Search

Background:: Nimotuzumab is a humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody, nowadays used for tumour immunochemotherapy. This study aimed to label the conjugate DOTA-nimotuzumab with yttrium-90, in order to provide a β- emitting radioimmunoconjugate (90Y-DOTA-nimotuzumab) potentially useful to assess the feasibility of a new radio-guided surgery approach. Methods:: The synthesis of 90Y-DOTA-nimotuzumab was performed in two days. Nimotuzumab was conjugated with a 50 fold excess of DOTA and then labelled with 90Y3+. The 90Y-DOTA-nimotuzumab preparation was optimized considering several parameters such as pH, temperature and reaction volume. Moreover, the 90Y-DOTA-nimotuzumab stability was evaluated in human plasma. Results:: The radioimmunoconjugate 90Y-DOTA-nimotuzumab was obtained with a radiochemical purity greater than 96%, and showed a good stability at 20°C as well as at 37°C in human plasma. Conclusions:: The optimized conditions for a mild and easy preparation of 90Y-DOTA-nimotuzumab joined to a promising stability under physiological conditions suggest to propose this radioimmunoconjugate as a potential diagnostic radiopharmaceutical for β- radio-guided surgery.

Cardiotoxicity is a relatively frequent and potentially serious side effect of anticancer treatments, particularly anthracyclines and trastuzumab, widely used in the treatment of breast cancer. The increase in cancer survivors has generated a growing interest in the prevention of cardiotoxicity. Although early studies suggested an overall benefit on cardiac function with the use of ACE inhibitors (ACEIs) and beta blockers (BBs), more recent randomized trials have demonstrated little or no effect of pharmacological interventions. Even the various meta-analyses conducted in this area have provided weak results in favour of cardioprotective therapies for which the benefit would not always justify the risk of developing side effects. Given the incompleteness of the evidence, there is no clear consensus on which patients should initiate cardioprotective therapy. As recommended in the new guidelines of the European Society of Cardiology, risk stratification before treatment is crucial to identify high-risk patients who would benefit most from the use of cardioprotective therapy. Randomized trials are currently underway to evaluate other therapeutic strategies such as sacubitril/valsartan, and the possibility of using gliflozins in the future cannot be excluded. However, rigorous control and treatment of risk factors remain the primary focus in the management of these patients.

Nitroimidazoles are a class of chemicals with a remarkable broad spectrum of applications from the production of explosives to the use as radiosensitizers in radiotherapy. The understanding of thedynamics of their fragmentation induced by ionizing sources is of fundamental interest. The goal of this work is to theoretically investigate the kinetic competition between the two most important decomposition channels of 2, 4 and 5-Nitroimidazole cations: the NO and NO2 losses. The calculated rate constants of the two processes are in very good agreement with the experimental Photoelectron-Photoion Coincidence (PEPICO) branching ratio. This study solves the intriguing and theoretically unexplained experimental observation that 2-Nitroimidazole, at variance with the other two regio-isomers is a source for only NO at low energies (

A 73 year–old man was referred by his general practitioner to our ambulatory for worsening dyspnea. He also reported substantial weight loss (almost 20 kg during the last three months), new onset dysphonia and dry cough. The patient’s medical history also included a former tobacco addiction, arterial hypertension and dyslipidemia. There was not history of cardiomiopathy. Electrocardiogram, showed: sinus rhythm, 60/min with inferior and anterior–lateral abnormality of repolarization. No laboratory exams were available at the first visit. An echocardiogram was performed, showing: marked septal hypertrophy (IVSd= 23 mm), septal hypokinesia, with an ejection fraction at lower limits of normality (EF= 54%), neither systolic anterior motion of the mitral valve. Minimal pericardial effusion was seen. We required a CT scan of the chest, that showed a large (5x8x11cm) mass in the left upper lobe with ipsilateral mediastinal lymphadenopathy. The mass directly extended into the mediastinum with infiltration of pericardial leaflet, left atrium and the left wall of the aortic arch. A hypodense formation of approximately 4 cm in the interventricular septum in the apical portion was reported. PET–CT with FDG was performed, which documented hypercaptation of the radioactive tracer at the level of the above–mentioned lesions. The patient underwent fine–needle aspiration biopsy of the lung mass and the histological examination led to the diagnosis of squamous cell carcinoma of the lung. Systemic treatment with carboplatin plus placlitaxel and pembrolizumab was subsequently started. A cardiac CMR was performed, which documented an area of 30x17x31 mm located at the septal (mid–apical portion), apex and parapical portion of the free wall of the right ventricle with transmural extension. At this area, extensive late gadolinium enanchement (LGE) at marginal level with a central non–capillary core and hyperintense in T2 sequences (compatible with central necrotic lesion). The pericardium also showed LGE and a mild pericardial effusion (maximum 8 mm); left atrium involvement, seen on CT, was not documented . After he completed the third cycle of CHT, at 5 months from the diagnosis, the echocardiogram showed a substantial disappearance of the mass infiltrating the interventricular septum without evidence of pericardial effusion. The ecg was substantially unchanged. The patient stopped carboplatin and paclitaxel after 3 cycles and kept maintenance pembrolizumab still ongoing.

