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Limiting warming by the end of the century to 1.5°C compared to pre-Industrial times requires reaching and sustaining net zero global carbon dioxide (CO2) emissions and declining radiative forcing from non-CO2 greenhouse gas (GHG) sources such as methane (CH4). This implies eliminating CO2 emissions or balancing them with removals while mitigating CH4 emissions to reduce their radiative forcing over time. The global cattle sector (including Buffalo) mainly emits CH4 and N2O and will benefit from understanding the extent and speed of CH4 reductions necessary to align its mitigation ambitions with global temperature goals. This study explores the utility of an alternative usage of global warming potentials (GWP*) in combination with the Transient Climate Response to cumulative carbon Emissions (TCRE) to compare retrospective and projected climate impacts of global livestock emission pathways with other sectors (e.g. fossil fuel and land use change). To illustrate this, we estimated the amount and fraction of total warming attributable to direct CH4 livestock emissions from 1750 to 2019 using existing emissions datasets and projected their contributions to future warming under three historical and three future emission scenarios. These historical and projected estimates were transformed into cumulative CO2 equivalent (GWP100) and warming equivalent (GWP*) emissions that were multiplied by a TCRE coefficient to express induced warming as globally averaged surface temperature change. In general, temperature change estimates from this study are comparable to those obtained from other climate models. Sustained annual reductions in CH4 emissions of 0.32% by the global cattle sector would stabilize their future effect on global temperature while greater reductions would reverse historical past contributions to global warming by the sector in a similar fashion to increasing C sinks. The extent and speed with which CH4 mitigation interventions are introduced by the sector will determine the peak temperature achieved in the path to net-zero GHG.

Background Italy records very alarming levels antimicrobial resistance (AMR), so a National Action Plan on Antimicrobial resistance (PNCAR) was developed, adopting the AMR European Union’s recommendations based on the results of the ECDC site visit of January 2017. For achieving PNCAR objectives, it is necessary to support and harmonize the implementation of recommendations in all the different healthcare levels (regional authorities and local trusts), so the SPiNCAR project was launched to create a tool for reaching this goal. Methods We developed a framework based on a scientific literature and national and international guidelines. Firstly, we identified the major intervention areas for tackling AMR, then, for each area, we built a set of standards, both for regional authorities than for local trusts. Every standard is composed by a set of essential and additional criteria, which refer to a minimum or supplemental performance level respectively. The contents were firstly discussed by the project’s team during face-to-face kick-off meetings, then confirmed with Delphi methodology and finally validated through a pilot study. Results The final framework consists of seven different areas that reflect the PNCAR structure: Governance, Surveillance and Monitoring, Appropriate Use of antimicrobials, Healthcare-associated Infections (HAIs) control and prevention, Education and Training, Alliance among Stakeholders, Implementation. The total number of standards for the regional framework was 34 with 264 criteria and for the local version 36 criteria with 279 standards. Conclusion The ongoing use of this tool, developed on international evidences and recommendations that were tailored on the Italian specific context, allows monitoring the improvement achieved over time and plan the next steps.

Among one of the key challenges in dairy production is the management of manure in a way that is beneficial for agricultural production, with minimal environmental and public health impacts. Manure management systems (MMS)—the entire system of handling, storage, and application of manure—are diverse in countries with developed dairy industries such as the United States, enabled by a number of different technologies. The ways in which dairy farmers manage manure is driven by varying tradeoffs, including economic, social, and environmental; however, existing research has not examined the relationships between components of MMS. Here we use data from the National Animal Health Monitoring System’s Dairy 2014 study to explore the ways in which manure handling, storage, and application are related, using a series of logistic regression models and network associations. We found significant associations between how manure is handled, stored, and applied, especially driven by the consistency of manure. For solid manure, we found highly heterogeneous systems, where farmers may have a suite of alternative manure management strategies available to them, and substitution is viable. Conversely, farms using liquid manure systems have very few substitutes in their MMS, suggesting greater investment in certain infrastructures, which are not easily changed. Such findings have important implications for shifting farmers towards management practices with minimal environmental and public health impacts, demonstrating that not all farm systems are easily changed. We highlight these results in light of current policies, which may not fully capture the relationships across the MMS, and suggest that greater financing may be necessary to shift MMS on some farms. Furthermore, we suggest that different MMS have varying tradeoffs across environmental, social, and economic aspects, which demonstrates that MMS are highly individualized to a given farm’s goals and priorities.

