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The identification of genes involved in replicative stress is key to understanding cancer evolution and to identify therapeutic targets. Here, we show that CDK12 prevents transcription-replication conflicts (TRCs) and the activation of cytotoxic replicative stress upon deregulation of the MYC oncogene. CDK12 was recruited at damaged genes by PARP-dependent DDR-signaling and elongation-competent RNAPII, to repress transcription. Either loss or chemical inhibition of CDK12 led to DDR-resistant transcription of damaged genes. Loss of CDK12 exacerbated TRCs in MYC-overexpressing cells and led to the accumulation of double-strand DNA breaks, occurring between co-directional early-replicating regions and transcribed genes. Overall, our data demonstrate that CDK12 protects genome integrity by repressing transcription of damaged genes, which is required for proper resolution of DSBs at oncogene-induced TRCs. This provides a rationale that explains both how CDK12 deficiency can promote tandem duplications of early-replicated regions during tumor evolution, and how CDK12 targeting can exacerbate replicative-stress in tumors., (© 2024. The Author(s).)

It has been shown that vertical transmission of the SARS-CoV-2 strain is relatively rare, and there is still limited information on the specific impact of maternal SARS-CoV-2 infection on vertical transmission. The current study focuses on a transcriptomics analysis aimed at examining differences in gene expression between placentas from mother-newborn pairs affected by COVID-19 and those from unaffected controls. Additionally, it investigates the in situ expression of molecules involved in placental inflammation. The Papa Giovanni XXIII Hospital in Bergamo, Italy, has recorded three instances of intrauterine transmission of SARS-CoV-2. The first two cases occurred early in the pandemic and involved pregnant women in their third trimester who were diagnosed with SARS-CoV-2. The third case involved an asymptomatic woman in her second trimester with a twin pregnancy, who unfortunately delivered two stillborn fetuses due to the premature rupture of membranes. Transcriptomic analysis revealed significant differences in gene expression between the placentae of COVID-19-affected mother/newborn pairs and two matched controls. The infected and control placentae were matched for gestational age. According to the Benjamani-Hochberg method, 305 genes met the criterion of an adjusted p -value of less than 0.05, and 219 genes met the criterion of less than 0.01. Up-regulated genes involved in cell signaling (e.g., CCL20, C3, MARCO) and immune response (e.g., LILRA3, CXCL10, CD48, CD86, IL1RN, IL-18R1) suggest their potential role in the inflammatory response to SARS-CoV-2. RNAscope ® technology, coupled with image analysis, was utilized to quantify the surface area covered by SARS-CoV-2, ACE2, IL-1β, IL-6, IL-8, IL-10, and TNF-α on both the maternal and fetal sides of the placenta. A non-statistically significant gradient for SARS-CoV-2 was observed, with a higher surface coverage on the fetal side (2.42 ± 3.71%) compared to the maternal side (0.74 ± 1.19%) of the placenta. Although not statistically significant, the surface area covered by ACE2 mRNA was higher on the maternal side (0.02 ± 0.04%) compared to the fetal side (0.01 ± 0.01%) of the placenta. IL-6 and IL-8 were more prevalent on the fetal side (0.03 ± 0.04% and 0.06 ± 0.08%, respectively) compared to the maternal side (0.02 ± 0.01% and 0.02 ± 0.02%, respectively). The mean surface areas of IL-1β and IL-10 were found to be equal on both the fetal (0.04 ± 0.04% and 0.01 ± 0.01%, respectively) and maternal sides of the placenta (0.04 ± 0.05% and 0.01 ± 0.01%, respectively). The mean surface area of TNF-α was found to be equal on both the fetal and maternal sides of the placenta (0.02 ± 0.02% and 0.02 ± 0.02%, respectively). On the maternal side, ACE-2 and all examined interleukins, but not TNF-α, exhibited an inverse mRNA amount compared to SARS-CoV-2. On the fetal side, ACE-2, IL-6 and IL-8 were inversely correlated with SARS-CoV-2 (r = -0.3, r = -0.1 and r = -0.4, respectively), while IL-1β and IL-10 showed positive correlations (r = 0.9, p = 0.005 and r = 0.5, respectively). TNF-α exhibited a positive correlation with SARS-CoV-2 on both maternal (r = 0.4) and fetal sides (r = 0.9) of the placenta. Further research is needed to evaluate the correlation between cell signaling and immune response genes in the placenta and the vertical transmission of SARS-CoV-2. Nonetheless, the current study extends our comprehension of the molecular and immunological factors involved in SARS-CoV-2 placental infection underlying maternal-fetal transmission.

Coronary artery disease represents a global health challenge. Accurate diagnosis and evaluation of hemodynamic parameters are crucial for optimizing patient management and outcomes. Nowadays a wide range of both non-invasive and invasive methods are available to assess the hemodynamic impact of both epicardial coronary stenosis and vasomotor disorders. In fact, over the years, important developments have reshaped the nature of both invasive and non-invasive diagnostic techniques, and the future holds promises for further innovation and integration. Non-invasive techniques have progressively evolved and currently a broad spectrum of methods are available, from cardiac magnetic resonance imaging with pharmacological stress and coronary computed tomography (CT) to the newer application of FFR-CT and perfusion CT. Invasive methods, on the contrary, have developed to a full-physiology approach, able not only to identify functionally significant lesions but also to evaluate microcirculation and vasospastic disease. The aim of this review is to summarize the current state-of-the-art of invasive and non-invasive hemodynamic assessment for CAD management.

