Advances in Technologies for Highly Active Omega-3 Fatty Acids from Krill Oil: Clinical Applications

Euphausia superba, commonly known as krill, is a small marine crustacean from the Antarctic Ocean that plays an important role in the marine ecosystem, serving as feed for most fish. It is a known source of highly bioavailable omega-3 polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid). In preclinical studies, krill oil showed metabolic, anti-inflammatory, neuroprotective and chemo preventive effects, while in clinical trials it showed significant metabolic, vascular and ergogenic actions. Solvent extraction is the most conventional method to obtain krill oil. However, different solvents must be used to extract all lipids from krill because of the diversity of the polarities of the lipid compounds in the biomass. This review aims to provide an overview of the chemical composition, bioavailability and bioaccessibility of krill oil, as well as the mechanisms of action, classic and non-conventional extraction techniques, health benefits and current applications of this marine crustacean

Multicentric Case-Control Study on Azathioprine Dose and Pharmacokinetics in Early-onset Pediatric Inflammatory Bowel Disease

BACKGROUND: Early-onset inflammatory bowel disease (IBD) is generally aggressive, with a high probability of complications and need of surgery. Despite the introduction of highly effective biological drugs, treatment with azathioprine continues to be important even for early-onset IBD; however, in these patients azathioprine response seems to be reduced. This study evaluated azathioprine doses, metabolite concentrations, and their associations with patients' age in children with IBD treated at 6 tertiary pediatric referral centers. METHODS: Azathioprine doses, metabolites, and clinical effects were assessed after at least 3 months of therapy in 17 early-onset (age 12 and <18 yrs, controls) patients with IBD. Azathioprine dose was titrated on therapeutic efficacy (response and adverse effects). Azathioprine metabolites and thiopurine methyltransferase activity were determined by high-performance liquid chromatography with ultra violet-vis detection (HPLC-UV) methods. RESULTS: Frequency of patients in remission was similar among early-onset and control groups, respectively (82% and 84%, P value = 0.72). Early-onset patients required higher doses of azathioprine (median 2.7 versus 2.0 mg\ub7kg\ub7d, P value = 1.1 7 10). Different doses resulted in comparable azathioprine active thioguanine nucleotide metabolite concentrations (median 263 versus 366 pmol/8 7 10 erythrocytes, P value = 0.41) and methylmercaptopurine nucleotide concentrations (median 1455 versus 1532 pmol/8 7 10 erythrocytes, P value = 0.60). Lower ratios between thioguanine nucleotide metabolites and azathioprine doses were found in early-onset patients (median 98 versus 184 pmol/8 7 10 erythrocytes\ub7mg\ub7kg\ub7d, P value = 0.017). Interestingly, early-onset patients presented also higher thiopurine methyltransferase activity (median 476 versus 350 nmol methylmercaptopurine/mg hemoglobin/h, P-value = 0.046). CONCLUSIONS: This study demonstrated that patients with early-onset IBD present increased inactivating azathioprine metabolism, likely because of elevated activity of the enzyme thiopurine methyltransferase

Phenoxy resin-based vinylogous urethane covalent adaptable networks

This work presents a post-polymerization approach to the preparation of vitrimers, exploiting the transamination of vinylogous urethane in linear phenoxy resins. Phenoxy vitrimers are obtained by a two-steps synthesis from a commercial phenoxy resin via partial conversion of hydroxyl groups to acetoacetates (AcAc), followed by network formation by reaction with m-xylylendiamine (XYDIA) as crosslinker. Three different vitrimers with variable crosslinking density are obtained by tuning the density of AcAc moieties along the phenoxy resin scaffold (5%, 10% and 15% conversion of hydroxyl groups). The conversion of linear polymers to dynamic crosslinked networks is confirmed by Dynamic Mechanical Thermal Analyzer (DMTA) and rheology measurements, followed by stress relaxation tests to investigate the kinetics of bond exchanges. Tensile tests as a function of reprocessing cycles reveal an increase of the maximum elongation and stress at break and prove the good recyclability of the vitrimers. Enhanced adhesive properties compared to pristine phenoxy resins are demonstrated, including the possibility to thermally re-join the assembly after its mechanical failure. Finally, the solvent-free preparation of vitrimer is explored for 5% crosslinked vitrimer via melt reactive blending, providing a valuable alternative to the less environmentally sustainable synthesis in solution

Different substrates of non-sustained ventricular tachycardia in post-infarction patients with and without left ventricular dilatation

