gamete quality in a multistressor environment

Over the past few decades, accumulated evidence confirms that the global environment conditions are changing rapidly. Urban industrialization, agriculture and globalization have generated water, air and soil pollution, giving rise to an environment with a growing number of stress factors, which has a serious impact on the fitness, reproduction and survival of living organisms. The issue raises considerable concern on biodiversity conservation, which is now at risk: it is estimated that a number of species will be extinct in the near future. Sexual reproduction is the process that allows the formation of a new individual and is underpinned by gamete quality defined as the ability of spermatozoa and oocytes to interact during fertilization leading to the creation and development of a normal embryo.This review aimed to provide the current state of knowledge regarding the impact of a broad spectrum of environmental stressors on diverse parameters used to estimate and evaluate gamete quality in humans and in canonical animal models used for experimental research.Effects of metals, biocides, herbicides, nanoparticles, plastics, temperature rise, ocean acidification, air pollution and lifestyle on the physiological parameters that underlie gamete fertilization competence are described supporting the concept that environmental stressors represent a serious hazard to gamete quality with reproductive disorders and living organism failure. Although clear evidence is still limited, gamete capacity to maintain and/or recover physiological conditions is recently demonstrated providing further clues about the plasticity of organisms and their tolerance to the pressures of pollution that may facilitate the reproduction and the persistence of species within the scenario of global change.Changes in the global environment must be urgently placed at the forefront of public attention, with a massive effort invested in further studies aimed towards implementing current knowledge and identifying new methodologies and markers to predict impairment of gamete quality. Keywords: Gamete quality, Environmental stress, Fertilization, Xenobiotic, Climate change, Life styl

Biohydrogen production from food waste: Influence of the inoculum-to-substrate ratio

In this study, the influence of the inoculum-to-substrate ratio (ISR) on dark fermentative hydrogen production from food waste (FW) was evaluated. ISR values ranging from 0.05 to 0.25 g VSinoculum/g VSsubstrate were investigated by performing batch tests at T = 39 °C and pH = 6.5, the latter being the optimal value identified based on a previous study. The ISR was found to affect the fermentation process, clearly showing that an adequate ISR is essential in order to optimise the process kinetics and the H2 yield. An ISR of 0.14 proved to optimum, leading to a maximum H2 yield of 88.8 L H2/kg VSFW and a maximum production rate of 10.8 L H2/kg VSFW∙h. The analysis of the fermentation products indicated that the observed highest H2 production mostly derived from the typical acetate/butyrate-type fermentation

D-aspartic acid in vertebrate reproduction: Animal models and experimental designs

This article reviews the animal models and experimental designs that have been used during the past twenty years to demonstrate the prominent role played by d-aspartate (d-Asp) in the reproduction of vertebrates, from amphibians to humans. We have tabulated the findings of in vivo and in vitro experiments that demonstrate the effects of d-Asp uptake on hormone production and gametogenesis in vertebrate animal models. The contribution of each animal model to the existing knowledge on the role of d-Asp in reproductive processes has been discussed. A critical analysis of experimental designs has also been carried out. Experiments performed on wild animal species suggest a role of d-Asp in the mechanisms that regulate the reproductive cycle. Several in vivo and in vitro studies carried out on mouse and rat models have facilitated an understanding of the molecular pathways activated by D-Asp in both steroidogenesis and spermatogenesis, with particular emphasis on testosterone biosynthesis. Some attempts using d-Asp for the improvement of reproductive activity in animals of commercial interest have yielded mixed results. The increased transcriptome activity of enzymes and receptors involved in the reproductive activity in d-Asp-treated broiler roosters revealed further details on the mechanism of action of d-Asp on the reproductive processes. The close relationship between d-Asp and reproductive activity has emerged, particularly in relation to its effects exerted on semen quality, proposing therapeutic applications of this amino acid in andrology and in medically-assisted procreation techniques.This article reviews the animal models and experimental designs that have been used during the past twenty years to demonstrate the prominent role played by D-aspartate (D-Asp) in the reproduction of vertebrates, from amphibians to humans. We have tabulated the findings of in vivo and in vitro experiments that demonstrate the effects of D-Asp uptake on hormone production and gametogenesis in vertebrate animal models. The contribution of each animal model to the existing knowledge on the role of D-Asp in reproductive processes has been discussed. A critical analysis of experimental designs has also been carried out. Experiments performed on wild animal species suggest a role of D-Asp in the mechanisms that regulate the reproductive cycle. Several in vivo and in vitro studies carried out on mouse and rat models have facilitated an understanding of the molecular pathways activated by D-Asp in both steroidogenesis and spermatogenesis, with particular emphasis on testosterone biosynthesis. Some attempts using D-Asp for the improvement of reproductive activity in animals of commercial interest have yielded mixed results. The increased transcriptome activity of enzymes and receptors involved in the reproductive activity in D-Asptreated broiler roosters revealed further details on the mechanism of action of D-Asp on the reproductive processes. The close relationship between D-Asp and reproductive activity has emerged, particularly in relation to its effects exerted on semen quality, proposing therapeutic applications of this amino acid in andrology and in medically-assisted procreation techniques

