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Two (consecutive) reductions of the complete Gatenby–Gawlinski model for cancer invasion are proposed in order to investigate the mathematical framework, mainly from a computational perspective. After a brief overview of the full model, we proceed by examining the case of a two-equations-based and one-equation-based reduction, both obtained by means of a quasi-steady-state assumption. We focus on invasion fronts, exploiting a numerical strategy based on a finite volume approximation, and perform corresponding computational simulations to study the sharpness/smoothness of the traveling waves. Then, we employ a space-averaged wave speed estimate—referred to as the LeVeque–Yee formula—to quantitatively approach the propagation phenomenon. Concerning the one-equation-based model, we propose a scalar degenerate reaction-diffusion equation, which proves to be effective in order to qualitatively recover the typical trends arising from the Gatenby–Gawlinski model. Finally, we carry out some numerical tests in a specific case where the analytical solution is available. [ABSTRACT FROM AUTHOR]

Synapsin I (SynI) is a synaptic vesicle (SV)-associated phosphoprotein that modulates neurotransmission by controlling SV trafficking. The SynI C-domain contains a highly conserved ATP binding site mediating SynI oligomerization and SV clustering and an adjacent main Ca2+ binding site, whose physiological role is unexplored. Molecular dynamics simulations revealed that the E373K point mutation irreversibly deletes Ca2+ binding to SynI, still allowing ATP binding, but inducing a destabilization of the SynI oligomerization interface. Here, we analyzed the effects of this mutation on neurotransmitter release and short-term plasticity in excitatory and inhibitory synapses from primary hippocampal neurons. Patch-clamp recordings showed an increase in the frequency of miniature excitatory postsynaptic currents (EPSCs) that was totally occluded by exogenous Ca2+ chelators and associated with a constitutive increase in resting terminal Ca2+ concentrations. Evoked EPSC amplitude was also reduced, due to a decreased readily releasable pool (RRP) size. Moreover, in both excitatory and inhibitory synapses, we observed a marked impaired recovery from synaptic depression, associated with impaired RRP refilling and depletion of the recycling pool of SVs. Our study identifies SynI as a novel Ca2+ buffer in excitatory terminals. Blocking Ca2+ binding to SynI results in higher constitutive Ca2+ levels that increase the probability of spontaneous release and disperse SVs. This causes a decreased size of the RRP and an impaired recovery from depression due to the failure of SV reclustering after sustained high-frequency stimulation. The results indicate a physiological role of Ca2+ binding to SynI in the regulation of SV clustering and trafficking in nerve terminals. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor (FGF) receptor 4 (FGFR4) and its cognate ligand, FGF19, are implicated in a range of cellular processes, including differentiation, metabolism and proliferation. Indeed, their aberrant activation has been associated with the development of hepatic tumours. Despite great advances in early diagnosis and the development of new therapies, liver cancer is still associated with a high mortality rate, owing primarily to high molecular heterogeneity and unclear molecular targeting. The development of FGFR4 inhibitors is a promising tool in patients with concomitant supraphysiological levels of FGF19 and several clinical trials are testing these treatments for patients with advanced hepatocellular carcinoma (HCC). Conversely, using FGF19 analogues to activate FGFR4-KLOTHO β represents a novel therapeutic strategy in patients presenting with cholestatic liver disorders and non-alcoholic steatohepatitis, which could potentially prevent the development of metabolic HCC. Herein, we provide an overview of the currently available therapeutic options for targeting FGFR4 in HCC and other liver diseases, highlighting the need to carefully stratify patients and personalise therapeutic strategies. [ABSTRACT FROM AUTHOR]

This article examines the use of coins by enslaved and indentured communities in nineteenth-century British Guiana and the visual imagery of these practices. Both Afro-Guianese and Indo-Guianese people appropriated the portability of coins for spiritual and aesthetic purposes as a response to the common experience of a violent plantation society. The development of photography during the migration of Indian indentured labour to British Guiana and the popularisation of the image of Indian indentured women wearing jewellery made from coins as representative of indenture at large, however, has overshadowed this shared history. By charting the afterlife of minted coins across economic, spiritual and aesthetic realms, this article offers a more nuanced understanding of worn silver and the people who wore it. [ABSTRACT FROM AUTHOR]

Abstract Industrial energy efficiency has been widely recognized as a major contributor to the reduction of greenhouse gases emissions and improvement of industrial competitiveness. Nevertheless, a broad set of studies have pointed out the existence of barriers limiting the adoption of promising Energy Efficiency Measures (EEMs). Recently, scholars have shown the relevance of the so-called "non-energy benefits" (NEBs) coming from the adoption of EEMs for overcoming those barriers. Still, the existence of such benefits has been pointed out from specific studies and manuals for practitioners, but an overall framework describing them in terms of savings and benefits, as well as technical and management implications, is missing yet. Moreover, a considerable part of the scholars and of the practitioners just focuses on the identification and definition of the positive benefits deriving from these measures after they have been completely adopted, thus neglecting to describe the full set of both positive and negative effects occurring also during the implementation phase. Thus, starting from a literature review of scientific as well as practitioners' studies, we have proposed a novel framework and characterization of the relevant items to be considered by an industrial decision-maker when deciding whether to adopt an EEM considering both the implementation and service phases. Hence, by taking this perspective, we have tested and validated the framework and the characterization in a two-step process: firstly, considering a set of EEMs well diffused and adopted in industry; secondly, investigating benefits and losses in ad-hoc selected manufacturing companies. Finally, considerations and implications are drawn from the preliminary validation and suggestion for further research are proposed, for both industrial decision-making as well as policy-making purposes. Graphical abstract Framework displaying the set of impacts from adoption of an Energy Efficiency Measure (EEM), in which focus is given to both positive (benefits) or negative (losses) impacts, as well as in implementation and service phase. Image 1 Highlights • Review of existing studies over Non-Energy Benefits. • Novel framework characterizing impact of energy efficiency measures. • Benefits as well as Losses should be considered by industrial decision-makers. • Beside service phase, major relevance of implementation phase highlighted. • EEMs should be characterized also by impacts on the operations. [ABSTRACT FROM AUTHOR]

