Multiplying individuals, ethical implications of the human reproductive cloning

In 1996 the birth of ‘Dolly’, the first mammal cloned, has opened discussions among biologists and the public about the desirability of such a technology (Terragni 1999, Dijck 1998). This is surprising when we think that cloning was not a new technology. The first experiments of nuclear transfer with amphibians (Rana pipiens and Xenoplus laevis) were performed in the United States and Britain during 1950s (Gordon & Colman 2000:743-746). Nuclear transfer experiments were performed in amphibians in the 1960s, in mice in the 1970s, in sheep in the 1980s, and in monkeys in the 1990s. In this paper I deal with ethical issues related to human reproductive cloning. I will claim that we have no reason to oppose human reproductive cloning a priori

Nutrient removal by apple, pear and cherry nursery trees

Given that nursery is a peculiar environment, the amount of nutrients removed by nursery trees represents a fundamental acquisition to optimize fertilization strategies, with economic and environmental implications. In this context, we determined nutrient removal by apple, pear and cherry nursery trees at the end of the nursery growing cycle. We randomly removed 5 leafless apple (Golden Delicious/EMLA M9; density of 30,000 trees ha-1), pear (Santa Maria/Adams; density of 30,000 trees ha-1) and cherry (AlexTM/Gisela\uae; density of 40,000 trees ha-1) trees from a commercial nursery. Trees were divided into roots (below the root collar), rootstock (aboveground between root collar and grafting point) and variety (1-year old above the grafting point). For each organ we determined biomass, macro (N, P, K, Ca, Mg, S,) and micro (Fe, Mn, Zn, Cu, and B) nutrient concentration. Pear trees were the most developed (650 g tree-1, equal to 1.75 and 2.78 folds than apple and cherry trees, respectively) whereas, independently of the species, variety mostly contributed (>50%) to the total tree biomass, followed by roots and then aboveground rootstock. However, the dry biomass and nutrient amount measured in rootstocks (including roots) represent the cumulative amount of 2 and 3seasons, for Gisela\uae 6 (tissue culture) and pome fruit species (generated by mound layering), respectively. Macro and micronutrients were mostly concentrated in roots, followed by variety and rootstock, irrespective of the species. Independently of the tissue, macronutrients concentration hierarchy was N>Ca>K> P>Mg>S. Removed N by whole tree accounted for 6.58, 3.53 and 2.49 g tree-1 for pear, apple and cherry, respectively, correspondingto almost 200, 107 and 100 kg N ha-1, respectively. High amounts of K and Ca were used by pear (130-140 kg ha-1) and apple trees (~50 and 130 kg ha-1 of K and Ca, respectively), while ~25 kg K ha-1 and 55 kg Ca ha-1 were calculated for cherry nursery trees. Among micronutrients, Fe was the most required (~3 kg ha-1) independently of the species. B removal ranged between 1.2 and 2.4 kg ha-1 (80, 40 and 30 mg tree-1 for pear, apple and cherry, respectively) whereas Mn, Cu and Zn accounted for few hundred g ha-1, irrespective of the species. Given that nutrient concentration among tissues resulted within the same order of magnitude, irrespective of the species, differences in removal were mainly driven by the tree biomass as proved by the significant correlations between plant dry biomass with most of the nutrients we observed

The galectin-3/RAGE dyad modulates vascular osteogenesis in atherosclerosis

Vascular calcification correlates with inflammation and plaque instability in a dual manner, depending on the spotty/granular (micro) or sheet-like/lamellated (macro) pattern of calcification. Modified lipoproteins trigger both inflammation and calcification via receptors for advanced lipoxidation/glycation endproducts (ALEs/AGEs). This study compared the roles of galectin-3 and receptor for AGEs (RAGE), two ALEs/AGEs-receptors with diverging effects on inflammation and bone metabolism, in the process of vascular calcification. We evaluated galectin-3 and RAGE expression/localization in 62 human carotid plaques and its relation to calcification pattern, plaque phenotype, and markers of inflammation and vascular osteogenesis; and the effect of galectin-3 ablation and/or exposure to an ALE/AGE on vascular smooth muscle cell (VSMC) osteogenic differentiation. While RAGE co-localized with inflammatory cells in unstable regions with microcalcification, galectin-3 was expressed also by VSMCs, especially in macrocalcified areas, where it co-localized with alkaline phosphatase. Expression of galectin-3 and osteogenic markers was higher in macrocalcified plaques, whereas the opposite occurred for RAGE and inflammatory markers. Galectin-3-deficient VSMCs exhibited defective osteogenic differentiation, as shown by altered expression of osteogenic transcription factors and proteins, blunted activation of pro-osteoblastogenic Wnt/β-catenin signalling and proliferation, enhanced apoptosis, and disorganized mineralization. These abnormalities were associated with RAGE up-regulation, but were only in part prevented by RAGE silencing, and were partially mimicked or exacerbated by treatment with an AGE/ALE. These data indicate a novel molecular mechanism by which galectin-3 and RAGE modulate in divergent ways, not only inflammation, but also vascular osteogenesis, by modulating Wnt/β-catenin signalling, and independently of ALEs/AGEs

