Deformation and fluid flow in the Munsiari Thrust (NW India): A preliminary fluid inclusion study

A fluid inclusion study was carried out on quartz veins deformed during the activity of the Munsiari Thrust in the Garhwal Himalaya (India, Western Himalaya). These veins are hosted in mylonitic phyllites, with a greenschist mineral assemblage made of quartz-white mica-biotite-chlorite-epidote and minor calcite and plagioclase. Within the veins two groups of isolated “early fluid” inclusions and trails of small secondary fluid inclusions have been observed. Two types of inclusions preserved in isolated groups have been petrographycally recognized: (i) a two liquids and a vapor phase (L1+L2+V) that is the most common type and (ii) a less frequent liquid and a vapor phase (L+V). Both types of fluid inclusions were investigated through optical microthermometric experiments. For “early fluid” inclusions, assuming a trapping temperature based on quartz dynamic recrystallization mechanisms and previous P-T estimates, in the range of 500-520 °C, a corresponding trapping pressure in the range of c. 0.50-0.53 GPa is estimated. The trapping pressure range evaluated in the present contribution support that these fluid inclusions have been entrapped during the early stages of the activity of the Munsiari Thrust

Time Course of Paclitaxel-Induced Apoptosis in an Experimental Model of Virus-Induced Breast Cancer

Early assessment of the efficacy of treatment is important in patients with breast cancer, whose routine adjuvant regimen frequently includes chemotherapy. Irrespective of the exact mechanisms involved in induction, the common early phenotypic marker of apoptosis is the expression on the outer cell membrane surface of phosphatidylserine, which avidly binds annexin V. 99mTc-labeled annexin V has been proposed for in vivo scintigraphic detection of apoptosis, albeit with contradicting results. This study was performed to define the time course of apoptosis induced by the chemotherapeutic agent paclitaxel in a model of virus-induced murine breast cancer. Methods: The RIII virus induces an estrogen-dependent, slow-growing breast cancer; BALB-c/cRIII female mice with breast tumors averaging 10 mm were studied, both in baseline conditions and at various times after the intravenous administration of paclitaxel (equivalent to a human dose of 20 mg/70 kg of body weight). The biodistribution of 99mTc-annexin V was evaluated at baseline and then at 1, 3, 6, and 24 h after paclitaxel administration. Apoptotic and antiapoptotic markers were also evaluated in tumor samples obtained at the same time points: DNA breaks (terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling [TUNEL]), active caspase-3, apoptosis-inducing factor, and Bcl-2 protein. Results: Baseline uptake of 99mTc-annexin V in breast tumors was about 2-fold higher than the uptake in normal breast tissue (demonstrating some ongoing apoptosis); tracer uptake increased at 1 and 3 h after paclitaxel administration (to almost double the baseline value) and then declined to levels even lower than baseline. Although no activation of the apoptosis-inducing factor mechanism was detected, a peak in TUNEL-positive tumor cells was reached 3 h after paclitaxel administration (to more than 6-fold the baseline level). The antiapoptotic marker Bcl-2 exhibited a biphasic pattern, with a maximum drop at 3 h, followed by return toward baseline levels at 6 h. Conclusion: These results define the time course of various biologic events taking place in this model of murine breast cancer after a proapoptotic insult (single-dose paclitaxel). Although confirming that in vivo uptake of 99mTc-annexin V reflects the degree of apoptosis, the study also suggests that the apoptotic response to antitumor therapy may differ from tumor type to tumor type. Therefore, contradicting results previously reported may depend on an inadequate time window chosen for imaging with 99mTc-annexin V

Microplastics ingestion in the ephyra stage of Aurelia sp. triggers acute and behavioral responses

For the first time, we report a correspondence between microplastics (MP) ingestion and ecotoxicological effects in gelatinous zooplankton (Cnidarian jellyfish). The ephyra stage of the jellyfish Aurelia sp. was exposed to both environmental and high concentrations of fluorescent 1–4 μm polyethylene MP (0.01–10 mg/L). After 24 and 48 h, MP accumulation, acute (Immobility) and behavioral (Frequency pulsation) endpoints were investigated. MP were detected by confocal and tomographic investigations on gelatinous body and mouth, either attached on the surface or ingested. This interaction was responsible for impairing ephyrae survival and behavior at all tested concentrations after 24 h. Acute and behavioral effects were also related to mechanical disturbance, caused by MP, triggering a loss of radial symmetry. Contaminated ephyrae exposed to clean seawater showed full recovery after 72 h highlighting the organisms without the microspheres, attached on body jellyfish surface around the mouth and lappets. In conclusion, short-term exposure to MP affects ephyrae jellyfish health, impairing both their survival and behavior. Polyethylene MP temporarily affect both Immobility and Frequency of pulsation of Aurelia sp. jellyfish. This study provides a first step towards understanding and clarifying the potential impacts of MP contamination in gelatinous zooplankton

