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Antisynthetase syndrome (ASSD) is an autoimmune disease characterized by the positivity of autoantibodies against different aminoacyl transfer RNA (tRNA) synthetases. Morbidity and mortality of this disease are highly affected by interstitial lung disease (ILD) which is present in about 80% of patients. In this study, we investigated possible differences in 84 immune-related circulating miRNAs between ASSD patients with and without ILD; we enrolled 15 ASSD patients, 11 with ILD (ILD+) and 4 without ILD (ILD-), and 5 patients with idiopathic pulmonary fibrosis (IPF) as an additional control group. All patients were at disease onset and not on therapy at the time of inclusion. Differentially expressed miRNAs were identified in plasma-derived exosomes, using an miRNA PCR array (MIHS-111ZG, Qiagen, Hilden, Germany); miR-30a-5p and miR-29c-3p were upregulated in ASSD-ILD patients compared to patients without lung involvement (adjusted p-value < 0.05). IPF patients showed higher miR-29c-3p expression levels with respect to both ASSD and ASSD-ILD (p = 0.0005), whereas levels of miR-30a-5p were not different. miR-29c-3p and miR-30a-5p are overexpressed in ASSD-ILD+ patients compared with ILD−. These miRNAs are involved in the regulation of inflammation and fibrosis through their action on NF-κB and TGF-β1. Although the mechanistic role of these miRNAs in ASSD-ILD development has to be elucidated, we suggest that their exosome levels could be useful in identifying patients at risk of ILD.

Background: Smell and taste disturbances are among the most frequent neurological symptoms in patients with COVID-19. A concomitant impairment of the trigeminal nerve has been suggested in subjects with olfactory dysfunction, although it has not been confirmed with objective measurement techniques. In this study, we explored the trigeminal function and its correlations with clinical features in COVID-19 patients with impaired smell perception using electrophysiological testing., Methods: We enrolled 16 consecutive patients with mild COVID-19 and smell impairment and 14 healthy controls (HCs). Olfactory and gustatory symptoms were assessed with self-reported questionnaires. Electrophysiological evaluation of the masseter inhibitory reflex (MIR) and blink reflex (BR) was carried out to test the trigeminal function and its connections within the brainstem., Results: Masseter inhibitory reflex (MIR) analysis revealed higher latency of ipsilateral and contralateral early silent period in patients when compared with HCs. No significant differences between groups were detected as regards the duration of the early and late silent period. However, several patients showed a prolonged duration of the early silent period. BR evaluation disclosed only an increased amplitude of early components in patients., Conclusions: Patients with COVID-19 and smell impairment show a subclinical trigeminal nerve impairment. Trigeminal alterations mainly involve the oligosynaptic pathway, as a result of either direct viral damage or secondary neuroinflammation of the peripheral trigeminal fibers, whereas the polysynaptic ponto-medullary circuits seem to be spared. The prolonged duration of the early silent period and the increased amplitude of early BR response might reflect a compensatory upregulation of the trigeminal function as a consequence of the olfactory dysfunction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cosentino, Maiorano, Todisco, Prunetti, Antoniazzi, Tammam, Quartesan, Lettieri, De Icco, Corsico, Benazzo, Pisani, Tassorelli and Alfonsi.)

Background: PAP is an ultra-rare respiratory syndrome characterized by the accumulation of surfactant within the alveoli. Whole lung lavage (WLL) is the current standard of care of PAP, however it is not a standardized procedure and the total amount of fluid used to wash each lung is still debated. Considering ICU hospitalization associated risks, a "mini-WLL" with anticipated manual clapping and reduced total infusion volume and has been proposed in our center. The aim of the study is to retrospectively analyze the efficacy of mini-WLL compared to standard WLL at the Pavia center., Methods: 13 autoimmune PAP patients eligible for WLL were included: 7 patients were admitted to mini-WLL (9 L total infusion volume for each lung) and 6 patients underwent standard WLL (14 L of infusion volume). Functional data (VC%, FVC%, TLC%, DLCO%) and alveolar-arterial gradient values (A-aO2) were collected at the baseline and 1, 3, 6, 12, 18 months after the procedure., Results: A statistically significant improvement of VC% (p = 0.013, 95%CI 3.49-30.19), FVC% (p = 0.016, 95%CI 3.37-32.09), TLC% (p = 0.001, 95%CI 7.38-30.34) was observed in the mini-WLL group in comparison with the standard WLL group, while no significant difference in DLCO% and A-aO2 mean values were reported., Conclusion: Mini-WLL has demonstrated higher efficacy in ameliorating lung volumes, suggesting that a lower infusion volume is sufficient to remove the surfactant accumulation and possibly allows a reduced mechanical insult of the bronchi walls and the alveoli. However, no statistically significant differences were found in terms of DLCO% and Aa-O2., (© 2022. The Author(s).)

Background and Objective: Translational research is a source of continuous innovation in medicine, more particularly for clinical research on new treatment modalities in idiopathic pulmonary fibrosis (IPF) patients. However, the heterogeneity of the disease is well recognized, and different pathological and molecular settings have been identified. The molecular mechanisms by which IPF proceeds in time and space remains poorly understood. Although some IPF features are reminiscent of cancer, the dynamics of malignant divergent clonal selective pressure and heterogeneity clearly differ from those occurring in IPF. This is reflected in the absence of patient proper selection and stratification to biological agents (pirfenidone, nintedanib) which limit therapeutic efficacy. Consequently, increased costs are related to the clinical management of advanced IPF patients. Steady collaboration and fluid communication between pneumo-oncologists, radiologists and molecular biologists is a clear priority for the correct interpretation of tests and the definition of effective personalized strategies against this orphan disease. The present work aims at providing the most relevant hints shared by cancer and IPF., Methods: A systematic literature review was performed to identify all relevant data. The examined databases were Scopus, Web of Science, Cochrane, Google Scholar, and PubMed. The last search was run on January 5, 2022. We have primarily conducted separated research for lung cancer, IPF, genetics, epigenetics, surgery in IPF and cancer., Key Content and Findings: The data here presented mainly focus on gene mutations, epigenetics and novel therapeutic approaches. Moreover, epidemiology, prognostic variables and in new treatment strategies adopted in patients with IPF and lung cancer are discussed as well., Conclusions: Overall, the findings of this narrative review will be of help in defining the key molecular features that could applied in IPF setting with promising rationale to improve therapy and to better manage those cases carrying IPF and cancer concomitantly., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-21-880/coif). The authors have no conflicts of interest to declare., (2022 Translational Lung Cancer Research. All rights reserved.)