Malignant peritoneal mesothelioma (MPM) is a rare disease with a wide clinical spectrum. It arises from the peritoneal lining and commonly presents with diffuse, extensive spread throughout the abdomen and, more rarely, metastatic spread beyond the abdominal cavity. Computed tomography, magnetic resonance imaging and positron-emission tomography are important diagnostic tools used for the preoperative staging of MPM. The definitive diagnosis is based on histopathological analysis, mainly via immunohistochemistry. In this regard, pairedbox gene 8 negativity represents a useful diagnostic biomarker for differentiating MPM from ovarian carcinoma. In addition, BRCA1-associated protein-1 (BAP1) loss is specific to MPM and allows it to be distinguished from both benign mesothelial lesions and ovarian serous tumors. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has become an increasingly important therapeutic approach, while systemic therapies are still being developed. Histology, Ki-67, completeness of cytoreduction, age, sex, and baseline thrombocytosis are commonly used to optimize patient selection for CRS with HIPEC. Additionally, it is well recognized that, compared to other subtypes, an epithelial morphology is associated with a favorable prognosis, whereas baseline thrombocytosis predicts an aggressive biologicalbehavior. Platelets and other immunologic cytokines have been evaluated as potential novel therapeutic targets. Epigenetic modifiers, including BAP1, SETD2 and DDX3X, are crucial in mesothelial tumorigenesis and provide opportunities for targeted treatment. Overexpression of the closely interacting phosphoinositide 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR) pathways appears crucial in regulation of the malignant phenotype. The use of targeted therapies with PI3K-mTOR-based inhibitors requires further clinical assessment as a novel approach. [ABSTRACT FROM AUTHOR]

Executive deficits and impulsiveness are extensively reported in juvenile myoclonic epilepsy (JME). Previous literature suggests that intelligence may mediate these deficits. In this study, we evaluated and compared the performance of adults with JME with high and low intelligence quotient (IQ) and controls on tasks for executive function (EF) and impulsive traits. We investigated the neuropsychological performance of 53 adults with JME and below average IQ (57% women; 26.9 [± 7.88] years; mean IQ: 89.8 [± 5.1]), 26 adults with JME and average or above average IQ (53.8% women; 28.2 [± 9.33] years; mean IQ: 110.7 [± 8.3]), 38 controls with below average IQ (55% women; 28.4 [± 8.4] years; mean IQ: 90.1 [± 5.8]), and 31 controls with average or above average IQ (61.3% women; 32.20 [± 11.3] years; mean IQ: 111.6 [± 10.5]) with a comprehensive battery of neuropsychological tests that measure executive/attentional function. Impulsive traits were assessed using the Cloninger et al.'s Temperament and Character Inventory (novelty seeking (NS) domain). The group with JME with higher IQ presented worse performance compared with controls with higher IQ on Controlled Oral Word Association (COWA) and Wisconsin Card Sorting Test (WCST) (errors). This group showed worse performance than controls with lower IQ on Stroop Color–Word Test (SCT) 1, Trail Making (TM) A, COWA, and WCST (errors). Patients with lower IQ showed worse performance than controls with higher IQ on Digit Span Forward (DSF), Digit Span Backward (DSB), SCT1, SCT2, SCT3, TM A, COWA, and WCST (errors and failure to maintain set). Patients with lower IQ showed worse performance than controls with lower IQ on DSF, DSB, SCT1, SCT2, SCT3, TM A, TM B, COWA, and WCST (errors and failure to maintain set). Patients from groups with low and high IQ showed higher scores than controls with higher and lower IQ on impulsivity for NS1 and NS2 (except for patients with higher IQ versus controls with lower IQ). Adults with JME and higher IQ show less evidence of EF deficits compared with those with JME and below average IQ, suggesting that a higher degree of intellectual efficiency may act as a compensatory mechanism. However, it does not minimize some aspects of impulsive traits. Patients with JME and higher cognitive reserve may create strategies to dodge their cognitive obstacles. In this context, intelligence may protect and, at the same time, “mask” impairments that could be detected earlier. [ABSTRACT FROM AUTHOR]

The present paper aims at investigating the impact of an airfoil design on the propulsion system for a Martian rotary wing micro air vehicle. The main challenge for flying on Mars is the atmosphere’s density and speed of sound that are significantly lower than on Earth. It leads to compressible ultra-low Reynolds number ( Rec<104) flows for a coaxial rotorcraft with a 30 cm diameter . Since those flows are unknown in the biosphere, numerical tools have not been validated yet. Therefore, the test section from a known depressurized experiment is simulated in 3D for solver assessment. XFoil, a program for the analysis of subsonic airfoil, is also evaluated in the Martian flow conditions for evaluating its ability to be used in an optimization process. Based on the XFoil’s performance evaluations, both the camber line and thickness distribution are optimized in 2D incompressible and compressible flows. Optimal shape is a highly cambered airfoil shifting the boundary layer separation downstream. For optimization assessment, airfoils from each optimization step are numerically evaluated with the validated solver showing that small variations in the airfoil design has little impact on the 2D aerodynamic performance. A compressible optimal airfoil is also proven to be more aerodynamically effective than the experimentally effective airfoils from literature. Finally, the impact of airfoil shapes on the 3D rotor performance is evaluated with a depressurized experimental campaign recreating the Martian atmosphere in terms of kinematic viscosity. The impact of gas composition is also assessed in subsonic flows. [ABSTRACT FROM AUTHOR]

The management of gestational ovarian cancer can be challenging because of the risk of fetal wastage, and the possibility of treatment-related complications to the fetus; it is based on insufficient data from retrospective studies and case series. Here, a literature review of the diagnostic and surgical approaches to the gestational ovarian cancer has been performed; moreover, data on safety of chemotherapeutic treatments in pregnancy, including both oncologic and fetal outcomes, have also been reviewed. Up to now, 193 cases of ovarian cancers during pregnancy have been reported in the English literature. Treatment of ovarian malignancies during pregnancy depends on histology, stage, and gestational weeks. When possible, surgical excision is indicated, and fertility-sparing surgery can be offered to stage I epithelial ovarian tumours (EOC), germ cell ovarian, or sex-cord stromal ovarian tumours. Neoadjuvant and/or adjuvant chemotherapy for advanced ovarian tumours is indicated as in non-pregnant women. Administration of chemotherapy after the first trimester, can cause fetal growth restriction, while being seemingly safe. The therapeutic approach of ovarian cancer in pregnancy should be individualized and intended in specialized centers. [ABSTRACT FROM AUTHOR]