Antitumor Activity of Lurbinectedin, a Selective Inhibitor of Oncogene Transcription, in Patients with Relapsed Ewing Sarcoma: Results of a Basket Phase II Study

Ewing Sarcoma; LurbinectedinSarcoma de Ewing; LurbinectedinaSarcoma d'Ewing; LurbinectedinaPurpose: Lurbinectedin suppresses the oncogenic transcription factor EWS-FLI1 through relocalization to the nucleolus, and delays tumor growth in mice bearing Ewing sarcoma xenografts. On the basis of this rationale, lurbinectedin was evaluated in patients with relapsed Ewing sarcoma. Patients and Methods: This open-label, single-arm, Basket phase II trial included a cohort of 28 treated adult patients with confirmed Ewing sarcoma, measurable disease as per Response Evaluation Criteria In Solid Tumors (RECIST) v.1.1, Eastern Cooperative Oncology Group performance status ≤2, adequate organ function, no central nervous system metastasis, and pretreated with ≤2 chemotherapy lines for metastatic/recurrent disease. Patients received lurbinectedin 3.2 mg/m2 as a 1-hour infusion every 3 weeks. Primary endpoint was overall response rate (ORR) as per RECIST v.1.1. Secondary endpoints included time-to-event parameters and safety profile. Results: ORR was 14.3% [95% confidence interval (CI), 4.0%–32.7%], with median duration of response of 4.2 months (95% CI, 2.9–5.5 months). Median progression-free survival was 2.7 months (95% CI, 1.4–4.3 months), clinical benefit rate was 39.3%, and disease control rate was 57.1%. With 39% censoring, median overall survival was 12.0 months (95% CI, 8.5–18.5 months). Most common grade 3/4 adverse events were neutropenia (57%), anemia, thrombocytopenia, and treatment-related febrile neutropenia (14% each). No deaths or discontinuations were due to toxicity. Conclusions: Lurbinectedin was active in the treatment of relapsed Ewing sarcoma and had a manageable safety profile. Lurbinectedin could represent a valuable addition to therapies for Ewing sarcoma, and is currently being evaluated in combination with irinotecan in advanced Ewing sarcoma in a phase Ib/II trial

Immune and Reproductive Biomarkers in Female Sea Urchins Paracentrotus lividus under Heat Stress