Time-resolved photoluminescence (TRPL) analysis is often performed to assess the qualitative features of semiconductor crystals using predetermined functions (e.g., double- or multi-exponentials) to fit the decays of PL intensity. However, in many cases-including the notable case of interband PL in direct gap semiconductors-this approach just provides phenomenological parameters and not fundamental physical quantities. In the present work, we highlight that within a properly chosen range of laser excitation, the TRPL of zinc oxide (ZnO) bulk crystals can be described with excellent precision with second-order kinetics for the total recombination rate. We show that this allows us to define an original method for data analysis, based on evaluating the "instantaneous" recombination rate that drives the initial slope of the decay curves, acquired as a function of the excitation laser fluence. The method is used to fit experimental data, determining useful information on fundamental quantities that appear in the second-order recombination rate, namely the PL (unimolecular) lifetime, the bimolecular recombination coefficient, the non-radiative lifetime and the equilibrium free-carrier concentration. Results reasonably close to those typically obtained in direct gap semiconductors are extracted. The method may represent a useful tool for gaining insight into the recombination processes of a charge carrier in ZnO, and for obtaining quantitative information on ZnO excitonic dynamics.

In this study, we report on an easy-to-assemble amperometric electrochemical biosensor incorporating thylakoid membranes for the detection of photosynthetic herbicides. These molecules interfere with the light-induced photosynthetic electron transport occurring at the level of the photosystems within the thylakoid membranes, thus reducing the current of the associated bioelectrode. Thylakoid membranes isolated from pea plants were adsorbed directly on a bare carbon paper working electrode and placed in the measurement cell in the absence of any electrochemical mediator, obtaining a fully environmental-friendly biodevice capable of photocurrent densities up to 14 μA/cm 2 . Three photosynthetic herbicides inhibiting Photosystem II and belonging to different chemical classes, namely diuron, terbuthylazine and metribuzin, were detected by measuring the electrode photocurrent, which decreased reproducibly in a concentration-dependent manner in a range between 10 -7 - 5 × 10 -5  M of each herbicide. The limit of detection for the three herbicides was between 4-6 × 10 -7  M. Storage stability tests revealed for the biosensor a half-life longer than 15 days at 4 °C and full stability up to 4 months at -80 °C. This study provides a simple, environmental-friendly and cost-effective procedure for the fabrication of a mediatorless carbon paper-based electrochemical biosensor characterized by high photocurrents, long storage stability, reproducible detections and good sensitivity., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: To define the clinical spectrum time-course and prognosis of non-Asian patients positive for anti-MDA5 antibodies., Methods: We conducted a multicentre, international, retrospective cohort study., Results: 149 anti-MDA5 positive patients (median onset age 53 years, median disease duration 18 months), mainly females (100, 67%), were included. Dermatomyositis (64, 43%) and amyopathic dermatomyositis (47, 31%), were the main diagnosis; 15 patients (10%) were classified as interstitial pneumonia with autoimmune features (IPAF) and 7 (5%) as rheumatoid arthritis. The main clinical findings observed were myositis (84, 56%), interstitial lung disease (ILD) (108, 78%), skin lesions (111, 74%), and arthritis (76, 51%). The onset of these manifestations was not concomitant in 74 cases (50%). Of note, 32 (21.5%) patients were admitted to the intensive care unit for rapidly progressive-ILD, which occurred in median 2 months from lung involvement detection, in the majority of cases (28, 19%) despite previous immunosuppressive treatment. One-third of patients (47, 32% each) was ANA and anti-ENA antibodies negative and a similar percentage was anti-Ro52 kDa antibodies positive. Non-specific interstitial pneumonia (65, 60%), organising pneumonia (23, 21%), and usual interstitial pneumonia-like pattern (14, 13%) were the main ILD patterns observed. Twenty-six patients died (17%), 19 (13%) had a rapidly progressive-ILD., Conclusions: The clinical spectrum of the anti-MDA5 antibodies-related disease is heterogeneous. Rapidly-progressive ILD deeply impacts the prognosis also in non-Asian patients, occurring early during the disease course. Anti-MDA5 antibody positivity should be considered even when baseline autoimmune screening is negative, anti-Ro52 kDa antibodies are positive, and radiology findings show a NSIP pattern.

Malignant Pleural Mesothelioma (MPM) is a rare and aggressive neoplasm of the pleural mesothelium, mainly associated with asbestos exposure and still lacking effective therapies. Modern targeted biological strategies that have revolutionized the therapy of other solid tumors have not had success so far in the MPM. Combination immunotherapy might achieve better results over chemotherapy alone, but there is still a need for more effective therapeutic approaches. Based on the peculiar disease features of MPM, several strategies for local therapeutic delivery have been developed over the past years. The common rationale of these approaches is: (i) to reduce the risk of drug inactivation before reaching the target tumor cells; (ii) to increase the concentration of active drugs in the tumor micro-environment and their bioavailability; (iii) to reduce toxic effects on normal, non-transformed cells, because of much lower drug doses than those used for systemic chemotherapy. The complex interactions between drugs and the local immune-inflammatory micro-environment modulate the subsequent clinical response. In this perspective, the main interest is currently addressed to the development of local drug delivery platforms, both cell therapy and engineered nanotools. We here propose a review aimed at deep investigation of the biologic effects of the current local therapies for MPM, including cell therapies, and the mechanisms of interaction with the tumor micro-environment.

Chronic lung allograft dysfunction (CLAD) and interstitial lung disease associated with collagen tissue diseases (CTD-ILD) are two end-stage lung disorders in which different chronic triggers induce activation of myo-/fibroblasts (LFs). Everolimus, an mTOR inhibitor, can be adopted as a potential strategy for CLAD and CTD-ILD, however it exerts important side effects. This study aims to exploit nanomedicine to reduce everolimus side effects encapsulating it inside liposomes targeted against LFs, expressing a high rate of CD44. PEGylated liposomes were modified with high molecular weight hyaluronic acid and loaded with everolimus (PEG-LIP(ev)-HA400kDa). Liposomes were tested by in vitro experiments using LFs derived from broncholveolar lavage (BAL) of patients affected by CLAD and CTD-ILD, and on alveolar macrophages (AM) and lymphocytes isolated, respectively, from BAL and peripheral blood. PEG-LIP-HA400kDa demonstrated to be specific for LFs, but not for CD44-negative cells, and after loading everolimus, PEG-LIP(ev)-HA400kDa were able to arrest cell cycle arrest and to decrease phospho-mTOR level. PEG-LIP(ev)-HA400kDa showed anti-inflammatory effect on immune cells. This study opens the possibility to use everolimus in lung fibrotic diseases, demonstrating that our lipids-based vehicles can vehicle everolimus inside cells exerting the same drug molecular effect, not only in LFs, but also in immune cells.

