Bio-logging tags are an important tool for the study of cetaceans, but superficial tags inevitably increase hydrodynamic loading. Substantial forces can be generated by tags on fast-swimming animals, ...potentially affecting behavior and energetics or promoting early tag removal. Streamlined forms have been used to reduce loading, but these designs can accelerate flow over the top of the tag. This non-axisymmetric flow results in large lift forces (normal to the animal) that become the dominant force component at high speeds. In order to reduce lift and minimize total hydrodynamic loading this work presents a new tag design (Model A) that incorporates a hydrodynamic body, a channel to reduce fluid speed differences above and below the housing and wing to redirect flow to counter lift. Additionally, three derivatives of the Model A design were used to examine the contribution of individual flow control features to overall performance. Hydrodynamic loadings of four models were compared using computational fluid dynamics (CFD). The Model A design eliminated all lift force and generated up to ~30 N of downward force in simulated 6 m/s aligned flow. The simulations were validated using particle image velocimetry (PIV) to experimentally characterize the flow around the tag design. The results of these experiments confirm the trends predicted by the simulations and demonstrate the potential benefit of flow control elements for the reduction of tag induced forces on the animal.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
► Consumption rates advisory to minimize risks to human health have been estimated. ► THQ values suggest that humans should minimize meals/week of species analyzed. ► It is assumed an acceptable risk ...for cancer in consuming fish for As concentrations.
The present study evaluate concentrations of arsenic (As), cadmium (Cd), chromium (Cr), lead (Pb), manganese (Mn), nickel (Ni), vanadium (V) and zinc (Zn) in fish and shellfish from the Gulf of Catania. Heavy metal analysis was carried on with an ICP-MS, and consumption rates advisory for minimizing chronic systemic and non cancer endpoints in child and adults have been estimated. Among metals investigated, only Cd and Pb have a limit set by European Community for human consumption, and the thresholds were not been exceeded in analyzed species. The As, toxic in its inorganic form, have not a regulatory limit yet, but the Environmental Protection Agency and the World Health Organization provide a reference dose, a cancer slope factor and a tolerable intake, applicable in the risk factors assessment. Arsenic target hazard quotient (THQ) values, suggest that human should minimizing meals/week of analyzed species to avoid deleterious effect during lifetime, furthermore, with As cancer risk assessment, for most of the fish, the risk for cancer is greater than the acceptable lifetime risk of 10–5. Our results give important finding about the consumption limits on certain metals, especially for As, all for minimizing potential health risks in population.
•Bevacizumab in combination with RT increase the rates of complications in elderly patients.•In elderly patients the combination of primary RT with cetuximab seems feasible but with higher reported ...skin toxicities.•Patients’ age should not be limited the association of trastuzumab and RT.•The concurrent administration of EGFR targeting TKIs and RT appears to be feasible and effective.•The tolerance of Immune Check Point inhibitors and RT seems good. RT plus vismodegib/sonidegib remains investigational.
Aim of the present review is to assess present data about the use of the association of Radiotherapy (RT) and targeted therapy/immunotherapy (TT/IT) in elderly people.
PubMed database was searched for English literature published up to December 2017 using the keywords "radiotherapy" combined with "bevacizumab", "cetuximab", "trastuzumab", "erlotinib", "gefitinib", "sorafenib", "sunitinib", "vismodegib", "sonidegib", "ipilimumab", "pembrolizumab", "nivolumab". Studies performing RT and TT/IT in people aged >65-years were evaluated focusing on safety, toxicity and efficacy. Studies eligible for inclusion were: case reports, retrospective/prospective studies in which RT and new drugs were used concomitantly or sequentially, focusing on elderly sub-group.
The systematic search identified 626 records. After exclusion of duplicates, full-text review, cross-referencing and paper that did not respect the inclusion criteria, 81 studies were included in this review. In elderly patients the combination of RT with cetuximab or bevacizumab seems feasible but with higher reported side effects. Patients’ age should not limit the association of trastuzumab and RT in HER2 positive breast cancer. The concurrent administration of TKIs and RT appears to be feasible and effective. Regarding the Immune Check Point inhibitors and RT, tolerance seems similar among older and younger people but definitive data are lacking. Instead, the association of RT and vismodegib/sonidegib remains investigational.
