Novel route synthesis of porous and solid gold nanoparticles for investigating their comparative performance as contrast agent in computed tomography scan and effect on liver and kidney function.
Gold nanoparticles (GNPs) with dimension in the range of 1-100 nm have a prominent role in a number of biomedical applications like imaging, drug delivery, and cancer therapy owing to their unique optical features and biocompatibility. In this work, we report a novel technique for the synthesis of two types of GNPs namely porous gold nanoparticles (PGNPs) and solid gold nanoparticles (SGNPs). PGNPs of size 35 nm were fabricated by reduction of gold (III) solution with lecithin followed by addition of L-ascorbic acid and tri-sodium citrate, whereas SGNPs with a dimension of 28 nm were prepared by reflux method using lecithin as a single reducing agent. Comparative studies using PGNPs (λmax 560 nm) and SGNPs (λmax 548 nm) were conducted for evaluating their use as a contrast agent. These studies reveled that in direct computed tomography scan, PGNPs exhibited brighter contrast (45 HU) than SGNPs (26 HU). To investigate the effect of PGNPs and SGNPs on the liver and kidney profile, male rabbits were intravenously injected with an equal dose of 1 mg/kg weight of PGNPs and SGNPs. The effect on biochemical parameters was evaluated 72 hours after intravenous (IV) injection including liver function profile, renal (kidney) function biomarker, random blood glucose value, and cholesterol level. During one comparison of contrast in CT scan, PGNPs showed significantly enhanced contrast in whole-rabbit and organ CT scan as compared to SGNPs 6 hours after injection. Our findings suggested that the novel PGNPs enhance CT scan image with higher efficacy as compared to SGNPs. The results showed that IV administration of synthesized PGNPs increases the levels of aspartate aminotransferase (AST), alkaline phosphate (ALP), serum creatinine, and blood glucose, whereas that of SGNPs increases the levels of AST, ALP, and blood glucose.


Site-selective heat boosting electrochemiluminescence for single cell imaging.
In operando visualization of local electrochemical reactions provides mechanical insights into the dynamic transport of interfacial charge and reactant/product. Electrochemiluminescence is a crossover technique that quantitatively determines Faraday current and mass transport in a straightforward manner. However, the sensitivity is hindered by the low collision efficiency of radicals and side reactions at high voltage. Here, we report a site-selective heat boosting electrochemiluminescence microscopy. By generating a micron-scale heat point in situ at the electrode-solution interface, we achieved an enhancement of luminescence intensity up to 63 times, along with an advance of 0.2 V in applied voltage. Experimental results and finite element simulation demonstrate that the fundamental reasons are accelerated reaction rate and thermal convection via a photothermal effect. The concentrated electrochemiluminescence not only boosts the contrast of single cells by 20.54 times but also enables the site-selective cell-by-cell analysis of the heterogeneous membrane protein abundance. This electrochemical visualization method has great potential in the highly sensitive and selective analysis of local electron transfer events.


Development of a New Structural Class of Broadly Acting HCV Non-Nucleoside Inhibitors Leading to the Discovery of MK-8876.
Studies directed at developing a broadly acting non-nucleoside inhibitor of HCV NS5B led to the discovery of a novel structural class of 5-aryl benzofurans that simultaneously interact with both the palm I and palm II binding regions. An initial candidate was potent in vitro against HCV GT1a and GT1b replicons, and induced multi-log reductions in HCV viral load when orally dosed to chronic GT1 infected chimpanzees. However, in vitro potency losses against clinically relevant GT1a variants prompted a further effort to develop compounds with sustained potency across a broader array of HCV genotypes and mutants. Ultimately, a biology and medicinal chemistry collaboration led to the discovery of the development candidate MK-8876. MK-8876 demonstrated a pan-genotypic potency profile and maintained potency against clinically relevant mutants. It demonstrated moderate bioavailability in rats and dogs, but showed low plasma clearance characteristics consistent with once-daily dosing. Herein we describe the efforts which led to the discovery of MK-8876, which advanced into Phase 1 monotherapy studies for evaluation and characterization as a component of an all-oral direct-acting drug regimen for the treatment of chronic HCV infection.


In vivo Direct Conversion of Astrocytes to Neurons Maybe a Potential Alternative Strategy for Neurodegenerative Diseases.
Partly because of extensions in lifespan, the incidence of neurodegenerative diseases is increasing, while there is no effective approach to slow or prevent neuronal degeneration. As we all know, neurons cannot self-regenerate and may not be replaced once being damaged or degenerated in human brain. Astrocytes are widely distributed in the central nervous system (CNS) and proliferate once CNS injury or neurodegeneration occur. Actually, direct reprogramming astrocytes into functional neurons has been attracting more and more attention in recent years. Human astrocytes can be successfully converted into neurons in vitro. Notably, in vivo direct reprogramming of astrocytes into functional neurons were achieved in the adult mouse and non-human primate brains. In this review, we briefly summarized in vivo direct reprogramming of astrocytes into functional neurons as regenerative strategies for CNS diseases, mainly focusing on neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington's disease (HD). We highlight and outline the advantages and challenges of direct neuronal reprogramming from astrocytes in vivo for future neuroregenerative medicine.


Water Treatment for Hemodialysis: What You Must Know to Keep Patients Safe.
It is critical for all staff members to work together to keep patients safe. Nephrology nurses with responsibility for hemodialysis (HD) need to know and understand the clinical ramifications of water treatment and dialysate preparation. Although some HD programs may have full-time technical staff who operate and test the water treatment and dialysate preparation systems, many programs rely on nursing staff members for the dayto- day operation and testing of these systems. This article details the reasons safe water and dialysate are critical for patients on HD; and reviews components of water treatment systems, dialysate concentrate preparation, and the monitoring and testing necessary to assure that both water and dialysate are safe for patient use. Integrated HD systems (i.e., those that combine water treatment and dialysate preparation and delivery in an individual machine "package") are also described.


Three Cases of Combined Therapy in Primary Breast Lymphoma (PBL) with Successful Outcomes.
Primary malignant lymphoma of the breast is a rare tumor, defined as a tumor localized in the breast with or without axillary lymph-node metastases. Such a tumor is mainly found in female patients and located more frequently in the right breast. It is difficult to make primary breast lymphoma (PBL) diagnosis before operation, and PBL diagnosis is mainly based on pathological biopsy and immunohistochemical staining. In this paper, the cases of three patients who had PBL, and who were treated for it at the Institute for Oncology and Radiology of Serbia between 2008 and 2012, are reviewed and discussed. These cases of PBL had no recorded reoccurrence of the disease and were originally treated by surgery, radiotherapy R-CHOP, and/or chemotherapy. While there is no consensus to the question of how to best treat PBL (ie, with chemotherapy, radiotherapy, or combined therapy), it is hoped that this review will offer insight into successful treatment procedures for tumors of this category.


