Coupling solid and fluid stresses with brain tumour growth and white matter tract deformations in a neuroimaging-informed model

Brain tumours are among the deadliest types of cancer, since they display a strong ability to invade the surrounding tissues and an extensive resistance to common therapeutic treatments. It is therefore important to reproduce the heterogeneity of brain microstructure through mathematical and computational models, that can provide powerful instruments to investigate cancer progression. However, only a few models include a proper mechanical and constitutive description of brain tissue, which instead may be relevant to predict the progression of the pathology and to analyse the reorganization of healthy tissues occurring during tumour growth and, possibly, after surgical resection. Motivated by the need to enrich the description of brain cancer growth through mechanics, in this paper we present a mathematical multiphase model that explicitly includes brain hyperelasticity. We find that our mechanical description allows to evaluate the impact of the growing tumour mass on the surrounding healthy tissue, quantifying the displacements, deformations, and stresses induced by its proliferation. At the same time, the knowledge of the mechanical variables may be used to model the stress-induced inhibition of growth, as well as to properly modify the preferential directions of white matter tracts as a consequence of deformations caused by the tumour. Finally, the simulations of our model are implemented in a personalized framework, which allows to incorporate the realistic brain geometry, the patient-specific diffusion and permeability tensors reconstructed from imaging data and to modify them as a consequence of the mechanical deformation due to cancer growth

Molecularly Imprinted Polymer as Selective Sorbent for the Extraction of Zearalenone in Edible Vegetable Oils

A method based on the selective extraction of zearalenone (ZON) from edible vegetable oils using molecularly imprinted polymer (MIP) has been developed and validated. Ultra-high-pressure liquid chromatography coupled with a fluorescence detection system was employed for the detection of zearalenone. The method was applied to the analysis of zearalenone in maize oil samples spiked at four concentration levels within the maximum permitted amount specified by the European Commission Regulation (EC) No. 1126/2007. As a result, the proposed methodology provided high recoveries (>72%) with good linearity (R2 > 0.999) in the range of 10-2000 μg/kg and a repeatability relative standard deviation below 1.8%. These findings meet the analytical performance criteria specified by the European Commission Regulation No. 401/2006 and reveal that the proposed methodology can be successfully applied for monitoring zearalenone at trace levels in different edible vegetable oils. A comparison of MIP behavior with the ones of QuEChERS and liquid-liquid extraction was also performed, showing higher extraction rates and precision of MIP. Finally, the evolution of ZON contamination during the maize oil refining process was also investigated, demonstrating how the process is unable to completely remove (60%) ZON from oil samples

The Effect of Optimally Timed Osteopathic Manipulative Treatment on Length of Hospital Stay in Moderate and Late Preterm Infants: Results from a RCT

Introduction. Little research has been conducted looking at the effects of osteopathic manipulative treatment (OMT) on preterm infants. Aim of the Study. This study hypothesized that osteopathic care is effective in reducing length of hospital stay and that early OMT produces the most pronounced benefit, compared to moderately early and late OMT. A secondary outcome was to estimate hospital cost savings by the use of OMT. Methods. 110 newborns ranging from 32- to 37-week gestation were randomized to receive either OMT or usual pediatric care. Early, moderately early, and late OMT were defined as <4, <9, and <14 days from birth, respectively. Result. Hospital stay was shorter in infants receiving late OMT (−2.03; 95% CI −3.15, −0.91; P<0.01) than controls. Subgroup analysis of infants receiving early and moderately early OMT resulted in shorter LOS (early OMT: −4.16; −6.05, −2.27; P<0.001; moderately early OMT: −3.12; −4.36, −1.89; P<0.001). Costs analysis showed that OMT significantly produced a net saving of €740 (−1309.54, −170.33; P=0.01) per newborn per LOS. Conclusions. This study shows evidence that the sooner OMT is provided, the shorter their hospital stay is. There is also a positive association of OMT with overall reduction in cost of care

Genomic alterations in rectal tumors and response to neoadjuvant chemoradiotherapy: an exploratory study