The functioning of the immune and reproductive systems is crucial for the fitness and survival of species and is strongly influenced by the environment. To evaluate the effects of shortterm heat stress (HS) on these systems, confirming and deepening previous studies, female sea urchin Paracentrotus lividus were exposed for 7 days to 17 degrees C, 23 and 28 degrees C. Several biomarkers were detected such as the ferric reducing power (FRAP), ABTS-based total antioxidant capacity (TAC-ABTS), nitric oxide metabolites (NOx), total thiol levels (TTL), myeloperoxidase (MPO) and protease (PA) activities in the coelomic fluid (CF) and mitochondrial membrane potential (MMP), H2O2 content and intracellular pH (pH(i)) in eggs and coelomocytes, in which TAC-ABTS and reactive nitrogen species (RNS) were also analyzed. In the sea urchins exposed to HS, CF analysis showed a decrease in FRAP levels and an increase in TAC-ABTS, TTL, MPO and PA levels; in coelomocytes, RNS, MMP and H2O2 content increased, whereas pHi decreased; in eggs, increases in MMP, H2O2 content and pHi were found. In conclusion, short-term HS leads to changes in five out of the six CF biomarkers analyzed and functional alterations in the cells involved in either reproductive or immune activities

Postoperative infections after oesophageal resections: the role of blood transfusions

BACKGROUND: Perioperative blood transfusion carries numerous potential risks concerning the transmission of infective diseases and immunodepression that can facilitate the occurrence of postoperative infectious complications. Explanation of connections between perioperative blood transfusion and postoperative septic complication worldwide is not well documented. Many studies have described a correlation between perioperative blood transfusions and postoperative infections. On the contrary, other studies indicate that factors influencing the need for blood transfusions during surgery have a greater bearing than blood transfusion per se on the occurrence of postoperative complications. PATIENTS AND METHODS: A prospective study was conducted in our Department on 110 consecutive patients undergoing oesophageal resection for primary cancer, in order to evaluate the incidence of postoperative infections related to perioperative allogenic blood transfusions. For each patient we preoperatively recorded in a computerized data-base several known risk-factors for postoperative infections; in detail we registered the administration of allogenic perioperative blood transfusions (period of administration, number of packages administered). RESULTS: Among the enrolled 110 patients, 53 (48%) received perioperative blood transfusions: in this group postoperative infections (overall infective complications) occurred in 27 patients. After a multivariate analysis we observed that perioperative blood transfusions significantly affected as an independent variable the development of wound infections (p = 0.02). CONCLUSION: Blood transfusions independently affected the incidence of wound infections in patients who underwent oesophageal resection for primary cancer

Metabolic regulation of the HBV-specific T cell function.

Chronically HBV infected subjects are more than 260 million worldwide; cirrhosis and liver cancer represent possible outcomes which affect around 700,000 patients per year. Both innate and adaptive immune responses are necessary for viral control and both have been shown to be defective in chronic patients. Metabolic remodeling is an essential process in T cell biology, particularly for T cell activation, differentiation and survival. Cellular metabolism relies on the conversion of nutrients into energy to support intracellular processes, and to generate fundamental intermediate components for cell proliferation and growth. Adaptive immune responses are the central mechanisms for the resolution of primary human infections leading to the activation of pathogen-specific B and T cell functions. In chronic HBV infection the anti-viral immune response fails to contain the virus and leads to persistent hepatic tissue damage which may finally result in liver cirrhosis and cancer. This T cell failure is associated with metabolic alterations suggesting that control of nutrient uptake and intracellular utilization as well as correct regulation of intracellular metabolic pathways are strategic for T cell differentiation during persistent chronic infections. This review will discuss some of the main features of the T cell metabolic processes which are relevant to the generation of an efficient antiviral response, with specific focus on their clinical relevance in chronic HBV infection in the perspective of possible strategies to correct deregulated metabolic pathways underlying T cell dysfunction of chronic HBV patients

Sperm Motility Impairment in Free Spawning Invertebrates Under Near-Future Level of Ocean Acidification: Uncovering the Mechanism

