The ObReco-360°: a new ecological tool to memory assessment using 360° immersive technology

Virtual Reality - One important feature of a neuropsychological test is its ecological validity, which defines how much patients’ test scores are linked to real-life functioning. However,...     

A rapid interview protocol supporting patient-centered quality improvement: hearing the parent's voice in a pediatric cancer unit

BACKGROUND: The Institute of Medicine's 2001 report on quality delimits six dimensions of optimal care: safety, effectiveness, efficiency, timeliness, patient centeredness, and equity. In fall 2001 parents of pediatric cancer patients were interviewed to determine how well they thought these dimensions were addressed with respect to medication administration. Immediate goals were to identify system weaknesses and devise strategies to prevent future errors. A higher-order goal was to develop and demonstrate a model protocol for rapid-cycle interview assessments. METHODS: Hematology/oncology directors worked with a research expert to develop a semistructured interview protocol. After training, which included directed reading, oral instruction, and role-playing, a convenience sample of 20 English- and Spanish-speaking parents of inpatients was recruited. Parents were asked to characterize current medication administration practices and to describe problems that they had experienced or witnessed. Rapid content analysis techniques were used to identify issues of importance to the parents. FINDINGS: Parents' medication concerns centered on their children's comfort. Parents called for communication improvements, standardization of all nursing procedures and techniques, and a guide or an outline providing a clear understanding of what to expect when and from whom. Viewing these concerns in relation to the Institute of Medicine's quality domains allowed the department to frame an improvement action plan aligned with organizational and national priorities. IMPLICATIONS: With good supervision and limited focused training, inexperienced staff can successfully administer semistructured qualitative interviews and help analyze findings for rapid cycle improvement purposes. The protocol can be adapted for use in organizations interested in rapid qualitative assessments of patient and parent preferences.     

Self‐welding 1‐butene/ethylene copolymers from metallocene catalysts: Structure,morphology, and mechanical properties

Samples of random copolymers consisting of 1‐butene modified with a low ethylene content (4, 5, 8% by weight) produced with metallocene catalysts were studied to elucidate the polymorphic behavior of this new class of materials and to characterize them from a structural, morphological, and mechanical point of view. The samples cooled down from the melt are in amorphous phase and crystallize in a mixture of form I and I′ or in pure form I′ with aging time, according to the C2 content. Infrared and nuclear magnetic resonance spectroscopy, X‐ray diffraction and microscopic techniques were used to follow the changes of the material with aging time and to correlate the structural and morphological behavior with the peculiar mechanical properties that differentiate the samples with increasing C2 content. The presence, in the aged samples with higher C2 content, of the pure form I′ induces the peculiar ability to self‐welding and these copolymers combine high flexibility with good elasticity and ductility and can be processed directly or used as modifying agents in polymers. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40119.     

Controlling the Er content of porous silicon using the doping current intensity

The results of an investigation on the Er doping of porous silicon are presented. Electrochemical impedance spectroscopy, optical reflectivity, and spatially resolved energy dispersive spectroscopy (EDS) coupled to scanning electron microscopy measurements were used to investigate on the transient during the first stages of constant current Er doping. Depending on the applied current intensity, the voltage transient displays two very different behaviors, signature of two different chemical processes. The measurements show that, for equal transferred charge and identical porous silicon (PSi) layers, the applied current intensity also influences the final Er content. An interpretative model is proposed in order to describe the two distinct chemical processes. The results can be useful for a better control over the doping process.

PACS

81.05.Rm; 82.45.Rr     

Colorectal Cancer Apoptosis Induced by Dietary δ-Valerobetaine Involves PINK1/Parkin Dependent-Mitophagy and SIRT3

Understanding the mechanisms of colorectal cancer progression is crucial in the setting of strategies for its prevention. δ-Valerobetaine (δVB) is an emerging dietary metabolite showing cytotoxic activity in colon cancer cells via autophagy and apoptosis. Here, we aimed to deepen current knowledge on the mechanism of δVB-induced colon cancer cell death by investigating the apoptotic cascade in colorectal adenocarcinoma SW480 and SW620 cells and evaluating the molecular players of mitochondrial dysfunction. Results indicated that δVB reduced cell viability in a time-dependent manner, reaching IC50 after 72 h of incubation with δVB 1.5 mM, and caused a G2/M cell cycle arrest with upregulation of cyclin A and cyclin B protein levels. The increased apoptotic cell rate occurred via caspase-3 activation with a concomitant loss in mitochondrial membrane potential and SIRT3 downregulation. Functional studies indicated that δVB activated mitochondrial apoptosis through PINK1/Parkin pathways, as upregulation of PINK1, Parkin, and LC3B protein levels was observed (p < 0.0001). Together, these findings support a critical role of PINK1/Parkin-mediated mitophagy in mitochondrial dysfunction and apoptosis induced by δVB in SW480 and SW620 colon cancer cells.     