<p>Abstract</p> <p>Background</p> <p>Neoadjuvant chemoradiotherapy is the treatment of choice in advanced rectal cancer, even though there are many patients who will not benefit from it. There are still no effective methods for predicting which patients will respond or not. The present study aimed to define the genomic profile of rectal tumors and to identify alterations that are predictive of response in order to optimize therapeutic strategies.</p> <p>Methods</p> <p>Forty-eight candidates for neoadjuvant chemoradiotherapy were recruited and their pretherapy biopsies analyzed by array Comparative Genomic Hybridization (aCGH). Pathologic response was evaluated by tumor regression grade.</p> <p>Results</p> <p>Both Hidden Markov Model and Smoothing approaches identified similar alterations, with a prevalence of DNA gains. Non responsive patients had a different alteration profile from responsive ones, with a higher number of genome changes mainly located on 2q21, 3q29, 7p22-21, 7q21, 7q36, 8q23-24, 10p14-13, 13q12, 13q31-34, 16p13, 17p13-12 and 18q23 chromosomal regions.</p> <p>Conclusions</p> <p>This exploratory study suggests that an in depth characterization of chromosomal alterations by aCGH would provide useful predictive information on response to neoadjuvant chemoradiotherapy and could help to optimize therapy in rectal cancer patients.</p> <p>The data discussed in this study are available on the NCBI Gene Expression Omnibus [GEO: GSE25885].</p

Fifteen years trends of cardiogenic shock and mortality in patients with diabetes and acute coronary syndromes

PURPOSE: Our study was intended to examine time trends of management and mortality of acute coronary syndrome patients with associated diabetes mellitus. METHODS: We analyzed data from 5 nationwide registries established between 2001 and 2014, including consecutive acute coronary syndrome patients admitted to the Italian Intensive Cardiac Care Units. RESULTS: Of 28,225 participants, 8521 (30.2%) had diabetes: as compared with patients without diabetes, they were older and had significantly higher rates of prior myocardial infarction and comorbidities (all P &lt; .0001). Prevalence of diabetes and comorbidities increased over time (P for trend &lt; .0001). Cardiogenic shock rates were higher in patients with diabetes, as compared with those without diabetes (7.8% vs 2.8%, P &lt; .0001), and decreased significantly over time only in patients without diabetes (P = .007). Revascularization rates increased over time in patients both with and without diabetes (both P for trend &lt; .0001), although with persistingly lower rates in patients with diabetes. All-cause in-hospital mortality was higher in patients with diabetes (5.4 vs 2.5%, respectively, P &lt; .0001) and decreased more consistently in patients without diabetes (P for trend = .007 and &lt; .0001, respectively). At multivariable analysis, diabetes remains an independent predictor of both cardiogenic shock (odds ratio 2.03; 95% confidence interval, 1.77-2.32; P &lt; .0001) and mortality (odds ratio 1.95; 95% confidence interval, 1.69-2.26; P &lt; .0001). CONCLUSIONS: Despite significant mortality reductions observed over 15 years in acute coronary syndromes, patients with diabetes continue to show threefold higher rates of cardiogenic shock and lower revascularization rates as compared with patients without diabetes. These findings may explain the persistingly higher mortality of patients with diabetes and acute coronary syndromes

Prescription appropriateness of anti-diabetes drugs in elderly patients hospitalized in a clinical setting: evidence from the REPOSI Register

Diabetes is an increasing global health burden with the highest prevalence (24.0%) observed in elderly people. Older diabetic adults have a greater risk of hospitalization and several geriatric syndromes than older nondiabetic adults. For these conditions, special care is required in prescribing therapies including anti- diabetes drugs. Aim of this study was to evaluate the appropriateness and the adherence to safety recommendations in the prescriptions of glucose-lowering drugs in hospitalized elderly patients with diabetes. Data for this cross-sectional study were obtained from the REgistro POliterapie-Società Italiana Medicina Interna (REPOSI) that collected clinical information on patients aged ≥ 65 years acutely admitted to Italian internal medicine and geriatric non-intensive care units (ICU) from 2010 up to 2019. Prescription appropriateness was assessed according to the 2019 AGS Beers Criteria and anti-diabetes drug data sheets.Among 5349 patients, 1624 (30.3%) had diagnosis of type 2 diabetes. At admission, 37.7% of diabetic patients received treatment with metformin, 37.3% insulin therapy, 16.4% sulfonylureas, and 11.4% glinides. Surprisingly, only 3.1% of diabetic patients were treated with new classes of anti- diabetes drugs. According to prescription criteria, at admission 15.4% of patients treated with metformin and 2.6% with sulfonylureas received inappropriately these treatments. At discharge, the inappropriateness of metformin therapy decreased (10.2%, P &lt; 0.0001). According to Beers criteria, the inappropriate prescriptions of sulfonylureas raised to 29% both at admission and at discharge. This study shows a poor adherence to current guidelines on diabetes management in hospitalized elderly people with a high prevalence of inappropriate use of sulfonylureas according to the Beers criteria

