Occurence of legacy and emerging persistent organic pollutants at the Ross Sea and circumpolar deep water convergence (Antarctica)

Persistent organic pollutants (POPs) have attracted the attention of scientists and policy makers in recent decades due to their extreme persistence, semi-volatility, capacity to bio-accumulate in the food chain, and toxic properties. Despite its geographical isolation, extreme meteorological conditions and an almost total absence of local point sources, the Antarctic continent is vulnerable to contamination by POPs, due to the ability of these chemicals to undergo long range atmospheric transport (LRAT) and deposition in the open sea. In a few cases and for limited areas, POPs may be also introduced into the Antarctic ecosystem by human activities (scientific stations, fishing, tourism, accidental oil pills, waste incineration and sewage). Even if various studiesi.e.1,2,3,4,5 have revealed the presence of POPs in air, seawater, sediments and biota in Antarctica, more investigations are needed to implement the number of observations, integrate the data series and meet the indications of the Stockholm Convention and the UNECE protocol in terms of improving knowledge of the temporal and spatial trends of POPs in biotic and abiotic environmental compartments. In this study we present POP concentrations in water samples collected along vertical water columns from seven oceanographic stations located in the Ross Sea and close to the Circumpolar Convergence (see Figure 1). Moreover, the occurrence of emerging and legacy POPs, including polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), polychlorinated naphthalenes (PCNs), organochlorine pesticides (OCPs) and polybrominated diphenylethers (PBDEs) were investigated in order to evaluate their possible sources and relationship with physical and biological processes taking place in the water column. The Ross sea is the formation site of two shelf waters which constitute an important part of the Antarctic Bottom Water (AABWs): the High Salinity Shelf Water (HSSW), which is relatively cold and generated inside the Ross Sea basin and the Ice Shelf Water (ISW). The Ross sea is influenced by only one water mass of external origin, the Circumpolar Deep Water (CDW), which is the largest circulation feature of the Southern Ocean, manly responsible for possible exchange processes between the Antarctic seas and the outer oceans, and thus a possible source of persistent organic pollutants (POPs)2 . The CDW is a relatively warm, salty and nutrient rich water mass carried around Antarctica by the Antarctic Circumpolar Current (ACC)6. Associated with the ACC is the Antarctic Convergence where the cold Antarctic waters meet the warmer waters of the subantarctic creating a zone of upwelling nutrients. Moreover, the Drygalski Glacie Tongue plays an important role in the Polynya development in the Terra Nova Bay, in the Ross sea. An important environmental concern is the accelerated glacier and snow melting that represent a massive release of both naturally occurring chemical substances and organic/inorganic pollutants of anthropogenic origin, which are stored in the deeper layers of the ice and may be delivered to surrounding ecosystems

Prefronto-cerebellar transcranial direct current stimulation increases amplituded and decreases latency of P3b component in patients with euthymic bipolar disorder

INTRODUCTION: Neurocognitive impairments have been observed in patients with bipolar disorder (BD) even during the euthymic phase of the disease, potentially representing trait-associated rather than state-associated characteristics of the disorder. In the present study, we used transcranial direct current stimulation (tDCS) applied to cerebellar and prefrontal cortices to improve the neurophysiological performances of patients with euthymic BD. METHODS: Twenty-five outpatients with BD underwent open-label prefrontocerebellar tDCS for 3 consecutive weeks. Neurophysiological performances were assessed through the examination of the P3b and P3a subcomponents of P300 event-related potential at baseline and after stimulation. RESULTS: Compared to baseline, P3b component after tDCS showed significantly higher amplitude and shorter latency (latency: Fz P=0.02, Cz P=0.03, and Pz P=0.04; amplitude: Fz P=0.24, Cz P=0.02, and Pz P=0.35). CONCLUSION: In our sample of patients with euthymic BD, concomitant prefrontoexcitatory and cerebellar-inhibitory modulations led to improved brain information processing stream. This improvement may at least partially result from neuroplastic modulation of prefrontocerebellar circuitry activity

Systematic age-related differences in chronic disease management in a population-based cohort study: a new paradigm of primary care is required