Background: Axillary vein puncture (AVP) and cephalic vein surgical cutdown are recommended in international guidelines because of their low risk of pneumothorax and chronic lead complications. Directly visualizing and puncturing the axillary vein under ultrasound guidance reduces radiation exposure, provides direct needle visualization, and lowers periprocedural complications. Our hypothesis is that ultrasound-guided axillary access is safer and more feasible than the standard fluoroscopic technique., Objectives: The purpose of this study was to assess the efficacy and safety of ultrasound-guided axillary venous access during cardiac lead implantation for pacemakers (PMs) and implantable cardioverter-defibrillator (ICD) implantations., Methods: Patients were randomized in a 1:1 fashion to either axillary venous access under fluoroscopic guidance or ultrasound-guided axillary venous access. The composite outcome, including pneumothorax, hemothorax, inadvertent arterial puncture, pocket hematoma, pocket infection, lead dislodgement, and death, was evaluated 30 days after implantation., Results: We randomized 270 patients into 2 groups: the standard group for fluoroguided AVP (n = 134) and the experimental group for ultrasound-guided AVP (n = 136). No disparities in baseline characteristics were observed between the groups. The median age of the patients was 81 years, with women comprising 41% of the population. The majority of patients received single- and dual-chamber PMs (87% vs 88%; P = 1.00), and slightly over 10% in both groups received ICDs (13% vs 12%; P = 0.85). In total, we placed 357 leads in PMs and 48 leads in ICDs. Among these, 295 leads were inserted via axillary vein access and 110 via cephalic vein access. Notably, the subclavian vein was never used as a vascular access. The composite outcome was lower in the ultrasound group according to intention-to-treat analysis (OR: 0.55; 95% CI: 0.31-0.99; P = 0.034). The main difference within the composite outcome was the lower incidence of inadvertent axillary arterial puncture in the experimental group (17% vs 6%; P = 0.004). The ultrasound group also exhibited lower total procedural x-ray exposure (10,344 μGy × cm 2 vs 7,119 μGy × cm 2 ; P = 0.002) while achieving the same rate of success at the first attempt (61% vs 69%; P = 0.375)., Conclusions: Ultrasound-guided AVP is safer than the fluoroscopy-guided approach because it achieves the same rate of acute success while maintaining low total procedural radiation exposure. Ultrasound AVP should be considered the optimal venous access method for cardiac lead implantation. (Ultrasound Guided Axillary Access vs Standard Fluoroscopic Technique for Cardiac Lead Implantation [ZEROFLUOROAXI]; NCT05101720)., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Immune checkpoint molecules like cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1) or its ligand, programmed cell death ligand 1 (PD-L1), play a critical role in regulating the immune response, and immune checkpoint inhibitors (ICIs) targeting these checkpoints have shown clinical efficacy in cancer treatment; however, their use is associated with immune-related adverse events (irAEs), including cardiac complications. The prevalence of cardiac irAEs, particularly myocarditis, is relatively low, but they can become a severe and potentially life-threatening condition, usually occurring shortly after initiating ICI treatment; moreover, diagnosing ICI-related myocarditis can be challenging. Diagnostic tools include serum cardiac biomarkers, electrocardiography (ECG), echocardiography, cardiac magnetic resonance (CMR) and endomyocardial biopsy (EMB). The treatment of ICI-induced myocarditis involves high-dose corticosteroids, which have been shown to reduce the risk of major adverse cardiac events (MACE). In refractory cases, second-line immunosuppressive drugs may be considered, although their effectiveness is based on limited data. The mortality rates of ICI-induced myocarditis, particularly in severe cases, are high (38-46%). Therapy rechallenge after myocarditis is associated with a risk of recurrence and severe complications. The decision to rechallenge should be made on a case-by-case basis, involving a multidisciplinary team of cardiologists and oncologists. Further research and guidance are needed to optimize the management of cancer patients who have experienced such complications, evaluating the risks and benefits of therapy rechallenge. The purpose of this review is to summarize the available evidence on cardiovascular complications from ICI therapy, with a particular focus on myocarditis and, specifically, the rechallenge of immunotherapy after a cardiac adverse event.

Introduction: Marfan Syndrome (MFS) is a rare and complex genetic disorder associated with increased aortic growth and aortic disease. The effectiveness of cardiovascular medical therapies aiming to slow down aortic growth has been tested in several trials, particularly beta-blockers and angiotensin receptor blockers, however showing conflicting results., Evidence Acquisition: We conducted a systematic review on PubMed (Medline), Cochrane library, Google Scholar, and Biomed Central databases between January and February 2022. We selected relevant articles focusing on patients with MFS treated with beta-blockers, angiotensin receptors blockers, or both, and reporting data on the effect of the drugs on 1) slowing down aortic dilatation; 2) the reduction of aortic complication (aortic dissection, mortality, aortic surgery); and with a 3) follow-up length of at least two years. A total of 16 studies were selected., Evidence Synthesis: Beta-blockers remain the mainstay of therapy as they have proven to slow aortic enlargement. Angiotensin receptor blockers are a useful alternative and with proven benefit as an add-on therapy to limit aortic growth. Neither beta-blockers, nor angiotensin receptor blockers have shown meaningful results on clinical aortic endpoints., Conclusions: The current evidence of pharmacological treatment for MFS patients is conflicting due to the lack of large, randomized clinical trials with adequate follow-up studies and homogeneous age grouping. Beta-blockers and angiotensin receptor blockers are the only available treatments to reduce aortic growth. A recently published patient-level meta-analysis confirmed that angiotensin receptor blockers and beta-blockers have a similar effect on reducing the rate of increase of the aortic root Z score, used singularly or as add-on therapy. Considering the current evidence on new features related with MFS (such as mitral annular disjunction - MAD) bearing a potential additional increased arrhythmic risk, it is of paramount importance to establish the role of beta-blockers and angiotensin receptor blockers in clinical endpoints of this population as well.

Background: Physiological pacing has gained significant interest due to its potential to achieve optimal hemodynamic response. This study aimed to assess left ventricular performance in terms of electrical parameters, specifically QRS duration and mechanical performance, evaluated as myocardial work. We compared His Bundle Pacing (HBP) and Left Bundle Branch Area Pacing (LBBAP) to evaluate their effects., Methods: Twenty-four patients with class I or IIa indications for pacing were enrolled in this study, with twelve patients undergoing HBP implantation and another twelve undergoing LBBAP implantation. A comprehensive analysis of myocardial work was conducted., Results: Our findings indicate that there were no major differences in terms of spontaneous and HBP activation in myocardial work, except for global wasted work (217 mmHg% vs. 283 mmHg%; p 0.016) and global work efficiency (87 mmHg% vs. 82 mmHg%; p 0.049). No significant differences were observed in myocardial work between spontaneous activation and LBBAP. Similarly, no significant differences in myocardial work were found between HBP and LBBAP., Conclusions: Both pacing modalities provide physiological ventricular activation without significant differences when compared to each other. Moreover, there were no significant differences in QRS duration between HBP and LBBAP. However, LBBAP demonstrated advantages in terms of feasibility, as it achieved better lead electrical parameters compared to HBP (threshold@0.4 ms 0.6 V vs. 1 V; p = 0.045-sensing 9.4 mV vs. 2.4 mV; p < 0.001). Additionally, LBBAP required less fluoroscopy time (6 min vs. 13 min; p = 0.010) and procedural time (81 min vs. 125 min; p = 0.004) compared to HBP.

This paper studies how fiscal decentralization affects local services. It explores a 1993 reform that increased the fiscal autonomy of Italian municipalities by replacing government transfers with revenues from a local property tax. Our identification leverages cross-municipal variation in the degree of decentralization that stems from differences in the average age of buildings caused by bombings during WWII. Decentralization reduced local spending but expanded municipal services, such as nursery schools. These effects are larger in areas with greater political competition. The paper also investigates how the reform affected labor markets. Decentralization increased female labor supply-probably through expanded availability of nursery schools- thereby reducing the gender gap in employment.

Cardiac ventricular outpouchings and invaginations are rare structural abnormalities and usually incidental findings during cardiac imaging. A definitive diagnosis is possible through the use of multimodality imaging. A systematic review of the literature was carried out in November 2022 to identify studies regarding ventricular outpouchings and invaginations. The main aim of the review is to summarize knowledge regarding epidemiology, etiology, diagnosis and prognosis of patients with ventricular outpouchings (aneurisms or diverticula) and invaginations (crypts and recesses). Overall, 26 studies published between 2000 and 2020 were included in the review. Diverticula and congenital aneurysms incidence ranges between 0.6 and 4.1%. Myocardial recesses and crypts range between 9% in the general population and up to 25% in patients with hypertrophic cardiomyopathy. The combined use of echocardiography, cardiac computed tomography (CCT) and cardiac magnetic resonance (CMR) is useful to establish tissue contractility, fibrosis, extension and relationship with adjacent structures for differential diagnosis of both invaginations and outpouchings. In conclusion, both outpouchings and invaginations are rare entities: a definitive diagnosis may be aided by the use of combining multiple imaging techniques, and the treatment depends both on the lesion-specific risk of complications and on the potential association of some lesions with cardiomyopathy.

