Stimuli-responsive NLO properties of tetrathiafulvalene-fused donor-acceptor chromophores.

The second-order nonlinear optical (NLO) properties of two tetrathiafulvalene (TTF)-fused electron donor-acceptor dyads have been determined using the Electric Field Induced Second Harmonic generation (EFISH) technique and theoretically rationalized. Dyads TTF-dppz (1) and TTF-BTD (2) were obtained by direct fusion of a TTF electron donor unit either with a dipyrido[3,2-a:2',3'-c]phenazine (dppz) or a benzothiadiazole (BTD) electron acceptor moiety. Dyad 1 acts as a reversible acido-triggered NLO switch by protonation/deprotonation at two nitrogen atoms of the dppz acceptor moiety induced by sequential exposure to HCl and ammonia vapors. Dyad 2, on the other hand, displays redox-tunable NLO properties upon two consecutive oxidations to its radical cation 2+˙ and dication 22+ species. The resulting final dication 22+ exhibits an inversion of the sign of ß0, due to a completely inverted distribution of the frontier molecular orbitals with respect to those of its neutral species, leading to a scarcely polar species in the excited state, as indicated by the theoretical calculations.

Preserved cardiorespiratory function and NT-proBNP levels before and during exercise in patients with recent onset of rheumatoid arthritis: the clinical challenge of stratifying the patient cardiovascular risks.

Rheumatoid arthritis (RA) is associated with an increased risk of myocardial infarction and congestive heart failure. In RA patients, elevated NT-proBNP levels have been reported to be a prognostic marker of left ventricular dysfunction. In this study, we evaluated cardiorespiratory functional capacity and NT-proBNP levels before and during cardiopulmonary exercise test in early RA (ERA) patients. Twenty ERA patients and 10 healthy controls were studied by color Doppler echocardiography to evaluate ventricular systolic and diastolic function. Arterial stiffness and wave reflections were quantified non-invasively using applanation tonometry of the radial artery. Cardiopulmonary treadmill test was performed to measure peak VO2 and VE/VCO2 parameters. NT-proBNP plasma levels were measured before and at the exercise peak during cardiopulmonary exercise. The peak oxygen uptake [VO2 (ml/min/kg)], the ventilatory equivalents for carbon dioxide (EqCO2), respiratory exchange ratio and arterial stiffness were similar between patients and controls during cardiopulmonary exercise test. Basal and peak cardiopulmonary exercise NT-proBNP plasma levels were comparable in ERA patients with respect to healthy controls. When we analyzed patients according to disease characteristics and cardiovascular risk factors, ERA patients with high disease activity, BMI > 25 kg/m2 and ACPA positivity presented significantly higher baseline and exercise peak NT-proBNP levels. Cardiorespiratory function is preserved in patients with recent onset of rheumatoid arthritis. The increased basal and exercise peak NT-proBNP plasma levels in patients with negative disease prognostic factors represent a possible marker to stratify the cardiovascular risk in patients with early rheumatoid arthritis.

Long-living optical gain induced by solvent viscosity in a push-pull molecule.

The combination of continuum and ultrafast pump-probe spectroscopy with DFT and TDDFT calculations, in viscous and non-viscous environments, is effective in unraveling important features of the twisted intramolecular charge transfer mechanism in a new push-pull molecule that possesses aggregation induced emission properties. Long-living optical gain is found when this mechanism is inhibited, highlighting the importance of the environment rigidity in the design of materials for photonic applications.

PTCH1 gene haplotype association with basal cell carcinoma after transplantation.

