Microplastics in marine mussels, biological effects and human risk of intake: A case study in a multi-stressor environment.

This study documented seasonal levels of microplastics (MPs) and biomarkers (condition index, neurotoxicity, energy, oxidative stress) in mussels (Mytilus galloprovincialis), and water physico-chemical parameters in the Douro estuary (NE Atlantic coast), and estimated the human risk of MP intake (HRI) through mussels. Mussel stress was determined through the Integrated Biomarker Response (IBR). HRI was estimated from mussel MP concentrations and consumer habits. MPs were mainly micro-fibres (72 %) with varied chemical composition. Seasonal MP means (±SEM) in mussels ranged from 0.111 ± 0.044 (spring) to 0.312 ± 0.092 MPs/g (summer). Seasonal variations of mussel stress (IBR: 1.4 spring to 9.7 summer) and MP concentrations were not related. MeO-BDEs, PBDEs, temperature, salinity and other factors likely contributed to mussel stress variation. HRI ranged from 2438 to 2650 MPs/year. Compared to the literature, MP contamination in mussels is low, as well as the human risk of MP intake through their consumption.

Evaluation of paediatric pulmonary vein stenosis by cardiac CT angiography: a comparative study with transthoracic echocardiography and catheter angiogram.

AIM: To compare prospective electrocardiogram (ECG)-gated cardiac computed tomographic angiography (CCTA) with transthoracic echocardiography (TTE) and cardiac catheter angiography (CCA) for paediatric pulmonary vein (PV) stenosis. MATERIALS AND METHODS: Retrospective chart review was undertaken of all patients who underwent CCTA for PV evaluation over a 4-year period. Patient demographics, findings of CCTA, TTE, and CCA, as well as interventions performed, were recorded for each PV. RESULTS: Thirty-five patients were included (23 male patients). All patients had a prior TTE with time interval between TTE and CCTA ranging from 0 to 90 days. CCTA detected 92 abnormalities in 32 patients. TTE missed 16 PV abnormalities (16/92, 17%), detected 37 abnormalities with certainty (37/92, 40%), and was suggestive in 39 abnormalities (39/92, 42%). CCTA was negative for PV abnormalities when TTE was positive or suspicious in three patients. Nineteen patients underwent CCA (18 patients with 52 abnormalities and one patient with normal PV), confirming CCTA findings. Thirty-nine were treated with angioplasty/stenting (39/52,75%). Failed recanalisation occurred in three PVs (3/52, 6%) and no intervention was attempted for the rest as the gradient was not significant (10/52,19%). Nine patients underwent surgical repair (26/92, 28%). Five patients (14/92, 15%) were managed with no intervention based on CCTA findings and poor clinical prognosis. CONCLUSIONS: CCTA plays an important role in detecting paediatric PV stenosis and identifies additional findings compared to TTE that have direct surgical/interventional implications. CCTA complements TTE in imaging these patients and helps guide management.

One-year variation in quantity and properties of microplastics in mussels (Mytilus galloprovincialis) and cockles (Cerastoderma edule) from Aveiro lagoon.

As filter feeders, marine bivalves inhabiting estuarine and coastal areas are directly exposed to microplastics (MPs) in water. To assess whether MPs number, and their shape, size, colour, and polymer type present in mussels (Mytilus galloprovincialis) and cockles (Cerastoderma edule) varied over one year, bivalves were collected over the year of 2019 in the lower part of the coastal Aveiro lagoon, Portugal. After extraction from the bivalve's whole-body soft tissues, a subset of the visually inspected particles was randomly separated for identification using the Fourier-transform mid-infrared (FT-MIR) spectroscopy. A fraction of the inspected particles, 26-32% of particles >100 µm, and 59-100% of smaller ones were confirmed as MPs. Concentrations varied within the intervals of 0.77-4.3 items g-1 in mussels and 0.83-5.1 items g-1 in cockles, with the lowest values observed in January. In winter, the accumulation of large-sized fibers was composed of a mixture of plastic types, which contrasted against the most abundant MPs in summer consisting mainly of polyethylene of diverse size classes and shapes. Temperature decrease registered in winter might have triggered a lower filtration rate, resulting in lower MPs concentrations in the whole-soft body tissues of organisms. Different properties of MPs found in bivalves between January-February and August-September appear to reflect changes in the characteristics of MPs available in the Aveiro lagoon.

Ring-Fused meso-Tetraarylchlorins as Auspicious PDT Sensitizers: Synthesis, Structural Characterization, Photophysics, and Biological Evaluation.