Background Our interest in chronic conditions is due to the fact that, worldwide, chronic diseases have overtaken infectious diseases as the leading cause of death and disability, so their management represents an important challenge for health systems. The aim of this study was to compare the performance of primary health care services in managing diabetes, congestive heart failure (CHF) and coronary heart disease (CHD), by age group. Methods This population-based retrospective cohort study was conducted in Italy, enrolling 1,948,622 residents 6516 years old. A multilevel regression model was applied to analyze compliance to care processes with explanatory variables at both patient and district level, using age group as an independent variable, and adjusting for sex, citizenship, disease duration, and Charlson index on the first level, and for District Health Unit on the second level. Results The quality of chronic disease management showed an inverted U-shaped relationship with age. In particular, our findings indicate lower levels for young adults (16\u201344 year-olds), adults (45\u201364), and oldest old (+85) than for patients aged 65\u201374 in almost all quality indicators of CHD, CHF and diabetes management. Young adults (16\u201344 y), adults (45\u201364 y), the very old (75\u201384 y) and the oldest old (+85 y) patients with CHD, CHF and diabetes are less likely than 65\u201374 year-old patients to be monitored and treated using evidence-based therapies, with the exceptions of echocardiographic monitoring for CHF in young adult patients, and renal monitoring for CHF and diabetes in the very old. Conclusion Our study shows that more effort is needed to ensure that primary health care systems are sensitive to chronic conditions in the young and in the very elderly

Chloride intracellular channel 1 activity is not required for glioblastoma development but its inhibition dictates glioma stem cell responsivity to novel biguanide derivatives

Background: Chloride intracellular channel-1 (CLIC1) activity controls glioblastoma proliferation. Metformin exerts antitumor effects in glioblastoma stem cells (GSCs) inhibiting CLIC1 activity, but its low potency hampers its translation in clinical settings. Methods: We synthesized a small library of novel biguanide-based compounds that were tested as antiproliferative agents for GSCs derived from human glioblastomas, in vitro using 2D and 3D cultures and in vivo in the zebrafish model. Compounds were compared to metformin for both potency and efficacy in the inhibition of GSC proliferation in vitro (MTT, Trypan blue exclusion assays, and EdU labeling) and in vivo (zebrafish model), migration (Boyden chamber assay), invasiveness (Matrigel invasion assay), self-renewal (spherogenesis assay), and CLIC1 activity (electrophysiology recordings), as well as for the absence of off-target toxicity (effects on normal stem cells and toxicity for zebrafish and chick embryos). Results: We identified Q48 and Q54 as two novel CLIC1 blockers, characterized by higher antiproliferative potency than metformin in vitro, in both GSC 2D cultures and 3D spheroids. Q48 and Q54 also impaired GSC self-renewal, migration and invasion, and displayed low systemic in vivo toxicity. Q54 reduced in vivo proliferation of GSCs xenotransplanted in zebrafish hindbrain. Target specificity was confirmed by recombinant CLIC1 binding experiments using microscale thermophoresis approach. Finally, we characterized GSCs from GBMs spontaneously expressing low CLIC1 protein, demonstrating their ability to grow in vivo and to retain stem-like phenotype and functional features in vitro. In these GSCs, Q48 and Q54 displayed reduced potency and efficacy as antiproliferative agents as compared to high CLIC1-expressing tumors. However, in 3D cultures, metformin and Q48 (but not Q54) inhibited proliferation, which was dependent on the inhibition dihydrofolate reductase activity. Conclusions: These data highlight that, while CLIC1 is dispensable for the development of a subset of glioblastomas, it acts as a booster of proliferation in the majority of these tumors and its functional expression is required for biguanide antitumor class-effects. In particular, the biguanide-based derivatives Q48 and Q54, represent the leads to develop novel compounds endowed with better pharmacological profiles than metformin, to act as CLIC1-blockers for the treatment of CLIC1-expressing glioblastomas, in a precision medicine approach

Postoperative respiratory failure in liver transplantation: Risk factors and effect on prognosis