Introduction Clinical record (CR) is the primary tool used by healthcare workers (HCWs) to record clinical information and its completeness can help achieve safer practices. CR is the most appropriate source in order to measure and evaluate the quality of care. In order to achieve a safety climate is fundamental to involve a responsive healthcare workforce thorough peer-review and feedbacks. This study aims to develop a peer-review tool for clinical records quality assurance, presenting the seven-year experience in the evolution of it; secondary aims are to describe the CR completeness and HCWs’ diligence toward recording information in it. Methods To assess the completeness of CRs a peer-review tool was developed in a large Academic Hospital of Northern Italy. This tool included measurable items that examined different themes, moments and levels of the clinical process. Data were collected every three months between 2010 and 2016 by appointed and trained HCWs from 42 Units; the hospital Quality Unit was responsible for of processing and validating them. Variations in the proportion of CR completeness were assessed using Cochran-Armitage test for trends. Results A total of 9,408 CRs were evaluated. Overall CR completeness improved significantly from 79.6% in 2010 to 86.5% in 2016 (pConclusions This peer-review tool enabled the Quality Unit and hospital leadership to obtain a reliable picture of CRs completeness, while involving the HCWs in the quality evaluation. The completeness of CR showed an overall positive and significant trend during these seven years.

Standard Infliximab infusion consists of a 2-hour intravenous administration. Recently, Infliximab shortened infusion has been included in the Infliximab label as possible maintenance regimen for patients tolerating Infliximab induction therapy.To verify if accelerated 1-hour Infliximab infusions are as safe as standard administrations, in patients with Inflammatory Bowel Disease.Seventy-four patients treated between September 2008 and November 2014 were evaluated. Patients were eligible for 1-hour infusion if they had no history of infusion reactions during the previous 2-hour infusions.Twenty-three patients received 2-hour infusions, 16 patients received 1-hour infusions, 35 patients received 2-hour infusions followed by 1-hour infusions. A total of 1,123 Infliximab infusions were administered. The proportion of patients experiencing infusion reaction was: 4% over the 1-hour infusions and 9% over the 2-hour (P = 0.318). Adverse reaction/infusion rate was 0.55% over the 1-hour infusions and 0.66% over the 2-hour (P = 0.835). In the logistic model, accelerated infusion was the only statistically significant predictor of infusion reaction risk reduction (-90%; P = 0.024). Mean satisfaction was 8/10 (±0.84) with 1-hour regimen and 6/10 (±0.56) with 2-hour infusions (P = 0.000). The mean total cost was reduced by 47% with the 1-hour regimen (133.54€ and 250.86€ for 1-hour and 2-hour infusions, respectively).Accelerated Infliximab infusion does not increase the acute infusion reaction incidence. In patients with inflammatory bowel disease, the 1-hour regimen should be preferred to 2-hour protocol also due to positive effects on indirect costs and patient's satisfaction.

