The first LA-ICP-MS U–Pb detrital zircon ages from quartzites located below (three samples) and above (one sample) the Upper Ordovician unconformity in the Central Pyrenees (the Rabassa Dome, ...Andorra) were investigated. The maximum depositional age for the Jújols Group, below the unconformity, based on the youngest detrital zircon population, is around 475Ma (Early Ordovician), whereas for the Bar Quartzite Fm., above the unconformity, the presence of only two zircons of 442 and 443Ma precludes obtaining a precise maximum sedimentation age. A time gap of ~20 million years for the Upper Ordovician unconformity in the Pyrenees can be proposed, similar to that of the Sardic unconformity in Sardinia. The similar age patterns obtained on both sides of the Upper Ordovician unconformity suggest that there was no change in the source area of these series, while the absence of a Middle Ordovician age population may be due to a lack of sedimentation at that time. The four study samples present very similar U–Pb age patterns: the main age populations correspond to Neoproterozoic (Ediacarian–Cryogenian, ca. 550–750Ma); Grenvillian (Tonian–Stenian, ca. 850–1100Ma); Paleoproterozoic (Orosirian, ca.1900–2100Ma) and Neoarchean (ca. 2500–2650Ma). The similarity with the Sardinian age distribution suggests that these two terranes could share the same source area and that they were paleogeographically close in Ordovician times in front of the Arabian–Nubian Shield.
•LA-ICP-MS U-Pb detrital zircon analysis have been used to suggest a maximum depositional age for the Cambro-Ordovician rocks of the Pyrenees.•The main detrital zircon age populations from these rocks are described.•The main age populations have been compared with age populations from other Perigondwanan terrains in order to better locate the Pyrenees in the northern Gondwana margin.
Immune checkpoint inhibitors (ICIs) induce acute interstitial nephritis (AIN) in 2-5% of patients, with a clearly higher incidence when they are combined with platinum derivatives. Unfortunately, ...suitable disease models and non-invasive biomarkers are lacking. To fill this gap in our understanding, we investigated the renal effects of cisplatin and anti-PD-L1 antibodies in mice, assessing PD-1 renal expression and cytokine levels in mice with AIN, and then we compared these findings with those in AIN-diagnosed cancer patients.
Twenty C57BL6J mice received 200 µg of anti-PD-L1 antibody and 5 mg/kg cisplatin intraperitoneally and were compared with those receiving cisplatin (n = 6), anti-PD-L1 (n = 7), or saline (n = 6). After 7 days, the mice were euthanized. Serum and urinary concentrations of TNFα, CXCL10, IL-6, and MCP-1 were measured by Luminex. The kidney sections were stained to determine PD-1 tissue expression. Thirty-nine cancer patients with AKI were enrolled (AIN n = 33, acute tubular necrosis (ATN) n = 6), urine MCP-1 (uMCP-1) was measured, and kidney sections were stained to assess PD-1 expression.
Cisplatin and anti PD-L1 treatment led to 40% AIN development (p = 0.03) in mice, accompanied by elevated serum creatinine and uMCP1. AIN-diagnosed cancer patients also had higher uMCP1 levels than ATN-diagnosed patients, confirming our previous findings. Mice with AIN exhibited interstitial PD-1 staining and stronger glomerular PD-1 expression, especially with combination treatment. Conversely, human AIN patients only showed interstitial PD-1 positivity.
Only mice receiving cisplatin and anti-PDL1 concomitantly developed AIN, accompanied with a more severe kidney injury. AIN induced by this drug combination was linked to elevated uMCP1, consistently with human AIN, suggesting that uMCP1 can be potentially used as an AIN biomarker.
