Background and Aims
Patients with hepatitis C virus (HCV) and advanced fibrosis remain at risk of hepatocellular carcinoma (HCC) after sustained viral response (SVR) and need lifelong surveillance. ...Because HCC risk is not homogenous and may decrease with fibrosis regression, we aimed to identify patients with low HCC risk based on the prediction of noninvasive markers and its changes after SVR.
Approach and Results
This is a multicenter cohort study, including patients with HCV and compensated advanced fibrosis that achieved SVR after direct antivirals. Clinical and transient elastography (TE) data were registered at baseline, 1 year, and 3 years after the end of treatment (EOT). All patients underwent liver ultrasound scan every 6 months. Patients with clinical evaluation 1 year after EOT were eligible. Univariate and multivariate Cox regression analysis were performed, and predictive models were constructed. HCC occurrence rates were evaluated by Kaplan‐Meier. Nine hundred and ninety‐three patients were eligible (56% male; 44% female; median age 62 years), 35 developed HCC (3.9%), and the median follow‐up was 45 months (range 13‐53). Baseline liver stiffness measurement (LSM) (HR 1.040; 95% CI 1.017‐1.064), serum albumin (HR 0.400; 95% CI 0.174‐0.923), 1‐year DeltaLSM (HR 0.993; 95% CI 0.987‐0.998), and 1‐year FIB‐4 score (HR 1.095; 95% CI 1.046‐1.146) were independent factors associated with HCC. The TE‐based HCC risk model predicted 0% of HCC occurrence at 3 years in patients with score 0 (baseline LSM ≤ 17.3 kPa, albumin >4.2 g/dL, and 1‐year DeltaLSM > 25.5%) versus 5.2% in patients with score 1‐3 (Harrell’s C 0.779; log‐rank 0.002). An alternative model with FIB‐4 similarly predicted HCC risk.
Conclusions
A combination of baseline and dynamic changes in noninvasive markers may help to identify patients with a very low risk of HCC development after SVR.
Nissle 1917 (EcN) is a probiotic strain with proven efficacy in inducing and maintaining remission of ulcerative colitis. However, the microbial factors that mediate these beneficial effects are not ...fully known. Gram-negative bacteria release outer membrane vesicles (OMVs) as a direct pathway for delivering selected bacterial proteins and active compounds to the host. In fact, vesicles released by gut microbiota are emerging as key players in signaling processes in the intestinal mucosa. In the present study, the dextran sodium sulfate (DSS)-induced colitis mouse model was used to investigate the potential of EcN OMVs to ameliorate mucosal injury and inflammation in the gut. The experimental protocol involved pre-treatment with OMVs for 10 days before DSS intake, and a 5-day recovery period. Oral administration of purified EcN OMVs (5 μg/day) significantly reduced DSS-induced weight loss and ameliorated clinical symptoms and histological scores. OMVs treatment counteracted altered expression of cytokines and markers of intestinal barrier function. This study shows for the first time that EcN OMVs can mediate the anti-inflammatory and barrier protection effects previously reported for this probiotic in experimental colitis. Remarkably, translation of probiotics to human healthcare requires knowledge of the molecular mechanisms involved in probiotic-host interactions. Thus, OMVs, as a non-replicative bacterial form, could be explored as a new probiotic-derived therapeutic approach, with even lower risk of adverse events than probiotic administration.
Breast cancer patients under neoadjuvant chemotherapy includes a heterogeneous group of patients who eventually develop distal disease, not detectable by current methods. We propose the use of ...exosomal miRNAs and circulating tumor cells as diagnostic and predictive biomarkers in these patients.
Fifty-three breast cancer women initially diagnosed with localized breast cancer under neoadjuvant chemotherapy were prospectively enrolled in this study. However, six of them were later re-evaluated and diagnosed as metastatic breast cancer patients by PET-CT scan. Additionally, eight healthy donors were included. Circulating tumor cells and serum exosomal miRNAs were isolated from blood samples before and at the middle of neoadjuvant therapy and exosomal miRNA levels analyzed by qPCR.
Before neoadjuvant therapy, exosomal miRNA-21 and 105 expression levels were higher in metastatic versus non-metastatic patients and healthy donors. Likewise, higher levels of miRNA-222 were observed in basal-like (p = 0.037) and in luminal B versus luminal A (p = 0.0145) tumor subtypes. Exosomal miRNA-222 levels correlated with clinical and pathological variables such as progesterone receptor status (p = 0.017) and Ki67 (p = 0.05). During neoadjuvant treatment, exosomal miRNA-21 expression levels directly correlated with tumor size (p = 0.039) and inversely with Ki67 expression (p = 0.031). Finally, higher levels of exosomal miRNA-21, miRNA-222, and miRNA-155 were significantly associated with the presence of circulating tumor cells.