Stress echocardiography is an imaging methodology that is widely used in cardiopathic patients for the optimization of diagnosis and prognosis of patients with valvular heart diseases, in defining the response to physical stress in patients with ischemic heart disease, hypertrophic cardiomyopathy, congenital heart disease, or heart failure. However, this method is not yet sufficiently used in clinical practice. Therefore, the aim of this literature review is to describe the main fields of application of stress echocardiography with echo-bike, describing its main advantages and limitations.

Background: In cardiology, the global phenomenon of population ageing poses new major challenges, ranging from more comorbid and frail patients to the presence of complex, calcified and multiple coronary lesions. Considering that elderly patients are under-represented in randomized clinical trials (RCT), the aim of this systematic review is to summarize the current knowledge on the revascularization of the elderly patient with myocardial infarction and multivessel coronary artery disease., Methods: A systematic review following PRISMA guidelines has been performed. The search was conducted on Pubmed (Medline), Cochrane library, Google Scholar and Biomed Central databases between January and February 2022. We selected the articles focusing on patients hospitalized for myocardial infarction (MI) with multivessel disease and aged 75 years or older. A total of 36 studies have been included., Results: Multivessel coronary artery disease is present in around 50-60% of older patients with MI. The in-hospital mortality rate of patients older than 75 years is double compared to their younger counterpart, and the most prevalent complications after revascularization are bleeding and renal failure. In the treatment of patients with ST elevation MI (STEMI), primary percutaneous coronary intervention should be the first choice over fibrinolysis. However, it is not clear whether this population would benefit from complete revascularization or not. In patients with non-ST elevation MI (NSTEMI), an invasive approach with either percutaneous coronary intervention or coronary artery bypass graft may be chosen, but a conservative strategy is also accepted. There are no data from large trials about the comparison of possible revascularization strategies in NSTEMI patients., Conclusions: This systematic review shows that this field of research lacks randomized clinical trials to guide revascularization strategy in older STEMI or NSTEMI patients with MI. New results are expected from ongoing trials., Competing Interests: The authors declare no conflict of interest. Gianluca Campo is serving as Guest Editor of this journal. We declare that Gianluca Campo had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Jerome L. Fleg., (Copyright: © 2022 The Author(s). Published by IMR Press.)

This paper examines the long-term and spillover effects of management interventions on firm performance. Under the Training Within Industry (TWI) program, the U.S. government provided management training to firms involved in war production between 1940 and 1945. Using a newly collected panel dataset on all 11,575 U.S. firms that applied to the program, we find that the TWI training had positive and long-lasting effects on firm performance and the adoption of beneficial managerial practices. Moreover, it generated complementarities among different types of training and had positive spillover effects on the supply chain of trained firms.

Petrochemical industries and oil refineries are sources of hazardous chemicals into the aquatic environments, and often a leading cause of reduced oxygen availability, thus resulting in adverse effects in biota. This study is an expansion of our previous work on the assessment of the BioFilm-Membrane Bioreactor (BF-MBR) to mitigate the impact of oil-polluted wastewater on marine environments. Specifically, this study evaluated the reduction of selected chemical constituents (hydrocarbons and trace metals) and toxicity related to hypoxia and DNA damage to mussels Mytilus galloprovincialis, before and after treatment of oil-polluted wastewater with the BF-MBR. The application of a multidisciplinary approach provided evidence of the efficiency of BF-MBR to significantly reducing the pollutants load from oily contaminated seawaters. As result, the health status of mussels was preserved by a hypoxic condition due to oily pollutants, as evidenced by the modulation in the gene expression of HIF-1α and PHD and changes in the level of hypotaurine and taurine. Moreover, ameliorative effects in the energy metabolism were also found in mussel gills showing increased levels of glycogen, glucose and ATP, as well as a mitigated genotoxicity was revealed by the Micronucleus and Comet assays. Overall, findings from this study support the use of the BF-MBR as a promising treatment biotechnology to avoid or limiting the compromise of marine environments from oil pollution., (Copyright © 2021. Published by Elsevier B.V.)

This study compiles data to determine if procalcitonin (PCT) values may predict both the risk of bacterial infection and potentially negative long-term outcomes in patients with acute coronary syndromes (ACS). All patients with a diagnosis of ACS that had PCT levels assessed during the first 24 h of hospitalization were enrolled in this study. The primary outcome was to detect the presence of bacterial infection defined as the occurrence of fever and at least one positive blood or urinary culture with clinical signs of infection. The secondary outcome was to monitor the occurrence after 1 year of the composite outcome of all-cause mortality, stroke and myocardial infarction. Overall, 569 patients were enrolled (mean age 69.37 ± 14 years, 30% females). Of these, 44 (8%) met the criteria for bacterial infection. After multivariate analysis, PCT and SBP were found to be independent predictors of bacterial infections (OR for PCT above the cut-off 2.67, 95% CI 1.09-6.53, p = 0.032 and OR for SBP 0.98, 95% CI 0.97-0.99, p = 0.043). After 1 year, the composite outcome of all-cause death, MI and stroke occurred in 104 patients (18%). PCT was not found to be an independent predictor of these outcomes. In conclusion, when assessing ACS, we found that testing for PCT levels during hospital admissions procedures was a good predictor of bacterial infections but not of all-cause mortality, stroke, or myocardial infarction. Clinicaltrial.org identifier: NCT02438085.

Androgen deprivation therapy (ADT) is the gold standard treatment in patients with locally advanced or metastatic prostate cancer (PC). Emerging evidence has documented a tight association between ADT and body composition, along with metabolic profile impairment. These alterations might underpin the observed ADT-related increase in cardiovascular (CV) and thromboembolic (venous thromboembolism, VTE) mortality and morbidity. However, the specific mechanisms underlying these associations have not yet been completely elucidated. In the present review we summarize and discussed the available evidence linking ADT to increased cardio-metabolic risk, using both preclinical and clinical data. When possible, meta-analytic studies were preferred. Preclinical evidence, using a rabbit model of gonadotrophin-releasing hormone analogue-induced hypogonadism, indicates that the induced condition is associated with a dramatic increase in visceral adiposity and with an impairment of acetylcholine induced vascular relaxation, along with an increased propensity towards fatty liver. This suggests a direct role of ADT in inducing a worsened metabolic profile. In contrast, available clinical data are not sufficient to clarify a direct pathogeniclink between reduced testosterone (T) and altered metabolism. In fact, although T deprivation is associated with an altered metabolism, it is possible that the association between ADT and CV or VTE risk could simply be the result of a selection bias, related to the poor health status of patients with advanced PC. Despite the aforementioned considerations, all patients who are candidatesfor ADT should be screened for CV risk factors at baseline and monitored during the therapy. Life-style modifications and physical exercise are strongly encouraged., Competing Interests: The authors have nothing to disclose., (Copyright © 2021 Korean Society for Sexual Medicine and Andrology.)