Some recent studies have shown an association between sleep disordered breathing (SDB) and cancer mortality and incidence but no study has focused on a specific type of cancer. The objective of this ...study was to analyse the relationship between the severity of SDB and factors related to cutaneous malignant melanoma (CMM) aggressiveness. We performed a multicentre observational study in 82 consecutive patients diagnosed with CMM. 56 patients in whom melanoma measurements were available were finally included in the study. Melanoma measurements of aggressiveness included: tumour mitotic rate, Breslow index, presence of ulceration, stage of disease and growth rate of melanoma. A sleep study was performed in all the included patients. Multivariate analyses were used to examine the independent relationship between SDB severity (apnoea-hypopnea index (AHI) and nocturnal oxygen desaturation indexes (ODI3% and ODI4%)) and measures of CMM aggressiveness. 60.7% of patients had SDB (AHI ≥ 5) and 14.3% severe obstructive sleep apnoea (AHI ≥ 30). In fully adjusted multivariate analyses, AHI (OR 1.08, 95% CI 1.02-1.14), ODI3% (OR 1.08, 95% CI 1.02-1.11) and ODI4% (OR 1.1, 95% CI 1.02-1.2) were independently associated with an increased melanoma growth rate. Furthermore, AHI, ODI4% and ODI3% were significantly correlated with other aggressiveness factors of CMM, such as Breslow index, presence of ulceration and mitotic index. SDB severity markers are associated with some aggressiveness markers of CMM.
Acute kidney injury in patients who suffer a malignancy is a common complication. Due to its high prevalence and effective treatment, one of the most frequent causes that both oncologists and ...nephrologists must be aware of is acute tubulointerstitial nephritis (ATIN). ATIN is an immunomediated condition and the hallmark of the disease, with the presence of a tubulointerstitial inflammatory infiltrate in the renal parenchyma. This infiltrate is composed mainly of T lymphocytes that can be accompanied by macrophages, neutrophils, or eosinophils among other cells. One of the major causes is drug-related ATIN, and some antineoplastic treatments have been related to this condition. Worthy of note are the novel immunotherapy treatments aimed at enhancing natural immunity in order to defeat cancer cells. In the context of the immunosuppression status affecting ATIN patients, some pathogen antigens can trigger the development of the disease. Finally, hematological malignancies can also manifest in the kidney leading to ATIN, even at the debut of the disease. In this review, we aim to comprehensively examine differential diagnosis of ATIN in the setting of a neoplastic patient.
Severe stroke patients are known to be associated with larger rehabilitation length of stay (LOS) but other factors besides severity may be contributing. We aim to identify LOS predictors within a ...population of mostly severe patients and analyze the impact of socioeconomic situation in functionality at admission.A retrospective observational cohort study was conducted including 172 inpatients admitted to a rehabilitation center between 2007 and 2019. Associations with LOS were examined among 30 potential predictor variables using bivariate correlations. Significantly correlated (P < .002, Bonferroni adjustment) variables were entered into 9 different multiple linear regression models.No mild participants were included, 63.37% severe and 36.63% moderate. Most significant LOS determinants were: 1) total functional independence measure (FIM) (P < .001) and hemiparesis (P = .0108) (adjusted R = 0.24), 2) cognitive FIM (P = .002) and severity (P = .001) (adjusted R = 0.22), and 3) home accessibility (P = .043) and hemiparesis (P = 0.032) (adjusted R = 0.19).Known LOS predictors (e.g., depression, ataxia) within the full stroke severities were not found significant in our dataset.Socioeconomic situation was found moderately correlated with total FIM (r = -0.32, P < .0001).When stratifying the patients' socioeconomic situation into mild, important, and severe social risk, their respective median total FIM at admission were 61.5, 50, and 41, with significant differences between the mild and important group (P < .001); also significant differences were found between mild and severe groups (P < .001).A few of the variables identified in the literature as significant predictors of LOS within the full stroke population were also significant for our dataset (National Institutes of Health Stroke Scale, FIM, home accessibility) explaining less than 25% of the LOS variance. Most of the 30 analyzed known predictors were not significant (e.g., depression, age, recurrent stroke, ataxia, orientation, verbal communication, etc) suggesting that factors outside functional, socioeconomic, medical, and demographics not included in this study (e.g., rehabilitation sessions intensity) have important influences on LOS for severe patients.Patients at mild social risk obtained significantly higher total FIM at admission than patients at important and severe social risk. The importance of socioeconomic situation has been scarcely studied in the literature in relation to functionality at admission; our results suggest that it requires to be considered.