Tension pneumomediastinum in patients with COVID-19

open5nonot presentopenCampisi A.; Poletti V.; Ciarrocchi A.P.; Salvi M.; Stella F.Campisi A.; Poletti V.; Ciarrocchi A.P.; Salvi M.; Stella F

COVID-19-Related Social Isolation Predispose to Problematic Internet and Online Video Gaming Use in Italy

COVID-19 pandemic and its related containment measures have been associated with increased levels of stress, anxiety and depression in the general population. While the use of digital media has been greatly promoted by national governments and international authorities to maintain social contacts and healthy lifestyle behaviors, its increased access may also bear the risk of inappropriate or excessive use of internet-related resources. The present study, part of the COVID Mental hEalth Trial (COMET) study, aims at investigating the possible relationship between social isolation, the use of digital resources and the development of their problematic use. A cross sectional survey was carried out to explore the prevalence of internet addiction, excessive use of social media, problematic video gaming and binge watching, during Italian phase II (May-June 2020) and III (June-September 2020) of the pandemic in 1385 individuals (62.5% female, mean age 32.5 +/- 12.9) mainly living in Central Italy (52.4%). Data were stratified according to phase II/III and three groups of Italian regions (northern, central and southern). Compared to the larger COMET study, most participants exhibited significant higher levels of severe-to-extremely-severe depressive symptoms (46.3% vs. 12.4%; p < 0.01) and extremely severe anxiety symptoms (77.8% vs. 7.5%; p < 0.01). We also observed a rise in problematic internet use and excessive gaming over time. Mediation analyses revealed that COVID-19-related general psychopathology, stress, anxiety, depression and social isolation play a significant role in the emergence of problematic internet use, social media addiction and problematic video gaming. Professional gamers and younger subjects emerged as sub-populations particularly at risk of developing digital addictions. If confirmed in larger and more homogenous samples, our findings may help in shedding light on possible preventive and treatment strategies for digital addictions

The PDE4 Inhibitor Tanimilast Restrains the Tissue-Damaging Properties of Human Neutrophils

: Neutrophils, the most abundant subset of leukocytes in the blood, play a pivotal role in host response against invading pathogens. However, in respiratory diseases, excessive infiltration and activation of neutrophils can lead to tissue damage. Tanimilast-international non-proprietary name of CHF6001-is a novel inhaled phosphodiesterase 4 (PDE4) inhibitor in advanced clinical development for the treatment of chronic obstructive pulmonary disease (COPD), a chronic inflammatory lung disease where neutrophilic inflammation plays a key pathological role. Human neutrophils from healthy donors were exposed to pro-inflammatory stimuli in the presence or absence of tanimilast and budesonide-a typical inhaled corticosteroid drug-to investigate the modulation of effector functions including adherence to endothelial cells, granule protein exocytosis, release of extracellular DNA traps, cytokine secretion, and cell survival. Tanimilast significantly decreased neutrophil-endothelium adhesion, degranulation, extracellular DNA traps casting, and cytokine secretion. In contrast, it promoted neutrophil survival by decreasing both spontaneous apoptosis and cell death in the presence of pro-survival factors. The present work suggests that tanimilast can alleviate the severe tissue damage caused by massive recruitment and activation of neutrophils in inflammatory diseases such as COPD

Bendamustine in combination with gemcitabine and vinorelbine is an effective regimen as induction chemotherapy before autologous stem-cell transplantation for relapsed or refractory Hodgkin lymphoma: Final results of a multicenter phase II study