Background: We investigated the relationship between nonsustained ventricular tachycardia (NSVT) and left ventricular (LV) dilatation, function, remodeling, and scar tissue extent in patients with previous myocardial infarction (MI). Methods and Results: Eighty-two patients (ages 64610 years) with first previous MI were referred for 24-hour electrocardiogram recording and cine and delayed enhancement (DE) cardiac magnetic resonance (CMR). LVvolumes, ejection fraction, systolic wall thickening, sphericity index, and core and peri-infarctual areas of scar tissue by CMR were evaluated. LV dilatation was observed in 39 patients. Episodes of NSVT were recorded in 32 patients: 23 with LV dilatation and 9 without. In the entire population, NSVTwas related to ejection fraction, LV volumes, LV mass, and sphericity index; end-systolic volume (P5.001) resulted in the only independent predictor at multivariate analysis. In patients without LV dilatation, the occurrence of NSVTwas only positively related with percentage of contracting segments with DE (P5.008). Conversely, in patients with LV dilatation, increase in LV mass (P5.020) and end-systolic volume (P5.038) were independent predictors of NSVT. Conclusions: Necrotic and viable myocardium coexistence within the same wall segments predicted occurrence of NSVT in patients without LV dilatation, whereas LV mass and end-systolic volume were predictors of NSVT in those with LV dilatation. (J Cardiac Fail 2010;16:61e68

New OCT and OCTA Insights in Inherited Retinal Dystrophies

Optical coherence tomography (OCT) and OCT angiography (OCTA) radically changed the diagnostics of inherited retinal dystrophies (IRD), providing new information regarding the microstructural changes occurring in each disease. The introduction of quantitative metrics provided even more steps forward in the understanding of IRD pathogenesis and course, allowing to propose new ways to categorize different subgroups of patients, characterized by remarkably different characteristics and prognosis. All these informations provided insights regarding how heterogeneous the clinical spectrum of IRD is. In the present study, we provide an updated description of OCT and OCTA findings in the main IRD, including retinitis pigmentosa, Stargardt disease, and Best vitelliform macular dystrophy. Moreover, we discuss imaging findings in pigmented paravenous retinochoroidal atrophy, a rare condition that is undergoing even growing scientific and clinical interest. In addition, we provided a brief updated scenario on imaging findings in pattern dystrophies. We discuss in detail the current state-of-the-art and the new insights provided by quantitative OCT and OCTA approaches, offering a complete description that might be helpful both for expert and nonexpert researchers interested in IRD

Extrafoveal Müller cells detection in vivo in the human retina: A pilot study based on optical coherence tomography.

Abstract Muller cells (MC) represent a key element for the metabolic and functional regulation of the vertebrate retina. The aim of the present study was to test the feasibility of a new method for the in-vivo detection and quantification of extrafoveal MC in human retina. We developed a new approach to isolate and analyse extrafoveal MC in vivo, starting from structural optical coherence tomography data. Our pilot investigation was based on the optical properties of MC, which are known to not interfere with the light reaching the outer retinal structures. We reconstructed MC in the macular region of 18 healthy subjects and the quantitative analyses revealed ~42,000/9 mm2 cells detected. Furthermore, we included 2 patients affected by peripheral intraocular melanoma, with macular sparing, needing surgical enucleation. We used these two eyes to perform a qualitative comparison between our reconstructions and histological findings. Our study represents the first pilot investigation dedicated on the non-invasive isolation and quantification of MC, in-vivo, in human retina. Although we are aware that our study has several limitations, first of all related with the proper detection of foveal MC, because of the peculiar z-shape morphology, this approach may open new opportunities for the non-invasive in vivo analysis of MC, providing also potential useful perspectives in retinal diseases

Stilbene polyphenols in the brown red wood of Vitis vinifera cv. Sangiovese affected by "esca proper"*