MR-proADM as prognostic factor of outcome in COVID-19 patients

17siMid Regional pro-ADM (MR-proADM) is a promising novel biomarker in the evaluation of deteriorating patients and an emergent prognosis factor in patients with sepsis, septic shock and organ failure. It can be induced by bacteria, fungi or viruses. We hypothesized that the assessment of MR-proADM, with or without other inflammatory cytokines, as part of a clinical assessment of COVID-19 patients at hospital admission, may assist in identifying those likely to develop severe disease. A pragmatic retrospective analysis was performed on a complete data set from 111 patients admitted to Udine University Hospital, in northern Italy, from 25th March to 15th May 2020, affected by SARS-CoV-2 pneumonia. Clinical scoring systems (SOFA score, WHO disease severity class, SIMEU clinical phenotype), cytokines (IL-6, IL-1b, IL-8, TNF-α), and MR-proADM were measured. Demographic, clinical and outcome data were collected for analysis. At multivariate analysis, high MR-proADM levels were significantly associated with negative outcome (death or orotracheal intubation, IOT), with an odds ratio of 4.284 [1.893–11.413], together with increased neutrophil count (OR = 1.029 [1.011–1.049]) and WHO disease severity class (OR = 7.632 [5.871–19.496]). AUROC analysis showed a good discriminative performance of MR-proADM (AUROC: 0.849 [95% Cl 0.771–0.730]; p < 0.0001). The optimal value of MR-proADM to discriminate combined event of death or IOT is 0.895 nmol/l, with a sensitivity of 0.857 [95% Cl 0.728–0.987] and a specificity of 0.687 [95% Cl 0.587–0.787]. This study shows an association between MR-proADM levels and the severity of COVID-19. The assessment of MR-proADM combined with clinical scoring systems could be of great value in triaging, evaluating possible escalation of therapies, and admission avoidance or inclusion into trials. Larger prospective and controlled studies are needed to confirm these findings.openopenSozio E.; Tascini C.; Fabris M.; D'Aurizio F.; De Carlo C.; Graziano E.; Bassi F.; Sbrana F.; Ripoli A.; Pagotto A.; Giacinta A.; Gerussi V.; Visentini D.; De Stefanis P.; Merelli M.; Saeed K.; Curcio F.Sozio, E.; Tascini, C.; Fabris, M.; D'Aurizio, F.; De Carlo, C.; Graziano, E.; Bassi, F.; Sbrana, F.; Ripoli, A.; Pagotto, A.; Giacinta, A.; Gerussi, V.; Visentini, D.; De Stefanis, P.; Merelli, M.; Saeed, K.; Curcio, F

Il Fenomeno delle Dipendenze nella Regione Liguria. Anno 2010

-Il Report analizza il fenomeno delle dipendenze nella regione Liguria. La descrizione del fenomeno si sviluppa intorno all\u27analisi degli indicatori individuati dall\u27Osservatorio Europeo delle Dipendenze di Lisbona (OEDT): 1-uso di sostanze nella popolazione generale (questo indicatore va a rilevare i comportamenti nei confronti di alcol e sostanze psicoattive da parte della popolazione generale); 2-prevalenza d\u27uso problematico delle sostanze psicoattive; 3-domanda di trattamento degli utilizzatori di sostanze; 4-mortalit? degli utilizzatori di sostanze; 5-malattie infettive. Altri due importanti indicatori che si stanno sviluppando, e che vengono qui illustrati, sono l\u27analisi delle Schede di Dimissione Ospedaliera (SDO) e gli indicatori relativi alle conseguenza sociali dell\u27uso di droghe (criminalit? droga correlata). Inoltre sono state applicate diverse metodologie standard di stima sia per quantificare la quota parte sconosciuta di utilizzatori di sostanze che non afferiscono ai servizi, sia per identificarne alcune caratteristiche