Abstract: Central giant cell granuloma (CGCG) is a relatively uncommon benign bony lesion accounting for approximately 7% of all non-neoplastic lesions of the jaw. The clinical behavior of CGCG can vary from a slow-growing, painless lesion to fast-growing and locally destructive. When such a lesion involves the mandible, this can be quite debilitating for the patient, inhibiting oral intake and requiring an extensive resection and bone graft reconstruction. The authors present a case of effectively decreasing the surgical morbidity associated with a large and rapidly growing CGCG of the mandible in a pediatric patient. Neoadjuvant immunotherapy with denosumab (human monoclonal antibody) facilitated treatment of the tumor without the need for a large resection which would have otherwise necessitated a vascularized bony mandibular reconstruction. Consideration of neoadjuvant medical management of CGCG as the primary treatment is advocated., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 by Mutaz B. Habal, MD.)

Photocatalysis based technologies have a key role in addressing important challenges of the ecological transition, such as environment remediation and conversion of renewable energies. Photocatalysts can in fact be used in hydrogen (H 2 ) production (e.g., via water splitting or photo-reforming of organic substrates), CO 2 reduction, pollution mitigation and water or air remediation via oxidation (photodegradation) of pollutants. Titanium dioxide (TiO 2 ) is a "benchmark" photocatalyst, thanks to many favorable characteristics. We here review the basic knowledge on the charge carrier processes that define the optical and photophysical properties of intrinsic TiO 2 . We describe the main characteristics and advantages of TiO 2 as photocatalyst, followed by a summary of historical facts about its application. Next, the dynamics of photogenerated electrons and holes is reviewed, including energy levels and trapping states, charge separation and charge recombination. A section on optical absorption and optical properties follows, including a discussion on TiO 2 photoluminescence and on the effect of molecular oxygen (O 2 ) on radiative recombination. We next summarize the elementary photocatalytic processes in aqueous solution, including the photogeneration of reactive oxygen species (ROS) and the hydrogen evolution reaction. We pinpoint the TiO 2 limitations and possible ways to overcome them by discussing some of the "hottest" research trends toward solar hydrogen production, which are classified in two categories: (1) approaches based on the use of engineered TiO 2 without any cocatalysts. Discussed topics are highly-reduced "black TiO 2 ", grey and colored TiO 2 , surface-engineered anatase nanocrystals; (2) strategies based on heterojunction photocatalysts, where TiO 2 is electronically coupled with a different material acting as cocatalyst or as sensitizer. Examples discussed include TiO 2 composites or heterostructures with metals (e.g., Pt-TiO 2 , Au-TiO 2 ), with other metal oxides (e.g., Cu 2 O, NiO, etc.), direct Z-scheme heterojunctions with g-C 3 N 4 (graphitic carbon nitride) and dye-sensitized TiO 2 .

Idiopathic pulmonary fibrosis (IPF) identifies a specific entity characterized by chronic, progressive fibrosing interstitial pneumonia of unknown cause, still lacking effective therapies. Growing evidence suggests that the biologic processes occurring in IPF recall those which orchestrate cancer onset and progression and these findings have already been exploited for therapeutic purposes. Notably, the incidence of lung cancer in patients already affected by IPF is significantly higher than expected. Recent advances in the knowledge of the cancer immune microenvironment have allowed a paradigm shift in cancer therapy. From this perspective, recent experimental reports suggest a rationale for immune checkpoint inhibition in IPF. Here, we recapitulate the most recent knowledge on lung cancer immune stroma and how it can be translated into the IPF context, with both diagnostic and therapeutic implications.

Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy that most commonly affects the pleural lining of the lungs. It has a strong association with exposure to biopersistent fibers, mainly asbestos (80% of cases) and-in specific geographic regions-erionite, zeolites, ophiolites, and fluoro-edenite. Individuals with a chronic exposure to asbestos generally have a long latency with no or few symptoms. Then, when patients do become symptomatic, they present with advanced disease and a worse overall survival (about 13/15 months). The fibers from industrial production not only pose a substantial risk to workers, but also to their relatives and to the surrounding community. Modern targeted therapies that have shown benefit in other human tumors have thus far failed in MPM. Overall, MPM has been listed as orphan disease by the European Union. However, molecular high-throughput profiling is currently unveiling novel biomarkers and actionable targets. We here discuss the natural evolution, mainly focusing on the novel concept of molecular epidemiology. The application of innovative endpoints, quantification of genetic damages, and definition of genetic susceptibility are reviewed, with the ultimate goal to point out new tools for screening of exposed subject and for designing more efficient diagnostic and therapeutic strategies.

Zinc oxide (ZnO) is one of the main functional materials used to realize chemiresistive gas sensors. In addition, ZnO can be grown through many different methods obtaining the widest family of unique morphologies. However, the relationship between the ZnO morphologies and their gas sensing properties needs more detailed investigations, also with the aim to improve the sensor performances. In this work, seven nanoforms (such as leaves, bisphenoids, flowers, needles, etc.) were prepared through simple wet chemical synthesis. Morphological and structural characterizations were performed to figure out their growth mechanisms. Then, the obtained powders were deposited through screen-printing technique to realize thick film gas sensors. The gas sensing behavior was tested toward some traditional target gases and some volatile organic compounds (acetone, acetaldehyde, etc.) and compared with ZnO morphologies. Results showed a direct correlation between the sensors responses and the powders features (morphology and size), which depend on the specific synthesis process. The sensors can be divided in two behavioral classes, following the two main morphology kinds: aggregates of nanocrystals (leaves and bisphenoids), exhibiting best performances versus all tested gases and monocrystal based (stars, needle, long needles, flowers, and prisms).