Whence CRIPTO: The Reemergence of an Oncofetal Factor in ‘Wounds’ That Fail to Heal

There exists a set of factors termed oncofetal proteins that play key roles in ontogeny before they decline or disappear as the organism’s tissues achieve homeostasis, only to then re-emerge in cancer. Although the unique therapeutic potential presented by such factors has been recognized for more than a century, their clinical utility has yet to be fully realized1. This review highlights the small signaling protein CRIPTO encoded by the tumor derived growth factor 1 (TDGF1/Tdgf1) gene, an oft cited oncofetal protein whose presence in the cancer literature as a tumor promoter, diagnostic marker and viable therapeutic target continues to grow. We touch lightly on features well established and well-reviewed since its discovery more than 30 years ago, including CRIPTO’s early developmental roles and modulation of SMAD2/3 activation by a selected set of transforming growth factor β (TGF-β) family ligands. We predominantly focus instead on more recent and less well understood additions to the CRIPTO signaling repertoire, on its potential upstream regulators and on new conceptual ground for understanding its mode of action in the multicellular and often stressful contexts of neoplastic transformation and progression. We ask whence it re-emerges in cancer and where it ‘hides’ between the time of its fetal activity and its oncogenic reemergence. In this regard, we examine CRIPTO’s restriction to rare cells in the adult, its potential for paracrine crosstalk, and its emerging role in inflammation and tissue regeneration—roles it may reprise in tumorigenesis, acting on subsets of tumor cells to foster cancer initiation and progression. We also consider critical gaps in knowledge and resources that stand between the recent, exciting momentum in the CRIPTO field and highly actionable CRIPTO manipulation for cancer therapy and beyond.     

SGLT2is and Renal Protection: From Biological Mechanisms to Real-World Clinical Benefits

In recent years, following the publication of results from several RCTs, first on cardiovascular and more recently on renal outcomes, SGLT2is have become the standard of care to prevent diabetic kidney disease and slow its progression. This narrative review focuses on biological mechanisms, both renal and extrarenal, underlying kidney protection with SGLT2is. Furthermore, data from cardiovascular as well as renal outcome trials, mostly conducted in diabetic patients, are presented and discussed to provide an overview of current uses as well as the future therapeutic potential of these drugs.     

Inflammatory Cutaneous Diseases in Renal Transplant Recipients

Kidney transplant recipients frequently suffer from skin infections and malignancies, possibly due to the effects of long-term immunosuppressive therapy. While the relationships between immunosuppression and these pathological conditions have been widely investigated, little is known about the relative incidence and characteristics of inflammatory skin diseases in this type of patient. In this study, we analyze the incidence of a number of inflammatory cutaneous diseases in a cohort of patients who underwent kidney transplantation. Although our study shows a relatively low incidence of these pathologies in transplanted patients—in agreement with the general action of immunosuppressant therapies in reducing inflammation—we scored a different efficacy of the various immunosuppressive regimens on inflammatory and autoimmune skin diseases. This information can be key for designing immunosuppressive regimens and devising accurate follow-up protocols.     

Bioreduction of α‐Acetoxymethyl Enones: Proposal for an SN2′ Mechanism Catalyzed by Enereductase

(Z)‐3‐Acetoxymethyl‐4‐R‐3‐buten‐2‐ones (R=aryl, alkyl) and (Z)‐3‐methyl‐4‐R‐3‐buten‐2‐ones (R=aryl) were synthesized and submitted to reduction by the yeast Saccharomyces cerevisiae producing the (R)‐ and (S)‐4‐R‐3‐methybutan‐2‐ones, respectively. This stereochemistry control strategy was applied in the syntheses of (R)‐ and (S)‐Tropional® with moderate to high enantiomeric excesses. Other (Z)‐3‐acyloxymethyl‐4‐phenyl‐3‐buten‐2‐ones showed similar behavior to the (Z)‐3‐acetoxymethyl counterpart, and the acylated Morita–Baylis–Hillman adduct 1‐acetoxy‐2‐methylene‐1‐phenylbutan‐3‐one produced a mixture of products, with and without the acetoxy group, via three different reaction pathways. In addition to experiments employing whole cells, those in which isolated enereductases were used suggested that the main pathway through which the loss of the acetoxy group occurs during the biocatalytic cascade is an S_N2′‐type reaction, rather than formal hydrogen addition followed by acetic acid elimination. Finally, related ethyl enones were reduced enantioselectively by the yeast Candida albicans, producing both (R)‐ and (S)‐reduction products, depending on the presence of the acetoxy group in the starting material.

     

Tracking Hidden Binding Pockets Along the Molecular Recognition Path of l-Trp to Indoleamine 2,3-Dioxygenase 1

Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the oxidative cleavage of l -Tryptophan (l -Trp) to yield N-formyl-kynurenine in the first and rate limiting step of the kynurenine pathway. Bioactive metabolites, involved in the regulation of important immunological responses and neurological processes, are then produced by downstream enzymes along the pathway. Inhibitors of IDO1 are being designed and developed as therapeutic agents for immuno-oncology. In this work, we investigated the molecular recognition path of l -Trp to IDO1, integrating biophysical methods with supervised molecular dynamics (suMD) and mutagenesis experiments. Results allowed disclosing for the first time high and low dissociation constants of l -Trp to IDO1, and the presence of a metastable interaction site located at the upper part of a channel whose borders are defined by the EF-loop and the C-terminal part of the JK-loop. Collectively, our results provide new clues for the design of next-generation IDO1 ligands.