The compass depressors (CDs) of the sea-urchin lantern are ligaments consisting mainly of discontinuous collagen fibrils associated with a small population of myocytes. They are mutable collagenous structures, which can change their mechanical properties rapidly and reversibly under nervous control. The aims of this investigation were to characterise the baseline (i.e. unmanipulated) static mechanical properties of the CDs of Paracentrotus lividus by means of creep tests and incremental force-extension tests, and to determine the effects on their mechanical behaviour of a range of agents. Under constant load the CDs exhibited a three-phase creep curve, the mean coefficient of viscosity being 561±365 MPa.s. The stress-strain curve showed toe, linear and yield regions; the mean strain at the toe-linear inflection was 0.86±0.61; the mean Young's modulus was 18.62±10.30 MPa; and the mean tensile strength was 8.14±5.73 MPa. Hyaluronidase from Streptomyces hyalurolyticus had no effect on creep behaviour, whilst chondroitinase ABC prolonged primary creep but had no effect on secondary creep or on any force-extension parameters; it thus appears that neither hyaluronic acid nor sulphated glycosaminoglycans have an interfibrillar load transfer function in the CD. Acetylcholine, the muscarinic agonists arecoline and methacholine, and the nicotinic agonists nicotine and 1-[1-(3,4-dimethyl-phenyl)-ethyl]-piperazine produced an abrupt increase in CD viscosity; the CDs were not differentially sensitive to muscarinic or nicotinic agonists. CDs showed either no, or no consistent, response to adrenaline, L-glutamic acid, 5-hydroxytryptamine and γ-aminobutyric acid. Synthetic echinoid tensilin-like protein had a weak and inconsistent stiffening effect, indicating that, in contrast to holothurian tensilins, the echinoid molecule may not be involved in the regulation of collagenous tissue tensility. We compare in detail the mechanical behaviour of the CD with that of mammalian tendon and highlight its potential as a model system for investigating poorly understood aspects of the ontogeny and phylogeny of vertebrate collagenous tissues.

MicroRNAs (miRNAs), a class of small non-protein-encoding RNAs, regulate gene expression via suppression of target mRNAs. MiRNAs are present in body fluids in a remarkable stable form as packaged in microvesicles of endocytic origin, named exosomes. In the present study, we have assessed miRNA expression in urinary exosomes from type 1 diabetic patients with and without incipient diabetic nephropathy. Results showed that miR-130a and miR-145 were enriched, while miR-155 and miR-424 reduced in urinary exosomes from patients with microalbuminuria. Similarly, in an animal model of early experimental diabetic nephropathy, urinary exosomal miR-145 levels were increased and this was paralleled by miR-145 overexpression within the glomeruli. Exposure of cultured mesangial cells to high glucose increased miR-145 content in both mesangial cells and mesangial cells-derived exosomes, providing a potential mechanism for diabetes-induced miR-145 overexpression. In conclusion, urinary exosomal miRNA content is altered in type 1 diabetic patients with incipient diabetic nephropathy and miR-145 may represent a novel candidate biomarker/player in the complication.

Emerging evidences suggest that Ca(2+)activated-K(+)-(BK) channel is involved in the regulation of cell viability. The changes of the cell viability observed under hyperkalemia (15 mEq/L) or hypokalemia (0.55 mEq/L) conditions were investigated in HEK293 cells expressing the hslo subunit (hslo-HEK293) in the presence or absence of BK channel modulators. The BK channel openers(10(-11)-10(-3)M) were: acetazolamide(ACTZ), Dichlorphenamide(DCP), methazolamide(MTZ), bendroflumethiazide(BFT), ethoxzolamide(ETX), hydrochlorthiazide(HCT), quercetin(QUERC), resveratrol(RESV) and NS1619; and the BK channel blockers(2 x 10(-7)M-5 x 10(-3)M) were: tetraethylammonium(TEA), iberiotoxin(IbTx) and charybdotoxin(ChTX). Experiments on cell viability and channel currents were performed using cell counting kit-8 and patch-clamp techniques, respectively. Hslo whole-cell current was potentiated by BK channel openers with different potency and efficacy in hslo-HEK293. The efficacy ranking of the openers at -60 mV(Vm) was BFT> ACTZ >DCP ≥RESV≥ ETX> NS1619> MTZ≥ QUERC; HCT was not effective. Cell viability after 24 h of incubation under hyperkalemia was enhanced by 82+6% and 33+7% in hslo-HEK293 cells and HEK293 cells, respectively. IbTx, ChTX and TEA enhanced cell viability in hslo-HEK293. BK openers prevented the enhancement of the cell viability induced by hyperkalemia or IbTx in hslo-HEK293 showing an efficacy which was comparable with that observed as BK openers. BK channel modulators failed to affect cell currents and viability under hyperkalemia conditions in the absence of hslo subunit. In contrast, under hypokalemia cell viability was reduced by -22+4% and -23+6% in hslo-HEK293 and HEK293 cells, respectively; the BK channel modulators failed to affect this parameter in these cells. In conclusion, BK channel regulates cell viability under hyperkalemia but not hypokalemia conditions. BFT and ACTZ were the most potent drugs either in activating the BK current and in preventing the cell proliferation induced by hyperkalemia. These findings may have relevance in disorders associated with abnormal K(+) ion homeostasis including periodic paralysis and myotonia.