The first arrivals of hominin populations into Eurasia during the Early Pleistocene are currently considered to have occurred as short and poorly dated biological dispersions. Questions as to the ...tempo and mode of these early prehistoric settlements have given rise to debates concerning the taxonomic significance of the lithic assemblages, as trace fossils, and the geographical distribution of the technological traditions found in the Lower Palaeolithic record. Here, we report on the Barranc de la Boella site which has yielded a lithic assemblage dating to ∼1 million years ago that includes large cutting tools (LCT). We argue that distinct technological traditions coexisted in the Iberian archaeological repertoires of the late Early Pleistocene age in a similar way to the earliest sub-Saharan African artefact assemblages. These differences between stone tool assemblages may be attributed to the different chronologies of hominin dispersal events. The archaeological record of Barranc de la Boella completes the geographical distribution of LCT assemblages across southern Eurasia during the EMPT (Early-Middle Pleistocene Transition, circa 942 to 641 kyr). Up to now, chronology of the earliest European LCT assemblages is based on the abundant Palaeolithic record found in terrace river sequences which have been dated to the end of the EMPT and later. However, the findings at Barranc de la Boella suggest that early LCT lithic assemblages appeared in the SW of Europe during earlier hominin dispersal episodes before the definitive colonization of temperate Eurasia took place.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Human immunodeficiency virus (HIV) infection is considered a chronic disease. Antiretroviral therapy has allowed persons with HIV (PLWHIV) to achieve the 90-90-90 objectives proposed by the World ...Health Organization for 2020; but an additional challenge is getting an adequate health-related quality of life. A determining factor in the health-related quality of life of PLWHIV is the health care they perceive to receive. In this sense, we aimed to assess the perception of the outpatient care provided and to identify possible areas for improvement in a single-center, cross-sectional study at the HIV unit of Hospital Clínic, Barcelona. We sought patient reported experience measures by an anonymous e-survey with 11 statements based on a 1 to 6 Likert scale, and a final question measuring user satisfaction and loyalty through the Net Promoter Score (NPS). All PLWHIV with at least a clinical visit between January 1, 2020 and October 14, 2021 were invited. Of 5493 PLWHIV e-mailed, 1633 (30%) responded to the survey. The overall evaluation of clinical care was very favorable. The evaluation of the physical environment and facilities and the time spent in the waiting room received the lowest scores. According to the Net Promoter Score test results, 66% of respondents were willing to recommend this service, and 11% were not. Thus, monitoring patient reported experience measures in PLWHIV actively receiving outpatient care in our hospital allowed to identify the users' perception on quality of the care received, to determine the rate of satisfaction with the care, and to identify areas for improvement.
In patients with obstructive sleep apnoea (OSA), intermittent hypoxia induces overexpression of paraspeckle component (PSPC)1, a master modulator of transforming growth factor (TGF)-β signalling, ...which promotes cell cancer progression through epithelial-mesenchymal transition (EMT) and acquisition of cancer stem cell (CSC)-like features. However, the persistence of intermittent hypoxia-induced effects on PSPC1, and their consequences in cancer patients are not known. To this effect, circulating PSPC1 levels were compared in patients with cutaneous melanoma with or without OSA, and their relationship with tumour aggressiveness along with the
effects of soluble PSPC1 and intermittent hypoxia on melanoma cell aggressiveness mechanisms were assessed.
In 292 cutaneous melanoma patients, sleep studies and serum levels of PSPC1 and TGF-β were evaluated. The effect of PSPC1 on expression of EMT and CSC transcription factors was assessed using melanoma cell lines with patient sera under both normoxia and intermittent hypoxia conditions.