Catastrophe theory model for decelerations of fetal heart rate.
Decelerations of fetal heart rate (FHR) are the results of many pathophysiological factors that modulate the intrinsic rate of the heart. FHR change is a complex phenomenon and can be viewed as a type of nonlinear dynamic system. This paper presents a qualitative model of FHR decelerations based on catastrophe theory, especially to account for abrupt heart rate changes seen in variable decelerations. One of the elementary catastrophes, the cusp catastrophe, was used to model FHR changes seen in variable, late, and early decelerations. Catastrophe theory describes typical variable decelerations as an abrupt response to a slowly changing force of attack (uterine contraction) and physiological defense. Because of its three-dimensionality and topological features, the cusp catastrophe model provides a qualitatively satisfying description of FHR decelerations. The organized complexity of living systems offers the best hope for the application of catastrophe theory. The nature of the elementary catastrophes will be essential knowledge in the mathematical analysis of biology.


Rapid analysis for the isolation of novel genes encoding putative effectors to the position-specific regulatory element of murine Hoxa-7.
Hox genes are known to play a critical role in pattern formation during vertebrate development by being expressed at the specific time and in the specific position along the antero-posterior body axis. In order to understand the regulatory mechanism for the position-specific expression of murine Hoxa-7, yeast one-hybrid system was applied. DNA fragment conferring a position specificity to the Hoxa-7 gene was placed just upstream from the yeast CYC1 promoter and lacZ gene in a reporter. Selection of LacZ positive clones after cotransformation of the reporter and mouse embryonic cDNA library as an effector, which was designed to be expressed as fusion proteins to the GAL4 activation domain, allowed us to isolate putative factors interacting with the position-specific regulatory element of murine Hoxa-7. A total of 28 positive clones were screened from 5 x 10(5) yeast transformants. About 70% of the clones turned out to be novel and most of the candidate clones selected in this study showed a temporally restricted expression pattern during embryonic development, suggesting that this method could provide an efficient way for isolating novel genes whose expressions are temporally regulated during embryogenesis.


Magnetic resonance imaging volume of the angular gyri predicts financial skill deficits in people with amnestic mild cognitive impairment.
To better understand how brain atrophy in amnestic mild cognitive impairment (MCI) as measured using magnetic resonance imaging (MRI) volumetrics could affect instrumental activities of daily living (IADLs) such as financial abilities. Controlled, matched-sample, cross-sectional analysis regressing MRI volumetrics with financial performance measures. University medical and research center. Thirty-eight people with MCI and 28 older adult controls. MRI volumetric measurement of the hippocampi, angular gyri, precunei, and medial frontal lobes. Participants also completed neuropsychological tests and the Financial Capacity Instrument (FCI). Correlations were performed between FCI scores and MRI volumes in the group with MCI. People with MCI performed significantly below controls on the FCI and had significantly smaller hippocampi. Among people with MCI, performance on the FCI was moderately correlated with angular gyri and precunei volumes. Regression models demonstrated that angular gyrus volumes were predictive of FCI scores. Tests of mediation showed that measures of arithmetic and possibly attention partially mediated the relationship between angular gyrus volume and FCI score. Impaired financial abilities in amnestic MCI correspond with volume of the angular gyri as mediated by arithmetic knowledge. The findings suggest that early neuropathology within the lateral parietal region in MCI leads to a breakdown of cognitive abilities that affect everyday financial skills. The findings have implications for diagnosis and clinical care of people with MCI and AD.


O-GlcNAc regulation of autophagy and α-synuclein homeostasis; implications for Parkinson's disease.
Post-translational modification on protein Ser/Thr residues by O-linked attachment of ß-N-acetyl-glucosamine (O-GlcNAcylation) is a key mechanism integrating redox signaling, metabolism and stress responses. One of the most common neurodegenerative diseases that exhibit aberrant redox signaling, metabolism and stress response is Parkinson's disease, suggesting a potential role for O-GlcNAcylation in its pathology. To determine whether abnormal O-GlcNAcylation occurs in Parkinson's disease, we analyzed lysates from the postmortem temporal cortex of Parkinson's disease patients and compared them to age matched controls and found increased protein O-GlcNAcylation levels. To determine whether increased O-GlcNAcylation affects neuronal function and survival, we exposed rat primary cortical neurons to thiamet G, a highly selective inhibitor of the enzyme which removes the O-GlcNAc modification from target proteins, O-GlcNAcase (OGA). We found that inhibition of OGA by thiamet G at nanomolar concentrations significantly increased protein O-GlcNAcylation, activated MTOR, decreased autophagic flux, and increased α-synuclein accumulation, while sparing proteasomal activities. Inhibition of MTOR by rapamycin decreased basal levels of protein O-GlcNAcylation, decreased AKT activation and partially reversed the effect of thiamet G on α-synuclein monomer accumulation. Taken together we have provided evidence that excessive O-GlcNAcylation is detrimental to neurons by inhibition of autophagy and by increasing α-synuclein accumulation.


Maternal Embryonic Leucine Zipper Kinase (MELK), a Potential Therapeutic Target for Neuroblastoma.
Maternal embryonic leucine zipper kinase (MELK) activates pathways that mediate aggressive tumor growth and therapy resistance in many types of adult cancers. Pharmacologic and genomic inhibition of MELK impairs tumor growth and increases sensitivity to radiation and chemotherapy. On the basis of these promising preclinical studies, early-phase adult clinical trials testing the MELK inhibitor OTS167 are ongoing. To investigate whether MELK is also a therapeutic target in neuroblastoma, we analyzed MELK expression in primary tumors and cell lines, and examined the effects of OTS167 on neuroblastoma growth. In primary tumors, high levels of MELK were associated with advanced stage disease and inferior survival. Higher levels of MELK were also detected in tumorigenic versus nontumorigenic neuroblastoma cell lines, and cells with higher levels of MELK expression were more sensitive to OTS167 than low-MELK expressing cells. OTS167 suppressed the growth of neuroblastoma xenografts, and in a preclinical model of minimal residual disease, survival was prolonged with MELK inhibition. OTS167 treatment downregulated MELK and its target enhancer of zeste homolog 2 (EZH2), a component of the polycomb repressive complex 2 (PRC2) that is known to modulate the DNA damage response. We also show that OTS167 reduced the formation of collapsed replication forks induced by camptothecin or radiation. Taken together, our results indicate that MELK indirectly mediates efficient processing of replication-associated DNA lesions in neuroblastoma, and that OTS167 sensitizes cells to DNA-damaging agents by abrogating this process. Further studies evaluating the activity of combination treatment regimens with OTS167 in neuroblastoma are warranted.