Il Fenomeno delle Dipendenze nella Regione Abruzzo. Rapporto Anno 2009

Report on the state of legal and illegal substances use in the territory of Abruzzo RegionIl Report analizza il fenomeno delle dipendenze nella Regione Abruzzo. La descrizione del fenomeno si sviluppa intorno all\u27analisi degli indicatori individuati dall\u27Osservatorio Europeo delle Dipendenze di Lisbona (OEDT): 1-uso di sostanze nella popolazione generale (questo indicatore va a rilevare i comportamenti nei confronti di alcol e sostanze psicoattive da parte della popolazione generale); 2-prevalenza d\u27uso problematico delle sostanze psicoattive; 3-domanda di trattamento degli utilizzatori di sostanze; 4-mortalit? degli utilizzatori di sostanze; 5-malattie infettive. Altri due importanti indicatori che si stanno sviluppando, e che vengono qui illustrati, sono l\u27analisi delle Schede di Dimissione Ospedaliera (SDO) e gli indicatori relativi alle conseguenza sociali dell\u27uso di droghe (criminalit? droga correlata). Inoltre sono state applicate diverse metodologie standard di stima sia per quantificare la quota parte sconosciuta di utilizzatori di sostanze che non afferiscono ai servizi, sia per identificarne alcune caratteristiche

Estabilidad de las relaciones entre las agrupaciones de peces demersales y los factores ambientales-actividad pesquera a gran escala espacio-temporal en el norte del mar Mediterráneo

Trawling pressure and environmental changes may affect the composition of fish assemblages. Our knowledge on large spatio-temporal patterns of demersal fish composition remains incomplete for the Mediterranean Sea. We investigated (1) the spatio-temporal stability of demersal assemblages, (2) the relationships between these assemblages and potential structuring factors (trawling pressure and environmental conditions) in order to assess the dynamic of the assemblage structure at the scale of the northern Mediterranean Sea. We analysed a dataset of 18062 hauls from 10 to 800 m depth performed annually during the last two decades across 17 Geographical Sub-Areas (GSAs) (MEDITS program). A multi-table analysis (STATICO-CoA) evidenced a strong inter-GSAs stability in the organization of assemblages, with specificities for some GSAs. The most stable structuring factors were linked to combined gradients of chlorophyll a, phytoplancton carbon biomass and temperature, inversely correlated with depth, salinity and nutrient gradients (axis 1 of the STATICO-CoA compromise, 93.74% of the total variability). A common pattern linking the distribution of species to these environmental gradients was evidenced for most of the 17 GSAs. Estimate of trawling pressure showed a minor role in the organization of the assemblages for the spatial scale and years investigated (axis 2, 4.67%).La presión pesquera y los cambios ambientales pueden afectar a la composición de las agrupaciones de peces. En el Mediterráneo, nuestro conocimiento a gran escala sobre los patrones espacio-temporales de la composición de especies de peces demersales sigue siendo incompleto. Investigamos (1) la estabilidad espacio-temporal de las agrupaciones demersales (2) las relaciones entre dichas agrupaciones y los posibles factores estructurantes (presión pesquera de arrastre y condiciones ambientales) para evaluar la dinámica de la estructura de las agrupaciones en el norte del mar Mediterráneo. Analizamos un conjunto de 18062 lances entre 10 y 800 m. de profundidad realizados anualmente, durante las últimas dos décadas, en 17 sub-áreas geográficas (GSAs) (Proyecto MEDITS). El análisis multi-tablas (STATICO-CoA) evidenció una fuerte estabilidad inter-GSAs en la organización de agrupaciones, con especificidades para algunas GSAs. Los factores estructurantes más estables se relacionaron con los gradientes combinados de clorofila a, fitoplancton, carbono y temperatura, correlacionados inversamente con los gradientes de profundidad, salinidad y nutrientes (eje 1 del STATICO-CoA, 93.74% de la variabilidad total). En la mayoría de las GSAs encontramos un patrón común que vincula la distribución de las especies a estos gradientes ambientales. La estimación de la presión pesquera de arrastre mostró un papel menor en la organización de las agrupaciones para la escala espacial y los años investigados (eje 2, 4.67%)

Refinement of the diagnostic approach for the identification of children and adolescents affected by familial hypercholesterolemia: Evidence from the LIPIGEN study