BACKGROUND: Basal cell carcinoma (BCC) is 10 times more frequent in organ transplant recipients (OTRs) than in the general population. Factors in OTRs conferring increased susceptibility to BCC include ultraviolet radiation exposure, immunosuppression, viral infections such as human papillomavirus, phototype and genetic predisposition. The PTCH1 gene is a negative regulator of the hedgehog pathway, that provides mitogenic signals to basal cells in skin. PTCH1 gene mutations cause naevoid BCC syndrome, and contribute to the development of sporadic BCC and other types of cancers. Associations have been reported between PTCH1 polymorphisms and BCC susceptibility in nontransplanted individuals. OBJECTIVES: To search for novel common polymorphisms in the proximal 5' regulatory region upstream of PTCH1 gene exon 1B, and to investigate the possible association of PTCH1 polymorphisms and haplotypes with BCC risk after organ transplantation. METHODS: Three PTCH1 single nucleotide polymorphisms (rs2297086, rs2066836 and rs357564) were analysed by restriction fragment length polymorphism analysis in 161 northern Italian OTRs (56 BCC cases and 105 controls). Two regions of the PTCH1 gene promoter were screened by heteroduplex analysis in 30 cases and 30 controls. RESULTS: Single locus analysis showed no significant association. Haplotype T(1686)-T(3944) appeared to confer a significantly higher risk for BCC development (odds ratio 2.98, 95% confidence interval 2.55-3.48; P = 0.001). Two novel rare polymorphisms were identified at positions 176 and 179 of the 5'UTR. Two novel alleles of the -4 (CGG)(n) microsatellite were identified. No association of this microsatellite with BCC was observed. CONCLUSIONS: Haplotypes containing T(1686)-T(3944) alleles were shown to be associated with an increased BCC risk in our study population. These data appear to be of great interest for further investigations in a larger group of transplant individuals. Our results do not support the hypothesis that common polymorphisms in the proximal 5' regulatory region of the PTCH1 gene could represent an important risk factor for BCC after organ transplantation.

Emergency use of wearable left ventricular assist devices in patients not eligible for heart transplantation.

BACKGROUND: We reviewed our experience concerning the clinical outcomes of emergency implantation of left ventricular assist devices (LVAD) in patients not eligible for heart transplantation (HTX). PATIENTS AND METHODS: Between January 1998 and September 2006, 62 patients were referred for emergency HTX including 35 (55%) who received cardiac allografts; 9 (14%) died on the waiting list. The other 18 subjects (31%) did not meet listing criteria due to pulmonary hypertension with massive transpulmonary gradients (TPG), severe diabetes, or another factor; 7 patients had wearable LVAD implants and the remaining 11 who had contraindications both to HTX and to LVAD implantation remained on medical therapy. RESULTS: Twelve month actuarial survivals were 47% in LVAD G1 vs 1% in medical therapy G2 (P< .005). Four G1 patients died either due to cerebrovascular vascular episodes or to thromboembolic events. The beneficial use of LVAD in 3 patients led to consistent improvement in hemodynamic performance allowing listing for HTX. Two of them have been successfully transplanted; 1 is still waiting. Due to refractory heart failure, 90% of G2 died within the first months after evaluation. CONCLUSION: Our limited experience indicated that emergency use of LVAD ensued a satisfactory outcome allowing better actuarial survival.

Role of cooperativity in protein folding and protein mosaic assemblage relevance for protein conformational diseases.

Biological systems are organized in intricate and highly structured networks with hierarchies and multiple scales. Cells can be considered as "meso-scale level" systems placed between the "macro-scale level" (systems of cellular networks) and the "micro-scale level" (systems of molecular networks). In fact, cells represent complex biochemical machineries made by networks of molecules connected by biochemical reactions. Thus, the brain should be studied as a system of "networks of networks". Recently, the existence of a Global Molecular Network (GMN) enmeshing the entire CNS was proposed. This proposal is based on the evidence that the extra-cellular matrix is a dynamic molecular structure capable of storing and releasing signals and of interacting with receptors and proteins on the cell membranes. Proteins have a special role in molecular networks since they can be assembled into high-order molecular complexes, which have been defined as Protein Mosaics (PM). Protein monomers in a PM (the "tesserae" of the mosaic) can interact via classical and non-classical cooperativity behaviour involving allosteric interactions. In the present paper, new features of allostery and cooperativity for protein folding, assemblage and topological features of PM will be discussed. Against this background, alterations in PM via allosteric modulations and non-classical cooperativity mechanisms may lead to protein aggregates like beta amyloid fibrils. Such aggregates cause pathological changes in the GMN structure and function leading to neurodegenerative diseases such as Alzheimer's disease. Thus, a novel view of the so called Protein Conformational Diseases (PCD) is proposed.