HIV-related pulmonary hypertension.
With the availability of better treatment and prophylactic regimens for the infectious complications of human immunodeficiency virus (HIV), the non-infectious complications are gaining greater attention. HIV-related pulmonary arterial hypertension (HIV-PAH) is one of these. The incidence of HIV-PAH is estimated at 0.5% of HIV-infected individuals. The pathogenesis remains unclear. Patients present with symptoms as diverse as progressive shortness of breath, pedal edema, dry cough, fatigue, syncope, as well as chest pain. Chest X-ray always shows cardiomegaly and prominent pulmonary artery, and evidence of right ventricular hypertrophy can be seen from the electrocardiogram. The pulmonary arterial systolic pressure, diastolic pressure and pulmonary vascular resistance from right heart catheterization are increased. There are a few small studies showing the benefit of prostacyclin analog (epoprostenol and iloprost) and bosentan. The role of antiretrovirals remains controversial, as do those of other agents such as calcium channel blockers and anticoagulants. The prognosis of HIV-PAH is grave. Two thirds of HIV-PAH related mortality is usually secondary to consequences of pulmonary hypertension, with the worst survival noted in New York Heart Association (NYHA) functional class III-IV. The probability of survival in one series was 73%, 60% and 47% at one, two and three years, respectively.


A DEVELOPMENTAL CONSTRAINT IN CERION, WITH COMMENTS ON THE DEFINITION AND INTERPRETATION OF CONSTRAINT IN EVOLUTION.
Since orthodox evolutionary theory is functionalist, constraints attain their most important positive meaning as channels of change imposed by historical and formal determinants, rather than by immediate natural selection. Since ontogeny is the usual locus of expression for these determinants, developmental constraint is an appropriate, general term. A particular developmental constraint in Cerion, most variable of West Indian land snails, stands out for two reasons: 1) it is simply and inexorably defined as a consequence both of formal principles (coiling of tube about axis) and of historical contingencies in Cerion's invariant allometry of growth; 2) it is pervasive in its influence, underlying major patterns of variation in every Cerion study I have ever undertaken. I refer to this pattern as the "jigsaw constraint." When whorls are large and final size is limited, adult shells must grow fewer whorls. In Cerion, this obvious fact is promoted from trivial to important because complex allometries impose a substantial set of further consequences for form upon this basic trade-off of whorl size and whorl number. I show that this complex of consequences dominates patterns of natural variation in Cerion at all levels (among shells within samples, between samples in the geographic variation of single species, and between species in multitaxon faunas). It also sets patterns of hybridization between taxa. This paper is primarily a compendium of such examples. It is designed to illustrate the importance of this constraint by the fundamental criterion of relative frequency.


Homochiral, helical supramolecular metal-organic frameworks organized by strong π · · · π stacking interactions: single-crystal to single-crystal transformations in closely packed solids.
Enantiopure, trifunctional carboxylate ligands synthesized by linking the strong π · · · π stacking 1,8-naphthalimide supramolecular synthon to three naturally occurring amino acids using the azide/alkyne click reaction have been prepared [amino acid = glycine (L(gly)(-)), alanine (L(ala)(-)), and serine (L(ser)(-))]. These ligands have been used to form complexes of the formula [M(L(amino acid))2(4,4'-bipy)(H2O)2] · xH2O (M = Fe, Co, Ni, Cu, Zn; x = 4.25-5.52) when mixed with an appropriate metal salt and 4,4'-bipyridine by layering methods. These complexes are isostructural, with the central metal atom coordinated to two κ(1)-carboxylate ligands, two water molecules, and one end each of two 4,4'-bipyridine ligands in a distorted octahedral environment. Each ligand is oriented in a trans arrangement. These complexes all have homochiral, helical, supramolecular, three-dimensional metal-organic framework structures, with the helical organization of the individual metallic units held together solely by strong, noncovalent π · · · π stacking interactions of the naphthalimide; the other two dimensions are organized mainly by the bipyridine ligands. The helices are extremely large; one turn of the helix travels ∼ 60 Å and has a diameter of ca. 40 Å. For the achiral ligand L(gly)(-), the nickel complex forms two types of homochiral crystals in the same tube, a clear example of spontaneous resolution. Despite the large size of the individual helices, they are tightly interconnected and nestled closely together. Part of the interconnection comes from the interstitial water molecules held inside the framework of the complexes in isolated pockets by hydrogen-bonding interactions. For both [Cu(L(ala))2(4,4'-bipy)(H2O)2] · 4.25H2O and [Co(L(ser))2(4,4'-bipy)(H2O)2] · 4.68H2O, the interstitial water molecules can be removed by placing the crystals under a vacuum for several hours, a process that can be reversed by exposure to atmospheric moisture. This removal/reintroduction of the interstitial water molecules takes place with no loss of crystallinity, representing dramatic examples of single-crystal to single-crystal transformations. The structures undergo little change other than the pockets holding the interstitial water molecules in the hydrated complexes become void spaces in the dehydrated complexes. The removal/reintroduction of the water molecules in these closely packed solids is facilitated by the "soft" π · · · π stacking interactions organizing one dimension of the structures. The observed magnetic and Mössbauer spectral properties are typical of isolated, magnetically dilute, paramagnetic pseudooctahedral divalent transition-metal complexes.


Paper Spray Ionization Mass Spectrometry as a Potential Tool for Early Diagnosis of Cervical Cancer.
Squamous intraepithelial lesion is an abnormal growth of epithelial cells on the surface of the cervix that may lead to cervical cancer. Analytical protocols for the determination of squamous intraepithelial lesions are in high demand, since cervical cancer is the fourth most diagnosed cancer among women in the world. Here, paper spray ionization mass spectrometry (PSI-MS) is used to distinguish between healthy (negative for intraepithelial lesion or malignancy) and diseased (high-grade squamous intraepithelial lesion) blood plasmas. A total of 86 blood samples of different women (49 healthy samples, 37 diseased samples) were collected, and the plasmas were prepared. Then, 10 μL of each plasma sample was deposited onto triangular papers for PSI-MS analysis. No additional step of sample preparation was necessary. The interval-successive projection algorithm linear discriminant analysis (iSPA-LDA) was applied to the PSI mass spectra, showing six ions (mostly phospholipids) that were predictive of healthy and diseased plasmas. Values of 77% accuracy, 86% sensitivity, 80% positive predictive value (PPV), and 75% negative predictive value (NPV) were achieved. This study provides evidence that PSI-MS may potentially be used as a fast and simple analytical technique for the early diagnosis of cervical cancer.