The proper operation of a fluid power system in terms of efficiency and reliability is directly related to the fluid state; therefore, the monitoring of fluid ageing in real time is fundamental to prevent machine failures. For this aim, an innovative methodology based on fluid vapor analysis through metal oxide (shortened: MOX) gas sensors has been developed. Two apparatuses were designed and realized: (i) A dedicated test bench to fast-age the fluid under controlled conditions; (ii) a laboratory MOX sensor system to test the headspace of the aged fluid samples. To prepare the set of MOX gas sensors suitable to detect the analytes' concentrations in the fluid headspace, different functional materials were synthesized in the form of nanopowders, characterizing them by electron microscopy and X-ray diffraction. The powders were deposited through screen-printing technology, realizing thick-film gas sensors on which dynamical responses in the presence of the fluid headspace were obtained. It resulted that gas sensors based on solid solution Ti x Sn 1-x O 2 with x = 0.9 and 0.5 offered the best responses toward the fluid headspace with lower response and recovery times. Furthermore, a decrease in the responses (for all sensors) with fluid ageing was observed.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly reached pandemic proportions. Given that the main target of SARS-CoV-2 are lungs leading to severe pneumonia with hyperactivation of the inflammatory cascade, we conducted a prospective study to assess alveolar inflammatory status in patients with moderate to severe COVID-19., Methods: Diagnostic bronchoalveolar lavage (BAL) was performed in 33 adult patients with SARS-CoV-2 infection by real-time PCR on nasopharyngeal swab admitted to the Intensive care unit (ICU) (n = 28) and to the Intermediate Medicine Ward (IMW) (n = 5). We analyze the differential cell count, ultrastructure of cells and Interleukin (IL)6, 8 and 10 levels., Results: ICU patients showed a marked increase in neutrophils (1.24 × 10 5  ml - 1 , 0.85-2.07), lower lymphocyte (0.97 × 10 5  ml - 1 , 0.024-0.34) and macrophages fractions (0.43 × 10 5  ml - 1 , 0.34-1.62) compared to IMW patients (0.095 × 10 5  ml - 1 , 0.05-0.73; 0.47 × 10 5  ml - 1 , 0.28-1.01 and 2.14 × 10 5  ml - 1 , 1.17-3.01, respectively) (p < 0.01). Study of ICU patients BAL by electron transmission microscopy showed viral particles inside mononuclear cells confirmed by immunostaining with anti-viral capsid and spike antibodies. IL6 and IL8 were significantly higher in ICU patients than in IMW (IL6 p < 0.01, IL8 p < 0.0001), and also in patients who did not survive (IL6 p < 0.05, IL8 p = 0.05 vs. survivors). IL10 did not show a significant variation between groups. Dividing patients by treatment received, lower BAL concentrations of IL6 were found in patients treated with steroids as compared to those treated with tocilizumab (p < 0.1) or antivirals (p < 0.05)., Conclusions: Alveolitis, associated with COVID-19, is mainly sustained by innate effectors which showed features of extensive activation. The burden of pro-inflammatory cytokines IL6 and IL8 in the broncho-alveolar environment is associated with clinical outcome.

Despite the progress during the last decade, patients with advanced gastric and esophageal cancers still have poor prognosis. Finding optimal therapeutic strategies represents an unmet need in this field. Several prognostic and predictive factors have been evaluated and may guide clinicians in choosing a tailored treatment. Data from large studies investigating the role of immunotherapy in gastrointestinal cancers are promising but further investigations are necessary to better select those patients who can mostly benefit from these novel therapies. This review will focus on the treatment of metastatic esophageal and gastric cancer. We will review the standard of care and the role of novel therapies such as immunotherapies and CAR-T. Moreover, we will focus on the analysis of potential predictive biomarkers such as Modify as: Microsatellite Instability (MSI) and PD-L1, which may lead to treatment personalization and improved treatment outcomes. A multidisciplinary point of view is mandatory to generate an integrated approach to properly exploit these novel antiproliferative agents.

Cranio-orbital trauma is an uncommon yet devastating injury, especially one in the setting of a high-energy gunshot wound. Such injuries were historically reported in the setting of military conflict, and are associated with vision-threatening complications, often resulting in anophthalmos. The authors report a case of a self-inflicted gunshot wound to the eye, which requires orbital enucleation with exposed frontal lobe dura. To address the exposed dura, the extraocular muscles were utilized from the enucleation procedure to cover the defect in the acute setting prior to final staged reconstruction.

By pursuing the strategy of manipulating natural compounds to obtain functional materials, in this work, we report on the synthesis and characterization of a luminescent cationic iridium complex ( cis - 1 ), designed starting from the catecholic neurotransmitter dopamine, exhibiting the unusual cis arrangement of the C ∧ N ligands. Through an integrated experimental and theoretical approach, it was possible to delineate the optoelectronic properties of cis - 1 . In detail, (a) a series of absorption maxima in the range 300-400 nm was assigned to metal-to-ligand charge transfer and weak and broad absorption maxima at longer wavelengths (400-500 nm) were ascribable to spin-forbidden transitions with a mixed character; (b) there was an intense red phosphorescence with emission set in the range 580-710 nm; and (c) a highest occupied molecular orbital was mainly localized on the metal and the 2-phenylpiridine ligand and a lowest unoccupied molecular orbital was localized on the N ∧ N ligand, with a Δ H-L set at 2.20 eV. This investigation allowed the design of light-emitting electrochemical cell (LEEC) devices endowed with good performance. The poor literature reporting on the use of cis -iridium(III) complexes in LEECs prompted us to investigate the role played by the selected cathode and the thickness of the emitting layer, as well as the doping effect exerted by ionic liquids on the performance of the devices. All the devices exhibited a deep red emission, in some cases, quite near the pure color (devices #1, #4, and #8), expanding the panorama of the iridium-based red-to-near-infrared LEEC devices. The characteristics of the devices, such as the brightness reaching values of 162 cd/m 2 for device #7, suggested that the performances of cis - 1 are comparable to those of trans isomers, opening new perspective toward designing a new set of luminescent materials for optoelectronic devices., Competing Interests: The authors declare no competing financial interest.