Chemotherapy remains the mainstay of treatment for advanced pancreatic ductal adenocarcinoma (pda). Two randomized trials have demonstrated superiority of the combination regimens folfirinox (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) and gemcitabine plus nab-paclitaxel over gemcitabine monotherapy as a first-line treatment in adequately fit subjects. Selected pda patients progressing to first-line therapy can receive secondline treatment with moderate clinical benefit. Nevertheless, the optimal algorithm and the role of combination therapy in second-line are still unclear. Published second-line pda clinical trials enrolled patients progressing to gemcitabine-based therapies in use before the approval of nab-paclitaxel and folfirinox. The evolving scenario in second-line may affect the choice of the first-line treatment. For example, nanoliposomal irinotecan plus 5-fluouracil and leucovorin is a novel second-line option which will be suitable only for patients progressing to gemcitabinebased therapy. Therefore, clinical judgement and appropriate patient selection remain key elements in treatment decision. In this review, we aim to illustrate currently available options and define a possible algorithm to guide treatment choice. Future clinical trials taking into account sequential treatment as a new paradigm in pda will help define a standard algorithm. [ABSTRACT FROM AUTHOR]

Abstract: Heuristics for employing photoredox catalysts in coiled‐tube LED reactors for flow chemistry are presented. These heuristics focus on common reaction parameters (for example, reagent concentration, tube diameter and light intensity) designed to encompass as many photoredox systems as possible. A chemical actinometer based on a common photocatalyst, [Ru(bpy)3Cl2], is used to determine how each parameter affects the observed rate of reaction and the photon flux received in the reactor. These heuristics are then demonstrated using a photoredox reaction to see if they accurately predict flow reaction conditions that correspond to increased rates of reaction. [ABSTRACT FROM AUTHOR]

Non-epithelial ovarian cancers (NEOC) constitute a group of uncommon malignancies and their treatment is still a challenging task. Collectively, these tumours account for about 10% of all ovarian cancers and occur in all age groups from childhood to old-age. They include malignancies of germ cell origin, sex cord-stromal cell origin, and a variety of extremely rare ovarian cancers, such as small-cell carcinomas and sarcomas. Each of these classifications encompasses multiple histologic subtypes. It is imperative that these rare tumours are managed with accurate diagnosis, staging, and treatment, to optimise the outcome. The aetiology and molecular origins of each sub-group of NEOC remain largely unresolved, and international cooperation to promote high quality translational research is crucial. Much effort has been made into researching the molecular mechanisms underlying epithelial ovarian cancers, but far less is known about the genetic changes in NEOC. In this article, it is provided an overview of the current knowledge on the incidence, clinical presentation, pathology, genetics, therapeutic interventions, survival and prognostic factors of adult and juvenile granulosa cell tumours (GrCT), Sertoli-Leydig Cell tumours (SLCT) and small cell carcinoma of the ovary. We also consider future potential therapeutic targets in these rare cancers. [ABSTRACT FROM AUTHOR]

Introduction. Baseline neutrophil-to-lymphocyte ratio (NLR) has been repeatedly reported as a significant prognostic factor in advanced cancer patients. We explored whether changes in NLR may predict outcome of advanced cancer patients enrolled into phase 1 trials and treated with PD-1/PD-L1 inhibitors. Patients and Methods. Advanced cancer patients enrolled into phase 1 trials between September 2013 and May 2016 and treated with anti-PD-1/PD-L1 agents were included in this retrospective study. NLR was calculated at baseline and after 2 cycles of treatment. Royal Marsden Hospital (RMH) prognostic score and Eastern Cooperative Group (ECOG) performance status (PS) were determined at baseline. Kaplan-Meier estimation and Cox regression analyses were used to assess the impact of NLR dynamics on PFS. Results. Among the 55 patients eligible, 26 (47%) were treated with anti-PD-L1 monotherapy, 22 (40%) received single agent anti-PD-1, and 7 (13%) were given a tyrosine kinase inhibitor (TKI) plus a PD-1 inhibitor. Neither ECOG PS nor RMH prognostic score was significantly associated with PFS in our cohort, whereas changes in NLR significantly impacted on PFS. Conclusion. Changes in the NLR may be a useful predicting factor in advanced cancer patients treated with anti-PD-1/PD-L1 agents. Further prospective trials are needed to verify these findings. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) presents high mortality rate and about 25–46 % have mutation in the PIK3CA gene. Alpelisib is a PI3K inhibitor that acts on p110α, which is a subunit of the PI3K protein. The melatonin shown important anti-neoplastic effects and may increase the effectiveness of chemotherapy. This study evaluated the synergistic action of Alpelisib and Melatonin in BC lines carrying the H1047R mutation in PIK3CA , relative to the cellular dynamics and the PI3K/AKT/mTOR pathway. MDA-MB-468 (triple-ernegative), MDA-MB-453 (H1047R PIK3CA, HER2+) and T-47D cells (H1047R PIK3CA, ER+/PR+) were divided into four treatment groups: control; Melatonin (1 mM); Alpelisib (1 μM); and Alpelisib (1 μM) + Melatonin (1 mM). Cell viability and migration were investigated using the MTT assay and Transwell assay, respectively. Protein expression of PI3K, p-AKT, mTOR, HIF-1α, and caspase-3, was verified using immunocytochemistry. MTT assay revealed that MDA-MB-453 and T-47D showed reduction in cell viability in all groups, especially in the MDA-MB-453 treated with Melatonin + Alpelisib. MDA-MB-468 presents reduction in cell migration only with Melatonin, while in the lines with mutation, the treatment of Melatonin + Alpelisib caused inhibition of cell migration. PI3K, p-AKT, mTOR and HIF-1α were inhibited after treatment with Melatonin + Alpelisib in MDA-MB-453 and T-47D lines. The expression of caspase-3 increased in all groups in MDA-MB-453 and T-47D cells, being the increase more pronounced in the Melatonin + Alpelisib group. These results indicate that the combined use of Melatonin and Alpelisib may be more effective in inhibiting BC in women carrying the PIK3CA gene mutation than either treatment alone. [ABSTRACT FROM AUTHOR]

Optimal trajectory planning in a windy environment is a complex problem when airplane performance characteristics are considered. This paper introduces a novel form of Legendre pseudospectral optimization to solve boundary value problems in UAV trajectory planning. The proposed architecture applies Legendre–Gauss–Lobatto and Hamilton–Jacobi–Bellman equations to generate candidate pieces of trajectories with respect to the UAV dynamic constraints. Analytical performance-based solutions are also developed for sample cases to achieve an optimal criterion in trajectory planning. Moreover, the notion of wind soaring is exploited to use the beneficial effects of tailwind velocities in trajectory planning. Integral cost functions are handled by Gauss-type quadrature rules. Simulations demonstrate the efficiency of the pseudospectral method compared with other solvers, in eliminating the difficulties of boundary value problems by employing the boundary points in the interpolation equation. The effectiveness of the proposed approach is demonstrated through dynamic simulations. [ABSTRACT FROM AUTHOR]