Novel 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused meso-tetraarylchlorins, with different degrees of hydrophilicity (with methyl ester, hydroxymethyl, and carboxylic acid moieties), have been synthesized and their photophysical characterization as well as in vitro photocytotoxicity assessment against human melanoma and esophageal and bladder carcinomas was carried out. An integrated analysis of the photosensitizers' performance, considering the singlet oxygen generation data, cell internalization, and intracellular localization, allowed to establish relevant structure-photoactivity relationships and the rationalization of the observed photocytotoxicity. In the diacid and monoalcohol series, chlorins derived from meso-tetraphenylporphyrin proved to be the most efficient photodynamic therapy agents, showing IC50 values of 68 and 344 nM against A375 cells, respectively. These compounds were less active against OE19 and HT1376 cells, the diacid chlorin with IC50 values still in the nano-molar range, whereas the monohydroxymethyl-chlorin showed significantly higher IC50 values. The lead di(hydroxymethyl)-substituted meso-tetraphenylchlorin confirmed its remarkable photoactivity with IC50 values below 75 nM against the studied cancer cell lines. Subcellular accumulation of this chlorin in the mitochondria, endoplasmic reticulum, and plasma membrane was demonstrated.

Insights into the anticancer activity of chiral alkylidene-ß-lactams and alkylidene-γ-lactams: Synthesis and biological investigation.

Chiral alkylidene-ß-lactams and alkylidene-γ-lactams were synthesized and screened for their in vitro activity against four human cancer cell lines (melanoma, esophageal, lung and fibrosarcoma carcinoma). Alkylidene-ß-lactams were synthesized via Wittig reaction of diverse phosphorus ylides with benzhydryl 6-oxopenicillanate, derived from 6-aminopenicillanic acid. Moreover, novel chiral alkylidene-γ-lactams were synthesized through a multistep strategy starting from a chiral substrate (d-penicillamine). The in vitro assays allowed the identification of four compounds with IC50 values < 10 µM for A375 cell line, and three compounds with IC50 values < 10 µM for OE19 cell line. The effect of the most promising compounds on cell death mechanism, reactive oxygen species generation as well as the evaluation of their ability to act as MMP-9 inhibitors were studied. The reported results unveil the potential of alkylidene-ß-lactams as anticancer agents.

Elevated soluble TNFα levels and upregulated TNFα mRNA expression in purified peripheral blood monocyte subsets associated with high-grade hepatocellular carcinoma.

BACKGROUND: Chronic inflammation is involved in the initiation and progression of various cancers, including liver cancer. The current study focuses on the characterization of the peripheral immune response in hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) patients, before and after surgical procedure, in order to assess the effect of tumor resection in the immune system homeostasis and to determine possible prognostic factors associated with high-grade tumors. We developed a whole-blood assay to monitor immune alterations and functional competence of peripheral monocytes in a group of 10 healthy individuals (HG), in 20 HCC patients and 8 CCA patients, by multi-color flow cytometry, qRT-PCR, and ELISA techniques. RESULTS: The qRT-PCR analysis showed an upregulation of TNFα expression by classical and intermediate monocytes purified from HCC patients presenting tumors in grade G3-G4 as compared to G1-G2 HCC patients. Moreover, ELISA assay confirmed elevated serum levels of TNFα in G3-G4 compared to G1-G2 HCC patients. A significant decrease of circulating non-classical monocytes was detected in both CCA and HCC patients before and after surgical procedure. In addition, a functional defect in circulating classical and intermediate monocytes was observed in both groups of cancer patients when compared to the HG, with partial recovery after the surgical intervention. CONCLUSIONS: This integrated analysis permitted the identification of altered functional competence of monocyte subsets in CCA and HCC patients. In addition, our results point to a potential role of TNFα as a prognostic peripheral biomarker in HCC patients, indicating the presence of high-grade tumors that should be further validated.

Long-term impact of oral surgery with or without amoxicillin on the oral microbiome-A prospective cohort study.