Revisiting Geschwind's hypothesis on brain lateralisation: a functional MRI study of digit ratio (2D:4D) and sex interaction effects on spatial working memory.
The Geschwind-Behan-Galaburda (GBG) hypothesis links cerebral lateralisation with prenatal testosterone exposure. Digit ratio measures in adults have been established as potential markers of foetal sex hormonal milieu. The aim of the study was to evaluate the sex-dependent interaction of digit ratio measures and cerebral lateralization as well as their neurohemodynamic correlates using functional MRI (fMRI). Digit ratio measures-ratio of index finger (2D) length to ring finger (4D) length (2D:4D) and difference between 2D:4D of two hands, i.e., right minus left (DR-L)-were calculated using high resolution digital images in 70 right-handed participants (42 men) based on reliable and valid method. fMRI was acquired during the performance of a spatial working memory task in a subset of 25 individuals (14 men), and analysed using Statistical Parametric Mapping 8 (SPM8) and the Laterality Index toolbox for SPM8. Men had significantly less bilateral 2D:4D than women. There was a significant negative correlation between right 2D:4D and 2-Back task accuracy (2BACC) in women. A significant sex-by-right 2D:4D interaction was observed in left parahippocampal gyrus activation. Additionally, sex-by-DR-L interaction was observed in left IPL activation. DR-L showed a significant positive correlation with the whole brain Laterality Index (LI), and LI, in turn, demonstrated a significant negative correlation with 2BACC. Our study observations suggest several novel sex-differential relationships between 2D:4D measures and fMRI activation during spatial working memory task performance. Given the pre-existing background data supporting digit ratio measures as putative indicator of prenatal sex hormonal milieu, our study findings add support to the Geschwind-Behan-Galaburda (GBG) hypothesis.


Alcohol use reduction program in methadone maintained individuals with hepatitis C virus infection.
The purpose of this article was to investigate the personal and social barriers experienced by methadone maintained clients when seeking treatment for alcohol abuse along with strategies for engaging such clients in treatment programs. A qualitative design using semi-structured focus groups was used to obtain the perspectives of 41 methadone-maintained clients in Los Angeles, California. Sessions were recorded, transcribed, and content-analyzed. Attitudes of health care providers were considered critical factors for engaging clients in treatment programs. Other facilitators included incentives and forms of support (emotional, financial, or material aid), whereas barriers consisted of lack of provider knowledge and insensitivity to acquiring needed resources. Clients also discussed the importance of personal attributes in achieving successful behavioral change, such as personal motivation. The findings suggest that healthcare providers' strategies designed to boost motivation, combined with various types of support, may prove successful in alcohol reduction among methadone-maintained clients.


Exploring the Relationship Between Masseter and Cervical Vestibular Evoked Myogenic Potentials in Young Adults with Normal Hearing.
Cervical vestibular evoked myogenic potentials (cVEMPs) and masseter vestibular evoked myogenic potentials (mVEMPs) are considered to have a common saccular origin. While a few studies have examined both VEMPs in individuals with brainstem disorders as part of a test battery, the relation between these two potentials has rarely been the subject of discussion. The present study explored the relation between mVEMPs and cVEMPs using EMG-scaled parameters in normal-hearing young adults. Within-subject study design Study Sample: Twenty young adults between 18 to 39 years of age (11 males, 9 females) participated in the study. cVEMP and mVEMP were performed on all the participants at 95dBnHL with 500Hz tone burst stimuli. Various VEMP parameters were evaluated including P13 and N23 peak latencies, the amplitude of the P13-N23 complex, and the Interaural Amplitude Asymmetry Ratio (IAAR) in EMG-scaled and unscaled conditions. All participants exhibited a 100% response rate for cVEMP and mVEMP responses. There were no significant ears and gender effect for both cVEMP and mVEMP. No correlation was found between cVEMP and mVEMP. There was no significant difference found between P1 and N1 latency values of cVEMP and mVEMP; however, a significant variation was observed for peak to peak amplitude both in EMG scaled and unscaled conditions between cVEMP and mVEMP. Minimal to no association between any parameters of cVEMPs and mVEMPs suggests no significant relationship between these two VEMPs.


Experimental and Computational Study of Aminoacridines as MALDI(-)-MS Matrix Materials for the Analysis of Complex Samples.
Monoaminoacridines (1-, 2-, 3-, 4-, and 9-aminoacridine) were studied for suitability as matrices in the negative ion mode matrix-assisted laser desorption/ionization mass spectrometry (MALDI(-)-MS) analysis of various samples. This is the first study to examine 1-, 2-, and 4-aminoacridine as potential matrix material candidates for MALDI(-)-MS. In addition, spectral (UV-Vis absorption and fluorescence), proton transfer-related (basicity and autoprotolysis), and crystallization properties of these compounds were characterized experimentally and/or computationally. For testing the capabilities of these aminoacridines as matrix materials, four samples related to cultural heritage materials-stearic acid, colophony resin, dyer's madder dye, and a resinous case-study sample from a shipwreck-were analyzed with MALDI(-)-MS. A novel algorithm (implemented as an executable Python script) for MS data analysis was developed to compare the five matrix materials and to help mass spectrometrists rapidly identify peaks originating from the sample and matrix material. It was determined that all five of the studied aminoacridines can successfully be used as matrix materials in MALDI(-)-MS analysis. As an interesting finding, in several cases, the best mass spectra were obtained by using a relatively small amount of matrix material mixed with an excess amount of sample. 3- and 4-aminoacridine outperformed the other aminoacridines in the ease of obtaining acceptable spectra, average number of ions identified in the mass spectra, and low dependence of the sample-to-matrix mass ratio on experimental results.


Locoregional therapy for cholangiocarcinoma.
Cholangiocarcinoma has a poor prognosis. Surgical resection offers the only curative option and usually requires a major hepatic resection in addition to resection of the cholangiocarcinoma. Unfortunately, curative resection is possible in only about 30% of patients due to locally advanced disease, distant metastases or comorbidity in elderly patients. Even after resection, the recurrence rate is approximately 60%, resulting in a low 5-year overall survival (OS). In unresectable cholangiocarcinoma OS with systemic chemotherapy is less than 1 year. Since most cholangiocarcinoma patients develop distant metastases at late stages only, locoregional therapy is an interesting therapeutic strategy. Here, we review the locoregional concepts of cholangiocarcinoma therapy. Locoregional therapy studies in patients with intrahepatic cholangiocarcinoma employing radiofrequency ablation (RFA), transarterial chemoembolization (TACE) or external as well as internal radiation therapy yielded promising results in the last couple of years. In conclusion, locoregional therapies have been shown to be effective in patients with intrahepatic cholangiocarcinoma. Local tumour control may prolong OS and can be achieved by locoregional interventions applied either sequentially or in combination with systemic chemotherapies.