Background: Targeting BRAF V600E mutation has been proven effective in the treatment of several types of cancer. In endometrial adenocarcinoma, the BRAF V600E mutation has been rarely reported. Whether targeting BRAF oncogene may represent a plausible therapeutic strategy for the rare patients with BRAF-mutated endometrial cancer remains to be ascertained in prospective studies. Case presentation: We report herein the case of a heavily pre-treated patient with recurrent microsatellite instability high (MSI-H) BRAF V600E mutated endometrial adenocarcinoma, which was successfully treated with the V600E targeting agent dabrafenib. After developing resistance to this agent, the MEK targeting agent trametinib was added to dabrafenib achieving again a therapeutic response. Conclusions: This case shows that dabrafenib both as monotherapy and when combined with trametinib may exert significant therapeutic activity in heavily pretreated BRAF V600E mutated endometrial adenocarcinoma, and highlight potential benefits of personalized treatment in this disease. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to assess the diagnostic accuracy of virtual gastroscopy obtained by 320-row computed tomography (CT) examination in differentiating benign from malignant gastric ulcers (GUs). Materials and Methods: 49 patients (30 M, 19 F, mean age 58.6) with endoscopic and histological diagnosis of GU underwent CT examination. A hypotonizing drug was administered and gastric walls were distended by air in order to perform virtual endoscopy. Based on morphological features, GUs were subdivided into benign or malignant forms by two blinded radiologists. Interobserver agreement was evaluated using Cohen’s kappa (κ) test. CT results were then compared with endoscopic and histological findings, having the latter as the reference standard. Results: Thirty-five out of 49 patients (71%) were affected by malignant ulcers, while in the remaining 14 cases diagnosis of benign GU was made. Virtual gastroscopy showed diagnostic accuracy, sensitivity, and specificity values of 94%, 91%, and 100%, respectively, in differentiating benign from malignant ulcers. Almost perfect agreement between the two readers was found (κ = 0.86). Conclusion: CT virtual gastroscopy improves the identification of GUs and allows differentiating benign from malignant forms. [ABSTRACT FROM AUTHOR]

Objective: This study aims to evaluate the diagnostic accuracy of a new CT sign in order to define or exclude a malignant aetiology of bowel obstruction. Materials and Methods: CT scans of 137 patients affected by bowel obstruction were reviewed. Colonic obstruction occurred in 47 (34%) cases, small bowel obstruction in 90 (66%). Neoplastic aetiology was found in 42 cases (31%), while in the remaining 95 (69%) obstruction was caused by non-neoplastic conditions. Definitive diagnosis was surgically confirmed in all patients. CT images were evaluated searching for bowel obstruction's signs and for the presence of the "protruding lips" sign on the proximal surface of stenosis, which is represented by the evidence of a protrusion within the dilated loop. Results: The sign was found in 31 (23%) cases, all of neoplastic origin. When malignant obstruction was diagnosed, sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy values of the described sign were 74%, 100%, 100%, 90% and 92%, respectively. Conclusions: The "protruding lips" sign represents an alteration to be searched when bowel obstruction is diagnosed by CT examination. Its evidence correlates to a malignant condition with a 100% probability and when it is not found, the probability of a non-neoplastic condition is 90%. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the diagnostic accuracy of 16-row multidetector CT (MDCT) and vessel probe reconstructions in the T staging of gastric carcinoma. Fifty-three patients (39 men, 14 women, mean age 57.5) with an endoscopic diagnosis of gastric adenocarcinoma underwent CT examination. A hypotonic drug was administered, and the gastric walls were distended by the ingestion of 400-600 ml of water. A biphasic technique with 40-s and 70-s delay was used after endovenous contrast material injection. All patients underwent surgery, and preoperative and histological stagings were compared. The diagnostic accuracy of T staging was 68% for axial images and 94% for VP reconstructions. In the T1, T2, T3 and T4 parameter evaluation, diagnostic accuracy values were 87%, 73.5%, 81% and 96%, respectively, for axial images and 96%, 96%, 98% and 100%, respectively for VP reconstructions. MDCT is an accurate technique for the preoperative staging of gastric cancer. The VP reconstructions obtained by isotropic data can evaluate the T parameter with a higher accuracy. [ABSTRACT FROM AUTHOR]

The significant activity of poly(ADP-ribose)polymerase (PARP) inhibitors in the treatment of germline BRCA mutation-associated ovarian cancer, which represents ∼15% of HGS cases, has recently led to European Medicines Agency and food and drug administration approval of olaparib. Accumulating evidence suggests that PARP inhibitors may have a wider application in the treatment of sporadic ovarian cancers. Up to 50% of HGS ovarian cancer patients may exhibit homologous recombination deficiency (HRD) through mechanisms including germline BRCA mutations, somatic BRCA mutations, and BRCA promoter methylation. In this review, we discuss the role of somatic BRCA mutations and BRCA methylation in ovarian cancer. There is accumulating evidence for routine somatic BRCA mutation testing, but the relevance of BRCA epigenetic modifications is less clear. We explore the challenges that need to be addressed if the full potential of these markers of HRD is to be utilised in clinical practice. [ABSTRACT FROM AUTHOR]

Molecular dynamics simulations are performed to investigate the cooperatively catalyzed aldol condensation between acetone and 4-nitrobenzaldehyde on alkylamine (or alkylenamine)-grafted silica surfaces, focusing on the mechanism of the catalytic activation of the acetone and 4-nitrobenzaldehyde by the acidic surface silanols followed by the nucleophilic attack of the basic amine functional group toward the activated reactant. From the analysis of the correlations between the catalytically active acid-base sites and reactants, it is concluded that the catalytic cooperativity of the acid-base pair can be affected by two factors: (1) the competition between the silanol and the amine (or enamine) to form a hydrogen bond with a reactant and (2) the flexibility of the alkylamine (or alkylenamine) backbone. Increasing the flexibility of the alkylamine facilitates the nucleophilic attack of the amine on the reactants. From the molecular dynamics simulations, it is found that C3 propylamine and C4 butylamine linkers exhibit the highest probability of reaction, which is consistent with the experimental observation that the activity of the aldol reaction on mesoporous silica depends on the length of alkylamine grafted on the silica surface. This simulation work serves as a pioneering study demonstrating how the molecular simulation approach can be successfully employed to investigate the cooperative catalytic activity of such bifunctional acid-base catalysts. [ABSTRACT FROM AUTHOR]