A 75–year–old overweight man, affected by hypertension, diabetes mellitus and atrial fibrillation since 2020. After 3 unsuccessful attempts of electrical cardioversion it was opted for a strategy of rate control with beta blocker and anticoagulant therapy with Rivaroxaban 20 mg. Following episodes of rectal bleeding; adenocarcinoma of the colon was diagnosed. The patient underwent hemicolectomy and started therapy with Pembrolizumab. The anticoagulant was replaced with Edoxaban 60 mg. In August 2022, he was admitted to the emergency department for severe signs and symptoms of heart failure. On ECG, atrial fibrillation with a heart rate of 90 bpm and non–specific changes in ventricular repolarization. The echocardiogram showed a severe reduction of the ejection fraction (FE 30%), which was not present at previous controls. On blood tests, troponins were negative and BNP increased. The patient underwent coronarography which was negative for significant lesions, and heart failure therapy was prescribed. Three months later the patient came to our cardio–oncology outpatient clinic; we repeated the echocardiogram which showed a recovery of the ejection fraction to 45% and planned a cardiac MRI. Cardiac MRI (CMR) showed global left ventricular hypokinesia (FE 42%) and late subepicardial gadoline enhancement in the basal segment of the inferior wall and transmural in the basal segment of the lateral wall without signs of oedema. Report described as compatible with myocarditis. The case was discussed collegially with radiologists and oncologists, and it was decided to discontinue immunotherapy (ICI). Myocarditis is the most common cardiovascular adverse events of ICI therapy, although it has a very low incidence. Generally, myocarditis related to ICI therapy has a high mortality rate and requires discontinuation of ICI. In addition, CMR may have a lower sensitivity in this setting. There is also a possibility of developing left ventricular dysfunction without associated myocarditis in the absence of increase in cardiac troponin and active myocardial inflammation at CMR. Although our case has been defined as myocarditis, it presents some unclear aspects due in part to the early non–diagnosis as a complication of ICI therapy. Although cancer patients taking ICI has expanded considerably in recent years, the evidence on cardiovascular complications is scarce and unknown to the clinical cardiologist.

An extensive rearing system (ERS) for poultry requires an outdoor run, which enhances the foraging activity of chickens. Slow-growing (SG) strains are more adapted to ERS than fast-growing (FG); and generally, have higher levels of bioactive compounds in their meat. The aim of this paper was to assess the storage efficiency of n-3 and n-6 polyunsaturated fatty acids (PUFA), tocols and carotenes in the meat of seven commercial SG genotypes (SG1-7). One hundred SG chicks/strain of both sexes were included and their walking activity (High- or Low-W) was classified: SG1-4, HW comprised more than 10% of the time budget, and SG5-7, less than 10% (LW). Chickens were reared in pens (4 pens/strain) with indoor (0.10 m2/bird) and outdoor (4 m2/bird) areas, and they were fed the same dietad libitum(starter feed for 1–21 d, grower feed from 22 d to slaughter at 81 d). The chickens were weighed weekly; feed consumption and grass intake were also estimated. At 81 days of age, 32 chickens/genotype were selected on the basis of the average weight (1:1, M:F) and slaughtered. The breast, thigh and drumstick meat were excised from 30 carcasses/genotype, sampled and stored at -20°C until analysis. Nutrients (e.g., n-3, n-6, carotenes and tocols) of feed, grass and meat were analyzed. The storage efficiency of nutrients was estimated as the ratio between the amount deposited in the body muscles (OUT) and the dietary intake (feed and grass, IN). The genotype affected chickens foraging behavior and the intake of nutrients. For SG1, SG2 and SG3, more than 50% of the intake of n-3 came from grass, whereas in the other genotypes, less than 20%. Accordingly, chickens that foraged more showed better meat nutritional profiles (less fat, more n-3 and antioxidants), which, in ERS, was ascribed to grass ingestion. However, the storage efficiency of nutrients into meat was inversely correlated with the grass intake: strains with higher grass intake (SG1, SG2, and SG3) had lower storage rates. Several hypotheses were proposed to explain these trends.

Background: There is paucity of data on the potential value of early palliative home care for patients with hematologic malignancies. Objective: To compare costs, use of resources, and clinical out...

The exothermic hydrogen transfer from H

The influence of NGF in male reproduction in some animal species and humans has already been assessed. Many of these effects are mediated by the distribution and abundance of tropomyosin receptor kinase A (TrKA) and p75 neurotrophin (p75NTR) receptors on sperm cells. The aim of this research was to investigate the role of NGF and its receptors, TrKA and p75NTR, in rabbit sperm outcomes during in vitro storage. Major semen traits (kinetic parameters, apoptotic, necrotic and live sperm) were recorded in rabbit semen samples from 0 to 12 h of storage (every 4 h). Three experimental hypotheses were formulated: i) sperm storage changes NGF receptor abundance in rabbit sperm; ii) TrKA and p75NTR differently modulate NGF signalling (assessed by the neutralisation of receptors); iii) NGF-receptor interactions show different responses during storage (evaluated by the addition of exogenous NGF). The results demonstrate that: (i) the receptor number changed in a time-dependent manner with a significant increase in p75NTR after 8–12 h of storage; ii) the neutralisation of NGF receptors largely affected VCL, apoptotic, necrotic and live cells during sperm storage, i.e. blockade of TrKA significantly increased speed, capacitation, necrosis and apoptosis, whereas blockade of p75NTR improved motility and live cells; iii) the addition of exogenous human NGF (100 ng/mL) at different time points of storage (0, 4, 8 h) differently influenced sperm traits i.e. NGF addition at time 0 positively affected all the pro-vital traits (kinetic, live cells) whereas, after 4–8 h, the effect of NGF was null or negative. In conclusion, NGF affects kinetic and other physiological traits (capacitation, apoptosis and necrosis) of rabbit sperm in a time-dependent manner. Most of these modifications are modulated by the receptors involved (TrKA or p75NTR), which changed considerably during sperm storage (increase of p75NTR).

The nerve growth factor (NGF), a member of the neurotrophins family, plays an important role in the nervous system but also in the reproductive apparatus and in sperm traits. The aim of this review is to summarize the effect of NGF on sperm functions of mammals. NGF was detected in seminal plasma of many animal species and its receptors, TrkA and p75NTR, are present in both epididymal and ejaculated sperm. The NGF, either endogenous or exogenous, may affects the kinetics and other sperm traits (e.g. capacitation, apoptosis, necrosis and acrosome reaction) and these effects appear modulated by the different receptors involved (TrkA or p75NTR). Although the animal species can affect the localization of receptors, TrkA seems mainly to be confined in the head and p75NTR in the midpiece and tail. Considering that some seminal disorders and sperm traits have been correlated with a lower NGF concentration, this review provides recent insights on the role of NGF on sperm cells and the possible mechanism implicated.