Routine postoperative antibiotic prophylaxis is not recommended for third molar extractions. However, amoxicillin still continues to be used customarily in several clinical practices worldwide to prevent infections. A prospective cohort study was conducted in cohorts who underwent third molar extractions with (group EA, n = 20) or without (group E, n = 20) amoxicillin (250 mg three times daily for 5 days). Further, a control group without amoxicillin and extractions (group C, n = 17) was included. Salivary samples were collected at baseline, 1-, 2-, 3-, 4-weeks and 3 months to assess the bacterial shift and antibiotic resistance gene changes employing 16S rRNA gene sequencing (Illumina-Miseq) and quantitative polymerase chain reaction. A further 6-month follow-up was performed for groups E and EA. Seven operational taxonomic units reported a significant change from baseline to 3 months for group EA (adjusted p < 0.05). No significant change in relative abundance of bacteria and ß-lactamase resistance genes (TEM-1) was observed over 6 months for any group (adjusted p > 0.05). In conclusion, the salivary microbiome is resilient to an antibiotic challenge by a low-dose regimen of amoxicillin. Further studies evaluating the effect of routinely used higher dose regimens of amoxicillin on gram-negative bacteria and antibiotic resistance genes are warranted.

Functional and Phenotypic Characterization of Tumor-Infiltrating Leukocyte Subsets and Their Contribution to the Pathogenesis of Hepatocellular Carcinoma and Cholangiocarcinoma.

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) represent the most common primary liver malignancies whose outcome is influenced by the immune response. In the present study, we evaluated the tumor-infiltrating leukocyte (TIL) populations in 21 HCC patients and 8 CCA patients by flow cytometry immediately after the surgical procedure. Moreover, CD4+ T cells, CD8+ T cells, monocytes, and macrophages were purified by cell sorting for further analysis of gene expression by quantitative reverse-transcription polymerase chain reaction. Regarding tumor-infiltrating macrophages, we observed a significantly higher expression of markers associated with M2 phenotype and a higher expression of PD-L1 in patients with HCC in comparison to CCA. In addition, for HCC patients, we found a significant increase in the expression of CD200R in macrophages from tumors that were in grade G3-G4 as compared to tumors in grade G1-G2. Besides, a significantly higher frequency of tumor-infiltrating lymphocytes, CD8+CD56+ T cells, and natural killer cells was detected in HCC biopsies in comparison to CCA. In summary, this study has revealed functional and phenotypic differences in TIL cell subpopulations between CCA and HCC, as well as among different histopathological grades and tumor aggressiveness degrees, and it has provided evidence to better understand the tumor immune microenvironment of CCA and HCC.

Functional Impairment of Circulating FcεRI+ Monocytes and Myeloid Dendritic Cells in Hepatocellular Carcinoma and Cholangiocarcinoma Patients.

BACKGROUND: Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) represent the most common primary liver malignancies whose outcome is influenced by the immune response. METHODS: In this study, we have functionally characterized, by flow cytometry, circulating myeloid dendritic cells (mDCs) and FcεRI+ monocytes in a group of healthy individuals (n = 10) and in a group of patients with HCC (n = 19) and CCA (n = 8), at the time point of the surgical resection (T0) and once the patient had recovered from surgery (T1). Moreover, we proceeded to a more in depth phenotypic characterization of the FcεRI+ monocyte subpopulation. RESULTS: A significant decrease in the frequency of TNFα producing FcεRI+ monocytes and mDCs in HCC and CCA patients when compared to the group of healthy individuals was observed, and a close association between FcεRI+ monocytes and mDCs dysfunction was identified. In addition, the phenotypic characteristics of FcεRI+ monocytes from healthy individuals strongly suggest that this population drives to mDCs, which matches with the fact that both populations are functionally affected. CONCLUSIONS: The frequency and the function of circulating mDCs and FcεRI+ monocytes are affected in both HCC and CCA patients, and FcεRI+ monocytes could represent those fated to become mDCs. © 2019 International Clinical Cytometry Society.

The communal consultation video-Enhancing learning and broadening experience through observing dialogue.

INTRODUCTION: This study presents a novel, student-centred, on-demand video learning modality that supports students as they transition from theory to clinical practice. Authentic, one-to-one teacher and student consultations have been video recorded and uploaded online for the peers and subsequent years of students to consume and learn from. This study describes the development and use of these communal consultation videos (CCVs), examines how students perceive this novel intervention and proposes supporting educational theory. METHODS: A library of 28 CCVs has been archived online, to enable learning for students not present at the original staff consultation. A questionnaire was designed and administered to evaluate student perceptions of this novel learning intervention and administered to see how students used and perceived its benefit. RESULTS: The CCV has proven to be popular, well received and valued by students. Students reported the videos were interactive, engaged them cognitively and supported them for assessments and in preparation for the clinical care of their own patients. Students also reported that watching the videos broadened their "clinical" experience of others cases that were different to their own. CONCLUSION: This novel learning modality demonstrates new engaging learning opportunities for students and teachers that support students for assessments and clinical skill practice and afford observational clinical experience.

Glycolysis Inhibition as a Strategy for Hepatocellular Carcinoma Treatment?