Acute adrenal ischemia represents a rare cause of adrenal insufficiency which should be promptly diagnosed in order to preserve adrenal vitality and function. Our study aims to retrospectively evaluate the diagnostic accuracy of the CT capsular sign as an indicator of adrenal ischemia and its association with vascular involvement. Between January 2013 and January 2014, 69 consecutive patients (47 men, 22 women; mean age 46; range 22-67) with suspected adrenal insufficiency based on clinical and biochemical data underwent 320-row CT examination in our Emergency Department. Written informed consent was obtained for the CT examinations, and the institutional review board approval was obtained for our retrospective study. CT multi-planar images were retrospectively and independently analyzed by two radiologists searching for the patency of adrenal vessels, enlarged adrenals, the presence of the "capsular sign" represented by a peripheral subtle hyperdense line around a hypodense enlarged adrenal, and the presence of any periadrenal inflammatory changes. All CT findings were then compared with the surgical findings (n = 5), follow-up examinations (n = 20), or autopsy (n = 4). Sensitivity, specificity, diagnostic accuracy (DA), positive predictive value (PPV), and negative predictive value (NPV) were calculated for the "capsular sign" and were further evaluated by ROC analysis. Acute adrenal ischemia occurred in 29/69 patients (42 %), unilateral in 20, and bilateral in 9. Forty of sixty-nine patients (58 %) had no evidence of adrenal disease on CT. Thrombosis of the main adrenal vein was found in 20/29 (69 %) and non-venous ischemia in 9/29 (31 %). The capsular sign was found in 24/29 patients (83 %). Sensitivity, specificity, DA, PPV, and NPV values of 83, 100, 93, 100, and 89 %, respectively, were obtained. The capsular sign represents a CT indicator of acute adrenal ischemia, with a specificity of 100 % and leading to a prompt diagnosis in the early phase of the disease. [ABSTRACT FROM AUTHOR]

The effects of heteroatom substitution on the cooperative catalytic activity of a series of bifunctional acid–base aminosilica catalysts are probed in aldol and nitroaldol condensations. Three M 3+ (B, Al, and Ga) and three M 4+ (Ti, Zr, and Ce) heteroatoms are incorporated into different samples of SBA-15 silica and then grafted with aminosilanes to produce bifunctional acid–base catalysts. The catalytic activity of each material is measured in the aldol condensation of 4-nitrobenzaldehyde with acetone at 50 °C and the nitroaldol condensation of 4-nitrobenzaldehyde with nitromethane at 40 °C and compared to the catalytic activity of a heteroatom-free aminosilica catalyst. The heteroatom substitutions produce catalysts with larger amounts of strong Lewis acid sites compared to the heteroatom-free aminosilica catalyst. We rationalize these results in the context of the physical (e.g. surface area, pore diameter, particle size) and chemical properties (e.g. total number and strength of acid sites) of each material and the proposed catalytic mechanisms of the two reactions. The increase in the number of strong Lewis acid sites of each heteroatom material decreased its activity in the aldol condensation, though four heteroatom substitutions (B, Al, Ga, and Ti) increased the catalytic activity of the aminosilica catalyst in the nitroaldol condensation. The results suggest that inclusion of a small amount of Lewis acid sites in aminosilica materials can increase the cooperative catalytic activity of the materials in the nitroaldol condensation. The results also suggest that inclusion of Lewis acid sites in aminosilica materials decreases the cooperative catalytic activity of the materials in the aldol condensation. [ABSTRACT FROM AUTHOR]

Flexible composite polymer/oxide hollow fibers are used as flow reactors for heterogeneously catalyzed reactions in organic synthesis. The fiber synthesis allows for a variety of supported catalysts to be embedded in the walls of the fibers, thus leading to a diverse set of reactions that can be catalyzed in flow. Additionally, the fiber synthesis is scalable (e.g. several reactor beds containing many fibers in a module may be used) and thus they could potentially be used for the large-scale production of organic compounds. Incorporating heterogeneous catalysts in the walls of the fibers presents an alternative to a traditional packed-bed reactor and avoids large pressure drops, which is a crucial challenge when employing microreactors. [ABSTRACT FROM AUTHOR]

Flexible composite polymer/oxide hollow fibers are used as flow reactors for heterogeneously catalyzed reactions in organic synthesis. The fiber synthesis allows for a variety of supported catalysts to be embedded in the walls of the fibers, thus leading to a diverse set of reactions that can be catalyzed in flow. Additionally, the fiber synthesis is scalable (e.g. several reactor beds containing many fibers in a module may be used) and thus they could potentially be used for the large-scale production of organic compounds. Incorporating heterogeneous catalysts in the walls of the fibers presents an alternative to a traditional packed-bed reactor and avoids large pressure drops, which is a crucial challenge when employing microreactors. [ABSTRACT FROM AUTHOR]

Weak acids are known to enhance the activity of amines in aldol condensation reactions on silica-based catalysts. The effects of acid strength and arrangement of the promoting site with respect to a secondary amine have been investigated in the aldol condensation of 4-nitrobenzaldehyde with acetone. Changing the substituent of this secondary amine from a methyl to an ethyl group decreases the activity. An intramolecular OH function provided by a primary alcohol incorporated on the β-carbon of the amine substituent exhibits a similar cooperativity as an intermolecular OH function provided by neighboring surface silanols. A maximum activity was achieved when the secondary amine with the same primary alcohol-containing substituent was surrounded by surface silanols, indicating the potential advantage of simultaneously activating both reactants by the formation of a hydrogen bond in contrast to the consecutive activation when there is only one promoting site in the vicinity of the amine. Changing the alcohol to stronger acids resulted in a reduced cooperativity with increasing acid strength. After removing the silanols from the surface, the activity of the catalysts which exhibit an intramolecular cooperativity retained about 68–83% of their activities while the activity of the conventional secondary amine was reduced by a factor of four compared to its intermolecularly cooperative counterpart. [ABSTRACT FROM AUTHOR]