Heart transplantation in older candidates.

UNLABELLED: Over the last few years significant changes have occurred in both donor and recipient profiles for heart transplantation (HTX). New therapeutic approaches to chronic heart failure have created a novel class of patients aged between 61 and 70 years. Although they are older than the conventional upper limit, they may undergo HTX using marginal donors. We retrospectively reviewed the outcomes of suboptimal donor implants in older recipients to examine negative prognostic factor. METHODS: Among 272 patients who underwent HTX at our institution from May 1994 to December 2005, 75 (26.5%) were 61 to 72 years (group 1). The remaining 197 (73.5%) denoted as group 2 ranged in age from 18 to 60 years. The Sex distribution, cause of end-stage heart failure, preoperative pulmonary hypertension, pre-HTX clinical status and mean follow-up did not show any significant difference between the two groups. However, group 1 patients had their organs retrieved from marginal donors (89%) vs group 2 (29%; P < .005). They were deceased mainly due to cerebrovascular events, (namely, 82% vs 27%, respectively, P < .005). RESULTS: All analyzed variables-actuarial survival, perioperative mortality, 12-month acute rejection freedom, 100-month chronic rejection freedom, infection freedom, neoplasia freedom, chronic renal failure freedom-did not show any significant difference. CONCLUSION: Advances in chronic heart failure medical therapy have generated a new class of HTX candidates aged between 61 and 70 years who benefitted from transplantation of organs retrieved from suboptimal donors.

Cyclometalated Pt(ii) complexes with a bidentate Schiff-base ligand displaying unexpected cis/trans isomerism: synthesis, structures and electronic properties.

Square planar platinum complexes are an important class of compounds used in (nano)technology, optoelectronics, medicinal chemistry and catalysis. The major research interests in cyclometalated Pt(ii) complexes focus on the selective modulation of their electronic properties and the control of the (cis/trans) geometry. For the first time, we unveil and demonstrate that cis-trans isomers of Pt(ii) complexes can be obtained in a derivative carrying the 1-phenyl-pirazolate (Hppz) and 2-hydroxy-1-naphtyl-(N-phenyl)imine ligands. The two isomers display significant differences in both optical and electronic properties. While luminescence is quenched in solution, they are brightly emissive in the PMMA matrix at room temperature and in the 2MeTHF rigid matrix at 77 K. The phosphorescent emission of the cis isomer, blue-shifted compared to that of the trans one, results from the significantly different trans influence of the ppz ligand. Theoretical investigation highlights the almost isoenergetic potential energy of the two isomers therefore explaining their formation and evidences a large geometry distortion of their triplet state, which should be responsible for the observed luminescence efficiency.

WITHDRAWN: Prognostic Value of Pharmacologic Stress Echocardiography in Diabetic Patients.

The publisher regrets that this was an accidental duplication of an article that has already been published in Eur. J. Echocardiogr., 4 (2003) 202-208, . The duplicate article has therefore been withdrawn.

Chromosomal aberrations in lymphocytes predict human cancer independently of exposure to carcinogens. European Study Group on Cytogenetic Biomarkers and Health.

An increased risk of cancer in healthy individuals with high levels of chromosomal aberrations (CAs) in peripheral blood lymphocytes has been described in recent epidemiological studies. This association did not appear to be modified by sex, age, country, or time since CA test, whereas the role played by exposure to carcinogens is still uncertain because of the requisite information concerning occupation and lifestyle was lacking. We evaluated in the present study whether CAs predicted cancer because they were the result of past exposure to carcinogens or because they were an intermediate end point in the pathway leading to disease. A nested case-control study was performed on 93 incident cancer cases and 62 deceased cancer cases coming from two prospective cohort studies performed in Nordic countries (Denmark, Finland, Norway, and Sweden) and Italy. For each case, four controls matched by country, sex, year of birth, and year of CA test were randomly selected. Occupational exposure and smoking habit were assessed by a collaborative group of occupational hygienists. Logistic regression models indicated a statistically significant increase in risk for subjects with a high level of CAs compared to those with a low level in the Nordic cohort (odds ratio, 2.35; 95% confidence interval, 1.31-4.23) and in the Italian cohort (odds ratio, 2.66; 95% confidence interval, 1.26-5.62). These estimates were not affected by the inclusion of occupational exposure level and smoking habit in the regression model. The risk for high versus low levels of CAs was similar in subjects heavily exposed to carcinogens and in those who had never, to their knowledge, been exposed to any major carcinogenic agent during their lifetime, supporting the idea that chromosome damage itself is involved in the pathway to cancer. The results have important ramifications for the understanding of the role played by sporadic chromosome damage for the origin of neoplasia-associated CAs.