Aim To evaluate radiological and clinical outcomes of a case series of patients affected by glenohumeral instability (Bankart lesion) or superior labrum tear from anterior to posterior (SLAP) lesions treated by arthroscopic repair using all-suture anchors. Methods Patients were operated by a single surgeon at a single Institution. Exclusion criteria were chondral lesions of the glenoid, rotator cuff lesions, previous surgery at the index shoulder, or a bony Bankart lesion. Position and numbers of anchors used depended on the dimension and type of lesion. The DASH (Disability of the Arm, Shoulder and Hand) and Constant scores were used for subjective and clinical evaluation at follow-ups (FUs); also, at 1-year FU, MRI scan was obtained to evaluate bone reaction to the implanted devices. Results Fifty-four patients were included. A mean of 2.7 devices per patient (145 in total) were implanted. Mean FU was 30 (range 12 - 48) months. No patient reported recurrent instability, nor hardware-related complications were registered. MRI analyses showed that 119 (82%) implants did not alter surrounding bone (grade 0), 26 (18%) implants were surrounded by bone oedema (grade 1), while no bone tunnel enlargement nor a bone cyst (grade 2 or 3, respectively) were registered. Conclusion This study confirmed the efficacy and safety of a specific all-suture anchor system in the arthroscopic repair of the glenoid labrum for glenohumeral instability or a SLAP lesion. In the short- and mid-term period, these devices were associated with good clinical and radiological outcomes without clinical failures or reaction at bone-device interface., (Copyright© by the Medical Assotiation of Zenica-Doboj Canton.)

Aim To compare a medial pivot (MP) total knee arthroplasty (TKA) with posterior stabilized (PS) TKA designs from a subjective, clinical and biomechanical point of view, in a single-centre, single-surgeon, case-control non-randomized trial. Methods Sixteen patients were randomly picked up from case series into each group. Subjective outcome was assessed using the Forgotten Joint Score Questionnaire (FJSQ). Clinical evaluation included range of motion (ROM). All patients underwent gait analysis by a treadmill with force-measuring plaques and videorecording device; data were recorded for 30 seconds and included cadence, step length, stance time and walking speed. A blinded qualitative analysis of the pattern of gait was defined as biphasic or non-biphasic. Descriptive statistics for the continuous study variables and statistical significance were calculated for all parameters with independent-samples t-test and χ2 test to analyse difference in pattern of gait between groups. Results Mean FJSQ in the MP group was 91.87 (CI 95%: 88.12- 95.46) and 75.31 (CI 95%: 67.97-81.56) in the PS group (p=0.029). Mean post-operative ROM was 117° (CI 95%: 113°-122°) in the MP group and 112° (CI 95%: 108°-117°) in the PS group (p=0.14). No statistical difference was found between groups regarding all gait analysis parameters which have been recorded. Conclusion MP TKA design showed better subjective results using the FJSQ, but it did not improve significantly clinical and functional outcomes compared to PS TKA design, at a short-term follow-up., (Copyright© by the Medical Assotiation of Zenica-Doboj Canton.)

Abandoned mine sites are a cause of great environmental concern, being potential sources of toxic elements for adjacent aquatic ecosystems with intrinsic difficulties for their management (i.e. episodic nature of pollution, technical difficulties and high costs of monitoring, remoteness). Aquatic macrophytes can find effective application in these situations, providing cost-effective data for instream water quality assessment. In this study, native and transplanted specimens of the aquatic moss Platyhypnidium riparioides were used to evaluate metal(loid) contamination in a river receiving multiple acidic and metalliferous drainages from sulphide mineralized areas and derelict mines. Analysis of native P. riparioides thalli was used to identify, in the upland course of the river, the pattern of contamination (As, Cd, Cu, Pb and Zn) which was related to the geo-environmental features of the watershed and the nearby historical mining areas. Attenuation of metal(loid) availability in the lowland river, apparently due to eco-hydrological and physic-chemical processes, was also highlighted by spatial trends of concentrations data of native and transplanted moss. The latter, deployed for 21 days at specific stretches of the river and in a tributary hydrologically connected with a dismissed mine, supported the identification of point sources (i.e. mine effluents, metallurgical waste piles amassed on the banks of the river) and the reckoning of their quantitative impact on different segments of the watercourse. By exploring multi-elemental and native-to-transplant relationships, differences in metal(loid) accumulative capacities were recognized between sampled thalli and exposed moss bags in relation to the severity of the contamination. The observed discrepancy in the accumulation of As, Fe, Ni and Pb in highly contaminated areas between native and transplanted moss of P. riparioides raises questions on the possible competing mechanisms of element uptake and retention. These findings prompt studies to discern possible limitations of the transplanting moss technique under extreme stream-quality conditions., 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 © 2020 Elsevier B.V. All rights reserved.)

The research presented here was conducted to ascertain the effectiveness of recovery technologies in remediating a compromised marine environment. The multidisciplinary approach aims to integrate traditional chemical-physical analysis and to assess the biological parameters of Mytilus galloprovincialis within different experimental mesocosms (W, G, and B). In particular, this system was designed to reproduce sediment resuspension in a marine environment, which is thought to be one cause of contaminant release. The study combined morphological and ultrastructural observations with DNA damage assessment and mRNA expression of those genes involved in cellular stress responses. The tissues of mussels maintained in the polluted mesocosm showed a higher accumulation of Pb and Hg than in those maintained in restored mesocosm. This observation correlates well with mRNA expression of MT10 and data on DNA damage. The outcome of the biological evaluation consolidates the chemical characterization and supports the concept that the remediation method should be evaluated at an early stage, both to analytically determine the reduction of toxic components and to assess its ultimate impact on the biological system.

Due to its peculiarity to accumulate environmental contaminants, the osprey Pandion haliaetus is a sentinel species for the biomonitoring of contaminants in aquatic ecosystems. Despite this, no information on trace element concentration exists for the Mediterranean area, where relict and vulnerable osprey populations exist. We evaluated the geographical patterns of heavy metals and selenium in osprey eggs from three different populations of the Mediterranean basin (Balearic Islands, Corsica, and Tuscany), to identify any possible contaminant sources. Pattern of metal concentration followed the order: Fe > Zn > Cu > Se > Hg > Pb > Cd. Differences in contaminant concentrations between habitats and among egg components were found. Egg content and inner membrane showed higher mercury levels (1.06 ± 0.89 and 0.67 ± 0.62 mg/kg dw, respectively) than those recorded in the eggshell. Mercury concentration was ca. two times higher in marine than in wetland samples, and even higher (3.6 times) when referred to the eggshell. Cu, Fe, Zn, and Se had higher concentration in the inner membrane. We stress how the choice of the biological material can have significant implications for the correct evaluation of contamination. Our study represents a first regional scale survey for the vulnerable Mediterranean osprey populations and provides baseline data for their long-term biomonitoring.

We determined levels of mercury, cadmium, lead and selenium in muscle and liver of 29 specimens of a large pelagic fish rarely investigated, the Mediterranean spearfish Tetrapturus belone (Raf., 1810). The following element concentration ranking (mean ± S.D.; espressed in mg/kg dry weight) was recorded in muscle: Hg (3.401 ± 1.908) > Se (1.727 ± 0.232) > Pb (0.532 ± 0.322) > Cd (0.019 ± 0.015), and Se (6.577 ± 1.789) > Cd (5.815 ± 3.038) > Hg (2.698 ± 2.214) > Pb (0.661 ± 1.334) in liver. Levels of Hg, Se and Cd were compared to those reported for other Istiophoridae from oceanic areas and for other large predators of Mediterranean Sea, like swordfish and tuna. Organotropism of trace elements and their relation to size was discussed. Ecophysiological considerations regarding the Se-Hg relationship as well as Se-Cd indicate a possible detoxification mechanism. The implications for human consumption are briefly discussed., 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 © 2020 Elsevier Ltd. All rights reserved.)