Objective The Barratt Impulsiveness Scale (BIS-11) is the most widely used questionnaire to study impulsivity in persons with psychiatric disorders, but it has rarely been applied to persons with epilepsy. The present study aimed to evaluate the usefulness of BIS-11 as a tool to explore impulsivity in two distinct epilepsy syndromes. Method The BIS-11 was applied to 20 patients with juvenile myoclonic epilepsy (JME) (32.5 ± 8.95 years old), 20 patients with temporal lobe epilepsy (TLE) (37.7 ± 13.25 years old), and 26 healthy controls (31.86 ± 11.25 years old). The scores in motor, attentional, and lack of planning impulsivity were compared between groups. Results Patients with JME showed higher scores than patients with TLE and controls in all domains: motor (JME vs TLE: 28.60 vs 13.25 (mean score), p < 0.001 and JME vs controls: 28.60 vs 14.12, p < 0.001), attentional (JME vs TLE: 21.55 vs 13.45, p < 0.001 and JME vs controls: 21.55 vs 14.88, p < 0.001) and nonplanning (JME vs TLE: 28.05 vs 13.10, p < 0.001 and JME vs controls: 28.05 vs 16.15, p < 0.001). Conclusion Higher BIS-11 scores in all domains of impulsivity [i.e., motor, attentional, and lack of planning] corroborated previous findings described in patients with JME. On the other hand, BIS-11 could not demonstrate problem solving and inhibitory control deficits related to impulsive behavior, which were described in patients with TLE. Other behavioral measures may be more sensitive to some aspects of impulsivity in TLE. Our results reinforce the concept that distinct epileptic syndromes require different neuropsychological approaches, especially considering a complex construct such as impulsivity. [ABSTRACT FROM AUTHOR]

An anhydrous synthesis of aminosilicamaterials from alkyl halide-functionalizedmesoporous SBA-15 silica by post-grafting amination is introducedfor applications in CO2adsorption, cooperative catalysis,and 15N solid-state NMR spectroscopy. The synthesis isdemonstrated to convert terminal alkyl halide-functionalized silicamaterials containing Cl, Br, and I to primary alkylamines using anhydrousammonia in a high-pressure reactor. The benefits of the post-graftingamination procedure include (i) use of anhydrous isotopically labeledammonia, 15NH3, to create aminosilica materialsthat can be investigated using 15N solid-state NMR to elucidatepotential intermediates and surface species in CO2adsorptionprocesses and catalysis, (ii) similar CO2uptake in experimentsextracting CO2from dry simulated air experiments, and(iii) improved activity in acid–base bifunctional catalysiscompared to traditional amine-grafted materials. The effects of thetype of halide, the initial halide loading, and the total reactiontime on the conversion of the halides to primary amines are explored.Physical and chemical characterizations of the materials show thatthe textural properties of the silica are unaffected by the reactionconditions and that quantitative conversion to primary amines is achievedeven at short reaction times and high initial alkyl halide loadings.Additionally, preliminary 15N solid-state NMR experimentsindicate formation of nitrogen-containing species and demonstratethat the synthesis can be used to create materials useful for investigatingsurface species by NMR spectroscopy. The differences between the materialsprepared via post-grafting amination vs traditional aminosilane graftingare attributed to the slightly increased spacing of the amines synthesizedby amination because the alkylhalosilanes are initially better spacedon the silica surface after grafting, whereas the aminosilanes likelycluster to a greater extent when grafted on the silica surface. Aslight increase in amine spacing allows for more effective amine–silanolinteractions in cooperative catalysis without reducing the amine efficiencyin CO2uptake under the conditions used here. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is characterized by clonal expansion of malignant plasma cells in the bone marrow (BM). Despite the significant advances in treatment, MM is still a fatal malignancy. This is mainly due to the supportive role of the BM microenvironment in differentiation, migration, proliferation, survival, and drug resistance of the malignant plasma cells. The BM microenvironment is composed of a cellular compartment (stromal cells, osteoblasts, osteoclasts, endothelial cells, and immune cells) and a non-cellular compartment. In this review, we discuss the interaction between the malignant plasma cell and the BM microenvironment and the strategy to target them. [ABSTRACT FROM AUTHOR]

Objectives Diffusion-weighted imaging with background body signal suppression (DWIBS) provides both qualitative and quantitative imaging of breast lesions and are usually performed before contrast material injection (CMI). This study aims to assess whether the administration of gadolinium significantly affects DWIBS imaging. Methods 200 patients were prospectively evaluated by MRI with STIR, TSE-T2, pre-CMI DWIBS, contrast enhanced THRIVE-T1 and post-CMI DWIBS sequences. Pre and post-CMI DWIBS were analyzed searching for the presence of breast lesions and calculating the ADC value. ADC values of ≤ 1.44 × 10 - 3 mm 2 /s were considered suspicious for malignancy. This analysis was then compared with the histological findings. Sensitivity, specificity, diagnostic accuracy (DA), positive predictive value (PPV) and negative (NPV) were calculated for both sequences and represented by ROC analysis. Pre and post-CMI ADC values were compared by using the paired t test. Results In 150/200 (59%) patients, pre and post-CMI DWIBS indicated the presence of breast lesions, 53 (35%) with ADC values of > 1.44 × 10 - 3 mm 2 /s and 97 (65%) with ADC ≤ 1.44 × 10 - 3 mm 2 /s. Pre-CMI and post-DWIBS sequences obtained the same sensitivity, specificity, DA, PPV and NPV values of 97%, 83%, 89%, 79% and 98%. The mean ADC value of benign lesions was 1.831 ± 0.18 × 10 - 3 mm 2 /s before and 1.828 ± 0.18 × 10 - 3 mm 2 /s after CMI. The mean ADC value of the malignant lesions was 1.146 ± 0.16 × 10 - 3 mm 2 /s before and 1.144 ± 0.16 × 10 - 3 mm 2 /s after CMI. No significant difference was found between pre and post CMI ADC values (p > 0.05). Conclusion DWIBS imaging is not influenced by CMI. Breast MR protocol could be modified by placing DWIBS after dynamic contrast enhanced sequences in order to maximize patient cooperation. [ABSTRACT FROM AUTHOR]

Direct catalytic CH bond functionalization is a key challenge in synthetic chemistry, with many popular CH activation methodologies involving precious-metal catalysts. In recent years, iron catalysts have emerged as a possible alternative to the more common precious-metal catalysts, owing to its high abundance, low cost, and low toxicity. However, iron catalysts are plagued by two key factors: the ligand cost and the low turnover numbers (TONs) typically achieved. In this work, two approaches are presented to functionalize the popular N1, N2-dimethyl- N1, N2-bis(pyridin-2-ylmethyl)ethane-1,2-diamine (BPMEN) ligand, so that it can be supported on porous silica or polymer resin supports. Four new catalysts are prepared and evaluated in an array of catalytic CH functionalization reactions by using cyclohexane, cyclohexene, cyclooctane, adamantane, benzyl alcohol, and cumene with aqueous hydrogen peroxide. Catalyst recovery and recycling is demonstrated by using supported catalysts, which allows for a modest increase in the TON achieved with these catalysts. [ABSTRACT FROM AUTHOR]

Discusses the importance of social interest for married couples. Need for useful cooperation; Extension of one's self to maximize the other's well being; Embodiment of empathy, understanding and a sense of belonging; Supplying of emotional necessities through sustenance caring; Support for partner's growth; Respect for uniqueness and dignity of the other person.