4D-π-1A type ß-substituted ZnII-porphyrins: ideal green sensitizers for building-integrated photovoltaics.

Two novel green ß-substituted ZnII-porphyrins, G1 and G2, based on a 4D-π-1A type substitution pattern have been synthesized. Their enhanced push-pull character, by reduction of H-L energy gaps, promotes broadening and red-shifting of absorption bands. The effective synthetic pathway and the remarkable spectroscopic properties make G2 ideal for BIPV application.

Influence of sex on cytogenetic end points: evidence from a large human sample and review of the literature.

The planning and evaluation of human cytogenetic studies should contemplate various confounders and effect modifiers, among these, sex and sex-related factors. The association between this variable and cytogenetic damage has been extensively studied, but conclusive evidence has thus far not been reached, especially for the most recent assays, such as the micronucleus test (MN). In the attempt to quantitatively estimate the sex effect on sister chromatid exchange (SCE), chromosomal aberration (CA), and MN in peripheral blood lymphocytes, we reanalyzed the original data sets of several biomonitoring studies performed over the last decades in 10 Italian laboratories. This approach yielded a very large database, namely 2140, 2495, and 2131 subjects screened for SCE, CA, and MN, respectively. Differences between sexes were expressed in terms of relative risk (RR) of females versus males, after adjustment for age, smoking habits, occupation exposure and inter- and intralaboratory variation. No difference between sexes was found for the frequency of SCE [RR = 1.01; 95% confidence interval (CI) = 0.99-1.03] and CA (RR = 1.00; 95% CI = 0.92-1.08) even if the CI of the RR for SCE includes the 3% excess in females frequently reported by the literature. Conversely, a 29% overall increase of the MN rate in females was observed in the whole data set (RR = 1.29; 95% CI = 1.20-1.38). Different trends by age of the MN rate are described in the two sexes, focusing on the peak observed in females in the menopausal period and on the subsequent decrease.

Age-related increase of baseline frequencies of sister chromatid exchanges, chromosome aberrations, and micronuclei in human lymphocytes.

Intra- and interindividual variations of baseline frequencies of cytogenetic end points in lymphocytes of human populations have been reported by various authors. Personal characteristics seem to account for a significant proportion of this variability. Several studies investigating the role of age as a confounding factor in cytogenetic biomonitoring found an age-related increase of micronucleus (MN) frequency, whereas contradictory results were reported for chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs). We have quantitatively evaluated the effect of age on SCE, CA, and MN through the analysis of a population sample that included data from several biomonitoring studies performed over the last few decades in 12 Italian laboratories. The large size of the data set, i.e., more than 2000 tests for each end point, allowed us to estimate the independent effect of age, taking into account other covariates, such as sex, smoking habits, occupational exposure, and inter- and intralaboratory variability. A greater frequency of the mean standardized values by increasing of age was observed for all of the end points. A leveling off was evident in the last age classes in the trend of MN frequencies. Frequency ratios (FRs), which express the increase of the cytogenetic damage with respect to the first age classes, i.e., 1-19 years, were estimated using Poisson regression analysis after adjustment for the potential confounding factors and confirmed the increasing trend by age class for all three end points. The most dramatic increase was observed for MN, with a FR that approaches the value of 2 at the age class 50-59 (FR, 1.97; 95% confidence interval, 1.43-2.71) and remains substantially unchanged thereafter. The trend of FRs for CA is more homogeneous, with a constant rise even in the older classes, whereas the frequency of SCE increases with age to a lesser extent, reaching a plateau in the age class 40-49 and the maximum value of FR in the age class over 70 (FR, 1.14; 95% confidence interval, 1.07-1.23). In conclusion, our results point to an age-related increase of the chromosome damage in lymphocytes and emphasize the need to take into account the potential confounding effect of this variable in the design of biomonitoring studies based on chromosome damage.