Biosynthetic studies of arphamenines A and B.
The biosynthetic pathways of arphamenines A and B were studied. Arphamenine A was derived from acetic acid, L-arginine and L-phenylalanine, and arphamenine B from acetic acid, L-arginine and L-tyrosine.


Multidisciplinary work in oncology: Population-based analysis for seven invasive tumours.
The concept of multidisciplinary team meetings (MDTs) in cancer care is endorsed internationally, but its uptake varies considerably. In Belgium, MDT meetings were financially recognised in 2003 to encourage healthcare professionals to join their knowledge and competences to improve the quality and coordination of cancer care. This study aimed to evaluate for seven cancer types diagnosed between 2004 and 2011, the practices of MDT meetings in Belgium by means of population-based administrative databases. Results show a clear increase over time in the proportion of individual patients discussed at MDT meetings. Although this evolution may be partly explained by the legal implementation of several financial initiatives to stimulate MDT meetings, it also suggests an increase in specialists' awareness of the importance of such meetings. Nevertheless, there is still room for improvement, for specific cancer types as well as for certain subgroups such as older patients. From the specialists' point of view, reducing the administrative burden and time these meetings demand may entail a greater participation to MDT meetings. Further research is needed to identify the barriers to discuss more patients at MDT meetings and to elucidate the impact of MDT meetings on the quality of cancer care.


Time to eRAASe chronic inflammation: current advances and future perspectives on renin-angiotensin-aldosterone-system and chronic intestinal inflammation in dogs and humans.
Chronic idiopathic intestinal inflammation is an increasing worldwide problem that affects companion animals, especially dogs, and human patients. Although these disease entities have been intensely investigated recently, many questions remain, and alternative therapeutic options are needed. Diarrhea caused by dysregulation of intestinal electrolyte transport and subsequent fluid and electrolyte losses often leads to secondary consequences for the patient. Currently, it is not exactly clear which mechanisms are involved in the dysregulation of intestinal fluid absorption, but differences in intestinal electrolyte shifts between human and canine patients suggest species-specific regulatory or counterregulatory mechanisms. Several intestinal electrolyte transporters are differentially expressed in human patients with inflammatory bowel disease (IBD), whereas there are virtually no studies on electrolyte transporters and their endocrine regulation in canine chronic inflammatory enteropathy. An important mechanism involved in regulating fluid and electrolyte homeostasis is the renin-angiotensin-aldosterone-system (RAAS), which may affect intestinal Na+ transport. While RAAS has previously been considered a systemic regulator of blood pressure, additional complex roles of RAAS in inflammatory processes have been unraveled. These alternative RAAS pathways may pose attractive therapeutic targets to address diarrhea and, thus, electrolyte shifts in human IBD and canine chronic inflammatory enteropathy. This article comparatively summarizes the current knowledge about electrolyte transport in human IBD and canine chronic inflammatory enteropathy and the role of RAAS and offers perspectives for novel therapeutic avenues.


Snow-mediated plasticity does not prevent camouflage mismatch.
Global reduction in snow cover duration is one of the most consistent and widespread climate change outcomes. Declining snow duration has severe negative consequences for diverse taxa including seasonally color molting species, which rely on snow for camouflage. However, phenotypic plasticity may facilitate adaptation to reduced snow duration. Plastic responses could occur in the color molt phenology or through behavior that minimizes coat color mismatch or its consequences. We quantified molt phenology of 200 wild snowshoe hares (Lepus americanus), and measured microhabitat choice and local snow cover. Similar to other studies, we found that hares did not show behavioral plasticity to minimize coat color mismatch via background matching; instead they preferred colder, snow free areas regardless of their coat color. Furthermore, hares did not behaviorally mitigate the negative consequences of mismatch by choosing resting sites with denser vegetation cover when mismatched. Importantly, we demonstrated plasticity in the initiation and the rate of the molt and established the direct effect of snow on molt phenology; greater snow cover was associated with whiter hares and this association was not due to whiter hares preferring snowier areas. However, despite the observed snow-mediated plasticity in molt phenology, camouflage mismatch with white hares on brown snowless ground persisted and was more frequent during early snowmelt. Thus, we find no evidence that phenotypic plasticity in snowshoe hares is sufficient to facilitate adaptive rescue to camouflage mismatch under climate change.


Strategies for identifying hereditary nonpolyposis colon cancer.
Hereditary nonpolyposis colorectal cancer (HNPCC) is the term given to a predisposition syndrome caused by inherited mutations in one of at least five DNA mismatch repair (MMR) genes. Dominant mutations in these genes predispose individuals to a range of cancers in addition to the most frequent, colorectal cancer. Endometrial cancer is the most notable additional malignancy, followed by ovarian, gastric, upper urethelial, and biliary cancers, and gliomas. Recognition of HNPCC is important so that targeted screening can be effected that will reduce the incidence of the main cancers. While such clinical criteria as Amsterdam and modified Amsterdam are reasonably specific, they lack sensitivity. Thus, tumor-related features have been used to improve sensitivity for identifying patients who can be selected for the relatively expensive direct mutation analysis of the various genes. Microsatellite instability (MSI) and loss of antibody staining for the proteins have been widely vaunted but have their own drawbacks. No one approach has received universal acceptance, and therefore adoption of one of perhaps three strategies, including clinical- and laboratory-based approaches, is still appropriate until an easier, quicker, and cheaper approach can be developed.