TT/IT in association of RT seems to be safe, but in elderly patients data concerning safety and toxicity are limited. Specific clinical trials on this population are encouraged.
The Hippo pathway, a signaling cascade involved in the regulation of organ size and several other processes, acts as a conduit between extracellular matrix (ECM) cues and cellular responses. We asked ...whether the basement membrane (BM), a specialized ECM component known to induce quiescence and differentiation in mammary epithelial cells, would regulate the localization, activity, and interactome of YAP, a Hippo pathway effector. To address this question, we used a broad range of experimental approaches, including 2D and 3D cultures of both mouse and human mammary epithelial cells, as well as the developing mouse mammary gland. In contrast to malignant cells, nontumoral cells cultured with a reconstituted BM (rBM) displayed higher concentrations of YAP in the cytoplasm. Incidentally, when in the nucleus of rBM‐treated cells, YAP resided preferentially at the nuclear periphery. In agreement with our cell culture experiments, YAP exhibited cytoplasmic predominance in ductal cells of developing mammary epithelia, where a denser BM is found. Conversely, terminal end bud (TEB) cells with a thinner BM displayed higher nucleus‐to‐cytoplasm ratios of YAP. Bioinformatic analysis revealed that genes regulated by YAP were overrepresented in the transcriptomes of microdissected TEBs. Consistently, mouse epithelial cells exposed to the rBM expressed lower levels of YAP‐regulated genes, although the protein level of YAP and Hippo components were slightly altered by the treatment. Mass spectrometry analysis identified a differential set of proteins interacting with YAP in cytoplasmic fractions of mouse epithelial cells in the absence or presence of rBM. In untreated cells, YAP interactants were enriched in processes related to ubiquitin‐mediated proteolysis, whereas in cells exposed to rBM YAP interactants were mainly key proteins related to amino acid, amino sugar, and carbohydrate metabolism. Collectively, we unraveled that the BM induces YAP translocation or retention in the cytoplasm of nontumoral epithelial cells and that in the cytoplasm YAP seems to undertake novel functions in metabolic pathways.
Purpose
New RT techniques and data emerging from follow-up for several tumor sites suggest that treatment volume de-escalation may permit to minimize therapy-related side effects and/or obtain better ...clinical outcomes. Here, we summarize the main evidence about volume de-escalation in RT.
Method
The relevant literature from PubMed was reviewed in this article. The ClinicalTrials.gov database was searched for clinical trials related to the specific topic.
Results
In Lymphoma, large-volume techniques (extended- and involved-field RT) are being successfully replaced by involved-site RT and involved-node RT. In head and neck carcinoma, spare a part of elective neck is controversial. In early breast cancer, partial breast irradiation has been established as a treatment option in low-risk patients. In pancreatic cancer stereotactic body radiotherapy may be used to dose escalation. Stereotactic radiosurgery should be the treatment choice for patients with oligometastatic brain disease and a life expectancy of more than 3 months, and it should be considered an alternative to WBRT for patients with multiple brain metastases.
Conclusion
Further clinical trials are necessary to improve the identification of suitable patient cohorts and the extent of possible volume de-escalation that does not compromise tumor control.
•FDG-PET has an important and promising role for the definition of RT target volume, including Stereotactic body RT for pancreatic cancer.•Choline PET/CT could be useful for identifying high-risk RT ...volumes, including nodes, for prostate cancer; while PSMA PET/CT is still under evaluation for the RT target definition.•FDG-PET has an important and promising role for the definition of RT target volume, including Stereotactic body RT for pancreatic cancer.•FDG PET-CT is the most sensitive imaging modality for detecting nodes metastases in gynecological cancer and has been shown to impact external-beam radiotherapy planning by modifying the treatment field.•FDG-PET/CT can be used to evaluate features at presentation, therapy response and it could be useful for assessing the oncological outcomes of anal and rectal cancer
Positron Emission Tomography with Computed Tomography (PET/CT) has been proven to be useful in the definition of Radiotherapy (RT) target volume. In this regard, the present expert review summarizes existing data for pancreas, prostate, gynecological and rectum/anal cancer.