Ocean acidification (OA) refers to the decrease in ocean water pH resulting from the increasing absorption of atmospheric CO2. This will cause changes in the ocean's carbonate chemistry system with a resulting impact on reproduction of marine organisms. Reproduction is the fundamental process that allows the conservation of the species; in free-spawning marine invertebrates, this process is highly sensitive to changes in seawater quality and chemistry. To date, the majority of the studies concerned OA effects on reproduction has been focused on embryo and larval development. Despite several evidence for the impairment of reproductive success by environmental perturbations through altering gamete quality, sperm physiological responses to OA are poorly investigated. In this study, we evaluated the effects of exposure to acidified seawater (AcSW) (pH 7.8), which approximate the predicted global averages for oceanic surface waters at the end of this century, on sperm quality of the mussel Mytilus galloprovincialis and the ascidian Ciona robusta by evaluating several endpoints, such as motility, vitality, mitochondrial activity, oxidative state, and intracellular pH (pHi). Following sperm exposure to AcSW, the percentage of motile spermatozoa, mitochondrial activity and pHi decreased in comparison to the current seawater pH of 8.1, whereas vitality and oxidative state were unaffected by the low external pH in both the species. In broadcast spawners, a relationship between sperm intracellular pH and the initiation of motility are well known. Spermatozoa are immotile in the testes and motility is induced after the spermatozoa are released into seawater; the alkaline pH of seawater, in fact, increases the pHi activating motility and mitochondrial respiration. The results of this study suggest that the lowering of seawater pH as predicted to occur for 2100, through the inhibition of pHi increase, prevent sperm motility activation. Sperm motility is a key determinant of fertilization success; consequently, a corresponding drop in fertilization success would be expected with important implications for the fitness and the survival of marine invertebrates

COVID-19 Lockdown Impacts Among Patients with Cystic Fibrosis: An Italian Regional Reference Centre Experience

Coronavirus pandemic has influenced our society with social distancing and management of chronic disease such as cystic fibrosis (CF). During the Italian lockdown from March to May 2020, CF patients reduced the number of outpatient visits, limited social interactions and spent more time at home. The aim of this study is to evaluate the impact of the lockdown on body mass index (BMI) and lung function tests on CF patients.We retrospectively reviewed clinical data about 111 CF patients followed in our Regional Cystic Fibrosis Reference Centre (Policlinico Umberto I, Rome) according to two periods: pre-lockdown (from October 2019-March 2020) and post-lockdown (from May 2020-October 2020). We collected data on nutritional (BMI and body weight) and lung function status; we chose the best values of the 'pre-lockdown' and 'post-lockdown' period for each patient. Patients were divided into 3 groups according to FEV1 value (Forced Expiratory Volume in the 1st second): group 1 (FEV140%), group 2 (FEV1 40-70%), group 3 (FEV170%). All patients received a telephone interview asking for the number of hours per week devoted to physical activity, number of pulmonary acute exacerbations and subjective evaluation of adherence to medical therapy, respiratory physiotherapy and diet, during the two periods.Comparing weight, BMI and respiratory function between pre and post lockdown periods, we noticed an increase in weight during among overall patients. Male patients improved weight, BMI, FEF 25-75% (Forced Expiratory flow between 25% and 75% of vital capacity) and Tiffenau index more than female patients. The most severely compromised patients (group 1), showed a significant loss of both weight and BMI. Instead, patients with moderate respiratory function (group 2) showed a significant increase of both weight and BMI and a slightly reduced CVF (Forced Vital capacity). We found no differences among patients with good respiratory function (group 3). Comparing each clinical sub-groups, we noticed a significative improvement of weight (Lockdown period had benefit among CF patients in terms of weight in particular in male patient. The greatest benefit on nutritional state was observed in patients with moderate reduction of respiratory function. In addition, we noted a stabilization and sometimes a slight improvement of lung function, instead of a continuous and steady decline that is normally observed in CF patients. These beneficial effects are slight but significative, bearing in mind the general worsening that CF patients experience annually