Background :Postoperative respiratory failure (PRF, namely mechanical ventilation >48 hours) significantly affects morbidity and mortality in liver transplantation (LTx). Previous studies analyzed only one or two categories of PRF risk factors (preoperative, intraoperative or postoperative ones). The aims of this study were to identify PRF predictors, to assess the length of stay (LoS) in ICU and the 90-day survival according to the PRF in LTx patients. Methods: Two classification approaches were used: systematic classification (recipient-related preoperative factors; intraoperative factors; logistic factors; donor factors; postoperative ICU factors; postoperative surgical factors) and patient/organ classification (patient-related general factors; native-liver factors; new-liver factors; kidney factors; heart factors; brain factors; lung factors). Two hundred adult non-acute patients were included. Missing analysis was performed. The competitive role of each factor was assessed. Results: PRF occurred in 36.0% of cases. Among 28 significant PRF predictors at univariate analysis, 6 were excluded because of collinearity, 22 were investigated by ROC curves and by logistic regression analysis. Recipient age (OR = 1.05; p = 0.010), female sex (OR = 2.75; p = 0.018), Model for End-Stage Liver Disease (MELD, OR = 1.09; p<0.001), restrictive lung pattern (OR = 2.49; p = 0.027), intraoperative veno-venous bypass (VVBP, OR = 3.03; p = 0.008), pre-extubation PaCO 2 (OR = 1.11; p = 0.003) and Model for Early Allograft Function (MEAF, OR = 1.37; p<0.001) resulted independent PRF risk factors. As compared to patients without PRF, the PRF-group had longer LoS (10 days IQR 7-18 versus 5 days IQR 4-7, respectively; p<0.001) and lower day-90 survival (86.0% versus 97.6% respectively, p<0.001). Conclusion: In conclusion, MELD, restrictive lung pattern, surgical complexity as captured by VVBP, pre-extubation PaCO 2 and MEAF are the main predictors of PRF in non-acute LTx patients

Enteral versus intravenous approach for the sedation of critically ill patients: a randomized and controlled trial

Background. ICU patients must be kept conscious, calm, and cooperative even during the critical phases of illness. Enteral administration of sedative drugs might avoid oversedation, and would be as adequate as intravenous for awake patients, with fewer side effects and lower costs. This study compares two sedation strategies, in order to early reach and maintain the light sedation target. Methods. Multicenter, single-blind randomized and controlled trial carried out in 12 Italian ICUs, involving patients with expected mechanical ventilation duration >72 hours at ICU admission and predicted mortality >12% (Simplified Acute Physiology Score II >32 points) during the first 24 ICU hours. Patients were randomly assigned to receive intravenous (midazolam, propofol) or enteral (hydroxyzine, lorazepam, and melatonin) sedation. Primary outcome: percentage of work shifts with an observed Richmond Agitation-Sedation Scale (RASS) = target RASS \ub1 1. Secondary outcomes: protocol feasibility, delirium- and coma-free days, costs of drugs, length of ICU and hospital stay, ICU, hospital, and one-year mortality. Results. 348 patients were enrolled. There were no differences in the primary outcome: enteral 89.8 [74.1-100], intravenous 94.4 [78-100]%, p=0.20. Enteral-treated patients had more protocol violations: 81 (46.6%) vs 7 (4.2%), p<0.01, more self-extubations: 4 (2.4%) vs 14 (8.1%), p=0.03, a lighter sedative target (RASS = 0): 93 [71-100] vs 83 [61-100]%, p<0.01, and lower total costs for drugs: 2.39 [0.75- 9.78] vs 4.15 [1.20 -20.19] \u20ac/day with mechanical ventilation (p=0.01). Conclusions. Although enteral sedation of critically ill patients is cheaper and permits a lighter sedation target, it is not superior to intravenous sedation for reaching the RASS target. Trial registration. ClinicalTrials.gov, Clinical Trial #NCT01360346, registered 25 March 2011, https://clinicaltrials.gov/ct2/show/NCT01360346. Registered on 25 March 2011

Prevalence of chronic diseases by immigrant status and disparities in chronic disease management in immigrants: a population-based cohort study, Valore Project

BACKGROUND: For chronic conditions, disparities can take effect cumulatively at various times as the disease progresses, even when care is provided. The aim of this study was to quantify the prevalence of diabetes, congestive heart failure (CHF) and coronary heart disease (CHD) in adults by citizenship, and to compare the performance of primary care services in managing these chronic conditions, again by citizenship. METHODS: This is a population-based retrospective cohort study on 1,948,622 people aged 16 years or more residing in Italy. A multilevel regression model was applied to analyze adherence to care processes using explanatory variables at both patient and district level. RESULTS: The age-adjusted prevalence of diabetes was found higher among immigrants from high migratory pressure countries (HMPC) than among Italians, while the age-adjusted prevalence of cardiovascular disease was higher for Italians than for HMPC immigrants or those from highly-developed countries (HDC). Our results indicate lower levels in all quality management indicators for citizens from HMPC than for Italians, for all the chronic conditions considered. Patients from HDC did not differ from Italian in their adherence to disease management schemes. CONCLUSION: This study revealed a different prevalence of chronic diseases by citizenship, implying a different burden of primary care by citizenship. Our findings show that more effort is needed to guarantee migrant-sensitive primary health care