The efficiency of the stoichiometric non-covalent imprinting of the imide 2,3,5-tri-O-acetyluridine (TAU) with 2,6-bis(acrylamido)pyridine (BAAPy) as functional monomer due to their strong donor-acceptor-donor/acceptor-donor-acceptor (DAD/ADA) hydrogen bond array interaction has been evaluated by bulk imprinting. This study is the first to investigate the imprinting and template rebinding efficiencies of the TAU/BAAPy molecularly imprinted polymeric (MIP) system prepared by precipitation polymerisation. We found that the stoichiometric 1:1 T:FM ratio has not been maintained in precipitation polymerisation and an optimal TAU:BAAPy ratio of 1:2.5 was obtained in acetonitrile without agitation affording an affinity constant (1.7 × 10 4 M -1 ) and a binding capacity (3.69 μmol/g) higher than its bulk counterpart. Molecular modelling, NMR studies, and selectivity assays against analogues uridine and 2,3,5-tri-O-acetyl cytidine (TAC) indicate that, aside from the DAD/ADA hydrogen bond interaction, BAAPy also interacts with the acetyl groups of TAU. Template incorporation and rebinding in precipitation MIPs are favoured by a moderate initiator concentration, ie, initiator:total monomer (I:TM) ratio of 1:131, while low I:TM ratio (ie, 1:200) drastically reduced template incorporation and binding capacity. Vigorous agitation by stirring showed higher template incorporation but significantly lower template rebinding compared to that prepared without agitation. While the imprinting efficiencies for the best performing bulk and precipitation TAU MIPs generated in this study were moderate, 41% and 60%, respectively, their rebinding capacities were only between 3 and 4% of the incorporated template. We also present quantitative nuclear magnetic resonance spectroscopy as an efficient method for MIP characterisation., (Copyright © 2017 John Wiley & Sons, Ltd.)

Pseudouridine (Ψ) is an important urinary cancer biomarker, especially in human colorectal cancer (CRC). Disclosed herein is the first Ψ molecularly imprinted polymer (Ψ-MIP) material obtained from tailor-engineered functional monomers. The resulting MIP imprint exhibits a remarkable imprinting factor greater than 70. It is successfully used for the selective recognition of Ψ in spiked human urine. This selective functionalized material opens the route to the development of inexpensive disposable chemosensors for noninvasive CRC diagnosis and prognosis., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Over the past ten years, the global biopharmaceutical market has remarkably grown, with ten over the top twenty worldwide high performance medical treatment sales being biologics. Thus, biotech R&D (research and development) sector is becoming a key leading branch, with expanding revenues. Biotechnology offers considerable advantages compared to traditional therapeutic approaches, such as reducing side effects, specific treatments, higher patient compliance and therefore more effective treatments leading to lower healthcare costs. Within this sector, smart nanotechnology and colloidal self-assembling systems represent pivotal tools able to modulate the delivery of therapeutics. A comprehensive understanding of the processes involved in the self-assembly of the colloidal structures discussed therein is essential for the development of relevant biomedical applications. In this review we report the most promising and best performing platforms for specific classes of bioactive molecules and related target, spanning from siRNAs, gene/plasmids, proteins/growth factors, small synthetic therapeutics and bioimaging probes., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Multishell fullerenes, known as carbon nano-onions (CNOs), have emerged as a platform for bioimaging because of their cell-penetration properties and minimal systemic toxicity. Here, we describe the covalent functionalization of CNOs with a π-extended distyryl-substituted boron dipyrromethene (BODIPY) dye with on/off modulated fluorescence emission activated by an acidic environment. The switching properties are linked to the photoinduced electron transfer (PET) characteristics of the dimethylamino functionalities attached to the BODIPY core. The on/off emission of the fluorescent CNOs is fast and reversible both in solution and in vitro, making this nanomaterial suitable as pH-dependent probes for diagnostic applications.

We demonstrate exceptionally large modulation of PL intensity in hierarchical titanium dioxide (TiO 2 ) nanostructures exposed to molecular oxygen (O 2 ). Optical responsivities up to about 1100% at 20% O 2 concentrations are observed in hyperbranched anatase-phase hierarchical structures, outperforming those obtainable by commercial TiO 2 nanopowders (up to a factor of ∼7 for response to synthetic air) and significantly improving the ones typically reported in PL-based opto-chemical gas sensing using MOXs. The improved PL response is discussed in terms of the specific morphology of hierarchical structures, characterized by simultaneous presence of small nanoparticles, large surface areas, and large voids. These characteristics guarantee an optimal interplay between photogenerated charges, PL-active centers, and adsorbed gas molecules. The results highlight the potentialities offered by hierarchical structures based on TiO 2 or other MOXs and open interesting scenarios toward the development of all-optical and/or hybrid (opto/electrical) chemical sensors with improved sensitivity.

Purpose: The aim of this report was to present the first known case of coccidioidomycosis involving the temporomandibular joint, review the literature regarding dissemination to the mandible, and to provide treatment recommendations for this challenging condition., Methods: Coccidioidomycosis of the mandibular condyle was identified in a 30-year-old Somali male residing in Arizona. Due to the difficulty of surgical access and the anticipated temporomandibular joint morbidity of radical condylar debridement, primary medical management was performed., Results: Marked symptomatic improvement was observed after 10 days of IV antifungal therapy. Resolution of the abscess with residual bony destruction was observed on CT scan. Based on the results of this patient and review of the literature, an algorithm is presented to help guide management of coccidioidomycosis dissemination to the mandible., Conclusion: Prolonged antifungal therapy should be attempted for initial management of a Coccidioides abscess involving the condyle with early surgical intervention reserved for the more easily accessible and less functionally compromising portions of the mandible.

The weighted ensemble (WE) path sampling approach orchestrates an ensemble of parallel calculations with intermittent communication to enhance the sampling of rare events, such as molecular associations or conformational changes in proteins or peptides. Trajectories are replicated and pruned in a way that focuses computational effort on underexplored regions of configuration space while maintaining rigorous kinetics. To enable the simulation of rare events at any scale (e.g., atomistic, cellular), we have developed an open-source, interoperable, and highly scalable software package for the execution and analysis of WE simulations: WESTPA (The Weighted Ensemble Simulation Toolkit with Parallelization and Analysis). WESTPA scales to thousands of CPU cores and includes a suite of analysis tools that have been implemented in a massively parallel fashion. The software has been designed to interface conveniently with any dynamics engine and has already been used with a variety of molecular dynamics (e.g., GROMACS, NAMD, OpenMM, AMBER) and cell-modeling packages (e.g., BioNetGen, MCell). WESTPA has been in production use for over a year, and its utility has been demonstrated for a broad set of problems, ranging from atomically detailed host–guest associations to nonspatial chemical kinetics of cellular signaling networks. The following describes the design and features of WESTPA, including the facilities it provides for running WE simulations and storing and analyzing WE simulation data, as well as examples of input and output.