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Cell orientation under stretch: A review of experimental findings and mathematical modelling

The key role of electro-chemical signals in cellular processes had been known for many years, but more recently the interplay with mechanics has been put in evidence and attracted substantial research interests. Indeed, the sensitivity of cells to mechanical stimuli coming from the microenvironment turns out to be relevant in many biological and physiological circumstances. In particular, experimental evidence demonstrated that cells on elastic planar substrates undergoing periodic stretches, mimicking native cyclic strains in the tissue where they reside, actively reorient their cytoskeletal stress fibres. At the end of the realignment process, the cell axis forms a certain angle with the main stretching direction. Due to the importance of a deeper understanding of mechanotransduction, such a phenomenon was studied both from the experimental and the mathematical modelling point of view. The aim of this review is to collect and discuss both the experimental results on cell reorientation and the fundamental features of the mathematical models that have been proposed in the literature

On-Line HP(LC)-GC-FID Determination of Hydrocarbon Contaminants in Fresh and Packaged Fish and Fish Products

BACKGROUND: Fish products can be contaminated with mineral oil hydrocarbons (MOH), mainly as a result of environmental contamination (wild fish) or contaminated feeds (farmed fish). Packaged products may also be contaminated with polyolefin oligomeric hydrocarbons (POH), which, depending on the packaging, storage condition, matrix composition, and fat content, may migrate relatively easily from the packaging to the food.OBJECTIVE: A rapid, solvent-sparing method for determining hydrocarbon contaminants in fish products was developed, validated, and applied to farmed and wild fish products (both fresh and packaged samples, stored under different conditions).METHOD: Microwave-assisted saponification (MAS) was used in combination with on-line LC-GC-flame ionization detection (FID).RESULTS: The proposed method showed quantitative recovery, good repeatability, and high sensitivity. Farmed salmon had variable mineral oil saturated hydrocarbon contamination (from 0.5 to 4.3mg/kg), accompanied by mineral oil aromatic hydrocarbons (maximum 1.4mg/kg), while wild salmons had no detectable contamination. Samples of one farmed salmon and a swordfish, both sliced and packed under vacuum, resulted contaminated with POH migrated from the packaging. POH migration was also evident in a ready-to-eat meal.CONCLUSIONS: The proposed method showed good performance characteristics in terms of recovery, repeatability, and LOQ. Fatty fish products are more prone to contamination with hydrocarbon contaminants.HIGHLIGHTS: MAS allows for rapid and efficient sample preparation. An LC-GC-FID method for MOH/POH determination in fish products was validated. Fish products may be contaminated with variable amounts of hydrocarbon contaminants

AMOTL2 interaction with TAZ causes the inhibition of surfactant proteins expression in lung cells

Background: TAZ (Transcriptional co-Activator with PDZ-binding motif), is a biologically potent transcriptional coactivator and functions by binding to the PPXY motif present in several transcription factors. Notably, TAZ behaves as a transducer linking cytoplasmic signaling events to transcriptional regulation in the nucleus. Several different factors regulate TAZ expression and/or function. In particular, a major regulation of TAZ activity occurs through the Hippo pathway by a phosphorylation-mediated mechanism that causes its cytoplasmic sequestration or degradation. Results: Here we demonstrate that AMOTL2 robustly co-immunoprecipitates with TAZ, and their interaction is dependent on the WW domain of TAZ and the PPXY motif in the N-terminus of AMOTL2. Furthermore, we show that AMOTL2 colocalizes with TAZ in the cytoplasm of H441 human lung cells and regulates TAZ cytoplasm-to-nucleus translocation through direct protein-protein interaction. Interestingly, the overexpression of AMOTL2 inhibits the functional cooperation between the transcription factor TTF-1 and TAZ on the Surfactant C gene promoter, as well as the expression of other known target genes of these regulatory factors. Conclusions: Taken together, our results suggest an inhibitory role of AMOTL2 on TAZ ability to co-activate transcription and describe a different mechanism, Hippo pathway-independent, that modulates the activity of TAZ in lung cells through the interaction with Angiomotin-like 2 (AMOTL2)