Risk of Tuberculosis Among Patients on Dialysis: The Predictive Value of Serial Interferon-Gamma Release Assay.
Patients on long-term dialysis are at high risk for tuberculosis (TB). Although latent tuberculosis infection (LTBI) is good target for TB eradication, interferon-gamma release assay-defined LTBI has a high proportion of negative conversion and lacks active TB correlation among patients on dialysis.Patients on long-term dialysis were screened in multiple centers in Taiwan. QuantiFERON-TB Gold In-tube (QFT-GIT) was used to define LTBI and was performed thrice at 6-month intervals. The primary outcome was active TB diagnosed after LTBI screening. The incidence and predictive value of QFT-GIT were analyzed.The 940 dialysis patients enrolled had an average age of 59.3 years. The initial QFT-GIT results were positive in 193, including 49.6% with persistent positive results on second check. In an average follow-up period of 3 years, 7 patients had TB. Three (319.1 per 100,000 person-yrs) and 4 (141.8 per 100,000 person-yrs) of them were prevalent and incident TB cases, respectively. Persistent positive QFT-GIT for 2 and 3 times correlated with increased hazard ratio for TB (14.44 and 20.29, respectively) compared with a single positive result (hazard ratio 10.38). Among those with 3 positive QFT-GIT results, TB development rate was 4.5% and incidence rate was 1352.3 per 100,000 person-years. In contrast, none of the incident TB occurred in those with initial positive and then negative conversion of QFT-GIT.In an area of intermediate TB incidence, dialysis patients have high TB risk. LTBI status is a good predictor of TB development, especially for those with more than 1 positive result. After excluding prevalent TB cases, serial follow-up of LTBI may narrow the target population to reduce treatment costs.


[Health Economical Evaluation of antibiotic prophylaxis against postoperative endophthalmitis].
Two independent epidemiological studies recently suggested the prophylactic relevance of an intraocular antibiosis against endophthalmitis after cataract surgery. The resulting intervention programme, however, has not only ethical drawbacks, but also has a health economical dimension, which will be focussed in this paper. A cost analysis is performed to compare the direct costs saved by prevention of endophthalmitis cases and the costs generated by the prophylaxis itself. Furthermore, the clinics' indirect costs due to treatment of unprevented endophthalmitis cases are estimated. The overall gain in direct costs turns out to be about 368 000 Euro p. a., the indirect costs from the clinics' view can be reduced by about 260 000 Euro p. a. due to prevention of endophthalmitis cases by the antibiotic intervention. From an economical point of view, antibiotic prophylaxis can be suggested; the risk of longitudinally reduced antibiotic effectiveness of the antibiotic agents, however, strongly calls for an overall health political decision rather than for an immediate implementation of the corresponding intervention programme.


Addressing diversity and moving toward equity in hospital care.
Healthcare disparities are a major challenge for hospital and healthcare system leadership. Leaders must possess vision, visibility, and ability to drive organizational change toward an environment that fosters diversity and cultural competence. As challenging economic conditions force management to make difficult budgetary decisions, the integration of equity into the organization's core mission and strategic process is essential for sustainability. Building organizational capacity requires systematic actions including workforce composition, training and development, and policy advocacy. This article offers perspectives on the current state of diversity in hospitals, exemplars from pediatric hospitals, and considerations for the future. Healthcare leaders are influential in shaping the future of the organization through strategic planning and resource allocation to those efforts that enhance services, programs, and processes that support a culture of diversity and equity.


TNF Inhibitors Exert a "Hidden" Beneficial Effect in the Cardiovascular Lipoprotein Profile of RA Patients.
A high cardiovascular risk has been described in patients with rheumatoid arthritis (RA); the effects of different biological agents have also been described in these patients. The aim of the present study is to examine the effects of tumor necrosis factor inhibitors (TNFi) in the lipoprotein profile of RA patients using a broad laboratory assessment including a large number of non-routine tests. RA patients treated with and without TNFi (70 patients in each group) were cross-sectionally compared regarding a broad spectrum of lipoprotein parameters including serum levels of total and HDL, LDL and VLDL cholesterol triglycerides, lipoprotein A (LpA), apolipoprotein A1 (Apo A), B100 (Apo B) and paroxonase. For each lipoprotein subfraction (HDL, LDL and VLDL), we assess specific concentrations of cholesterol, triglycerides, phospholipids and proteins and total mass of each one. Additionally, HDL Apo A, LDL and VLDL Apo B concentrations and number of particles of LDL and VLDL were also determined. Exploratory univariate and multivariate analyses of the different variables were performed. Seventy patients in each subset were enrolled. Patients on treatment with TNFi showed a trend to be younger and to have a longer disease duration. Regarding the lipoprotein analyses, borderline significant higher levels of serum Apo A were detected and an independent association with lower HDL mass, LDL triglyceride, VLDL cholesterol, VLDL Apo B, VLDL mass, number of VLDL cholesterol molecules and number of particles of VLDL was clearly observed. TNFi treatment was associated with beneficial atherogenic effects at the lipoprotein level especially centered in the VLDL-related parameters consistent with a reduction of the atherogenic risk.


Quality of life among geriatric population residing in Bhavnagar city, Gujarat, Western India.
All of the health status, lifestyle, satisfaction, mental state, or well-being, all facets of health status together reflect the multidimensional nature of quality of life (QOL) in an individual. Our objective is to assess quality of life and factors affecting quality of life. We conducted a community-based cross-sectional study among 260 subjects (aged ≥ 60 years) residing in 13 wards of Bhavnagar city during September 2019-2020 after taking permission from ethics committee (no. 892) using the World Health Organization Quality of Life BREF-25 (WHO QOL BREF-25) scale. We assessed psychiatric morbidity using General Health Questionnaire-12 scale. Independent t-test was performed to find out factors associated with quality of life. Among 260 subjects, 36% were males. Study found highest score in psychological domain and lowest score in physical domain of WHO QOL BREF-25 scale. Physical health was better among Muslims, geriatrics <75 year of age, not addicted abusive substance and no co-morbid condition, whereas geriatrics belonged to upper socio-economic status and normal as per General Health Questionnaire-12 scale had better social relationship. Environmental domain score was significantly better among males and geriatric without co-morbidity. These findings highlight the importance of active ageing interventions in order to improve the quality of life.


Thermal conductivity in nanostructured films: from single cellulose nanocrystals to bulk films.
We achieved a multiscale description of the thermal conductivity of cellulose nanocrystals (CNCs) from single CNCs (∼0.72-5.7 W m(-1) K(-1)) to their organized nanostructured films (∼0.22-0.53 W m(-1) K(-1)) using experimental evidence and molecular dynamics (MD) simulation. The ratio of the approximate phonon mean free path (∼1.7-5.3 nm) to the lateral dimension of a single CNC (∼5-20 nm) suggested a contribution of crystal-crystal interfaces to polydisperse CNC film's heat transport. Based on this, we modeled the thermal conductivity of CNC films using MD-predicted single crystal and interface properties along with the degree of CNC alignment in the bulk films using Hermans order parameter. Film thermal conductivities were strongly correlated to the degree of CNC alignment and the direction of heat flow relative to the CNC chain axis. The low interfacial barrier to heat transport found for CNCs (∼9.4 to 12.6 m(2) K GW(-1)), and their versatile alignment capabilities offer unique opportunities in thermal conductivity control.