PSPC1 levels were higher in patients with moderate-severe OSA compared with mild OSA or non-OSA patients. Serum levels of PSPC1 were associated with several cutaneous melanoma clinical aggressiveness indicators. Both intermittent hypoxia exposures and serum from OSA patients upregulated TGF-β expression and amplified the expression of transcription factors associated with EMT activation and acquisition of CSC characteristics.
In cutaneous melanoma patients, OSA severity is associated with higher PSPC1 serum levels, which jointly with intermittent hypoxia would enhance the self-reprogramming capabilities of EMT and CSC feature acquisition of melanoma cells, promoting their intrinsic aggressiveness.
The periodic application of copper-based fungicides (Bourdeaux mixture) to vineyards of the Mediterranean region has generated an important pollution source that in some cases requires a quick ...intervention due to the high bioavailable copper content measured. Despite some vineyards were abandoned 40 years ago, noticeable amounts of Cu and other man-related metals are still nowadays detected in soils. In the present work, the development of a mobility test for the available heavy metal (Cu, Pb, Zn and As) content in soil has been performed using portable X-ray fluorescence (FP-XRF) combined with single leaching test, and was applied to a calcareous soil of a former vineyard area in Catalonia (NE Spain). The combined methodology has provided useful information for fast and detailed risk assessment, in terms of mobility and bioavailability of metals. The anthropogenic contribution was evaluated by means of the Concentration Enrichment Ratios (CER) in soil. The results reflect a clear anthropogenic contribution for Cu, a partial anthropogenic contribution for Pb proceeding from an external pollution source, and a non-significant external contribution for As and Zn. The topsoil concentration ranges for Cu (70–128 mg kg−1) were found to be above the background level and several samples above the regional governmental limits (Generic Reference Levels or GRL values) for soil ecosystem protection and for human health (90 mg kg−1). The present study reveals that the use of FP-XRF equipment constitute a highly valid option for quick decision making during the field location, characterization and quantitative elemental analysis of soil samples for screening of potential pollutants such as heavy metals.
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•In situ total soil heavy metals assessment by portable X-ray fluorescence.•FP-XRF combined with leaching test for fast risk assessment of metals' soil pollution.•Mapping and monitoring of polluted areas in a fast and cheap way.•Copper concentration found on soil was above the regional governmental limits.
Placental growth factor (PlGF) induces angiogenesis and promotes tissue repair, and plasma PlGF levels change markedly during acute myocardial infarction (AMI). Currently, the impact of obstructive ...sleep apnea (OSA) in patients with AMI is a subject of debate. Our objective was to evaluate the relationships between PlGF levels and both the severity of acute coronary syndrome (ACS) and short-term outcomes after ACS in patients with and without OSA.
A total of 538 consecutive patients (312 OSA patients and 226 controls) admitted for ACS were included in this study. All patients underwent polygraphy in the first 72 hours after hospital admission. The severity of disease and short-term prognoses were evaluated during the hospitalization period. Plasma PlGF levels were measured using an electrochemiluminescence immunoassay.
Patients with OSA were significantly older and more frequently hypertensive and had higher BMIs than those without OSA. After adjusting for age, smoking status, BMI and hypertension, PlGF levels were significantly elevated in patients with OSA compared with patients without OSA (19.9 pg/mL, interquartile range: 16.6-24.5 pg/mL; 18.5 pg/mL, interquartile range: 14.7-22.7 pg/mL; p<0.001), and a higher apnea-hypopnea index (AHI) was associated with higher PlGF concentrations (p<0.003). Patients with higher levels of PlGF had also an increased odds ratio for the presence of 3 or more diseased vessels and for a Killip score>1, even after adjustment.
The results of this study show that in patients with ACS, elevated plasma levels of PlGF are associated with the presence of OSA and with adverse outcomes during short-term follow-up.
ClinicalTrials.gov NCT01335087.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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