Hepatocellular carcinoma (HCC) is the most frequently detected primary malignant liver tumor, representing a worldwide public health problem due to its high morbidity and mortality rates. The HCC is commonly detected in advanced stage, precluding the use of treatments with curative intent. For this reason, it is crucial to find effective therapies for HCC. Cancer cells have a high dependence of glycolysis for ATP production, especially under hypoxic environment. Such dependence provides a reliable possible strategy to specifically target cancer cells based on the inhibition of glycolysis. HCC, such as other cancer types, presents a clinically well-known upregulation of several glycolytic key enzymes and proteins, including glucose transporters particularly glucose transporter 1 (GLUT1). Such enzymes and proteins constitute potential targets for therapy. Indeed, for some of these targets, several inhibitors were already reported, such as 2-Deoxyglucose, Imatinib or Flavonoids. Although the inhibition of glycolysis presents a great potential for an anticancer therapy, the development of glycolytic inhibitors as a new class of anticancer agents needs to be more explored. Herein, we propose to summarize, discuss and present an overview on the different approaches to inhibit the glycolytic metabolism in cancer cells, which may be very effective in the treatment of HCC.

A qualitative analysis of students' perceptions of videos to support learning in a psychomotor skills course.

INTRODUCTION: This qualitative study analysed students' experiences and perceptions about different types of videos in a psychomotor skills course, relating to clinical knowledge and skills and how they benefited learners in and out of the classroom. METHODS: Subjects were recruited from 4th and 5th year dental undergraduate programme. The recruitment was terminated after 24 students participated since data saturation was reached. A semi-structured interview was conducted with each participating student, digitally recorded and transcribed verbatim. A thematic analysis was performed using an inductive approach to identify key themes. RESULTS: Four key domains were identified from thematic analysis: functionality and access; learning and understanding; clinical skills preparation and performance and supplementary learning resources. Students perceived videos to be an important and vital learning tool relating to its on-demand access, control of functionality and use for particular needs that is not possible from textbooks or lectures. Video learning materials allows students to clarify knowledge, improve cognitive thinking and enhance revision of theoretical concepts and clinical skills. Two types of video were regarded as particularly useful as students reported being actively and cognitively engaged in the learning content and broadened their clinical experience. In addition, students reported mental preparation of clinical psychomotor skills using their own mental visualisation which enabled them to prepare for the clinical care of their patients. CONCLUSION: This qualitative research supports the benefits of learning from videos in relation to convenience of access and functionality of the videos. In addition, it shows novel aspects to learning from videos that are more cognitively engaging and in mental preparation of clinical skills prior to patient care.

Does the use of amoxicillin/amoxicillin-clavulanic acid in third molar surgery reduce the risk of postoperative infection? A systematic review with meta-analysis.

The objectives of this systematic review were to investigate the efficacy of amoxicillin/amoxicillin-clavulanic acid for reducing the risk of postoperative infection after third molar surgery and to evaluate the adverse outcomes in these patients, as well as in healthy volunteers. A systematic search of four databases was performed on May 26, 2017. Eleven studies qualified for the qualitative analysis and eight were found suitable for meta-analysis. The results suggest that both amoxicillin-clavulanic acid and amoxicillin significantly reduce the risk of infection after third molar extraction (overall relative risk (RR) 0.25, P<0.001). However, with the exclusion of randomized controlled trials with a split-mouth design (due to an inadequate crossover period after antibiotic treatment), only amoxicillin-clavulanic acid was found to be effective (RR 0.21, P<0.001). The risk of adverse effects was significantly higher in the amoxicillin-clavulanic acid group (RR=4.12, P=0.023) than in the amoxicillin group (RR 1.57, P=0.405). In conclusion, amoxicillin-clavulanic acid and amoxicillin may significantly reduce the risk of infection after third molar extraction. However, their use in third molar surgery should be viewed with caution, as recent clinical trials on healthy volunteers have shown evidence of the negative impact of amoxicillin use on bacterial diversity and antibiotic resistance.

Neumoperitoneo a tensión diferido tras colonoscopia / Delayed tension pneumoperitoneum after colonoscopy

No disponible

Stroma-derived IL-6, G-CSF and Activin-A mediated dedifferentiation of lung carcinoma cells into cancer stem cells.