Thiol isomerase ERp57 targets and modulates the lectin pathway of complement activation.
ER protein 57 (ERp57), a thiol isomerase secreted from vascular cells, is essential for complete thrombus formation in vivo, but other extracellular ERp57 functions remain unexplored. Here, we employed a kinetic substrate-trapping approach to identify extracellular protein substrates of ERp57 in platelet-rich plasma. MS-based identification with immunochemical confirmation combined with gene ontology enrichment analysis revealed that ERp57 targets, among other substrates, components of the lectin pathway of complement activation: mannose-binding lectin, ficolin-2, ficolin-3, collectin-10, collectin-11, mannose-binding lectin-associated serine protease-1, and mannose-binding lectin-associated serine protease-2. Ficolin-3, the most abundant lectin pathway initiator in humans, circulates as disulfide-linked multimers of a monomer. ERp57 attenuated ficolin-3 ligand recognition and complement activation by cleaving intermolecular disulfide bonds in large ficolin-3 multimers, thereby reducing multimer size and ligand-binding affinity. We used MS to identify the disulfide-bonding pattern in ficolin-3 multimers and the disulfide bonds targeted by ERp57 and found that Cys6 and Cys23 in the N-terminal region of ficolin-3 form the intermolecular disulfide bonds in ficolin-3 multimers that are reduced by ERp57. Our results not only demonstrate that ERp57 can negatively regulate complement activation, but also identify a control mechanism for lectin pathway initiation in the vasculature. We conclude that extensive multimerization in large ficolin-3 multimers leads to a high affinity for ligands and strong complement-activating potential and that ERp57 suppresses complement activation by cleaving disulfide bonds in ficolin-3 and reducing its multimer size.


Adolescents with full or subthreshold anorexia nervosa in a naturalistic sample - characteristics and treatment outcome.
Anorexia Nervosa (AN) destroys developmentally important early years of many young people and knowledge is insufficient regarding course, treatment outcome and prognosis. Only a few naturalistic studies have been conducted within the field of eating disorder (ED) research. In this naturalistic study we included adolescents with AN or subthreshold AN treated in outpatient care, and the overall aim was to examine sample characteristics and treatment outcome. Additional aims were to examine potential factors associated with remission as an outcome variable, and possible differences between three time periods for treatment onset. Participants were identified through the Swedish national quality register for eating disorder treatment (SwEat), in which patients are registered at treatment onset and followed up once a year until end of treatment (EOT). Inclusion criteria were: medical or self-referral to one of the participating treatment units between 1999 and 2014, 13-19 years of age at initial entry into SwEat and diagnosed with AN or subthreshold AN. The total sample consisted of 3997 patient from 83 different treatment units. The results show that 55% of the participants were in remission and approximately 85% were within a healthy weight range at EOT. Of those who ended treatment according to plan, 70% were in remission and 90% within a healthy weight range. The average treatment duration was approximately 15 months. About one third of the patients terminated treatment prematurely, which was associated with a decreased chance of achieving remission. Remission rates and weight recovery increased over time, while treatment duration decreased. Considering treatment outcome, the results did not show any differences between patients with AN or subthreshold AN. The present study shows a relatively good prognosis for adolescent patients with AN or subthreshold AN in routine care and the results indicate that treatment for adolescents with ED in Sweden has become more effective over the past 15 years. The results of the present study contribute to the scope of treatment research and the large-scale naturalistic setting secures the generalizability to a clinical environment. However, more research is needed into different forms of evidence, new research strategies and diversity of treatment approaches. Registered in FOU in Sweden (Researchweb.org) 2014-04-14, ID nr 147301.


Infections and dilated cardiomyopathy in Nigeria.
The relationship of infection to dilated cardiomyopathy is reviewed on the basis of 200 patients seen at University College Hospital, Ibadan. Evidence of infection with Toxoplasma and Coxsackie B viruses is presented. Clinically detectable myocarditis is rare in children, and the preponderance of dilated cardiomyopathy is in patients above the age of 30 years, possibly because there is a long latent period between the initial infection and the development of frank cardiomyopathy. This paper concluded that infections are probably the most important cause of dilated cardiomyopathy in Nigeria.


Morphology and vulcanizate properties of ethylene-propylene-diene rubber/ styrene-butadiene rubber blends.
Morphology and vulcanizate properties of EPDM/SBR blends were investigated. AAHR (a mixture of aliphatic and aromatic hydrocarbon resins) was used as a compatibilizer and bis(3-triethoxysilylpropyl)tetrasulfide (TESPT) was used as a coupling agent. The vulcanizate properties and the morphological studies revealed that EPDM and SBR were incompatible, and the addition of AAHR was very effective to enhance the compatibility between EPDM and SBR. The weight percent of bound rubbers was increased with increasing SBR contents. The addition of an AAHR increased the amounts of bound rubbers, and hence the vulcanizate properties such as tear strength and fatigue resistance of the EPDM/SBR blends were improved. The dynamic mechanical analysis and the morphological studies revealed that the addition of TESPT increased the weight of bound rubbers and provided better dispersion of carbon black, resulting in good mechanical properties such as tear strength and fatigue resistance of the vulcanized EPDM/SBR blends. The smaller particle of zinc oxide (i.e., 50 nm > 100 nm > 1000 nm) yielded to the better blending properties of the polymer blend.


Hemorheological aspects of the metabolic syndrome: markers of insulin resistance, obesity or hyperinsulinemia?
The metabolic syndrome is a major health problem in western countries, due to the deleterious metabolic consequences of sedentarity and rich diet in the large part of the population who exhibits the so-called "thrifty phenotype". This syndrome, which is at high risk for diabetes and atherothrombosis is associated with hemorheologic abnormalities. Initially, insulin resistance was considered as the core of the syndrome. However, it becomes clear that the syndrome is a cluster in which the combined effects of obesity, insulin resistance, and hyperinsulinemia can be inconstantly associated. Thus, we investigated in 157 nondiabetic subjects (53 males and 104 females, age 35.6+/-1.1 yr, mean BMI 29.2+/-0.6 kg/m2) the respective importance of each of these factors. Subjects were divided in 6 groups according to BMI (cut-off point 25 kg/m2) and insulin sensitivity (SI) measured with the minimal model (lowest quartile SI<1.1 min(-1)/(microU/ml) x 10(-4), highest quartile SI>9.5, middle zone between 1.1 and 9.5). Results show that whole blood viscosity at high shear rate is higher in obese subjects (p<0.01). Plasma viscosity is also higher in obese subjects 1.41+/-0.02 vs 1.34+/-0.012 (p<0.01), and, in addition, in lean subjects, is lower when SI is in the upper quartile. RBC rigidity index "Tk" is higher in obese subjects. A worsening effect of insulin resistance (SI<1.1) on Tk is found only in obese subjects. The aggregability index "M1" is increased when SI<1.1 in both obese and nonobese subjects. No clear effect of either SI or obesity on hematocrit is observed. On the whole, obesity and insulin resistance both impair blood rheology by acting on red cell rigidity and plasma viscosity. Whole blood viscosity at high shear rate reflects rather obesity than insulin resistance. Myrenne "M1" aggregation is rather a marker of hyperinsulinemia. Thus, the hemorheologic picture of the metabolic syndrome is far to be only a reflect of insulin resistance alone.


