9% with gastric carcinoma, 29/30 patients [96.7%) with duodenal ulcer and 30/40 patients (75.0%) with non-ulcer dyspepsia were seropositive for CagA protein. The prevalence of serum IgG antibody to CagA in the cancer patients was not significantly higher than in duodenal ulcer and non-ulcer dyspepsia patients. The prevalence of antibodies to VacA was not significantly different between gastric carcinoma and non-ulcer dyspepsia patients. In contrast the prevalence of systemic antibodies to heat skock protein B was significantly higher in gastric cancer patients (78.6%) than in duodenal ulcer (36.7%, p=0.002) or nonulcer dyspepsia patients (52.5%, p=0.029)., Conclusions: The detection of antibodies to heat shock protein B is proposed as an additional test which, in association with the determination of serum antibodies to CagA, could help in determining the risk of developing severe gastroduodenal disease, and gastric cancer, in particular.

(R)-3-(1-[2-(4-benzoyl-2-(3,4-difluorophenyl)-morpholin-2-yl)- ethyl]-4-phenylpiperidin-4-yl)-1-dimethylurea (SR 144190) is a new non-peptide antagonist of tachykinin NK2 receptors. SR 144190 potently and selectively inhibited neurokinin A binding to NK2 receptors from various species, including humans. In in vitro functional assays, it was a potent, selective and competitive antagonist of NK2 receptors with apparent affinities (pA2 values) between 9.08 and 10.10. In vivo, SR 144190 blocked [Nle10]neurokinin A-(4-10)-induced bronchoconstriction in guinea pigs (ID50 = 21 micrograms kg-1 i.v. and 250 micrograms kg-1 i.d.) and [beta Ala8]neurokinin A-(4-10)-induced urinary bladder contraction in rats (ID50 = 11 micrograms kg-1 i.v. and 190 micrograms kg-1 i.d.). It prevented citric acid-induced cough and airway hyperresponsiveness to acetylcholine in guinea pigs (1 mg kg-1 i.p.) as well as castor oil-induced diarrhoea in rats (0.01-10 micrograms kg-1 s.c. or p.o). Finally, it blocked the turning behaviour induced by intrastriatal injections of [Nle10]neurokinin A-(4-10) in mice (ID50 = 3 micrograms kg-1 i.v. and 16 micrograms kg-1 p.o.).

We investigated the putative common nature of the rat atypical beta-adrenoceptors mediating white adipocyte lipolysis and proximal colon motility inhibition, using the non-selective antagonist alprenolol and agonist isoprenaline and the selective agonists SR 58611A and BRL 37344. Results in either isolated intestinal and fat tissues were consistent with: isoprenaline acting through both typical (beta 1, beta 2) and typical beta-adrenoceptors; SR 58611A and BRL 37344 acting solely through the latter. The identical pA2 values obtained with alprenolol, irrespective of the tissue and the selective agonist (SR 58611A or BRL 37344) used, support the high functional homology of the atypical beta-adrenoceptors in rat colon and adipocytes.

Nalorphine, levallorphan and their quaternary analogs, N-(eq)allyl derivatives of the two diastereoisomers at the nitrogen atom (N-methyl nalorphine and N-methyl levallorphan) were tested for their peripheral selectivity. We compared their relative ability to prevent morphine-induced (5 mg/kg i.v.) antinociception (central antagonism) and constipation (peripheral antagonism) in the same rats. Nalorphine and levallorphan reduced morphine-induced antinociception to half maximal response at doses of 5.1 and 0.89 mg/kg s.c. and restored the intestinal transit to 50% of controls (AD50) respectively at doses of 0.25 and 0.12 mg/kg. N-methyl nalorphine up to 24 and N-methyl levallorphan up to 30 mg/kg given s.c. 10 min before morphine did not antagonize narcotic-induced antinociception, fully preventing constipation (AD50 0.65 and 0.32 mg/kg respectively), but when injected 50 min before morphine they partially lost their antagonist potency (AD50 2.3 and 2.6 mg/kg respectively) and peripheral selectivity. N-methyl nalorphine and N-methyl levallorphan thus seem more peripherally selective than their tertiary analogs and more potent than quaternary narcotic antagonists tested to date.