Agroforestry systems, which are based on the integration of trees and animals, represent a useful practice for implementing the “One Welfare” concept. Geese could adapt well to these systems due to their kinetic and grazing abilities. However, the lack of specific ethograms and animal-based measures have not yet allowed a deep assessment of their welfare and behavior. The aim of this study was to develop and validate a protocol to evaluate the behavior of geese reared in two agroforestry systems (i.e., apple orchard and vineyard). Thus, a behavior observation form (BOF) including a specific ethogram was proposed, and its interobserver reliability, content, criterion and construct validity were determined. Moreover, the influence of the time of day and type of agroforestry system on geese's behavior was also investigated. Agreement and principal component analyses, as well as the comparison between data collected through direct observation by the BOF and indirect observation by a computerized system, supported the reliability and validity of the proposed protocol. While the BOF also highlighted differences in the behavior expressed by the geese according to the time of day and the environmental context, both the vineyard and apple orchard systems seem to meet their biological and behavioral needs.

Anthracyclines represent the most effective chemotherapeutic agent in the treatment of non–Hodgkin‘s lymphoma (NHL), although their use is limited due to the risk of cardiac toxicity. This occurs mainly in elderly patients, those with a history of cardiovascular (CV) disease and/or multiple concomitant risk factors. Liposomal doxorubicin has been shown to reduce this toxicity. The aim of this retrospective study is to investigate the use of non–pegylated liposomal doxorubicin in high–risk patients in terms of haematological response rate and CV events. In a single centre, 15 patients undergoing R–COMP regimen (Rituximab, Prednisone, Cyclophosphamide, Vincristine, Myocet liposomal doxorubicin) were consecutively collected from January 2020 to December 2021. The mean age of patients was 73.9 years and 60% were male. The baseline mean left ventricular ejection fraction (LVEF) was 55.9%; four patients had a baseline FE of Conclusions Our results support the efficacy and safety of R–COMP in a population at high risk for cardiac events, otherwise excluded from anthracycline–containing therapy. Liposomal formulatio reduces doxorubicin cardiomyocyte accumulation and thus toxicity, providing the best possible treatment for the majority of the onco–haematological population.

39–year–old female, without cardiovascular risk factors. At the end of pregnancy she complained of progressive dyspnoea and so she was admitted to the emergency room. Blood tests showed elevated D–dimer and LDH values. A chest CT scan was performed showing a mediastinal mass of about 15 cm encompassing the ascending aorta, the left brachiocephalic trunk and the superior vena cava, both of which appeared thrombosed. Therapy with low molecular weight heparin was started. The patient underwent a mediastinal biopsy, which documented a primary mediastinal non–Hodgkin‘s lymphoma. The baseline cardiological evaluation showed a preserved ejection fraction (60%) at echocardiogram (ECHO). The first cycle of chemotherapy with R–CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine) was started. After an episode of hypoesthesia of the left upper limb, that regressed spontaneously within a few hours, she performed MRI that showed multiple areolas compatible with ischemic disease. Following these results the patient was submitted to an ECHO with saline solution injected through the right brachial vein that documented evidence of early opacification of the left atrium and subsequent opacification of the right sections (after 3 cardiac cycles) (Fig. 1–2). This finding suggested a right–to–left shunting, via the bronchial lower district to the left atrium (pulmonary veins). This suspicion was confirmed by CT angiography, which showed occlusion of the superior vena cava with passage of contrast into azygos and early opacification of peribronchial venous circles (Fig. 3). A patency of foramen ovale was ruled out by injection of saline solution through the femoral vein. After the second cycle of chemotherapy, ECHO showed diffuse hypokinesia and reduced EF to 50%. It was then decided to proceed with the third cycle according to the intensified R–DAEPOCH scheme, except for doxorubicin, because of the cardiotoxicity developed by the patient. A cardioprotective therapy was also started with bisoprolol and ramipril with rapid titration. At subsequent radiological controls, a progressive reduction of the mediastinal mass was found and after just one month, the echocardiogram showed a complete recovery of the EF. Contrast injection confirmed presence of a veno–venous shunt. Cardio–oncology is an intriguing and complex discipline that requires the development of local multidisciplinary teams for challenging situations that patients with cancer may ask us to address.

A 53–year–old woman was admitted for chest pain for over two weeks, fever, dry cough, fatigue and myalgia. Chest pain increased in supine position and inspiration. Nasopharyngeal swab was positive for SARS–CoV–2 RT–PCR assay. Admission ECG displayed mild ST–segment elevation (0,5 mm) in inferolateral leads and echocardiogram showed normal left ventricular volume, mildly decreased left ventricular EF (52%) and no regional wall motion abnormalities. Blood tests exhibited elevated values of high–sensitivity troponin I (818 pg/mL), proBNP (19.190 pg/mL), CRP (42 mg/dL), D–Dimer test (1090 ng/mL) and WBC (13000/uL, N 89%, L 7%). IL–6 resulted slightly increased (18 ng/mL). ECG after 24 hours showed T wave inversion in inferolateral leads. Coronary CT angiography revealed normal epicardial arteries. A new echocardiogram, after five days, showed infero–basal hypokinesia, improved global EF (57%) and minimal pericardial effusion. Aspirin and fondaparinoux were started. Myopericarditis was suspected and high dose steroids were administered. After a few days, symptoms improved and ECG, echocardiographic abnormalities and troponin levels were normalized. At 6 weeks follow–up the patient was asymptomatic, ECG and echocardiogram were both normal. Instead cardiac MRI showed signs of endothelial injury: presence of interstitial oedema in the inferoapical and anteroseptal wall (STIR–T2–weighted), without late gadolinium enhancement. We measured blood levels of endothelial dysfunction markers: soluble ICAM–1, VCAM–1 and von Willebrand factor (vWF). They all resulted elevated as compared to a laboratory pool of normal serum (535 ng/ml, 265 ng/ml, and 1659 ng/ml, respectively). Our case was suggestive of myopericarditis related to Sars–Cov–2, but echocardiogram and MRI did not show signs of myocarditis permanent damage. However MRI showed interstitial oedema and hyperemia, typical signs of endothelial injury. Moreover we found high levels of soluble endothelial adhesion molecules, vWF, ICAM–1 and VCAM–1, likely expression of the microcirculatory endothelial dysfunction due to myocardial endothelialitis. In conclusion, our case report suggests that, in COVID–19, acute myocardial injury associated with clinical and investigational signs of myocarditis can be due to myocardial endothelialitis rather than true myocarditis and that an early management with anti–inflammatory drugs (steroids) can be particularly beneficial in patients with unexplained elevated cardiac troponin.