In this paper, we describe the synthesis and evaluation of molecularly imprinted polymers (MIPs), prepared using 2',3',5'-tri-O-acyluridines as 'dummy' templates, for the selective recognition of uridine nucleosides. The MIPs were synthesised using a non-covalent approach with 2,6-bis-acrylamidopyridine (BAAPy) acting as the binding monomer and ethylene glycol dimethacrylate (EGDMA) as the cross-linking agent. The MIPs were evaluated in terms of capacity, selectivity and specificity by analytical and frontal liquid chromatography measurements. The results obtained in organic mobile phases suggest that the nucleosides are specifically bound to the polymer by the complementary hydrogen bonding motifs of the binding monomer and the nucleoside bases. The MIPs exhibited relatively high imprinting factors for 2',3',5'-tri-O-acyluridines, while they did not show any binding capacity for other nucleosides lacking the imide moiety on their base. Moreover, the presence of ester-COO groups in the EGDMA cross-linker may lead to the formation of additional hydrogen bonds with the 2',3' and/or 5'-OH of sugar part, allowing enhancement of the recognition of the uridine nucleosides. In aqueous media, results show that the binding is driven by hydrophobic interactions.

Background: Clinical weight loss in individuals typically stabilizes at 6 mo. However, validated models of dynamic energy balance have consistently shown weight plateaus between 1 and 2 y. The cause for this discrepancy is unclear., Objective: We developed 2 mathematical models on the basis of the first law of thermodynamics to investigate plausible explanations for reaching an early weight plateau at 6 mo., Design: The first model was an energy-expenditure adaptation model and was applied to determine the degree of metabolic adaptation required to generate this plateau. The second model was an intermittent lack-of-adherence model formulated by using a randomly fluctuating energy intake term accounting for intermittent noncompliance in dietary intake to reach this plateau. To set model variables, validate models, and compare free-living weight-loss patterns to in-residence supervised programs, we applied the following 4 different studies: The US NHANES 1999-2004, Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) weight-loss study, the Bouchard Twin overfeeding study, and the Minnesota Starvation Experiment., Results: The metabolic adaptation model increased final weight but did not affect the predicted plateau time point. The intermittent lack-of-adherence model generated oscillating weight graphs that have been frequently observed in weight-loss studies. The model showed that a 6-mo weight-loss plateau can be attained despite what can be considered as high diet adherence. The model was programmed as a downloadable application., Conclusions: An intermittent lack of diet adherence, not metabolic adaptation, is a major contributor to the frequently observed early weight-loss plateau. The new weight-loss prediction software, which incorporates an intermittent lack of adherence, can be used to guide and inform patients on realistic levels of adherence on the basis of patient lifestyle., (© 2014 American Society for Nutrition.)

Equilibrium formally can be represented as an ensemble of uncoupled systems undergoing unbiased dynamics in which detailed balance is maintained. Many nonequilibrium processes can be described by suitable subsets of the equilibrium ensemble. Here, we employ the "weighted ensemble" (WE) simulation protocol [Huber and Kim, Biophys. J. 1996 , 70 , 97-110] to generate equilibrium trajectory ensembles and extract nonequilibrium subsets for computing kinetic quantities. States do not need to be chosen in advance. The procedure formally allows estimation of kinetic rates between arbitrary states chosen after the simulation, along with their equilibrium populations. We also describe a related history-dependent matrix procedure for estimating equilibrium and nonequilibrium observables when phase space has been divided into arbitrary non-Markovian regions, whether in WE or ordinary simulation. In this proof-of-principle study, these methods are successfully applied and validated on two molecular systems: explicitly solvated methane association and the implicitly solvated Ala4 peptide. We comment on challenges remaining in WE calculations.

Despite theoretical evidence that the model commonly referred to as the 3500-kcal rule grossly overestimates actual weight loss, widespread application of the 3500-kcal formula continues to appear in textbooks, on respected government- and health-related websites, and scientific research publications. Here we demonstrate the risk of applying the 3500-kcal rule even as a convenient estimate by comparing predicted against actual weight loss in seven weight loss experiments conducted in confinement under total supervision or objectively measured energy intake. We offer three newly developed, downloadable applications housed in Microsoft Excel and Java, which simulates a rigorously validated, dynamic model of weight change. The first two tools available at http://www.pbrc.edu/sswcp, provide a convenient alternative method for providing patients with projected weight loss/gain estimates in response to changes in dietary intake. The second tool, which can be downloaded from the URL http://www.pbrc.edu/mswcp, projects estimated weight loss simultaneously for multiple subjects. This tool was developed to inform weight change experimental design and analysis. While complex dynamic models may not be directly tractable, the newly developed tools offer the opportunity to deliver dynamic model predictions as a convenient and significantly more accurate alternative to the 3500-kcal rule.

Building on our recently introduced library-based Monte Carlo (LBMC) approach, we describe a flexible protocol for mixed coarse-grained (CG)/all-atom (AA) simulation of proteins and ligands. In the present implementation of LBMC, protein side chain configurations are pre-calculated and stored in libraries, while bonded interactions along the backbone are treated explicitly. Because the AA side chain coordinates are maintained at minimal run-time cost, arbitrary sites and interaction terms can be turned on to create mixed-resolution models. For example, an AA region of interest such as a binding site can be coupled to a CG model for the rest of the protein. We have additionally developed a hybrid implementation of the generalized Born/surface area (GBSA) implicit solvent model suitable for mixed-resolution models, which in turn was ported to a graphics processing unit (GPU) for faster calculation. The new software was applied to study two systems: (i) the behavior of spin labels on the B1 domain of protein G (GB1) and (ii) docking of randomly initialized estradiol configurations to the ligand binding domain of the estrogen receptor (ERα). The performance of the GPU version of the code was also benchmarked in a number of additional systems.

Various aesthetic procedures have been developed over the past several decades for facial rejuvenation. One of the parallel goals is protection of vital structures such as the facial nerve. In this study, 10 cadaveric hemifacial dissections were performed, and the course of the lower portion of the facial nerve was studied with specific attention addressed toward the three-dimensional location of the nerve as it relates to the usual superficial tissue planes that are dissected during the course of an open facial rejuvenation procedure. The locations of the nerve as it runs within the different planes in addition to some suggestions to avoid injury to the lower branches of the facial nerve are discussed., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Typically, the most time consuming part of any atomistic molecular simulation is the repeated calculation of distances, energies, and forces between pairs of atoms. However, many molecules contain nearly rigid multi-atom groups such as rings and other conjugated moieties, whose rigidity can be exploited to significantly speed-up computations. The availability of GB-scale random-access memory (RAM) offers the possibility of tabulation (precalculation) of distance- and orientation-dependent interactions among such rigid molecular bodies. Here, we perform an investigation of this energy tabulation approach for a fluid of atomistic-but rigid-benzene molecules at standard temperature and density. In particular, using O(1) GB of RAM, we construct an energy look-up table, which encompasses the full range of allowed relative positions and orientations between a pair of whole molecules. We obtain a hardware-dependent speed-up of a factor of 24-50 as compared to an ordinary ("exact") Monte Carlo simulation and find excellent agreement between energetic and structural properties. Second, we examine the somewhat reduced fidelity of results obtained using energy tables based on much less memory use. Third, the energy table serves as a convenient platform to explore potential energy smoothing techniques, akin to coarse-graining. Simulations with smoothed tables exhibit near atomistic accuracy while increasing diffusivity. The combined speed-up in sampling from tabulation and smoothing exceeds a factor of 100. For future applications, greater speed-ups can be expected for larger rigid groups, such as those found in biomolecules., (Copyright © 2011 Wiley Periodicals, Inc.)