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Italian Ministry of Health Background Calcific aortic valve stenosis (CAVS) is the most common heart valve disease that affects 3% of the population. CAVS is a progressive, multifactorial disorder driven by several cellular and molecular pathological processes. Currently, there is no pharmacological therapy able to prevent CAVS progression. Little is known about the sex-related difference in molecular mechanisms. Recent studies reported that men showed a higher aortic valve calcium load than women, which in turn, developed more fibrosis in the stenotic aortic valve leaflets. Hence, it has been hypothesized that the mechanisms underlying CAVS progression could be different between the two sexes. Purpose To investigate sex-differences in CAVS molecular pathways, finding new sex-related pharmacological targets. Methods Valve interstitial cells (VIC) were isolated from 26 patients who underwent aortic valve replacement for aortic valve stenosis. RNA, extracted from VICs, was sequenced by third generation sequencing technology. We performed pro-fibrotic (TGFβ) treatment for 5 days and we evaluated soluble collagen expression by a colorimetric assay and αSMA expression by western blot. We evaluated extracellular calcium extent by a colorimetric assay on VICs exposed to pro-calcific (inorganic phosphate) medium for 7 days. We assessed the mitochondrial damage with mitoSOX staining by Imagestream. Results The gene expression analysis from sequenced VICs revealed 65 genes upregulated in men and 89 genes upregulated in women. The functional analysis showed that the TGFβ signaling resulted enriched in woman VICs, while the mitochondrial related genes were upregulated in man VICs. Only woman VICs secreted higher amount of collagen under TGFβ treatment respect to the untreated (1.22±0.03 fold change (FC) vs. untreated, p<0.001). αSMA expression (marker of VICs activation) was significantly higher both in men and women exposed to different concentrations of TGFβ (TGFβ 5ng/ml: 1.88±0.34 in men and 2.66±0.32 in women, FC vs. untreated, p=0.003 and p<0.0001, respectively; TGFβ 10ng/ml: 2.96±0.55 in men and 2.16±0.35 in women, FC vs. untreated, p=0.0003 and p=0.0006, respectively). The calcification potential of VICs exposed to pro-calcific medium was higher in men than in women (8.23±0.45 vs. 4.69±0.59 FC vs. untreated, respectively, p<0.0001). The mitochondrial superoxide formation in man VICs was higher than in woman VICs at steady state (51.0±2.1% vs. 29.5±0.9% of positive cells, respectively, p<0.0001) Conclusion CAVS progression seems to be driven by sex-dependent molecular pathways activation. In particular, pro-fibrotic pathways are upregulated in women, while pro-calcific pathways and mitochondrial damage in men. Our data pave the way to sex-dependent pharmacological target research, aiming to treat CAVS patients. [ABSTRACT FROM AUTHOR]

Proline-rich tyrosine kinase 2 (Pyk2) is a member of the focal adhesion kinase family that has been recently linked to tumor development. However, its role in modulating multiple myeloma (MM) biology and disease progression remains unexplored. We first demonstrated that patients with MM present with higher expression of Pyk2 compared with healthy individuals. By using loss-of-function approaches, we found that Pyk2 inhibition led to reduction of MM tumor growth in vivo as well as decreased cell proliferation, cellcycle progression, and adhesion ability in vitro. In turn, overexpression of Pyk2 promoted the malignant phenotype, substantiated by enhanced tumorgrowth and reduced survival. Mechanistically, inhibition of Pyk2 reduced activation of Wnt/β-catenin signaling by destabilizing β-catenin, leading to downregulation of c-Myc and Cyclin D1. Furthermore, treatment of MM cells with the FAK/Pyk2 inhibitor VS-4718 effectively inhibited MM cell growth both in vitro and in vivo. Collectively, our findings describe the tumor-promoting role of Pyk2 in MM, thus providing molecular evidence for a novel tyrosine kinase inhibitor as a new therapeutic option in MM. [ABSTRACT FROM AUTHOR]

Tumor associated macrophages (TAMs) are a rich source of pro-angiogenic cytokines and growth factors, and a relationship between the TAMs content, the rate of tumor growth and the extent of vascularization has been shown in several tumors. In this article, we have summarized the literature and our data concerning the involvement of TAMs in angiogenesis occurring in multiple myeloma. Finally, therapeutic aspects concerning the potential role of molecules which inhibit macrophage recruitment in the tumor side are also discussed. [ABSTRACT FROM AUTHOR]

The mammalian target of rapamycin ( mTOR) plays an important role in the regulation of protein translation, cell growth and metabolism. The mTOR protein forms two distinct multi-subunit complexes: mTORC1 and mTORC2. The mTORC1 complex is activated by diverse stimuli, such as growth factors, nutrients, energy and stress signals; and essential signalling pathways, such as PI3 K and MAPK, in order to control cell growth, proliferation and survival. mTORC1 also activates S6 K1 and 4 EBP1, which are involved in mRNA translation. The mTORC2 complex is resistant to rapamycin inhibitory activity and is generally insensitive to nutrient- and energy-dependent signals. It activates PKC-α and Akt and regulates the actin cytoskeleton. Deregulation of the mTOR-signalling pathway ( PI3 K amplification/mutation, PTEN loss of function, Akt overexpression, and S6 K1, 4 EBP1 and e IF4 E overexpression) is common in cancer, and alterations in components of the mTOR pathway have a major role in tumour progression. Therefore, mTOR is an appealing therapeutic target in many tumours. Here we summarize the upstream regulators and downstream effectors of the mTORC1 and mTORC2 pathways, the role of mTOR in cancer, and the potential therapeutic values and issues related to the novel agents targeting the mTOR-signalling pathway. [ABSTRACT FROM AUTHOR]