Liquid biopsies based on exosomal miRNAs and circulating tumor cells can be a complementary clinical tool for improving breast cancer diagnosis and prognosis.
Chirality plays a major role in nature, from particle physics to DNA, and its control is much sought-after due to the scientific and technological opportunities it unlocks. For magnetic materials, ...chiral interactions between spins promote the formation of sophisticated swirling magnetic states such as skyrmions, with rich topological properties and great potential for future technologies. Currently, chiral magnetism requires either a restricted group of natural materials or synthetic thin-film systems that exploit interfacial effects. Here, using state-of-the-art nanofabrication and magnetic X-ray microscopy, we demonstrate the imprinting of complex chiral spin states via three-dimensional geometric effects at the nanoscale. By balancing dipolar and exchange interactions in an artificial ferromagnetic double-helix nanostructure, we create magnetic domains and domain walls with a well-defined spin chirality, determined solely by the chiral geometry. We further demonstrate the ability to create confined 3D spin textures and topological defects by locally interfacing geometries of opposite chirality. The ability to create chiral spin textures via 3D nanopatterning alone enables exquisite control over the properties and location of complex topological magnetic states, of great importance for the development of future metamaterials and devices in which chirality provides enhanced functionality.
The deposition and manipulation of human remains in natural caves are well known for the Neolithic of Southern Iberia. The cultural meaning of these practices is however still largely unclear. Cueva ...de los Marmoles (CM, Priego-Córdoba) is one of the most important cave contexts from Southern Spain, which returned a large number of commingled skeletal remains suggesting its funerary use from the Neolithic to the Late Bronze Age. Here we discuss CM from a chronological and cultural perspective based on new radiocarbon, anthropological, and taphonomic analyses. These include the estimation of the minimum number of individuals, the exploration of fragmentation patterns characterizing different skeletal regions, and the macroscopic and microscopic analysis of modifications to the remains of possible anthropic origin. Radiocarbon data point to a funerary use of CM between the 5
th
-2
nd
millennium cal. BCE. MNI estimates reveal the presence of at least 12 individuals (seven adults and five nonadults). The low representation of elements from hands and feet suggests that individuals were placed in the cave while partially decomposed. Anthropic traces on the remains (e.g. fresh fractures, marrow canal modifications, and scraping marks) hint at their intentional fragmentation, cleaning from residual soft tissues, and in some cases reutilization. These practices are well-exemplified by the recovery of one "skull cup" and of two long bones used as tools. These data align with those from other cave contexts from the same geographic region, suggesting the presence, especially during the Neolithic period, of shared ideologies centered on the human body.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cardiotoxicity (CTox) is a major side effect of cancer therapies, but uniform diagnostic criteria to guide clinical and research practices are lacking.
We prospectively studied 865 patients, aged ...54.7 ± 13.9; 16.3% men, scheduled for anticancer therapy related with moderate/high CTox risk. Four groups of progressive myocardial damage/dysfunction were considered according to current guidelines: normal, normal biomarkers (high-sensitivity troponin T and N-terminal natriuretic pro-peptide), and left ventricular (LV) function; mild, abnormal biomarkers, and/or LV dysfunction (LVD) maintaining an LV ejection fraction (LVEF) ≥50%; moderate, LVD with LVEF 40-49%; and severe, LVD with LVEF ≤40% or symptomatic heart failure. Cardiotoxicity was defined as new or worsening of myocardial damage/ventricular function from baseline during follow-up. Patients were followed for a median of 24 months. Cardiotoxicity was identified in 37.5% patients during follow-up 95% confidence interval (CI) 34.22-40.8%, 31.6% with mild, 2.8% moderate, and 3.1% with severe myocardial damage/dysfunction. The mortality rate in the severe CTox group was 22.9 deaths per 100 patients-year vs. 2.3 deaths per 100 patients-year in the rest of groups, hazard ratio of 10.2 (95% CI 5.5-19.2) (P < 0.001).
The majority of patients present objective data of myocardial injury/dysfunction during or after cancer therapy. Nevertheless, severe CTox, with a strong prognostic relationship, was comparatively rare. This should be reflected in protocols for clinical and research practices.
Orthorexia nervosa (ON) is characterized by an obsession with healthy eating, which may lead to severe physical, psychological and social disorders. It is particularly important to research this ...problem in populations that do not receive clinical care in order to improve early detection and treatment.
The aim of this study was to research the prevalence of ON in a population of Spanish university students and to analyze the possible associations between ON and psychological traits and behaviors that are common to ED.
A cross-sectional study with 454 students from the University of Castilla La Mancha, Spain. In total, 295 women and 159 men participated, aged between 18 and 41 years. The ORTO-11-ES questionnaire and the Eating Disorder Inventory (EDI-2) were used for this study. The chi squared test was used to compare the homogeneity among the different groups.