A comprehensive search of published original article was made, based on SCOPUS and PubMed database, selecting the paper that evaluated the role of PET/CT in the definition of RT volume.
FDG-PET has an important and promising role for pancreatic cancer. Choline PET/CT could be useful for identifying high-risk volumes for prostate cancer; while PSMA PET/CT is still under evaluation. FDG PET/CT in gynecological cancers has been shown to impact external-beam RT planning. The role of FDG-PET for Gross Tumor volume identification is crucial, representing a useful and powerful tool for anal and rectal cancer.
Taken together, molecular and functional imaging approaches offer a major step to individualize radiotherapeutic approach.
Purpose
Combined modality therapy is a mainstay option for thoracic malignancies and head and neck cancers. The integration of different strategies is based on the multidisciplinary approach of ...modern clinical oncology. Radiation oncologists have to be educated, trained, and updated to provide state-of-the-art care to cancer patients and thus educational meetings are crucial.
Methods
The Italian Association of Radiation Oncology Young Members Working Group (AIRO Giovani) organized its 8th national meeting, focused on combination therapy in lung, esophageal, and head and neck cancer (with a specific focus on larynx-preservation strategies for larynx/hypopharynx tumors), involving young professionals working in Italy. The meeting was addressed to young radiation oncologists, presenting state-of-the-art knowledge, based on the latest evidence in this field. We performed a review of the current literature based on the highlights of the Congress.
Results
The multimodality approach of head and neck and thoracic malignancies includes surgery, chemotherapy, and radiotherapy, but also has to take into account new information and data coming from basic and translational research and including molecular biology, genetics, and immunology. All these aspects are crucial for the treatment of non-small-cell lung cancer and esophageal, esophagogastric junction, and larynx/hypopharynx malignancies. The integration of different treatments in the clinical decision-making process to combine therapies is crucial.
Conclusions
Combination therapy has proved to be a consolidated approach in these specific oncologic settings, highlighting the importance of multimodality management in modern clinical oncology. Dedicated meetings on specific topics are helpful to improve knowledge and skills of young professionals in radiation oncology.
Use of colistin in adult patients: A cross-sectional study Giacobbe, Daniele Roberto; Saffioti, Carolina; Losito, Angela Raffaella ...
Journal of global antimicrobial resistance.,
March 2020, 2020-03-00, 20200301, 2020-03-01, Letnik:
20
Journal Article
Recenzirano
Odprti dostop
•In a country endemic for MDR Gram-negative bacteria, colistin was mostly administered in combination with other agents.•A loading dose of 9 MU of colistimethate was administered in 79% of patients ...and adequate maintenance doses in 85%.•Empirical therapy and targeted therapy of CRE infection were associated with colistin use in combination with other agents.•Colistin was mostly used appropriately, but efforts might be necessary to further increase rates of adequate loading doses.
The aim of this study was to assess colistin use in a country endemic for multidrug-resistant Gram-negative bacteria (MDR-GNB).
Colistin prescription patterns were evaluated in 22 Italian centres. Factors associated with use of colistin in combination with other anti-MDR-GNB agents were also assessed.
A total of 221 adults receiving colistin were included in the study. Their median age was 64 years (interquartile range 52–73 years) and 134 (61%) were male. Colistin was mostly administered intravenously (203/221; 92%) and mainly for targeted therapy (168/221; 76%). The most frequent indications for colistin therapy were bloodstream infection and lower respiratory tract infection. Intravenous colistin was administered in combination with at least another anti-MDR-GNB agent in 80% of cases (163/203). A loading dose of 9 MU of colistimethate was administered in 79% of patients receiving i.v. colistin and adequate maintenance doses in 85%. In multivariable analysis, empirical therapy odds ratio (OR) = 3.25, 95% confidence interval (CI) 1.24–8.53;P = 0.017 and targeted therapy for carbapenem-resistant Enterobacterales infection (OR = 4.76, 95% CI 1.69–13.43; P = 0.003) were associated with use of colistin in combination with other agents, whilst chronic renal failure (OR = 0.39, 95% CI 0.17–0.88; P = 0.024) was associated with use of colistin monotherapy.