Prevention of left ventricular dysfunction predominantly induced by anthracyclines and/or trastuzumab still represents a challenge for cardio-oncology today. Indeed, this complication threatens to limit the significant gain in cancer survival achieved to date. Oncology strategies with cumulative dose limitation, continuous infusion, dexrazoxane, and liposomal formulations have been shown to decrease the risk of anthracycline cardiotoxicity. The preventive use of ace inhibitors, sartans, and/or beta-blockers has not yet provided convincing evidence and the positive effect on left ventricular ejection fraction decline appears poor without a clear clinical relevance. Assessment of the cardiovascular risk profile is a key aspect of the baseline evaluation of any patient scheduled for cancer therapy. Control and/or correction of modifiable cardiovascular risk factors is the first form of primary prevention of cardiotoxicity. It will be necessary to select populations at higher risk of developing cardiac dysfunction, identify patients genetically predisposed to develop cardiotoxicity in order to build the most appropriate strategies to correctly and timely target cardioprotective therapies.

Background Radiation therapy (RT) is widely diffused in the treatment of cancer; but it could lead to various negative consequences on the cardiovascular system, even several years after treatment end. They include also valvular heart diseases, arrythmias, coronary artery diseases, heart failure, pericardial diseases, systemic and pulmonary artery diseases. We report an interesting case about RT cardiotoxicity different manifestation occurred in the same patient. Case report: 79 years old patient, history of previous testicular seminoma when he was 54 years old (1997), treated through surgery and RT with betatron (total body cobalt). In 2008 aortic valve replacement with mechanical prothesis; in 2017 first hospitalization for heart failure during atrial fibrillation. In subsequent years, recurring episodes of atrial fibrillation (2 unsuccessful attempts at electrical cardioversion), and heart failure exacerbations with mild reduced ejection fraction, treated through medical therapy improvement. At follow–up echocardiogram (03/19) finding of ejection fraction mild reduced (45%), right sections increased in volumes, tricuspid valve moderate regurgitation. In January 2022, at the last cardiac check–up, he reported worsening dyspnoeic symptoms, and occasional episodes of retrosternal pain in last months. It was performed Coro–TC observing a 60% stenosis at distal tract of right coronary; in addition, patient underwent a transoesophageal echocardiogram which documented further reduction in left ventricle ejection fraction, and worsening tricuspid regurgitation to a severe degree, with anulus dilatation and partial failure of leaflets coaptation, which appeared fibro–elastic; inferior vena cava ectasia, Paps 40–45 mmHg circa. Holter–ECG showed atrial fibrillation for all 24 hours, plus 2000 BEV. The case was discussed in Heart Team, and an indication was placed for Triclip intervention. Discussion Nowadays great achievements of anticancer therapies improved patients’ survival, consequently increased the number of anticancer therapies complications; therefore, an accurate cardiac screening for early diagnosis and effective treatment of CV adverse effects is necessary. Several distinct factors contribute to determine the onset cardiotoxicity insurgence, such as the type of cancer, its anatomical localization; radiation techniques applied, total and fractional radiation doses; patient’s age and his comorbidity and risk factors for cardiovascular diseases.

Chicken meat is rich in unsaturated fatty acids. Therefore, it is more susceptible to lipid oxidation and production of volatile organic compounds (VOC). In this study, we evaluated the fatty acids, antioxidants, and VOC profiles of raw and cooked meat samples derived from 4 strains of chicken differing in their growth rates, which were as follows: slow-growing (SG, Leghorn), medium-growing (MG, Hubbard and Naked Neck), and fast-growing (FG, Ross). The VOC profile of meat was measured using proton-transfer reaction–mass spectrometry (PTR–MS). The VOC were identified using PTR–time of flight-MS (PTR-ToF-MS). The data were analyzed using both univariate and multivariate models. Twenty main VOC were identified, which were classified into the following chemical categories: aldehydes, alkadienes, alkenes, furans, amides, alcohols, and other compounds. Our results revealed that the chicken genotype and the method of cooking strongly influenced the VOC profile of the meat. Identifying the relationships between these traits allowed us to highlight the trade-off of the main substrates such as n-3 and n-6 polyunsaturated fatty acids (PUFA), protective substances (antioxidants), and degradation products (VOC) of the poultry meat produced during cooking. The extent of VOC production and n-3 loss was found to be higher for the SG genotype. Reduction of n-6 was higher in MG, whereas small losses in antioxidants and PUFA were observed in the FG genotype, consequently, resulting in the lowest production of VOC. The SG and MG are genotypes more active from a kinetic point of view respect to the FG ones. For this reason, in the FG genotypes, the antioxidants are less involved in the oxidative stress induced by the movement; thus, they were available to protect the lipid of the meat during the cooking process. These results suggested that the use of SG and MG genotypes requires a specific dietary protocol (i.e., increasing the antioxidants content) to counteract the lipid oxidations in all the phases: in vivo, postmortem, and during/after cooking.