Pleiotrophin (PTN) is a widespread cytokine involved in bone formation, neurite outgrowth, and angiogenesis. In skeletal muscle, PTN is upregulated during myogenesis, post-synaptic induction, and regeneration after crushing, but little is known regarding its effects on muscle function. Here, we describe the effects of PTN on the slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles in mice over-expressing PTN under the control of a bone promoter. The mice were maintained in normal loading or disuse condition, induced by hindlimb unloading (HU) for 14 days. Effects of exposition to near-zero gravity during a 3-months spaceflight (SF) into the Mice Drawer System are also reported. In normal loading, PTN overexpression had no effect on muscle fiber cross-sectional area, but shifted soleus muscle toward a slower phenotype, as shown by an increased number of oxidative type 1 fibers, and increased gene expression of cytochrome c oxidase subunit IV and citrate synthase. The cytokine increased soleus and EDL capillary-to-fiber ratio. PTN overexpression did not prevent soleus muscle atrophy, slow-to-fast transition, and capillary regression induced by SF and HU. Nevertheless, PTN exerted various effects on sarcolemma ion channel expression/function and resting cytosolic Ca(2+) concentration in soleus and EDL muscles, in normal loading and after HU. In conclusion, the results show very similar effects of HU and SF on mouse soleus muscle, including activation of specific gene programs. The EDL muscle is able to counterbalance this latter, probably by activating compensatory mechanisms. The numerous effects of PTN on muscle gene expression and functional parameters demonstrate the sensitivity of muscle fibers to the cytokine. Although little benefit was found in HU muscle disuse, PTN may emerge useful in various muscle diseases, because it exerts synergetic actions on muscle fibers and vessels, which could enforce oxidative metabolism and ameliorate muscle performance.

The molecular composition and drug responses of calcium-activated K(+) (BK) channels of skeletal muscle are unknown. Patch-clamp experiments combined with transcript scanning of the Kcnma1 gene encoding the alpha subunit of the BK channel were performed in rat slow-twitch soleus (Sol) and fast-twitch flexor digitorum brevis (FDB) skeletal muscles. Five splicing products of the Kcnma1 gene were isolated from Sol and FDB: the e17, e22, +29 aa, Slo27 and Slo0 variants. RT-PCR analysis demonstrated that the expression of e22 and Slo0 were 80-90% higher in FDB than Sol, whereas the expression of Slo27 was 60% higher in Sol than FDB, and the +29 aa variant was equally expressed in both muscle types. No beta 1-4 subunits were detected. In Sol, a large BK current with low Ca(2+) sensitivity was recorded. The BK channel of Sol also showed a reduced response to BK channel openers, such as NS1619, acetazolamide and related drugs. In FDB, a reduced BK current with high Ca(2+) sensitivity and an enhanced drug response was recorded. The total BK RNA content, which was 200% higher in Sol than in FDB, correlated with the BK currents in both muscles. Drug responses primarily correlated with e22 and Slo0 expression levels in FDB and to Slo27 expression in Sol muscle. In conclusion, phenotype-dependent BK channel biophysical and pharmacological properties correlated with the expression levels of the variants in muscles. These findings may be relevant to conditions affecting postural muscles, such as prolonged bed-rest, and to diseases affecting fast-twitch muscles, such as periodic paralysis. Down-regulation or up-regulation of the variants associated with pathological conditions may affect channel composition and drug responses.