Benzene-induced chromosome aberrations: a follow-up study.

To study the evolution of cytogenetic damage from past exposure to high concentrations of benzene and its health significance, chromosome aberrations (CA) in lymphocytes were reinvestigated after approximately 20 years in four subjects with past severe hemopathy and in seven controls studied in the late 1960s. Increased chromosome-type aberrations were still present up to 30 years after benzene toxicity, but blood counts were normal. The vital status at the end of 1993 was ascertained for 32 subjects with a history of benzene toxicity and for 31 controls studied for CA from 1965 to 1970, who differed significantly for CA rates. Of the 32 benzene-exposed subjects, 1 was lost to follow-up, 20 were still alive, and 11 had died at ages 36 to 83, between 1 and 20 years after the last CA study. Five deaths were from neoplasia (acute erythroleukemia, brain tumor, cancer of lung, paranasal cavity, esophagus). The decreased subjects had significantly higher rates of chromosome-type aberrations than those alive, and those who died of neoplasia had the highest rates of these aberrations in the last study before death or diagnosis of cancer. Out of the 31 controls, 12 had died from 4 to 23 years after the CA study. Three deaths were from neoplasia (two lung cancer, one brain tumor). Even if this is a small sample, the results suggest a higher risk of cancer for the benzene-exposed cohort, who had persistently high CA rates in lymphocytes.

Blood versus crystalloid cardioplegia for myocardial protection of donor hearts during transplantation: A prospective, randomized clinical trial.

OBJECTIVE: To assess the safety and efficacy of myocardial protection of the donor heart during transplantation with the use of blood cardioplegia, a prospective randomized clinical trial was undertaken between January 1997 and March 1998. METHODS: Forty-seven consecutive patients were assigned either to crystalloid (27 patients; group 1) or blood cardioplegia (20 patients; group 2). Comparison of recipient age (54 +/- 11 years vs 55 +/- 7 years; P =. 9), sex (89% vs 90% male patients; P =.9), diagnosis (63% vs 65% dilated cardiomyopathy; P =.8), elevated pulmonary vascular resistance (30% vs 30%; P =.9), prior cardiac operations (22% vs 30%; P =.5), need for urgent heart transplantation (7% vs 20%; P =. 2), donor age (32 +/- 11 years vs 31 +/- 13 years; P =.7), cause of death (33% vs 40% vascular; P =.5), and global myocardial ischemia (176 +/- 51 minutes vs 180 +/- 58 minutes; P =.5) showed no difference. Hemodynamically unstable donors (15% vs 45%; P =.02) were more prevalent in group 2. RESULTS: Operative mortality rates (4% vs 5%; P =.8), high-dose inotropic support (41% vs 30%; P = 0.6), and postoperative mechanical assistance (11% vs 10%; P = 0.9) were comparable in the 2 groups. Prevalence of acute right heart failure (27% vs 0; P =.02) and of temporary complete atrioventricular block (52% vs 20%; P =.02) were greater in group 1. Spontaneous sinus rhythm recovery was more prevalent in group 2 (11% vs 40%; P =.02). Higher peak creatine kinase (1429 +/- 725 u/L vs 868 +/- 466 u/L; P =.01) and creatine kinase MB (144 +/- 90 u/L vs 102 +/- 59 u/L; P =. 06) levels suggested more severe ischemic injury in group I. CONCLUSION: Use of blood cardioplegia was associated with a lower prevalence of right heart failure, cardiac rhythm dysfunction, and laboratory evidence of ischemia.