Colistin remains an important option for severe MDR-GNB infections when other treatments are not available. Despite inherent difficulties in optimising its use owing to peculiar pharmacokinetic/pharmacodynamic characteristics, colistin was mostly used appropriately in a country endemic for MDR-GNB.
Osteosarcoma (OS) is the most common type of bone cancer, with a peak incidence in the early childhood. Emerging evidence suggests that treatments targeting cancer stem cells (CSCs) within a tumor ...can halt cancer and improve patient survival. MicroRNAs (miRNAs) have been implicated in the maintenance of the CSC phenotype, thus, identification of CSC-related miRNAs would provide information for a better understanding of CSCs. Downregulation of miRNA-29 family members (miR-29a/b/c; miR-29s) was observed in human OS, however, little is known about the functions of miR-29s in human OS CSCs. Previously, during the characterization of 3AB-OS cells, a CSC line selected from human OS MG63 cells, we showed a potent downregulation of miR-29b. In this study, after stable transfection of 3AB-OS cells with miR-29b-1, we investigated the role of miR-29b-1 in regulating cell proliferation, sarcosphere-forming ability, clonogenic growth, chemosensitivity, migration and invasive ability of 3AB-OS cells, in vitro. We found that, miR-29b-1 overexpression consistently reduced both, 3AB-OS CSCs growth in two- and three-dimensional culture systems and their sarcosphere- and colony-forming ability. In addition, while miR-29b-1 overexpression sensitized 3AB-OS cells to chemotherapeutic drug-induced apoptosis, it did not influence their migratory and invasive capacities, thus suggesting a context-depending role of miR-29b-1. Using publicly available databases, we proceeded to identify potential miR-29b target genes, known to play a role in the above reported functions. Among these targets we analyzed CD133, N-Myc, CCND2, E2F1 and E2F2, Bcl-2 and IAP-2. We also analyzed the most important stemness markers as Oct3/4, Sox2 and Nanog. Real-time RT-PCR and western-blot analyses showed that miR-29b-1 negatively regulated the expression of these markers. Overall, the results show that miR-29b-1 suppresses stemness properties of 3AB-OS CSCs and suggest that developing miR-29b-1 as a novel therapeutic agent might offer benefits for OS treatment.
Aim
The difficulty in conducting meaningful clinical research is a multifactorial issue, involving political, financial and cultural problems, which can lead to unexpected negative long-term ...consequences, in terms of knowledge advancement and impact on patient care. The aims of the present review were to evaluate the publications of Italian radiotherapy (RT) groups during a 20-year period and to verify whether research is still appealing to young radiation oncologists (ROs) in Italy.
Methods
PubMed database was searched for English-language articles published by Italian groups from January 1985 to December 2005. Analyzed variables were: publication/year, kind of study, geographical area and age of the first author.
Results
The systematic review identified 3291 articles: 1207 papers fulfilled the inclusion criteria. The number of Italian published papers increased during the examined period. Retrospective analyses, prospective phase I–II trials and literature reviews were 44, 20 and 14.5% of all published manuscripts, respectively. Randomized trials showed a mild increase from 2000 to 2005, but their absolute number remained low respect to other types of studies (4%). Northern Italy produced the very most of Italian research papers (58.7%). The age of the first/second author was evaluated on 716 papers: In more than 50% of cases, the first author was younger than 40.
Conclusion
Despite a general gradual improvement, RT clinical research suffers in Italy (as elsewhere) from insufficient funding, with a negative impact on evidence production. It is worth noting that clinical research is still appealing and accessible to junior Italian RO.
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