Environmental enrichment may slow cognitive decay possibly acting through an improvement in vascular function. Aim of the study was to assess the effects of a 7-month cognitive, social, and physical training program on cognitive and vascular function in patients with mild cognitive impairment. In a single-center, randomized, parallel-group study, 113 patients (age, 65–89 years) were randomized to multidomain training (n=55) or usual care (n=58). All participants underwent neuropsychological tests and vascular evaluation, including brachial artery flow-mediated dilation, carotid–femoral pulse wave velocity, carotid distensibility, and assessment of circulating hematopoietic CD34+ and endothelial progenitor cells. At study entry, an age-matched control group (n=45) was also studied. Compared with controls, patients had at study entry a reduced flow-mediated dilation (2.97±2.14% versus 3.73±2.06%; P =0.03) and hyperemic stimulus (shear rate area under the curve, 19.1±15.7 versus 25.7±15.1×10 −3 ; P =0.009); only the latter remained significant after adjustment for confounders ( P =0.03). Training improved Alzheimer disease assessment scale cognitive (training, 14.0±4.8 to 13.1±5.5; nontraining, 12.1±3.9 to 13.2±4.8; P for interaction visit×training=0.02), flow-mediated dilation (2.82±2.19% to 3.40±1.81%, 3.05±2.08% to 2.24±1.59%; P =0.006; P =0.023 after adjustment for diameter and shear rate area under the curve), and circulating hematopoietic CD34 + cells and prevented the decline in carotid distensibility (18.4±5.3 to 20.0±6.6, 23.9±11.0 to 19.5±7.1 Pa −1 ; P =0.005). The only clinical predictor of improvement of cognitive function after training was established hypertension. There was no correlation between changes in measures of cognitive and vascular function. In conclusion, a multidomain training program slows cognitive decline, especially in hypertensive individuals. This effect is accompanied by improved systemic endothelial function, mobilization of progenitor CD34 + cells, and preserved carotid distensibility. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01725178.

Autologous stem cell transplantation (ASCT) has gained growing consideration as a treatment option for favorable-risk acute myeloid leukemia (FR-AML) in first complete remission (CR1), compared with chemotherapy.We report the long-term outcomes of 117 consecutive patients with FR-AML fit for intensive chemotherapy diagnosed in our center between 1999 and 2020, who underwent ASCT.Sixty-five of the 117 were eligible for intensive post-remission treatment, and 42 of those 65 received ASCT. Median follow up was 132 months. Overall survival (OS) and disease-free survival (DFS) were 75% and 76%. Higher doses of CD34 + stem cell infusions negatively impacted DFS in multivariate analysis. Core-binding factor (CBF) leukemia was an independent prognostic factor for improved DFS. No differences based on pre-transplant measurable residual disease (MRD) were observed. In CBF leukemia, 10-year DFS is 72% for MRD-positive patients versus 100% for MRD negative patients.ASCT is effective and safe in FR-AML patients. In CBF leukemia, ASCT provides excellent results regardless of achievement of bone marrow MRD negativity. In NPM1-mutated/FLT3-wild type (mNPM1) AML, early molecular response seems to have more impact on prognosis. Prospective investigation of the role of gemtuzumab ozogamicin in this setting is ongoing.

Objectives During the lockdown that started in Italy on 10 March 2020 to address the COVID-19 pandemic, aggressive procedures were implemented to prevent SARS-CoV-2 transmission in SARS-CoV-2-negative patients with haematological malignancies. These efforts progressively reduced Klebsiella pneumonia carbapenemase-producing K. pneumoniae (KPC-KP) spread among these patients. Here we evaluated the potential effects of measures against COVID-19 that reduced KPC-KP transmission. Patients and methods We analysed KPC-KP spread among 123 patients with haematological malignancies, hospitalized between March and August 2020, who were managed using measures against COVID-19. Their outcomes were compared with those of 80 patients hospitalized during the preceding 4 months (November 2019–February 2020). Results During March–August 2020, 15.5% of hospitalized patients were KPC-KP positive, compared with 52.5% in November 2019–February 2020 (P Conclusions Aggressive strategies to prevent SARS-CoV-2 transmission were applied to all hospitalized patients, characterized by high levels of KPC-KP endemicity and nosocomial transmission. Such measures prevented SARS-CoV-2 infection acquisition and KPC-KP horizontal transmission. Reduced KPC-KP spread, fewer associated clinical complications and decreased ceftazidime/avibactam consumption represented unexpected ‘collateral benefits’ of strategies to prevent COVID-19.

Nitroimidazoles are a class of chemicals with a remarkable broad spectrum of applications from the production of explosives to the use as radiosensitizers in radiotherapy. The understanding of thedynamics of their fragmentation induced by ionizing sources is of fundamental interest. The goal of this work is to theoretically investigate the kinetic competition between the two most important decomposition channels of 2, 4 and 5-Nitroimidazole cations: the NO and NO

The occurrence of an acute myeloid leukemia (AML) relapse is generally observed within 2–3 years after complete remission (CR) and affects the overall survival rate of these patients [1]. Few studi...

An extensive rearing system (ERS) for poultry requires an outdoor run, which enhances the foraging activity of chickens. Slow-growing (SG) strains are more adapted to ERS than fast-growing (FG); and generally, have higher levels of bioactive compounds in their meat. The aim of this paper was to assess the storage efficiency of n-3 and n-6 polyunsaturated fatty acids (PUFA), tocols and carotenes in the meat of seven commercial SG genotypes (SG1-7). One hundred SG chicks/strain of both sexes were included and their walking activity (High- or Low-W) was classified: SG1-4, HW comprised more than 10% of the time budget, and SG5-7, less than 10% (LW). Chickens were reared in pens (4 pens/strain) with indoor (0.10 m2/bird) and outdoor (4 m2/bird) areas, and they were fed the same diet ad libitum (starter feed for 1–21 d, grower feed from 22 d to slaughter at 81 d). The chickens were weighed weekly; feed consumption and grass intake were also estimated. At 81 days of age, 32 chickens/genotype were selected on the basis of the average weight (1:1, M:F) and slaughtered. The breast, thigh and drumstick meat were excised from 30 carcasses/genotype, sampled and stored at -20°C until analysis. Nutrients (e.g., n-3, n-6, carotenes and tocols) of feed, grass and meat were analyzed. The storage efficiency of nutrients was estimated as the ratio between the amount deposited in the body muscles (OUT) and the dietary intake (feed and grass, IN). The genotype affected chickens foraging behavior and the intake of nutrients. For SG1, SG2 and SG3, more than 50% of the intake of n-3 came from grass, whereas in the other genotypes, less than 20%. Accordingly, chickens that foraged more showed better meat nutritional profiles (less fat, more n-3 and antioxidants), which, in ERS, was ascribed to grass ingestion. However, the storage efficiency of nutrients into meat was inversely correlated with the grass intake: strains with higher grass intake (SG1, SG2, and SG3) had lower storage rates. Several hypotheses were proposed to explain these trends.