Background and aims: We aimed to describe the limitations of familiar hypercholesterolemia (FH) diagnosis in childhood based on the presence of the typical features of FH, such as physical sings of cholesterol accumulation and personal or family history of premature cardiovascular disease or hypercholesterolemia, comparing their prevalence in the adult and paediatric FH population, and to illustrate how additional information can lead to a more effective diagnosis of FH at a younger age.Methods: From the Italian LIPIGEN cohort, we selected 1188 (&gt;= 18 years) and 708 (&lt;18 years) genetically-confirmed heterozygous FH, with no missing personal FH features. The prevalence of personal and familial FH features was compared between the two groups. For a sub-group of the paediatric cohort (N = 374), data about premature coronary heart disease (CHD) in second-degree family members were also included in the evaluation.Results: The lower prevalence of typical FH features in children/adolescents vs adults was confirmed: the prevalence of tendon xanthoma was 2.1% vs 13.1%, and arcus cornealis was present in 1.6% vs 11.2% of the cohorts, respectively. No children presented clinical history of premature CHD or cerebral/peripheral vascular disease compared to 8.8% and 5.6% of adults, respectively. The prevalence of premature CHD in first-degree relatives was significantly higher in adults compared to children/adolescents (38.9% vs 19.7%). In the sub-cohort analysis, a premature CHD event in parents was reported in 63 out of 374 subjects (16.8%), but the percentage increased to 54.0% extending the evaluation also to second-degree relatives.Conclusions: In children, the typical FH features are clearly less informative than in adults. A more thorough data collection, adding information about second-degree relatives, could improve the diagnosis of FH at younger age

Spectrum of mutations in Italian patients with familial hypercholesterolemia: New results from the LIPIGEN study

Background Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by elevated plasma levels of LDL-cholesterol that confers an increased risk of premature atherosclerotic cardiovascular disease. Early identification and treatment of FH patients can improve prognosis and reduce the burden of cardiovascular mortality. Aim of this study was to perform the mutational analysis of FH patients identified through a collaboration of 20 Lipid Clinics in Italy (LIPIGEN Study). Methods We recruited 1592 individuals with a clinical diagnosis of definite or probable FH according to the Dutch Lipid Clinic Network criteria. We performed a parallel sequencing of the major candidate genes for monogenic hypercholesterolemia (LDLR, APOB, PCSK9, APOE, LDLRAP1, STAP1). Results A total of 213 variants were detected in 1076 subjects. About 90% of them had a pathogenic or likely pathogenic variants. More than 94% of patients carried pathogenic variants in LDLR gene, 27 of which were novel. Pathogenic variants in APOB and PCSK9 were exceedingly rare. We found 4 true homozygotes and 5 putative compound heterozygotes for pathogenic variants in LDLR gene, as well as 5 double heterozygotes for LDLR/APOB pathogenic variants. Two patients were homozygous for pathogenic variants in LDLRAP1 gene resulting in autosomal recessive hypercholesterolemia. One patient was found to be heterozygous for the ApoE variant p.(Leu167del), known to confer an FH phenotype. Conclusions This study shows the molecular characteristics of the FH patients identified in Italy over the last two years. Full phenotypic characterization of these patients and cascade screening of family members is now in progress

Lipoprotein(a) Genotype Influences the Clinical Diagnosis of Familial Hypercholesterolemia

: Background Evidence suggests that LPA risk genotypes are a possible contributor to the clinical diagnosis of familial hypercholesterolemia (FH). This study aimed at determining the prevalence of LPA risk variants in adult individuals with FH enrolled in the Italian LIPIGEN (Lipid Transport Disorders Italian Genetic Network) study, with (FH/M+) or without (FH/M-) a causative genetic variant. Methods and Results An lp(a) [lipoprotein(a)] genetic score was calculated by summing the number risk-increasing alleles inherited at rs3798220 and rs10455872 variants. Overall, in the 4.6% of 1695 patients with clinically diagnosed FH, the phenotype was not explained by a monogenic or polygenic cause but by genotype associated with high lp(a) levels. Among 765 subjects with FH/M- and 930 subjects with FH/M+, 133 (17.4%) and 95 (10.2%) were characterized by 1 copy of either rs10455872 or rs3798220 or 2 copies of either rs10455872 or rs3798220 (lp(a) score ≥1). Subjects with FH/M- also had lower mean levels of pretreatment low-density lipoprotein cholesterol than individuals with FH/M+ (t test for difference in means between FH/M- and FH/M+ groups &lt;0.0001); however, subjects with FH/M- and lp(a) score ≥1 had higher mean (SD) pretreatment low-density lipoprotein cholesterol levels (223.47 [50.40] mg/dL) compared with subjects with FH/M- and lp(a) score=0 (219.38 [54.54] mg/dL for), although not statistically significant. The adjustment of low-density lipoprotein cholesterol levels based on lp(a) concentration reduced from 68% to 42% the proportion of subjects with low-density lipoprotein cholesterol level ≥190 mg/dL (or from 68% to 50%, considering a more conservative formula). Conclusions Our study supports the importance of measuring lp(a) to perform the diagnosis of FH appropriately and to exclude that the observed phenotype is driven by elevated levels of lp(a) before performing the genetic test for FH