Pre-calculated libraries of molecular fragment configurations have previously been used as a basis for both equilibrium sampling (via library-based Monte Carlo) and for obtaining absolute free energies using a polymer-growth formalism. Here, we combine the two approaches to extend the size of systems for which free energies can be calculated. We study a series of all-atom poly-alanine systems in a simple dielectric solvent and find that precise free energies can be obtained rapidly. For instance, for 12 residues, less than an hour of single-processor time is required. The combined approach is formally equivalent to the annealed importance sampling algorithm; instead of annealing by decreasing temperature, however, interactions among fragments are gradually added as the molecule is grown. We discuss implications for future binding affinity calculations in which a ligand is grown into a binding site., (Copyright © 2010 Wiley Periodicals, Inc.)

The recombination dynamics of defect states in zinc oxide nanowires has been studied by developing a general expression for time-resolved photoluminescence intensity based on a second-order approximation for the radiative and non-radiative recombination rates. The model allows us to determine the parameters that characterize the recombination from deep defect states (defect concentration, unimolecular lifetime and bimolecular coefficient) through multi-fitting analysis of time-resolved photoluminescence measurements. Analyses conducted on zinc oxide nanowires gave deep state concentrations of the order of 10(18) cm(-3) and unimolecular lifetimes and bimolecular recombination coefficient comparable to those typical of interband recombination in direct gap semiconductors. The consistency of a 'two-channel decay' model (double exponential decay) has been tested by means of a similar analysis procedure. The results suggest that double exponential fitting of time-resolved photoluminescence data of zinc oxide nanowires may be just a mere phenomenological tool which does not reflect the real recombination dynamics of the visible emission band.

A recent Monte Carlo simulation determined the potential of mean force between two lysozyme molecules in various aqueous solutions [M. Lund, Phys. Rev. Lett. 100, 258105 (2008)]. The study involved a combination of explicit solvent and continuum model simulations and showed that there are significant ion-specific protein-protein interactions due to hydrophobic patches on the protein surfaces. In this paper we use the results of their study to determine the phase diagram for lysozyme for aqueous solutions of NaCl and NaI. Two of the three phase diagrams have a stable fluid-fluid critical point, while the third has a slightly metastable critical point. This results from a secondary extremum in the potential associated with a repulsive interaction. This repulsive interaction reduces the effective range of the attractive interaction and produces a metastable critical point. We compare the results of one of these phase diagrams with that for a model that includes ion-dispersion forces, but does not contain solvent structural effects.

We have chemically modified the frustules of the marine diatom Coscinodiscus concinnus Wm. Smith to properly bind a highly selective bioprobe such as an antibody. By measuring the changes in the photoluminescence emission of diatoms frustules, we have monitored the molecular recognition event between the antibody and its ligand: the dissociation constant estimated is of the same order of that measured by standard Biacore. The nanostructured silica frustules, a low-cost and natural available material, have shown high sensitivity, equal to 1.2+/-0.2 nm microM(-1), and a detection limit of 100 nM, and thus are quite ideal candidates for lab-on-particle applications.

Tin dioxide (SnO(2)) nanowires exhibit a strong visible photoluminescence that is not observed in bulk crystalline SnO(2). To explain such effect, oxygen vacancies are often invoked without clarifying if they represent the direct origin of luminescence or if their presence triggers other radiative processes. Here we report an investigation of the nature of the visible light emission in SnO(2) nanowires, showing that both experimental and theoretical ab initio analyses support the first hypothesis. On the basis of photoluminescence quenching analysis and of first-principles calculations we show that surface bridging oxygen vacancies in SnO(2) lead to formation of occupied and empty surface bands whose transition energies are in strong agreement with luminescence features and whose luminescence activity can be switched off by surface adsorption of oxidizing molecules. Finally, we discuss how such findings may explain the decoupling between "electrical-active" and "optical-active" states in SnO(2) gas nanosensors [G. Faglia et al., Appl. Phys. Lett. 86, 011923 (2005)].

We obtain accurate fluid-fluid coexistence curves for a recent simple model of interacting nanoparticles that includes the effects of ion-dispersion forces. It has been proposed that these ion-dispersion forces provide at least a partial explanation for the Hofmeister effect [M. Bostrom et al. Phys. Rev. Lett. 87, 168103 (2001)]. We study a model of aluminum oxide nanoparticle [Deniz et al., Colloids Surf. A 319, 98 (2008)] for three different electrolyte solutions with added salt type being sodium chloride, sodium iodide, and a nonpolarizable salt. We observe that the fluid-fluid coexistence curves depend substantially on the identity of added salt; this provides an efficient way of tuning the phase behavior of nanoparticles. The methods we employ include finite-size scaling (FSS), multicanonical histogram reweighting, and Gibbs ensemble methods. We show that, as expected, all three cases belong to the Ising universality class. The scaling fields and critical point parameters are obtained in the thermodynamic limit of infinite system size by extrapolation of our FSS results.

The phase diagrams for lysozyme are calculated for two different precipitant salts, NaCl and NaSCN, using a potential of mean force that takes into account contributions from ion-dispersion forces [M. Boström, J. Phys. Chem. B 110, 24757 (2006)]. Our results are consistent with a recent perturbation theory calculation (referenced above) in that the phase diagram for lysozyme with NaCl is quite different than for lysozyme with NaSCN for the same molar concentration (0.2M) . However, in contrast to the perturbation theory calculation, we find that the lysozyme phase diagram with NaCl has a metastable fluid-fluid coexistence curve and that the metastability gap in the case of NaSCN is much larger than predicted by perturbation theory.