Rationale: Galectin-1 is a carbohydrate-binding protein involved in apoptosis, cell-proliferation and differentiation, implicated in T-cell homeostasis and survival. The aim of the present study was to determine concentrations of galectin-1 in BAL fluid from patients with IPF and other interstitial lung diseases in order to validate proteomic previous findings., Methods: 36 IPF patients (16 females, mean age of 64.8 ± 8.9 years), 24 sarcoidosis patients (15 females, mean age of 56.3 ± 13.4), 7 interstitial lung diseases associated to systemic sclerosis (ILD-SSc) patients (5 females, mean age of 55.5 ± 16.4) and six healthy controls (4 females, mean age 47.8 ± 15.2) were included. Galectin-1 concentrations were determined in BAL samples by an ELISA assay., Results: Galectin-1 concentrations were significantly higher in BAL of IPF patients than in sarcoidosis and ILD-SSc patients and healthy controls. In IPF patients, galectin-1 levels showed significant inverse correlations with DL CO %, K CO % and BAL lymphocyte percentages and a positive correlation with BAL macrophage percentages. Former IPF smokers had higher concentrations of this protein compared with non-smoker IPF patients., Conclusion: Galectin-1 was confirmed a protein of interest in idiopathic pulmonary fibrosis. Its BAL concentrations were higher in IPF patients than in controls and correlated with disease severity. Galectin-1 was suggested to have a role in the pathogenesis of IPF, principally through the ERK/MAPK pathway and the inhibition of galectin-1 is a potential therapeutic target worthy of research., (Copyright © 2019 Elsevier B.V. All rights reserved.)

After publication of our article [1] the authors have notified us that one of the names has been incorrectly tagged.

Background: Serum chitotriosidase is a promising biomarker that has shown high specificity and sensitivity in patients with sarcoidosis. The aim of this study was to investigate correlations between serum chitotriosidase, clinical phenotypes, disease localizations and different radiological lung involvement and to identify clinical features associated with over-expression of chitotriosidase in a large cohort of sarcoidosis patients., Methods: Chitotriosidase activity was evaluated in a population of 694 consecutive patients (males 39%, age 55.8 ± 12.8 years). Clinical and respiratory functional characteristics, Clinical Outcome Scale (COS) classification, clinical phenotypes proposed by the GenPhenResA project, and radiological assessment, including CT scan, were collected. Serum sampling and clinical and functional assessments at follow-up were also included., Results: Significantly higher chitotriosidase activity was observed in sarcoidosis patients than in healthy controls (p < 0.0001). Evidence of lung fibrosis with reticular abnormalities and traction bronchiectasis at High resolution CT, presence of multiple extrapulmonary sarcoid localizations and increased 24-h urinary excretion of calcium were associated with significantly higher chitotriosidase activity (p < 0.005). Patients with remitted or minimal disease had lower values of chitotriosidase than patients with persistent disease. At follow-up, patients who required an increase in steroid dose showed an increase in its activity., Conclusions: Chitotriosidase is a reliable biomarker of sarcoidosis. It is increased in patients with sarcoidosis correlating with disease activity, severity and multiorgan dissemination. Steroid therapy tended to reduce chitotriosidase expression, however it responded in cases of disease relapse.

The incorporation of silver nanoparticles (AgNPs) in commercial products is increasing rapidly. The consequent release of AgNPs into domestic and industrial wastewater raises environmental concerns due to their anti-microbial properties and toxicity to non-target aquatic organisms. The aim of the present study was to investigate the effects of nanArgen™ (Nanotek S.A.), a AgNP-enabled consumer product, in the marine bivalve Mytilus galloprovincialis. Two environmentally relevant concentrations of nanArgen™ (1 and 10 μg/L) were tested in vivo for 96 h, and Ag was quantified in mussel soft tissue and natural seawater (NSW). nanArgen™ suspensions were characterized via TEM, SEM, EDS, DLS, and UV-vis optical analysis. Several molecular and biochemical responses were investigated in exposed mussels: lysosomal membrane stability by Neutral Red Retention Time (NRRT) assay; micronucleus (MN) frequency in hemocytes; metallothionein (MT) protein content and gene expression (mt10 and mt20); catalase (CAT) and glutathione-S-transferase (GST) activities; malondialdehyde (MDA) accumulation in digestive glands; and efflux activity of ATP-binding cassette transport proteins (ABC) in gill biopsies. SEM, TEM and DLS analyses confirmed the presence of well-defined AgNPs in nanArgen™ which were roughly spherical with an average particle size of approx. 30 ± 10 nm. DLS analysis revealed the formation of AgNP aggregates in nanArgen™ suspension in NSW (Z-average of 547.80 ± 90.23 nm; PDI of 0.044). A significant concentration-dependent accumulation of Ag was found in mussels' whole soft tissue in agreement with a concentration-dependent decrease in NRRT and an increase of MN frequency in hemocytes and GST activities in digestive glands. A significant increase in MDA levels and MT via both molecular and biochemical tests, were also observed but only at the highest nanArgen™ concentration (10 μg/L). No changes were observed in CAT activities. ABC efflux activities in gill biopsies showed a significant decrease (p <  0.05) only at the lowest concentration (1 μg/L). On such basis, nanArgen™ is shown to be able to induce toxicity and Ag accumulation in marine mussels similarly to AgNPs and in short-term exposure conditions at environmentally relevant concentrations. AgNP-enabled products, instead of pristine AgNPs, should be the focus of future ecotoxicity studies in order to address any risks associated to their widespread use, disposal and uncontrolled release into the aquatic environment for non target species., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: The choice of graft type in the anterior cruciate ligament (ACL) reconstruction remains a subject of controversy. The aim of this study was to assess the outcomes in ACL reconstructions performed using a four-strand hamstring tendon graft (4SHG) or a LARS ligament comparing the effectiveness of the two grafts at a medium follow-up of 8 years., Methods: This retrospective, single-centre, single surgeon study evaluated the clinical, functional and radiographic outcomes in 50 patients who underwent ACL reconstruction (25 4SHG and 25 LARS). Patients who underwent surgery after more than 6 months from injury and showed radiographically visible degenerative changes at time of surgery were excluded from the study., Results: None of the patients underwent re-surgery in the same knee. The range of motion of the operated knee, compared to the contralateral, was good for both groups. The anterior drawer test resulted negative in 21 patients (84%) in the LARS group and eight patients (32%) in the 4SHG group (P = 0.039). The Lachman test was negative in 19 patients (76%) in the LARS group and in 11 patients (44%) in the 4SHG group (P = 0.045). Although other results of ACL reconstruction measured by Lysholm scores, IKDC evaluation, Tegner scores and radiographic images showed using a LARS graft tended to be superior to using a 4SHG, there were no statistically significant differences calculated., Conclusion: Our results suggest that 4 years after ACL reconstruction using a LARS ligament or 4SHG dramatically improves the function outcome, while the patients in the LARS group displayed a higher knee stability than those in the 4SHG group.