Purpose: This multicenter, open-label, phase II study evaluated the combination of bendamustine, gemcitabine, and vinorelbine (BeGEV) as induction therapy before autologous stem-cell transplantation (ASCT) in patients with relapsed or refractory Hodgkin lymphoma (HL). Patients and Methods: Patients with HL who were refractory to or had relapsed after one previous chemotherapy line were eligible. The primary end point was complete response (CR) rate after four cycles of therapy. Secondary end points were: overall response rate, stem-cell mobilization activity, and toxicity. Progression-free and overall survival were also evaluated. Results: In total, 59 patients were enrolled. After four cycles of therapy, 43 patients (73%) achieved CR, and six (10%) achieved partial response, for an overall response rate of 83%. The most common grade 3 to 4 nonhematologic toxicities included febrile neutropenia (n = 7) and infection (n = 4). Regarding hematologic toxicities, grade 3 to 4 thrombocytopenia and neutropenia were each experienced by eight patients (13.5%). CD34+ cells were successfully harvested in 55 of 57 evaluable patients, and 43 of 49 responding patients underwent ASCT. With a median follow-up of 29 months, the 2-year progression-free and overall survival rates for the total population were 62.2% and 77.6%, respectively. The same figures for patients undergoing autograft were 80.8% and 89.3%, respectively. Conclusion: This phase II study demonstrates that BeGEV is an effective salvage regimen able to induce CR in a high proportion of patients with relapsed or refractory HL before ASCT. These data provide a strong rationale for further development of the BeGEV regimen

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Withdrawal of mechanical ventilation in amyotrophic lateral sclerosis patients: a multicenter Italian survey

Background: Law 219/2017 was approved in Italy in December 2017, after a years-long debate on the autonomy of healthcare choices. This Law, for the first time in Italian legislation, guarantees the patient's right to request for withdrawal of life-sustaining treatments, including mechanical ventilation (MV). Objective: To investigate the current status of MV withdrawal in amyotrophic lateral sclerosis (ALS) patients in Italy and to assess the impact of Law 219/2017 on this practice. Methods: We conducted a Web-based survey, addressed to Italian neurologists with expertise in ALS care, and members of the Motor Neuron Disease Study Group of the Italian Society of Neurology. Results: Out of 40 ALS Italian centers, 34 (85.0%) responded to the survey. Law 219/2017 was followed by an increasing trend in MV withdrawals, and a significant increase of neurologists involved in this procedure (p 0.004). However, variations across Italian ALS centers were observed, regarding the inconsistent involvement of community health services and palliative care (PC) services, and the intervention and composition of the multidisciplinary team. Conclusions: Law 219/2017 has had a positive impact on the practice of MV withdrawal in ALS patients in Italy. The recent growing public attention on end-of-life care choices, along with the cultural and social changes in Italy, requires further regulatory frameworks that strengthen tools for self-determination, increased investment of resources in community and PC health services, and practical recommendations and guidelines for health workers involved

Serum Albumin Is Inversely Associated With Portal Vein Thrombosis in Cirrhosis

We analyzed whether serum albumin is independently associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) and if a biologic plausibility exists. This study was divided into three parts. In part 1 (retrospective analysis), 753 consecutive patients with LC with ultrasound-detected PVT were retrospectively analyzed. In part 2, 112 patients with LC and 56 matched controls were entered in the cross-sectional study. In part 3, 5 patients with cirrhosis were entered in the in vivo study and 4 healthy subjects (HSs) were entered in the in vitro study to explore if albumin may affect platelet activation by modulating oxidative stress. In the 753 patients with LC, the prevalence of PVT was 16.7%; logistic analysis showed that only age (odds ratio [OR], 1.024; P = 0.012) and serum albumin (OR, -0.422; P = 0.0001) significantly predicted patients with PVT. Analyzing the 112 patients with LC and controls, soluble clusters of differentiation (CD)40-ligand (P = 0.0238), soluble Nox2-derived peptide (sNox2-dp; P < 0.0001), and urinary excretion of isoprostanes (P = 0.0078) were higher in patients with LC. In LC, albumin was correlated with sCD4OL (Spearman's rank correlation coefficient [r(s)], -0.33; P < 0.001), sNox2-dp (r(s), -0.57; P < 0.0001), and urinary excretion of isoprostanes (r(s), -0.48; P < 0.0001) levels. The in vivo study showed a progressive decrease in platelet aggregation, sNox2-dp, and urinary 8-iso prostaglandin F2 alpha-III formation 2 hours and 3 days after albumin infusion. Finally, platelet aggregation, sNox2-dp, and isoprostane formation significantly decreased in platelets from HSs incubated with scalar concentrations of albumin. Conclusion: Low serum albumin in LC is associated with PVT, suggesting that albumin could be a modulator of the hemostatic system through interference with mechanisms regulating platelet activation