Cancer stem cells (CSCs) are a small population of resistant cells inhabiting the tumors. Although comprising only nearly 3% of the tumor mass, these cells were demonstrated to orchestrate tumorigenesis and differentiation, underlie tumors' heterogeneity and mediate therapy resistance and tumor relapse. Here we show that CSCs may be formed by dedifferentiation of terminally differentiated tumor cells under stress conditions. Using a elegant co-culture cellular system, we were able to prove that nutrients and oxygen deprivation activated non-malignant stromal fibroblasts, which in turn established with tumor cells a paracrine loop mediated by Interleukine-6 (IL-6), Activin-A and Granulocyte colony-stimulating factor (G-CSF), that drove subsequent tumor formation and cellular dedifferentiation. However, by scavenging these cytokines from the media and/or blocking exosomes' mediated communication it was possible to abrogate dedifferentiation thus turning these mechanisms into potential therapeutic targets against cancer progression.

Targeted alpha therapy using Radium-223: From physics to biological effects.

With the advance of the use of ionizing radiation in therapy, targeted alpha therapy (TAT) has assumed an important role around the world. This kind of therapy can potentially reduce side effects caused by radiation in normal tissues and increased destructive radiobiological effects in tumor cells. However, in many countries, the use of this therapy is still in a pioneering phase. Radium-223 (223Ra), an alpha-emitting radionuclide, has been the first of its kind to be approved for the treatment of bone metastasis in metastatic castration-resistant prostate cancer. Nevertheless, the interaction mechanism and the direct effects of this radiopharmaceutical in tumor cells are not fully understood neither characterized at a molecular level. In fact, the ways how TAT is linked to radiobiological effects in cancer is not yet revised. Therefore, this review introduces some physical properties of TAT that leads to biological effects and links this information to the hallmarks of cancer. The authors also collected the studies developed with 223Ra to correlate with the three categories reviewed - properties of TAT, 5 R's of radiobiology and hallmarks of cancer- and with the promising future to this radiopharmaceutical.

An analysis of clinical transition stresses experienced by dental students: A qualitative methods approach.

INTRODUCTION: Stress in dental students is well established with potential psychological distress, emotional exhaustion and burnout-related symptoms. Little attention has been given to the problems encountered by dental students during the transition from theoretical or paraclinical training to the clinical environment. The aim of this study was to adopt a qualitative research methods approach to understand the perceived stressors during students' clinical transition and provide insights for curriculum planners to enhance learning. METHODS: This study analysed four groups of 2nd- and 3rd-year BDS students' experiences in focus group interviews relating to their pre-clinical and clinical transitions. The interviews were recorded and transcribed verbatim, and a thematic analysis was performed using an inductive qualitative approach. RESULTS: Key overlapping domains identified were the transition gap and stresses. The transition gap was subclassified into knowledge and skill (hard and soft), and stresses was subcategorised into internal and external stresses. On first coming to clinics, students experienced knowledge gaps of unfamiliar clinical treatments with mismatches between knowledge acquisition and clinical exposure. Students felt incompetent owing to the stresses attributable to curriculum design, staff and the patient. This negatively affected their confidence and clinical performance. CONCLUSION: A range of challenges have been identified that will allow curriculum designer's to plan a more supportive learning experience to help students during their transition to clinical practice giving them timely knowledge, confidence and clinical performance to better prepare them for entering clinics.

Global networking: Meeting the challenges, facilitating collaboration.

The constant change of information and technology advancement as well as the impact of social media has radically changed the world and education and, in particular, the needs of students, organisations and disadvantaged communities who share the aim of training and providing quality healthcare services. Dental organisations and education centres around the world have recognised the importance of networking in delivering effective education to students, healthcare professionals and communities. Networking is one way to meet the challenges of delivering healthcare education and services. This can be achieved by sharing of resources, expertise, knowledge and experience to benefit all the stakeholders in healthcare delivery. The joint ADEE/ADEA Meeting in London on 8-9 May 2017 has facilitated discussions amongst dental educators from all over the world during a workshop on "Global Networking: the how and why for dental educators." The aim of this workshop was to determine how can dental educators worldwide network to share ideas, experience, expertise and resources to improve both the curricula and the teaching and learning environment. A pre-conference survey was designed and implemented to identify the domains of interest and needs of participants. A structured questionnaire was administered, and this information was used to guide discussions on three main themes: curricula, faculty development and mobility of faculty and students. Four questions were then defined to help group leaders to frame discussions in the four working groups. The four groups engaged in parallel discussions, with the ideas recorded and collated by group leaders, which later served for the thematic analysis across the groups to draw the key points discussed. Overall, a great desire and potential to create a global networking to share and gain support and expertise at individual and organisational level was apparent and the working group has proposed an action plan, acknowledging that it requires great planning, effort and commitment.