Background: Risks to the frontal branch of the facial nerve, especially at the juncture of the zygomatic arch, have been well studied in connection with aesthetic procedures. The use of bicoronal incisions led to the observation that there is a second area in which injury to the frontal branch of the facial nerve is at risk: the transition plane between the area over the temporalis muscle and the pericranial region., Objective: A study was conducted to map out the frontal branch of the facial nerve as it passes through the dense galeal temporal fascia, because this is a zone of potential injury., Methods: Ten fresh frozen cadaver halves were dissected by use of a standard surgical bicoronal approach with surgical instrumentation and loupe magnification x 2.5., Results: In the area of interest, which included the region overlying the zygomatic arch, as well as the galeal frontalis fusion point, the nerve was found to be deep and within the fusion point. The nerve was cephalad to the sentinel vein in each instance, and the tissue was freely dissected medial and lateral to the fusion point of the galea and the temporal fascia. The fusion plane was dense and in a direct line in the vertical direction with the loose areolar plane on either side., Conclusion: The dense tissue within the galeal temporal region needs to be approached with caution, avoiding electrocautery and using sharp dissection. The cadaver study demonstrates the close proximity of the nerve in the deeper portion of the elevated superficial flap.

High-quality amorphous Silicon Nitride (a-Si(1-x)N(x):H) Fabry-Pérot microcavities can show resonant surface Second Harmonic Generation (SHG) effect. We consider two different layouts of planar microcavities with almost identical linear reflectance and show how the structure geometry can strongly affect SHG yield. In particular, a difference of more than one order of magnitude in the SHG intensity is observed when the fundamental beam is tuned at the cavity resonance frequency. We explain this finding on the basis of a theoretical model taking into account the spatial distribution of the electric fields of the pump and harmonic frequencies inside the structure. A satisfactory matching of experimental data with the theoretical model is obtained by considering the source of second-order nonlinearity as limited to surface contributions.

Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) are mild-to-life-threatening adverse reactions that have been described after exposure to fluoroquinolones. No published reports, however, exist of exfoliative disease after treatment with levofloxacin. A 78-year-old woman with many medical problems, including chronic obstructive pulmonary disease, was treated with parenteral levofloxacin for community-acquired pneumonia. She was discharged with oral levofloxacin to complete an additional 3 days of treatment as an outpatient. Two days after completing this regimen, the patient developed a rash with blistering. The rash progressed to TEN in 7 days, and she was transferred to a burn treatment center. She was treated with fluid resuscitation, wound dressing, and antibiotics. Her condition improved, and she was discharged after 22 days. To our knowledge, this case is the first published report of levofloxacin-induced TEN.

Complex open wounds of the distal third of the leg and ankle remain a reconstructive challenge for the plastic surgeon. In many cases, these wounds are best addressed with a free tissue transfer. Although this group has performed more than 400 free flaps to the leg during the past 6 years, free tissue transfer can be an arduous operation that requires a team approach and substantial donor site morbidity for the patient. In recent years, the authors have favored the reverse sural artery fasciocutaneous flap in 11 patients for its ease of dissection, limited morbidity, and preservation of major vessels to the limb. Caveats for successful performance of the reverse sural artery flap include Doppler evidence of patent peroneal perforators, placement of a lazy T-shape skin paddle over the distal gastrocnemius muscle bellies, inclusion of the lesser saphenous vein to augment venous drainage, and, lastly, careful dissection to provide a wide adipofascial pedicle.

Background and Study Aims: The increase in infectious diseases of the gastrointestinal tract related to immunosuppression is becoming an important topic for the endoscopist. To improve the diagnostic efficacy of tissue acquisition while at the same time restricting costs, we have developed a new device for obtaining material from the upper gastrointestinal tract that can also be used in the diagnosis of neoplastic disease., Patients and Methods: A total of 90 patients were examined and assigned to two groups according to indications. Group A consisted of 53 symptomatic patients with positive human immunodeficiency virus (HIV) serology with a suspicion of gastrointestinal infection. Group B included 37 patients in whom there was an endoscopic suspicion of neoplasia in the upper gastrointestinal tract. Cell fragments for cytological study were obtained using a device introduced through the endoscopic instrumentation channel (abrasive cytology). Different staining methods were used to isolate bacteria or diagnose tumors from cell fragments. The findings were compared with those obtained from conventional bioptic histology., Results: Potentially responsible pathogens were isolated in 48 of the 53 patients in Group A, while bioptic histology provided a diagnosis in only 32 patients. In the 37 patients in group B, the cytological diagnosis matched the histological results. The costs of this new technique are similar to those for conventional cytological staining, and the time from sampling to obtaining a final diagnosis is less than one hour., Conclusions: This new device provides a fast and low-cost method of isolating pathogens and obtaining cell fragments from the gastrointestinal mucosa during routine upper gastrointestinal endoscopy.

Background: Ductal carcinoma of the pancreas is unresectable for cure in the majority of patients. We reviewed our results and cost effectiveness of surgical and endoscopic biliary bypass for unresectable pancreatic cancer to evaluate the comparable outcomes., Methods: Between 1990 and 1992, 136 patients were managed operatively or endoscopically for pancreatic carcinoma. Excluding potentially curative resections and patients without follow-up, 34 patients endoscopically stented and 32 patients surgically bypassed were evaluated., Results: Mean patient age was older (72.1 vs. 69.3 years) but average performance status was comparable (0.8 vs. 0.9 Eastern Cooperative Oncology Group grading) in the medical treatment group. The initial hospital stay was significantly longer for surgical patients (mean 14 vs. 7 days, p < 0.001), with higher average charges ($18,325 vs. $9,663). Twelve stented patients required rehospitalization (average charge of $4,029), and eight surgical patients were readmitted (average charge of $6,776). An average of 1.7 stent changes (average charge $1,190) were required. Mean survival was longer for the stented group (9.7 vs. 7.3 months, p = 0.13)., Conclusions: Endoscopic stenting for unresectable pancreatic cancer provides equivalent duration of survival at reduced cost and shorter hospital stay, although subsequent stent changes are necessary. When curative resection is not possible, endoscopic biliary drainage should be considered a good first choice for palliative management.

Monochromatic targets presented at 30 degrees excentricity on orange, magenta and blue backgrouds are used. A small monochromatic light, 476 nm on orange, 551 nm on magenta and 621 nm on blue, is flashed at 3 cps-1 on the centre of the targets. The size of the targets is varied and their luminance adjusted using neutral filters until the flashing light is just not visible. This method allows the study of chromatic mechanism sensitivity and of retinal interactions (summation and inhibition). Some observations in normal as well as in pathological conditions are presented.