Immunochemotherapy for visceral leishmaniasis: a controlled pilot trial of antimony versus antimony plus interferon-gamma.

Twenty-four Kenyan patients with visceral leishmaniasis were treated for 30 days with either conventional therapy (daily pentavalent antimony, n = 14) or experimental immunochemotherapy (daily antimony plus interferon-gamma [IFN-gamma] every other day, n = 10). All 24 patients responded clinically to treatment, and microscopic splenic aspirate scores rapidly decreased in both groups. As judged by splenic aspirate culture results, IFN-gamma-treated patients responded more quickly (50% versus 22% culture-negative after one week and 75% versus 58% culture-negative after two weeks). While not statistically significant, these differences raise the possibility that combination therapy using IFN-gamma, which was safe and well-tolerated, may accelerate the early parasitologic response in patients with visceral leishmaniasis.

Topical aprotinin in cardiac operations.

We performed a prospective, randomized, double-blind trial of topical aprotinin versus placebo in 100 patients undergoing cardiac operations with cardiopulmonary bypass. Fifty-five patients received aprotinin. Forty underwent coronary artery bypass grafting (CABG) and 15 valve replacement +/- CABG. Of 45 patients in the control group 38 underwent CABG and 7 valve replacement +/- CABG. Aprotinin (50 mL; 70 mg) or placebo was applied topically to the heart, pericardium, and mediastinum before sternal closure. There were five reentries for bleeding with a surgical site identified in four. Mean blood loss was significantly less in the aprotinin group (653 versus 903 mL; p = 0.002), and fewer aprotinin patients received blood as a volume expander (67.5% versus 88%; p = 0.03). In coronary patients alone when aspirin administration was continued until the day of operation there was no difference between treatment and placebo groups (768 versus 879 mL). When aspirin administration was discontinued 2 weeks before operation there was a significant difference (558 versus 884 mL; p = 0.016) as in the group overall. This provides the potential for intrapericardial instillation for patients with excessive postoperative bleeding.

Are chromosome aberrations in circulating lymphocytes predictive of future cancer onset in humans? Preliminary results of an Italian cohort study.

To investigate the existence of an association between the frequency of chromosome aberrations (CA) in non-target tissues and cancer risk, a historical cohort study was carried out in a group of 1455 subjects screened for CA over the last 20 years in Italy. Statistically significant increases in standardized mortality ratio (SMR) for all cancers were found in subjects with medium and high levels of CA in peripheral blood lymphocytes (SMR = 178.5 and SMR = 182.0, respectively) and in subjects with high levels of CA for respiratory tract cancers (SMR = 250.8) and lymphatic and hematopoietic tissue neoplasms (SMR = 548.8). Significant trends in the SMRs were observed for these latter causes of death.

Cancer predictive value of cytogenetic markers used in occupational health surveillance programs.

It has not previously been clear whether cytogenetic biomarkers in healthy subjects will predict cancer. Earlier analyses of a Nordic and an Italian cohort indicated predictivity for chromosomal aberrations (CAS) but not for sister chromatid exchanges (SCES). A pooled analysis of the updated cohorts, forming a joint study base of 5271 subjects, will now be performed, allowing a more solid evaluation. The importance of potential effect modifiers, such as gender, age at testing, and time since testing, will be evaluated using Poisson regression models. Two other potential effect modifiers, occupational exposures and smoking, will be assessed in a case-referent study within the study base.

Comparison of chromosome aberrations and micronuclei in testing genotoxicity in humans.

Chromosome-type aberrations (CsA) and micronuclei (Mn) rates were compared in conventional 2-day lymphocyte cultures. In 67 healthy controls the mean rate of CsA was 0.54%, and that of Mn 2.38/1000 (median 1.66/1000). Mn were significantly correlated with age. The rate of Mn was higher in the 30 individuals with CsA > or = 1% than in the 37 subjects with no CsA. However, in 40 cadmium (Cd) workers, contrary to that found for CsA, the rates of Mn did not differ from those of the controls matched for age and smoking habits, not even in the subgroup with the highest Cd cumulative exposure index, while an age effect was evident both in the exposed and in the controls.