The scores on the ORTO-11-ES suggested that 17% of students were at risk of ON. The scores on the EDI-2 for the group at risk of ON were significant, compared to the remaining individuals, regarding their drive for thinness (17.1% vs 2.1%), bulimia (2.6% vs 0%), body dissatisfaction (26.3% vs. 12.4%), perfectionism (14.5% vs 4.8%), interoceptive awareness (13.2% vs 1.3%), asceticism (15.8% vs 3.7%) and impulsiveness (9.2% vs 1.9%).
These findings suggest that many of the psychological and behavioral aspects of ED are shared by people who are at risk of ON. Future research should use longitudinal data, examining the temporal relationship among these variables or other underlying variables that may contribute to the concurrence of ED and ON.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This work reports a systematic survey of over seventy individual pollutants in a Sewage Treatment Plant (STP) receiving urban wastewater. The compounds include mainly pharmaceuticals and personal ...care products, as well as some metabolites. The quantification in the ng/L range was performed by Liquid Chromatography–QTRAP–Mass Spectrometry and Gas Chromatography coupled to Mass Spectrometry. The results showed that paraxanthine, caffeine and acetaminophen were the main individual pollutants usually found in concentrations over 20
ppb.
N-formyl-4-amino-antipiryne and galaxolide were also detected in the ppb level. A group of compounds including the beta-blockers atenolol, metoprolol and propanolol; the lipid regulators bezafibrate and fenofibric acid; the antibiotics erythromycin, sulfamethoxazole and trimethoprim, the antiinflammatories diclofenac, indomethacin, ketoprofen and mefenamic acid, the antiepileptic carbamazepine and the antiacid omeprazole exhibited removal efficiencies below 20% in the STP treatment. Ozonation with doses lower than 90
μM allowed the removal of many individual pollutants including some of those more refractory to biological treatment. A kinetic model allowed the determination of second order kinetic constants for the ozonation of bezafibrate, cotinine, diuron and metronidazole. The results show that the hydroxyl radical reaction was the major pathway for the oxidative transformation of these compounds.
rock engraving made by Neanderthals in Gibraltar Rodríguez-Vidal, Joaquín; d'Errico, Francesco; Pacheco, Francisco Giles ...
Proceedings of the National Academy of Sciences - PNAS,
09/2014, Letnik:
111, Številka:
37
Journal Article
Recenzirano
Odprti dostop
Significance The production of purposely made painted or engraved designs on cave walls is recognized as a major cognitive step in human evolution, considered exclusive to modern humans. Here we ...present the first known example of an abstract pattern engraved by Neanderthals, from Gorham’s Cave in Gibraltar. It consists of a deeply impressed cross-hatching carved into the bedrock of the cave older than 39 cal kyr. The engraving was made before the accumulation of Mousterian layer IV. Most of the lines composing the design were made by repeatedly and carefully passing a pointed lithic tool into the grooves, excluding the possibility of an unintentional or utilitarian origin. This discovery demonstrates the Neanderthals’ capacity for abstract thought and expression.
The COVID-19 (SARS-CoV-2) pandemic is an ongoing public health challenge, also for the dentistry community. The main objective of this paper was to determine the economic and health-care impact of ...COVID-19 on dentists in the Autonomous Region of Galicia (Spain).
This was a descriptive observational study in which the data was collected by means of a self-administered survey (from 1 April 2020 to 30 April 2020).
A total of 400 dentists from Galicia responded to the survey. Only 12.3% of the participants could obtain personal protective equipment (PPE) including FFP2 masks. Of the male respondents, 33.1% suffered losses >€15,000 compared to 19.4% of female respondents (OR = 3.121,
< 0.001). Economic losses seem to have contributed to the applications for economic help as 29.5% of the respondents who applied for this measure recorded losses in excess of €15,000 (
= 0.03). Patients complained more about the fact that only emergency care was available during the State of Alarm, in dental surgeries that do not work with insurance companies or franchises. Only 4 professionals tested positive, 50% of whom worked exclusively in private practice and the other 50% who practised in both private and public surgeries. Dentists who practise in the public sector saw more urgent patients per week than those practising in private surgeries (
= 0.013).
The COVID-19 pandemic has had economic repercussions in dentistry as only urgent treatment was available during the State of Alarm. These repercussions seem to be higher in male participants, as the majority of the participants have revealed higher economic losses than females. The level of assistance has also been affected, reducing the number of treated patients, although this quantity has been different in private and public surgeries. By presenting these findings we look to highlight the role that dentists play in society in treating dental emergencies in our surgeries, and this must be recognised and addressed by the relevant authorities, who must provide PPEs as a priority to this group as well as providing special economic aid in accordance with the losses incurred by the sector.
PDF