The loggerhead sea turtle (Caretta caretta) is a long-lived carnivorous reptile included in the IUCN Red List. The IUCN assessment for this species underlines the lack of information regarding pollution and pathogens and indicates as a priority effort to investigate and reduce the impacts of these threats. In this contest, the aim of our study was to conduct the first ecotoxicological assessment of this species in the Mediterranean Sea using a nondestructive integrated methodology. We set up and applied a monitoring protocol which includes endpoints, such as CYP1A, LPO, ENA assay, B esterases, never investigated before in this species. Seventy-five loggerhead turtles were sampled in a nondestructive way in Italian Sea Turtle Rescue Centers or free-ranging along the Spanish coasts. Blood, skin and carapace samples were used to test biomarker responses (CYP1A, VTG, LPO, Comet and ENA assay, BChE, GGT) and contaminant (OCs, PAHs, Pb, Cd, Hg) levels. Elaboration of experimental results was carried out taking also into consideration different age classes of the specimens. Among the main results obtained we should underline the statistically significant correlation between carcinogenic PAHs in blood and DNA fragmentation as well as between Cd in carapace and GGT in plasma. We also evidenced as youngest animals showed significantly higher DNA fragmentations, BChE inhibition and increase of GGT. Older specimens showed the highest levels of erythrocyte nuclear abnormalities which may indicate a long term toxicological stress. This study contributed to expand the knowledge about the ecotoxicology of C. caretta in the Mediterranean. The nondestructive protocol could also be applied to other marine ecosystems and other sea turtle species., (Copyright © 2018. Published by Elsevier B.V.)

Context: Low testosterone (T) levels are often found in obese men with impaired glucose tolerance (IGT) and overt type 2 diabetes (T2DM); however, the mechanisms underlying this condition and its correct therapy are still under debate., Objective: To evaluate the effectiveness of clomiphene citrate (CC) in increasing endogenous T levels in obese men with low serum T and with IGT or T2DM treated with metformin (MET)., Design: Cross-over, randomized, double-blind, placebo-controlled study., Methods: 24 obese men, aged 47.3 ±. 6.3 (range 35-55 years), with low T level (≤3 ng/mL) and naïve diagnosis of IGT or T2DM were included. Subjects were randomized to CC 25 mg/day or placebo (Plac) with MET 2 g/day for 3 months. After a 6-week wash-out period, subjects were moved to the alternative arm for additional 3 months. Clinical evaluation and blood exams performed prior to and at the end of treatment., Results: Of 24 randomized, 21 were evaluable, classified as IGT (n = 11) or T2DM (n = 10). Compared to baseline levels, T levels increased significantly after 3 months of CC treatment (3.03±0.80 to 5.99±1.67 ng/mL P<0.001) but not after the Plac treatment (2.87±0.78 to 3.09±0.84 ng/mL P<0.001 between the treatments). T changes were similar in IGT and T2DM subjects. Gonadotropins as well raised significantly after CC treatment (LH 3.83±1.45 to 8.53±6.40 mU/mL; FSH 4.84±1.67 to 10.15±5.08 mU/mL P<0.001 respectively), whereas no changes for LH (3.51±1.59 to 3.63±1.39 mU/mL) but a smooth increased for FSH (4.61±2.49 to 5.39±2.65 mU/mL; P = 0.004) were shown after Plac treatment (LH P = 0.001 and FSH P = 0.002 between treatments). Furthermore, fasting glucose (106.8±23.2 to 101.1±25.7 mg/dL; P = 0.004), insulin (19.3±12.1 to 15.6±10.1 μU/mL; P = 0.010) and HOMA-IR (4.94±2.89 to 3.69±2.12; P = 0.001) decreased significantly during the CC treatment period, whereas no significant changes were observed in any of these parameters in the Plac treatment., Conclusions: A low dose of CC therapy was able to significantly increase serum T levels in all participants with mild modifications of clinical and metabolic parameters., Trial Registration: EudraCT 2011-000439-10.

In this paper non-linear backstepping control (BSC) is employed for high performance five-phase induction motor drive for low speed operation. The traditional control approaches such as direct torque control and indirect rotor field oriented control introduces stability problem at low speed. The proposed BSC is shown to offer stable operation in the sense of Lyapunov and high dynamics at low speed. Experimental results are provided to present the proprieties of the proposed approach at low speed in terms of stability, torque ripple, desired control performance, achievable dynamics and complexity of implementation etc., (Copyright © 2016. Published by Elsevier Ltd.)