Open-ended learning is a core research field of developmental robotics that aims to build learning machines and robots that can autonomously acquire knowledge and skills incrementally as infants and children do. Here we present a competition, in its third edition, that aims to create a standard benchmark within the field. The competition focuses on a simulated camera-arm robot that: (a) in a first ‘intrinsic phase’ acquires sensorimotor competence by autonomously interacting with objects through mechanisms such as curiosity, intrinsic motivations, self-generated goals, and reinforcement learning; (b) in a second ‘extrinsic phase’ is tested with tasks unknown in the intrinsic phase to measure the quality of knowledge and skills acquired in the first phase. Participants can install a simulated environment on their machines to handily develop and test their systems, then submit these to the online platform for evaluation and public ranking. As for infants, the benchmark requires the contextual solution of a number of challenges usually tackled in isolation, such as exploration, sparse rewards, object learning, generalisation, task/goal self-generation, and autonomous skill learning. The competition is contributing to foster the research in the field within different scientific communities, and to operationally define the multiple challenges posed by open-ended learning so as to compare how alternative systems can solve them.

Aim To assess the prevalence of insomnia and possible associated factors in patients with advanced lung cancer admitted to different settings of palliative care. Methods Secondary analysis of a consecutive sample of patients with advanced lung cancer receiving palliative care. Epidemiological and clinical data, treatments received in the last month, Karnofsky status, Edmonton Symptom Assessment System (ESAS), Athens Insomnia Scale (AIS) and the Hospital Anxiety and depression scale (HADS), as well as concomitant medical treatment were recorded. Results One-hundred-eight-two patients with advanced lung cancer were surveyed. The mean age was 69.9 years (SD 10.8), and 121 patients (66%) were men. The majority of patients showed consistent levels of insomnia. A poor Karnofsky level, pain, nausea, and drowsiness, time from diagnosis (1-3 years), HADS anxiety, and HADS depression, were positively associated with insomnia. Conclusions About 50% of patients with advanced lung cancer admitted to palliative care services had relevant insomnia. Several factors associated with insomnia have been identified and should prompt physicians for a careful examination and subsequent treatment.

Even if laboratory practice is essential for all scientific branches of knowledge, it is often neglected at High School, due to lack of time and/or resources. To establish a closer contact between school and experimental sciences, the University Sapienza of Roma and the Istituto Nazionale di Fisica Nucleare (INFN) launched the Lab2Go project, with the goal of spreading laboratory practice among students and teachers in high schools., in Italian

Mitochondria are essential for neurons and must be optimally distributed along their axon to fulfil local functions. A high density of mitochondria has been observed in retinal ganglion cell (RGC) axons of an unmyelinated region of the optic nerve, called the glial lamina (GL) in mouse (lamina cribrosa in human). In glaucoma, the world’s leading cause of irreversible blindness, the GL is the epicenter of RGC degeneration and is connected to mitochondrial dysfunction. It is generally accepted that the local accumulation of mitochondria in the GL is established due to the higher energy requirement of unmyelinated axons. Here we revisit the connection between mitochondrial positioning and myelin in RGC axons. We show that the high density of mitochondria in the GL is restricted to larger axons and is established before myelination. Thus, contrary to a longstanding belief in the field, the myelination pattern is not responsible for the establishment of the local accumulation of mitochondria in GL axons. Our findings open new research avenues likely critical to understanding the pathophysiology of glaucoma.

Chicken meat is becoming the most consumed in the world for both economic and nutritional reasons; regarding the latter, the lipid profile may play positive or negative roles in the prevention and treatment of diseases. In this study, we define the state of the art of lipid-based nutritional indexes and used the lipid content and fatty acid profile (both qualitative and quantitative) of breast meat of two poultry genotypes with different growth rates and meat traits. Further, we summarize and review the definitions, implications, and applications of nutritional indexes used in recent years and others of our own design to provide a useful tool to researchers working in the field of meat quality (not only in poultry) to select the most appropriate index for their own scientific purposes. All indexes show advantages and disadvantages; hence, a rational choice should be applied to consider the nutritional effect of meat on human health and for a possible assessment of the most suitable rearing systems (genotype, feeding, farming system or postmortem handling).

The study of ions in the gas phase has a long history and has involved both chemists and physicists. The interplay of their competences with the use of very sophisticated commercial and/or homemade instrumentations and theoretical models has improved the knowledge of thermodynamics and kinetics of many chemical reactions, even if still many stages of these processes need to be fully understood. The new technologies and the novel free-electron laser facilities based on plasma acceleration open new opportunities to investigate the chemical reactions in some unrevealed fundamental aspects. The synchrotron light source can be put beside the FELs, and by mass spectrometric techniques and spectroscopies coupled with versatile ion sources it is possible to really change the state of the art of the ion chemistry in different areas such as atmospheric and astro chemistry, plasma chemistry, biophysics, and interstellar medium (ISM). In this manuscript we review the works performed by a joint combination of the experimental studies of ion–molecule reactions with synchrotron radiation and theoretical models adapted and developed to the experimental evidence. The review concludes with the perspectives of ion–molecule reactions by using FEL instrumentations as well as pump probe measurements and the initial attempt in the development of more realistic theoretical models for the prospective improvement of our predictive capability.