A number of stilbene polyphenols, dimers, trimers and tetramers of resveratrol (viniferins), which are typical Vitaceae metabolites, were extracted from asymptomatic wood (AW) and symptomatic brown-reddiscoloured wood (BRW) of Vitis vinifera cv. Sangiovese affected by “esca proper”, the trunk disease caused by the fungal complex Phaeomoniella chlamydospora, Phaeoacremonium aleophilum and Fomitiporia mediterranea. Resveratrol and the same types of viniferins were found in both AW and BRW, with the exception of α-viniferin, which was only detected in AW, and ampelopsin B, only in BRW. The total concentration of stilbene polyphenols was higher in symptomatic wood (3.7% in BRW vs 1.2% in AW). The absolute variationsin molar concentrations of each stilbene polyphenol (i) between BRW and AW (Δi = CiBRW - CiAW), were higherfor ε-viniferin and resveratrol than the other compounds, while the relative variations (Δi/CiAW), were lower for ampelopsin H and isohopeaphenol, and higher for ampelopsin B, hopeaphenol, ampelopsin A, leachianol F and G, pallidol and ε-viniferin (in descending order), than the relative variation for resveratrol. Aspects relating to the biosynthesis of stilbene polyphenols and their role in the host-esca pathogen interaction are discussed

Automatically extracted machine learning features from preoperative CT to early predict microvascular invasion in HCC: the role of the Zone of Transition (ZOT)

open12noMicrovascular invasion (MVI) is a consolidated predictor of hepatocellular carcinoma (HCC) recurrence after treatments. No reliable radiological imaging findings are available for preoperatively diagnosing MVI, despite some progresses of radiomic analysis. Furthermore, current MVI radiomic studies have not been designed for small HCC nodules, for which a plethora of treatments exists. This study aimed to identify radiomic MVI predictors in nodules ≤3.0 cm by analysing the zone of transition (ZOT), crossing tumour and peritumour, automatically detected to face the uncertainties of radiologist’s tumour segmentation. Methods: The study considered 117 patients imaged by contrast-enhanced computed tomography; 78 patients were finally enrolled in the radiomic analysis. Radiomic features were extracted from the tumour and the ZOT, detected using an adaptive procedure based on local image contrast variations. After data oversampling, a support vector machine classifier was developed and validated. Classifier performance was assessed using receiver operating characteristic (ROC) curve analysis and related metrics. Results: The original 89 HCC nodules (32 MVI+ and 57 MVI−) became 169 (62 MVI+ and 107 MVI−) after oversampling. Of the four features within the signature, three are ZOT heterogeneity measures regarding both arterial and venous phases. On the test set (19MVI+ and 33MVI−), the classifier predicts MVI+ with area under the curve of 0.86 (95%CI (0.70–0.93), p∼10^−5), sensitivity = 79% and specificity = 82%. The classifier showed negative and positive predictive values of 87% and 71%, respectively. Conclusions: The classifier showed the highest diagnostic performance in the literature, disclosing the role of ZOT heterogeneity in predicting the MVI+ status.noneMatteo Renzulli, Margherita Mottola, Francesca Coppola, Maria Adriana Cocozza, Silvia Malavasi, Arrigo Cattabriga, Giulio Vara, Matteo Ravaioli, Matteo Cescon, Francesco Vasuri, Rita Golfieri, Alessandro BevilacquaMatteo Renzulli, Margherita Mottola, Francesca Coppola, Maria Adriana Cocozza, Silvia Malavasi, Arrigo Cattabriga, Giulio Vara, Matteo Ravaioli, Matteo Cescon, Francesco Vasuri, Rita Golfieri, Alessandro Bevilacqu

In-vivo anatomical reconstruction of the optic radiations in the human brain

The optic radiations are major white matter pathways funneling visual information from the lateral geniculate nuclei to the visual cortex in the occipital lobe. Given their relevance in visual processing and in several brain disorders, the optic radiations have been extensively investigated by using magnetic resonance imaging and diffusion tensor imaging tractography [1]. Herein, we use a powerful diffusion signal modeling, namely Constrained Spherical Deconvolution, in order to provide an exhaustive connectivity profile of the connections between the lateral geniculate nucleus and the visual cortex in the healthy brain, as well as pulvinar connectivity with visual-related structures. In addition, taking into account that visual deficits may precede motor symptoms’ onset in Parkinson’s Disease [2], we assessed whether the intracranial visual system can be involved at the early stage of the disease. Our connectivity analysis revealed that the optic radiations are mainly distributed in V1 and V2. Furthermore, we found significant alterations of optic radiations connectivity distribution in Parkinson’s Disease patients, with decreased lateral geniculate nucleus-V2 density as well as significant increase of optic radiations’ mean diffusivity. Voxel Based Morphometry analysis also showed significant reduction of visual cortical volumes and of the optic radiation in the patients group. In conclusion, our findings provide a reliable connectivity profile of the optic radiations, suggesting extrastriate-lateral geniculate nucleus connections in human brain. Finally, we showed that visual system alterations can be detected at early stages of Parkinson’s Disease