Assessing trace metal pollution using feathers has long attracted the attention of ecotoxicologists as a cost-effective and non-invasive biomonitoring method. In order to interpret the concentrations in feathers considering the external contamination due to lithic residue particles, we adopted a novel geochemical approach. We analysed 58 element concentrations in feathers of wild Eurasian Greater Flamingo Phoenicopterus roseus fledglings, from 4 colonies in Western Europe (Spain, France, Sardinia, and North-eastern Italy) and one group of adults from zoo. In addition, 53 elements were assessed in soil collected close to the nesting islets. This enabled to compare a wide selection of metals among the colonies, highlighting environmental anomalies and tackling possible causes of misinterpretation of feather results. Most trace elements in feathers (Al, Ce, Co, Cs, Fe, Ga, Li, Mn, Nb, Pb, Rb, Ti, V, Zr, and REEs) were of external origin. Some elements could be constitutive (Cu, Zn) or significantly bioaccumulated (Hg, Se) in flamingos. For As, Cr, and to a lesser extent Pb, it seems that bioaccumulation potentially could be revealed by highly exposed birds, provided feathers are well cleaned. This comprehensive study provides a new dataset and confirms that Hg has been accumulated in feathers in all sites to some extent, with particular concern for the Sardinian colony, which should be studied further including Cr. The Spanish colony appears critical for As pollution and should be urgently investigated in depth. Feathers collected from North-eastern Italy were the hardest to clean, but our methods allowed biological interpretation of Cr and Pb. Our study highlights the importance of external contamination when analysing trace elements in feathers and advances methodological recommendations in order to reduce the presence of residual particles carrying elements of external origin. Geochemical data, when available, can represent a valuable tool for a correct interpretation of the analytical results., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The Greenland shark Somniosus microcephalus is an opportunistic feeder, a top predator, and a very long-lived species. The brain, liver, red and white muscle, gonads, fat, skin, pancreas, and spleen of Greenland sharks from NE Greenland fjords were analysed for PCBs, PCDDs/DFs, PBDEs; DDT isomers; HCH isomers; dieldrin; endrin; HCB; Cd, Hg, Pb, and Se. PCBs (2.01-103 ng/g wet wt) and PBDEs (7.9-3050 pg/g wet wt) were detected in most of the samples. PCDDs/DFs showed high values when detected. DDTs, HCB and HCHs were only detected in some tissues. The ΣTEQ was 5.76 pg/g in muscle. Cadmium mainly accumulated in the pancreas and liver (19.6 and 10.7 mg/kg dry wt, respectively); mercury in red muscle (4.10-6.91 mg/kg dry wt); selenium in the pancreas (3.57 mg/kg dry wt) and spleen (1.95 mg/kg dry wt); lead in the skin (0.358 mg/kgd ry wt). The selenium-mercury ratio in the liver was also evaluated., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Perfluorinated compounds (PFCs), widely used for their hydro-oil repellent properties, are almost non-degradable in the environment; there is scientific evidence that indicate bioaccumulation. They represent a threat to many organisms, because they are toxic and are endocrine disruptors. Scientific studies have demonstrated the presence of PFCs in blood and liver samples of fish, turtles, birds and mammals of marine ecosystems in different geographical areas. The aim of this study was to determine the distribution of PFOS and PFOA in blood samples of the marine turtle Caretta caretta, using a minimally invasive sampling procedure. 49 blood samples of marine turtle, taken from several Italian marine turtle rescue centers, were analyzed. While PFOA was never detected, measurable concentrations of PFOS were found in 15 blood samples; the values show a range from 1.14 ng/g to 28.51 ng/g (wet wt.). No differences between groups of samples taken from different areas were found., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Sarcoidosis is a multisystem granulomatous disease of unknown etiology. No suitable biomarkers are available to evaluate the evolution of this disease, which still has an unpredictable clinical course. Some years ago our research group proposed chitotriosidase as a potential biomarker with prognostic value, that however needed to be validated., Aims and Methods: The aims of this study were to evaluate the sensitivity and specificity of chitotriosidase in a population of 232 sarcoidosis patients under the observation of our Sarcoidosis Regional Referral Centre in Siena and to analyse enzyme concentrations in different disease phenotypes (as defined by the recently published COS classification) to define its prognostic value., Results: Serum chitotriosidase concentrations were significantly higher in patients than in healthy controls (p<0.0001) and were directly correlated with ACE levels (r=0.25, p<0.0001). ROC curve analysis revealed 88.6 % sensitivity and 92.8 % specificity. Enzyme concentrations were significantly higher in stage 3 sarcoidosis than in stage 0 (p=0.02). The lowest concentrations of chitotriosidase were found in untreated patients in remission (COS-1), while the highest enzyme concentrations were found in symptomatic patients with persistent disease on steroids and with functional deterioration in the last year (COS-9). In COS-9 subgroup, chitotriosidase decreased significantly after the increasing of steroid dose or the introduction of a new immunosuppressant therapy (p<0.01)., Conclusion: Chitotriosidase proved to be a biomarker with good sensitivity and specificity that is easily detected in serum. It can be proposed in clinical practice to identify progressive patients requiring close follow-up, to detect relapses and to evaluate the effects of therapy.

Hexavalent Chromium Cr(VI) is an important contaminant considered as a model oxidative toxicant released from both domestic and industrial effluents, and represents the predominant chemical form of the metal in aquatic ecosystems. On the other hand, in mammals the reduced form Cr(III) is considered an essential microelement, involved in regulation of lipid and carbohydrate metabolism; moreover, recent evidence suggests that Cr may have endocrine effects. In this work, the effects of Cr(VI) were investigated in the digestive gland of the marine bivalve Mytilus galloprovincialis. Mussels were exposed to 0.1-1-10-100 μg Cr(VI) L(-1) animal(-1) for 96 h. At 100 μg L(-1), a large increase in total Cr tissue content was observed; in these conditions, the lysosomal membranes were completely destabilized, whereas other lysosomal biomarkers (neutral lipids-NL and lipofuscin-LF), as well as different enzyme activities and gene expression were unaffected, this indicating severe stress conditions in the tissue. On the other hand, at lower concentrations, changes in other histochemical, biochemical and molecular endpoints were observed. In particular, at both 1 and 10 μg L(-1), lysosomal destabilization was associated with significant NL and LF accumulation; however, no changes in catalase and GSH transferase (GST) activities were observed. At the same concentrations, GSSG reductase (GSR) activity was significantly increased, this probably reflecting the recycling of GSSG produced in the GSH-mediated intracellular reduction of Cr(VI). Increased activities of the key glycolytic enzymes PFK (phosphofructokinase) and PK (pyruvate kinase) were also observed, indicating that Cr(VI) could affect carbohydrate metabolism. Cr(VI) induced downregulation or no effects on the expression of metallothioneins MT10 and MT20, except for an increase in MT20 transcription in males. Moreover, significant up-regulation of the Mytilus estrogen receptor MeER2 and serotonin receptor (5-HTR) were observed in both sexes. The results demonstrate that exposure to Cr(VI) in the low ppb range did not result in strong toxicity or oxidative stress conditions in mussel digestive gland. On the other hand, our data support the hypothesis that low concentrations of the metal can exert pleiotropic effects on mussel physiology, from modulation of lipid and carbohydrate metabolism, to effects on the expression of estrogen-responsive genes., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Calgranulin B is a small calcium-binding protein with several immunological functions mainly involved in chronic inflammation and cancer. It can participate in recruitment of neutrophils and leukocytes in inflamed tissue, oxidant/antioxidant balance, adhesion of neutrophils to fibronectin, and regulation of apoptosis. In a previous proteomic study, we found that calgranulin B was up-regulated in the bronchoalveolar lavage (BAL) of patients with idiopathic pulmonary fibrosis (IPF) with respect to controls and patients with other interstitial lung diseases. The aims of this study are to compare calgranulin B concentrations in BAL of patients with IPF and sarcoidosis and controls by a quantitative method, to look for correlations with clinical data, and to evaluate calgranulin B expression in lung tissue of IPF patients by immunohistochemistry. A modification of a commercial ELISA was used to determine calgranulin B concentrations in BAL of 16 patients with IPF (a group of patients in which we previously performed proteomic analysis), 17 patients with sarcoidosis, and 7 controls. The immunohistochemistry was done in a subgroup of patients with IPF and a control group of lung transplant donors. Calgranulin B concentrations were significantly higher in patients with IPF than controls (p < 0.01); they were inversely correlated with FVC and DLCO values and directly correlated with neutrophil and eosinophil percentages in BAL. Immunohistochemistry revealed a patchy distribution of calgranulin B, predominantly around areas of fibrotic remodeling. Calgranulin B may be a trigger molecule involved in the evolution and progression of IPF, being overexpressed in BAL of patients with IPF with severe functional deterioration and in the peribronchiolar area bordering zones of honeycombing.

In the present study excreta and feathers of five species of adult passerine birds from Montepulciano wetland (Siena, Italy) were assayed for trace elements between January and August 2006. Lead concentrations varied from 16.31 to 26.50 mg/kg and were found strictly related to the age of feathers. Copper levels were found to be high mainly in insectivorous birds (9.68 mg/kg) and were probably influenced by local use of copper-based agricultural fungicides. Mercury accumulation in feathers varied between species from 0.08 to 0.73 mg/kg. The role offeeding habits on trace elements levels in feathers and excreta is discussed.