The most reared species of farm animal around the world is the chicken. However, the intensification of livestock systems has led to a gradual increase in the concentration of a limited number of breeds, resulting in substantial erosion to the genetic pool. The initial step of an ‘animal conservation program’ entails establishing the actual conservation statuses of the breeds concerned in a defined area, in this case, in Italy. To this end, a survey of breeds was performed by means of a census questionnaire divided into two parts. The first part collected information on breeds, breeders, housing facilities, and management aspects, the results of which are presented here. The second part of the questionnaire regarded chicken products and their markets, and these data will be reported in a second paper. The breed status of six chicken breeds was shown to be exceptionally worrying, with total numbers ranging from just 18 to 186 birds. Population sizes exceeding 1000 birds was identified for just four breeds, the maximum being 3400. Some improvements in status were noted in relation to breeds which had been the subject of conservation efforts in the past. The two most common breeds reported are the Bionda Piemontese, a double-purpose breed, and the Livorno egg-laying hen. Collo Nudo Italiano, Millefiori Piemontese, Pollo Trentino, and Tirolese chicken breeds and the Castano Precoce turkey breed were not listed by breeders at all. The most reported turkey breeds are the Bronzato Comune and the Ermellinato di Rovigo. The population sizes of native Italian poultry breeds were shown to be generally poor. Italian poultry farmers and the population at large are largely ignorant about indigenous poultry breeds. Thus, promoting the virtues of Italian breeds would help their conservation by encouraging breeders to rear these birds and consumers to buy their products. The identification of strategies to facilitate access to pure breed birds is essential, and will require the collaboration of university research centers, public entities, and breeders. The results presented in this paper constitute the initial part of a more complex conservation program.

A common view on the brain learning processes proposes that the three classic learning paradigms -- unsupervised, reinforcement, and supervised -- take place in respectively the cortex, the basal-ganglia, and the cerebellum. However, dopamine outbursts, usually assumed to encode reward, are not limited to the basal ganglia but also reach prefrontal, motor, and higher sensory cortices. We propose that in the cortex the same reward-based trial-and-error processes might support not only the acquisition of motor representations but also of sensory representations. In particular, reward signals might guide trial-and-error processes that mix with associative learning processes to support the acquisition of representations better serving downstream action selection. We tested the soundness of this hypothesis with a computational model that integrates unsupervised learning (Contrastive Divergence) and reinforcement learning (REINFORCE). The model was tested with a task requiring different responses to different visual images grouped in categories involving either colour, shape, or size. Results show that a balanced mix of unsupervised and reinforcement learning processes leads to the best performance. Indeed, excessive unsupervised learning tends to under-represent task-relevant features while excessive reinforcement learning tends to initially learn slowly and then to incur in local minima. These results stimulate future empirical studies on category learning directed to investigate similar effects in the extrastriate visual cortices. Moreover, they prompt further computational investigations directed to study the possible advantages of integrating unsupervised and reinforcement learning processes.

COVID-19 pandemic has changed the world and our lives, many economic activities have been suspended; consequently, many contracts have not been performed or there was a delay in performance. This paper aims to analyse the impact of COVID-19 on international trade contracts; in particular, whether or not COVID-19 can be considered force majeure. After a short definition of force majeure, the paper analyses the text of the Vienna Convention on International Sale of Goods (CISG) and the relative case law, then the impact of COVID-19 under English law. In the end, some conclusive remarks.

Background. KPC-K.pneumoniae bloodstream infection (KPC-KpBSI) mortality rate in patients with hematological malignancies is reported about 60%. The initial treatment active against KPC-K.pneumoniae is crucial for survival and KPC-K.pneumoniae rectal colonization usually precedes KPC-KpBSI. We evaluated the impact on KPC-KpBSI mortality of the preemptive use of antibiotics active against KPC-K.pneumoniae, as opposed to inactive or standard empiric antibiotics, for the empiric treatment of febrile neutropenia episodes in patients with hematological malignancy identified as KPC-K.pneumoniae intestinal carriers. Methods. We compared the outcomes of KPC-KpBSIs occurring in high-risk patients with hematological malignancy known to be colonized with KPC-K.pneumoniae, during two time periods: March 2012-December 2013 (Period 1, initial approach to KPC-K.pneumoniae spread) and January 2017-October 2018 (Period 2, full application of the preemptive strategy). The relative importance of the various prognostic factors that could influence death rates were assessed by forward stepwise logistic regression models.Results. KPC-KpBSI-related mortality in patients with hematological malignancies identified as KPC-K.pneumoniae carriers dropped from 50% in Period 1 to 6% in Period 2 (pK.pneumoniae carriers were treated with initial active therapy in 56% and 100% of cases in Period 1 and Period 2, respectively (pConclusions. In high-risk patients with hematological malignancies colonized by KPC-K.pneumoniae, the empiric treatment of febrile neutropenia active against KPC-K.pneumoniae reduced KPC-KpBSI-related mortality to 6% and prevented fatal breakthrough KPC-KpBSI.

Die soziale Integration ist als ein Prozess zu verstehen, welcher die Gesellschaft als Ganzes miteinbezieht. Laut dem Staatsekretariat für Migration ist ein friedliches Zusammenleben zwischen der Aufnahmegesellschaft und den Zugewanderten das Ziel. Soziale Integration aber betrifft nicht nur die Geflüchteten, sondern auch Gruppen, die sich sozial und finanziell in einer benachteiligten Lage befinden. Gemeinden und Städte werden in Bezug auf den Sozialraum vor neue Herausforderungen gestellt. Dies verlangt nach einem Umdenken und einer Anpassungsfähigkeit der Bautätigkeit und der Gestaltung von Raum, um auf die stetige Veränderung der Lebenswelten der Bewohnenden eingehen zu können, der Separierung von bestimmten Gruppen entgegenzuwirken und gleichzeitig deren Teilhabe-Chancen zu erhöhen. In Zürich Altstetten wurde durch eine Zusammenarbeit der Asylorganisation Zürich und des Jugendwohnnetzes mit der Siedlung der Stiftung Einfach Wohnen das erste Projekt der Schweiz gestartet, welches versucht die soziale Integration mit neuen Ansätzen anzugehen. Zum ersten Mal leben Geflüchtete und junge Erwachsene in Ausbildung in dieser Siedlung Tür an Tür. Dieses neuartige Projekt bildet der Untersuchungsgegenstand dieser Forschungsarbeit, wobei der Fokus auf das Zusammenleben der zwei unterschiedlichen Gruppen gerichtet wird. Verschiedene Faktoren, welche das Zusammenleben beeinflussen können, werden kritisch beleuchtet, um anschliessend aus den gewonnenen Erkenntnissen Handlungsempfehlungen abzuleiten., + Code Diss LU: hslusa basp be 2020 + hslusa bask be 2020 + Fussnote: Bachelor-Arbeit, Hochschule Luzern – Soziale Arbeit, Ausbildungsgang Sozialpädagogik & Soziokultur 2020 + NL-Code: NLLUHSA202008