BackgroundLittle is known about individual recognition (IR) in octopuses, although they have been abundantly studied for their sophisticated behaviour and learning capacities. Indeed, the ability of octopuses to recognise conspecifics is suggested by a number of clues emerging from both laboratory studies (where they appear to form and maintain dominance hierarchies) and field observations (octopuses of neighbouring dens display little agonism between each other). To fill this gap in knowledge, we investigated the behaviour of 24 size-matched pairs of Octopus vulgaris in laboratory conditions.Methodology/principal findingsThe experimental design was composed of 3 phases: Phase 1 (acclimatization): 12 "sight-allowed" (and 12 "isolated") pairs were maintained for 3 days in contiguous tanks separated by a transparent (and opaque) partition to allow (and block) the vision of the conspecific; Phase 2 (cohabitation): members of each pair (both sight-allowed and isolated) were transferred into an experimental tank and were allowed to interact for 15 min every day for 3 consecutive days; Phase 3 (test): each pair (both sight-allowed and isolated) was subject to a switch of an octopus to form pairs composed of either familiar ("sham switches") or unfamiliar conspecifics ("real switches"). Longer latencies (i.e. the time elapsed from the first interaction) and fewer physical contacts in the familiar pairs as opposed to the unfamiliar pairs were used as proxies for recognition.ConclusionsOctopuses appear able to recognise conspecifics and to remember the individual previously met for at least one day. To the best of our knowledge, this is the first experimental study showing the occurrence of a form of IR in cephalopods. Future studies should clarify whether this is a "true" IR.

Background: Italy records very alarming levels antimicrobial resistance (AMR), so a National Action Plan on Antimicrobial resistance (PNCAR) was developed, adopting the AMR European Union's recommendations based on the results of the ECDC site visit of January 2017. For achieving PNCAR objectives, it is necessary to support and harmonize the implementation of recommendations in all the different healthcare levels (regional authorities and local trusts), so the SPiNCAR project was launched to create a tool for reaching this goal., Methods: We developed a framework based on a scientific literature and national and international guidelines. Firstly, we identified the major intervention areas for tackling AMR, then, for each area, we built a set of standards, both for regional authorities than for local trusts. Every standard is composed by a set of essential and additional criteria, which refer to a minimum or supplemental performance level respectively. The contents were firstly discussed by the project's team during face-to-face kick-off meetings, then confirmed with Delphi methodology and finally validated through a pilot study., Results: The final framework consists of seven different areas that reflect the PNCAR structure: Governance, Surveillance and Monitoring, Appropriate Use of antimicrobials, Healthcare-associated Infections (HAIs) control and prevention, Education and Training, Alliance among Stakeholders, Implementation. The total number of standards for the regional framework was 34 with 264 criteria and for the local version 36 criteria with 279 standards., Conclusion: The ongoing use of this tool, developed on international evidences and recommendations that were tailored on the Italian specific context, allows monitoring the improvement achieved over time and plan the next steps., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Clinical record (CR) is the primary tool used by healthcare workers (HCWs) to record clinical information and its completeness can help achieve safer practices. CR is the most appropriate source in order to measure and evaluate the quality of care. In order to achieve a safety climate is fundamental to involve a responsive healthcare workforce thorough peer-review and feedbacks. This study aims to develop a peer-review tool for clinical records quality assurance, presenting the seven-year experience in the evolution of it; secondary aims are to describe the CR completeness and HCWs' diligence toward recording information in it., Methods: To assess the completeness of CRs a peer-review tool was developed in a large Academic Hospital of Northern Italy. This tool included measurable items that examined different themes, moments and levels of the clinical process. Data were collected every three months between 2010 and 2016 by appointed and trained HCWs from 42 Units; the hospital Quality Unit was responsible for of processing and validating them. Variations in the proportion of CR completeness were assessed using Cochran-Armitage test for trends., Results: A total of 9,408 CRs were evaluated. Overall CR completeness improved significantly from 79.6% in 2010 to 86.5% in 2016 (p<0.001). Doctors' attitude showed a trend similar to the overall completeness, while nurses improved more consistently (p<0.001). Most items exploring themes, moments and levels registered a significant improvement in the early years, then flattened in last years. Results of the validation process were always above the cut-off of 75%., Conclusions: This peer-review tool enabled the Quality Unit and hospital leadership to obtain a reliable picture of CRs completeness, while involving the HCWs in the quality evaluation. The completeness of CR showed an overall positive and significant trend during these seven years., Competing Interests: The authors have declared that no competing interests exist.