The mammalian target of rapamycin (mTOR) plays an important role in the regulation of protein translation, cell growth and metabolism. The mTOR protein forms two distinct multi-subunit complexes: mTORC1 and mTORC2. The mTORC1 complex is activated by diverse stimuli, such as growth factors, nutrients, energy and stress signals; and essential signalling pathways, such as PI3K and MAPK, in order to control cell growth, proliferation and survival. mTORC1 also activates S6K1 and 4EBP1, which are involved in mRNA translation. The mTORC2 complex is resistant to rapamycin inhibitory activity and is generally insensitive to nutrient- and energy-dependent signals. It activates PKC-α and Akt and regulates the actin cytoskeleton. Deregulation of the mTOR-signalling pathway (PI3K amplification/mutation, PTEN loss of function, Akt overexpression, and S6K1, 4EBP1 and eIF4E overexpression) is common in cancer, and alterations in components of the mTOR pathway have a major role in tumour progression. Therefore, mTOR is an appealing therapeutic target in many tumours. Here we summarize the upstream regulators and downstream effectors of the mTORC1 and mTORC2 pathways, the role of mTOR in cancer, and the potential therapeutic values and issues related to the novel agents targeting the mTOR-signalling pathway. [ABSTRACT FROM AUTHOR]

Tumor-associated neovasculature is a critical therapeutic target; however, despite significant progress made in the clinical efficacy of anti-vessel drugs, the effect of these agents remains transient: over time, most patients develop resistance, which inevitably leads to tumor progression. To develop more effective treatments, it is imperative that we better understand the mechanisms involved in tumor vessel formation, how they participate to the tumor progression and metastasis, and the best way to target them. Several mechanisms contribute to the formation of tumor-associated vasculature: i) neoangiogenesis; ii) vascular co-option; iii) mosaicism; iv) vasculogenic mimicry, and v) postnatal vasculogenesis. These mechanisms can also play a role in the development of resistance to anti-angiogenic drugs, and could serve as targets for designing new anti-vascular molecules to treat solid as well as hematological malignancies. Bone marrow-derived endothelial progenitor cell (EPC)-mediated vasculogenesis represents an important new target, especially at the early stage of tumor growth (when EPCs are critical for promoting the "angiogenic switch"), and during metastasis, when EPCs promote the transition from micro- to macro-metastases. In hematologic malignancies, the EPC population could be related to the neoplastic clone, and both may share a common ontogeny. Thus, characterization of tumor-associated EPCs in blood cancers may provide clues for more specific anti-vascular therapy that has both direct and indirect anti-tumor effects. Here, we review the role of vasculogenesis, mediated by bone marrow-derived EPCs, in the progression of cancer, with a particular focus on the role of these cells in promoting progression of hematological malignancies. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Diffusion imaging represents a new imaging tool for the diagnosis of breast cancer. This study aims to investigate the role of diffusion-weighted MRI with background body signal suppression (DWIBS) for evaluating breast lesions. Methods: 90 patients were prospectively evaluated by MRI with STIR, TSE-T2, contrast enhanced THRIVE-T1 and DWIBS sequences. DWIBS were analyzed searching for the presence of breast lesions and calculating the ADC value. ADC values of ≤1.44×10-3 mm2/s were considered suspicious for malignancy. This analysis was then compared with the histological findings. Sensitivity, specificity, diagnostic accuracy (DA), positive predictive value (PPV) and negative (NPV) were calculated. Results: In 53/90 (59%) patients, DWIBS indicated the presence of breast lesions, 16 (30%) with ADC values of >1.44 and 37 (70%) with ADC≤1.44. The comparison with histology showed 25 malignant and 28 benign lesions. DWIBS sequences obtained sensitivity, specificity, DA, PPV and NPV values of 100, 82, 87, 68 and 100%, respectively. Conclusion: DWIBS can be proposed in the MRI breast protocol representing an accurate diagnostic complement. [Copyright &y& Elsevier]

Abstract: Purpose: The aim of this study is to assess the prevalence, the site and the nature of extra-mammary findings on breast magnetic resonance imaging (MRI) and to determine its accuracy in the characterization of the discovered lesions. Materials and methods: A retrospective review of 308 female patients (mean age 50±20) who underwent breast MRI with 1.5T device was performed. 125 out of 308 (40.5%) had a positive personal history of breast cancer (pre-operative n =80; follow-up n =45), while the remaining 183 without history of breast cancer (high familiar risk for breast cancer n =80; dense breast n =103). All incidental findings were characterized by means of additional imaging (US; Bone scintigraphy-MRI; CT-PET-CT). Results: 59 incidental findings were found in 53/308 (17%) examined patients. 9/59 incidental findings (15%) were confirmed to be malignant while the remaining 50/59 (84%) benign. The most common site was the liver (33/59; 55.8%), followed by the lung (6/59; 10.1%), bone (6/59; 10.1%), diaphragm (6/59; 10.1%) spleen (3/59; 5%), kidney (2/59; 3.4%), gall bladder (1/5; 1.5%), ascending aorta (1/59; 1.5%), thyroid (1/59; 1.5%). The incidence of malignant incidental findings resulted to be higher in the group of patients with personal breast cancer (36%) than in the other one (8%). By comparing MRI findings with the additional definitive imaging tools, breast MRI allowed a correct diagnosis in 58/59 cases with a diagnostic accuracy value of 98%. Conclusion: Incidental extramammary findings on breast MRI are common. Benign lesions represent the most frequent findings, however malignant ones need to be searched especially in patients with personal history of breast cancer because they could influence the clinical patient management. Breast MRI can characterize incidental findings with high accuracy value. [Copyright &y& Elsevier]

Objective: To assess the performance of the Nursing Activities Score in a pediatric intensive care unit, compare its scores expressed as time spent on nursing activities to the corresponding ones calculated using the Simplified Therapeutic Intervention Scoring System, and correlate the results obtained by both instruments with severity, morbidity and mortality. Methods: Prospective, observational, and analytical cohort study conducted at a type III general pediatric intensive care unit. The study participants were all the children aged 29 days to 12 years admitted to the investigated pediatric intensive care unit from August 2008 to February 2009. Results: A total of 545 patients were studied, which corresponded to 2,951 assessments. The average score of the Simplified Therapeutic Intervention Scoring System was 28.79±10.37 (915±330 minutes), and that of the Nursing Activities Score was 55.6±11.82 (802±161 minutes). The number of minutes that resulted from the conversion of the Simplified Therapeutic Intervention Scoring System score was higher compared to that resulting from the Nursing Activities Score for all the assessments (p<0.001). The correlation between the instruments was significant, direct, positive, and moderate (R=0.564). Conclusions: The agreement between the investigated instruments was satisfactory, and both instruments also exhibited satisfactory discrimination of mortality; for that purpose, the best cutoff point was 16 nursing hours/patient day. [ABSTRACT FROM AUTHOR]