Sarcoidosis is a systemic granulomatous disease of unknown etiology characterized by activation of macrophages and T lymphocytes. Relatively little is known about the role of mast cells and their mediators in the pathogenesis of sarcoidosis. Tryptase is an enzyme produced by activated mast cells, regarded as a marker of mast cell activation. To analyse tryptase concentrations in serum of sarcoidosis patients in an attempt to define the role of tryptase and mast cells in the pathogenesis of sarcoidosis and to evaluate the potential of tryptase as marker of disease severity. Quantitative analysis of tryptase concentrations was performed in serum of patients with stable sarcoidosis (n = 12), progressive sarcoidosis (n = 23) and controls (n = 13). Patients enrolled in the study had been monitored at Siena Regional Referral Centre for Sarcoidosis from onset for at least 12 months. Significantly higher concentrations of tryptase were found in peripheral blood of sarcoidosis patients (6.08 +/- 3.98 microg/l) than controls (2.96 +/- 1.75microg/l; p = 0.012). Patients with progressive disease showed the highest tryptase concentrations in serum. Tryptase and mast cells may be involved in the immunopathogenesis of sarcoidosis and further studies are required to understand if tryptase may represent a marker of sarcoidosis severity.

Bird feathers have been widely used as a nondestructive biological material for monitoring heavy metals. Sources of metals taken up by feathers include diet (metals are incorporated during feather formation), preening, and direct contact with metals in water, air, dust, and plants. In the literature, data regarding the origin of trace elements in feathers are not univocal. Only in the vast literature concerning mercury (as methyl mercury) has endogenous origin been determined. In the present study, we investigate cadmium, lead, and mercury levels in feathers of prey of Falco eleonorae in relation to the ecological characteristics (molt, habitat, and contamination by soil) of the different species. Cluster analysis identified two main groups of species. Differences and correlations within and between groups identified by cluster analysis were then checked by nonparametric statistical analysis. The results showed that mercury levels had a pattern significantly different from those of cadmium and lead, which in turn showed a significant positive correlation, suggesting different origins. Nests of F. eleonorae proved to be a good source for feathers of small trans-Saharan passerines collected by a noninvasive method. They provided abundant feathers of the various species in a relatively small area--in this case, the falcon colony on the Isle of San Pietro, Sardinia, Italy.

Waterbirds are exposed to many contaminants, including lead from ingestion of shot and fishing sinkers. Lead poisoning had never been reported in flamingos wintering in Italian wetlands. Our investigation stems from a case of four flamingos found dead in Tuscany in 2002 with numerous lead shot in their gizzards. We therefore considered other specimens found dead in different Italian wetlands. Many lead shot found in gizzards and lead tissue concentrations confirmed the hypothesis of lead poisoning in two of the seven specimens analysed: concentrations in liver, kidney, and bone were 361.3, 265.09, and 43.31mug/g d.w., respectively. Lead organotropism was typical of acute poisoning. Cadmium and mercury were also determined, and found to be in line with what little data are available on this species in the literature. Although Italy recently endorsed the African-Eurasian Waterbird Agreement (AEWA) prohibiting use of lead shot for hunting in wetlands, our results reveal a first case of lead shot poisoning in flamingos wintering in Italian wetlands. This evidence sounds a further warning of the problem of spent lead shot in countries where hunting in wetlands is not strictly regulated.

Background: Sarcoidosis is a multisystemic granulomatous disease with an unpredictable clinical course characterized by accumulation of activated proliferating T lymphocytes and mononuclear phagocytes in affected organs., Aims and Methods: The aims of this study were to describe the clinical, radiological and immunological features of a population of sarcoidosis patients followed at the Sarcoidosis Regional Centre in Siena and to analyse chitotriosidase and sIL-2R concentrations in serum of these patients in order to understand their potential as disease markers., Results: Chitotriosidase and sIL-2R concentrations in serum of sarcoidosis patients were found to be significantly higher than in healthy controls (p<0.01) and a positive correlation between the two markers was documented for the first time. Moreover, chitotriosidase and sIL-2R were expressed differently in different radiographic stages of the disease., Conclusion: Chitotriosidase and sIL-2R are two markers of sarcoidosis of different origin, the values of which show a correlation in these patients; they are easily detectable in serum and could be useful clinical markers of progression.

Background: Sarcoidosis is a systemic granulomatous disease characterised by T-helper cell/macrophage alveolitis. Activated macrophages release mediators, such as cytokines, chemokines, oxygen radicals, and enzymes. In a previous paper we found higher levels of chitotriosidase, a macrophage derived enzyme, in serum of patients with sarcoidosis than in controls. Serum chitotriosidase levels were correlated with sarcoidosis radiological stages. Human chitotriosidase is involved in the pathogenesis of many lysosomal storage disorders and is selectively expressed in chronically activated tissue macrophages., Methods: In the present study we determined chitotriosidase concentrations in bronchoalveolar lavage of patients with newly diagnosed pulmonary sarcoidosis (divided into two groups according to clinical parameters) and of controls with an ELISA test., Results: Significantly different chitotriosidase concentrations were found in BAL of patients than controls, especially in patients with progressing disease., Conclusion: Chitotriosidase but not angiotensin converting enzyme concentrations correlated with sarcoidosis radiological stages, and also with the degree of lung infiltrate seen by CT-scan, suggesting that the former enzyme (detected locally and sistemically) may play a role in the pathogenesis of the disease. Further studies with a greater number of patients are needed to confirm this hypothesis and to determine whether chitotriosidase may be a marker of the severity of sarcoidosis.

Levels of Hg, Cd, Pb, Cu, Zn, Fe, and Mn were assessed by using Posidonia oceanica as a bioindicator in the Gulf of Naples (southern Italy). Lepidochronology, which enables retroactive dating of scales and rhizomes of this seagrass, was combined with atomic spectrometry to assess temporal trends of trace elements in dated scales and rhizomes over a 10-year period. Lepidochronology occasionally has been used to monitor Hg in dated scales, but never has been used to determine concentrations of other trace elements in dated rhizomes. Data were compared between various structural parts of seagrass and between sampling sites. Concentrations of some elements found in dated scales or rhizomes showed a similar trend in most of the sites; increasing for Hg and Cu and decreasing for Pb, Fe, and Zn. Contaminant levels indicated by seagrass meadows varied from metal to metal. Concentrations of Hg, Cd, and Pb fell within the ranges measured in other areas considered to have low levels of heavy metal pollution, whereas Cu, Mn, and Zn had higher concentrations only in some years. However, on the basis of other studies, none of the sampling sites are considered to have high contamination levels.

Soils in clay pigeon shooting ranges can be seriously contaminated by heavy metals. The pellets contained in ammunition are composed of Pb, Sb, Ni, Zn, Mn and Cu. The total concentrations of these metals in soils, and the effects of their increasing levels on the arthropod community were investigated at seven sampling sites in a clay pigeon shooting range and compared with two controls. Research revealed that the spatial distribution of Pb and Sb contamination in the shot-fall area was strongly correlated with the flight path of the pellets. Ordination obtained through Redundance Analysis showed that Collembola, Protura and Diplura were positively correlated with major detected contaminants (Pb, Sb), while Symphyla showed a negative correlation with these pollutants. Determination of the soluble lead fraction in soil, and of its bioaccumulation in the saprophagous Armadillidium sordidum (Isopoda) and the predator Ocypus olens (Coleoptera), showed that a significant portion of metallic Pb from spent pellets is bioavailable in the soil and can be bioaccumulated by edaphic organisms, entering the soil trophic network, but without biomagnification.