This study aimed to assess the effect of rearing system (intensive vs. free-range under vineyard) on the qualitative characteristics of goose meat. In particular, the integration of a goose raising system with an organic grape production was evaluated. Six hundred Romagnola geese of both sexes were divided into two groups at 21 d of age: Vineyard group (V) – 480 geese (120 geese/ha) pasturing in 4 ha of vineyard, and Control Group (C) – 120 geese of the same genotype in the experimental farm of Perugia, without any access to the pasture. Live weight, feed consumption and other performance were registered weekly on 30 selected and marked animals/group. At 160 days of age, 15 geese/group were slaughtered and characteristics of carcase, breast and drumstick (physical, chemical, oxidative status, fatty acids profile) were evaluated. The chemical analysis of diet and pasture and the ingestion of crude protein, digestible energy and bioactive compounds were also estimated. Vineyard geese, showed lower productive performance than the C ones (live and carcase weight), however, due to pasture availability, the intake of bioactive compounds (vitamin E, retinol, n-3 long-chain fatty acids) was higher and positively affected the antioxidant content of breast and drumstick. The higher kinetic activity of V geese reduced the fat amount of carcase and meat, whereas increased the development of drumstick muscle (higher meat/bone ratio) and worsened the oxidative status of meat. Concluding, the free-range vineyard geese resulted in a positive payoff on the geese meat quality viewpoint.Highlights Pasture enhance the amount of VIT E in goose muscle. Pasture reduce the amount of lipid in goose carcass and meat. Pasture enhance the amount of n-3 PUFA in goose meat.

Categorical perception identifies a tuning of human perceptual systems that can occur during the execution of a categorisation task. Despite the fact that experimental studies and computational models suggest that this tuning is influenced by task-independent effects (e.g., based on Hebbian and unsupervised learning, UL) and task-dependent effects (e.g., based on reward signals and reinforcement learning, RL), no model studies the UL/RL interaction during the emergence of categorical perception. Here we have investigated the effects of this interaction, proposing a system-level neuro-inspired computational architecture in which a perceptual component integrates UL and RL processes. The model has been tested with a categorisation task and the results show that a balanced mix of unsupervised and reinforcement learning leads to the emergence of a suitable categorical perception and the best performance in the task. Indeed, an excessive unsupervised learning contribution tends to not identify task-relevant features while an excessive reinforcement learning contribution tends to initially learn slowly and then to reach sub-optimal performance. These results are consistent with the experimental evidence regarding categorical activations of extrastriate cortices in healthy conditions. Finally, the results produced by the two extreme cases of our model can explain the existence of several factors that may lead to sensory alterations in autistic people.

The beneficial effects of n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) on human health are widely known. Humans are rather inefficient in synthesizing n-3 LC-PUFA; thus, these compounds should be supplemented in the diet. However, most Western human diets have unbalanced n-6/n-3 ratios resulting from eating habits and the fact that fish sources (rich in n-3 LC-PUFA) are not sufficient (worldwide deficit ~347,956 t/y) to meet the world requirements. In this context, it is necessary to find new and sustainable sources of n-3 LC-PUFA. Poultry products can provide humans n-3 LC-PUFA due to physiological characteristics and the wide consumption of meat and eggs. The present work aims to provide a general overview of the main strategies that should be adopted during rearing and postproduction to enrich and preserve n-3 LC-PUFA in poultry products. The strategies include dietary supplementation of α-Linolenic acid (ALA) or n-3 LC-PUFA, or enhancing n-3 LC-PUFA by improving the LA (Linoleic acid)/ALA ratio and antioxidant concentrations. Moreover, factors such as genotype, rearing system, transport, and cooking processes can impact the n-3 LC-PUFA in poultry products. The use of a multifactorial view in the entire production chain allows the relevant enrichment and preservation of n-3 LC-PUFA in poultry products.

The aim of the present study was to investigate the effect of transport on welfare traits, several haematological parameters and carcase hygiene in two different chicken genotypes (fast- and slow-growing strains) reared under free-range conditions. For this aim, two hundred male chicks, 100 from fast-growing (Ross 308, R) and 100 from slow-growing (Naked Neck, NN) strain were farmed. At the end of the rearing period, at 81 days of age, 56 birds/strain were randomly selected for slaughtering and submitted to two different pre-slaughter conditions: no transport (0h) or 4 hours of transport (4h). Tonic immobility (TI), blood parameters and carcase hygiene traits were determined. Strain and transport significantly affected TI of birds. Both experimental factors and their interaction significantly affected plasma creatine kinase, alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase. Cholesterol and triglycerides were not different between the experimental groups, whereas glucose decreased after 4 hours of transport in both strains. A significant difference between groups for the heterophils/lymphocytes ratio after transport was also observed, with NN being higher than Ross. Concerning the oxidative stress, we observed a higher ROS production in NN chickens. The carcase microbial characteristics showed a higher level of contamination after the transport (total viable counts), but not concerning the Enterobacteriaceae counts.

This conference paper analyzes "expedited procedures" under the rules of seven Asian arbitral institutions, having particular regard to provisions related to COVID-19 pandemic (if any). A table of comparison among the seven arbitral institutions is at the bottom of the paper.