Hepatocellular water and electrolyte secretion.
The study of hepatocellular water and electrolyte secretion has been hampered because of the inaccessibility of the hepatobiliary secretory lumen, the canaliculus. The advent of novel experimental models has allowed the application of electrophysiological techniques to investigate the ionic basis of hepatocellular secretion. The "hepatocyte couplet" isolated from the liver in primary monolayer cultures consists of two hepatocytes which enclose a single canalicular unit. The canaliculus of the couplet appears to behave as it would in vivo, exhibiting both secretory and contractile activity. Intracellular microelectrode recordings from this functional unit have permitted direct electrophysiological assessment of cellular and canalicular potentials and measurement of individual ion conductances across the basolateral membrane surface. Further, the application of patch-clamp electrophysiology to study hepatocellular ion transport pathways has characterized individual channel proteins. Intracellular and (or) patch-clamp electrophysiology has elucidated the ion conductance changes activated by bile salts like taurocholate, neurotransmitters like adrenaline, and hormones such as glucagon. These innovative approaches hold much promise in the future study of the ionic basis of hepatocellular secretion.


[The feasibility of the application of cryotherapy and radonotherapy for the treatment of the patients presenting with osteoarthritis].
Osteoarthritis (OA) is currently considered to be one of the most widespread diseases. Its main clinical symptoms include pain and dysfunction of joints. In the present review of the foreign and domestic literature, the questions of pathogenesis and risk factors underlying the development of osteoarthritis are discussed. The understanding of OA pathogenesis have altered essentially in the recent years which made necessary the search for the novel approaches to the treatment of this pathology. According to the modern views of OA origin and progression, its therapy should be based on the application of the combination of medicamentous and non-medicamentous modalities including, in particular, collective and individual activities focused on the implementation of the programs of therapeutic physical training as an obligatory component of ОА prophylaxis and treatment. The present review gives evidence of the feasibility of the application of the methods of cryotherapy and radonotherapy for the management of the patients suffering from osteoarthritis. It is emphasized that many recent publications report extensive investigations of the clinical and pathogenetic aspects of the application of these methods for the combined regenerative treatment of the patients presenting with gonarthrosis. The influence of cryotherapy and radonotherapy on the neuroendocrine and immune systems is discussed with special reference to the possibility of regulation of the metabolic processes and retardation of inflammation. It is concluded that the introduction of the above methods into the compulsory individual program for the regenerative treatment of patients presenting with osteoarthritis is pathologically substantiated since it greatly contributes to the reduction of pain and retardation of the progress of the disease. The main pharmaceutical preparations for the OA treatment remain to be slow-acting symptomatic medicines possessed of the chondro-protective effect.


Intimate partner violence and associated factors among pregnant women attending antenatal care service in Debre Markos town health facilities, Northwest Ethiopia.
Intimate partner violence is a thoughtful public health concern and human rights violation towards pregnant women for it has a significant negative health effect on the life of both the mother and her fetus. However, there is a scanty of information about the extent of intimate partner violence during pregnancy in Ethiopia, particularly in the study area. Therefore, the current study was conducted to determine the prevalence of intimate partner violence among pregnant women attending antenatal care and identify associated factors that cause it. An institution based cross-sectional study was conducted on 409 pregnant women who were attending antenatal care service in Debre Markos town from March 17, 2018 -April 28, 2018. Systematic random sampling technique was used to select study participants. A pre-tested structured questionnaire was used to collect the data. Bivariable and Multivariable logistic regression models were done. Adjusted odds ratio with 95% confidence interval was used to identify factors associated with intimate partner violence during pregnancy. The prevalence of intimate partner violence during current pregnancy was found to be 41.1% (95% confidence interval (CI): 36.0-46.0). Of this, the prevalence of psychological, physical, and sexual violence was 29.1%, 21%, 19.8% respectively. Lower educational status of partners (AOR = 3.26, 95%CI: 1.45-7.36), rural residency (AOR = 4.04, 95%CI: 1.17-13.93), frequent alcohol abuse by partner (AOR = 4.79, 95% CI: 2.08-11.04), early initiation of antenatal care (AOR = 0.44, 95% CI: 0.24-0.81), the age of women between 17-26 years (Adjusted odds ratio (AOR) = 0.21, 95%CI: 0.09-0.49),choice of partner by the women only (AOR = 3.26,95% CI:1.24-8.57) were statistically significant factors associated with intimate partner violence towards pregnant women. In this study, the prevalence of intimate partner violence during pregnancy is found to be high. As a result, interventions that would address the above mentioned factors need to be implemented.


Ameliorative Effect of Cactus (Opuntia ficus indica) Extract on Lithium-Induced Nephrocardiotoxicity: A Biochemical and Histopathological Study.
Opuntia ficus indica (family Cactaceae) is used in the treatment of a variety of conditions including metal-induced toxicity. The study reports the protective effects of Opuntia ficus indica (CCE) against lithium carbonate-induced toxicity in rats. Nephrocardiotoxicity was induced in male Wistar rats by single dose of lithium carbonate (25 mg/kg b.w twice daily for 30 days). Aqueous extract of Opuntia ficus indica was administered at the dose of 100 mg/kg of b.w by gavage for 60 days. Obtained results revealed that administration of lithium carbonate caused a significant increase in serum creatinine, uric acid, and urea levels. Additionally, a significant decrease in the level of renal and cardiac SOD, CAT, and GPx activities was associated with a significant increase of MDA levels in lithium carbonate group more than those of the control. However, the treatment of experimental rats with CCE prevented these alterations and maintained the antioxidant status. The histopathological observations supported the biochemical evidences of nephrocardioprotection. CCE supplementation could protect against lithium carbonate-induced renal and cardiac injuries in rats, plausibly by the upregulation of antioxidant enzymes and inhibition of MDA to confer the protective effect.


Research progress on iron absorption, transport, and molecular regulation strategy in plants.
Iron is a trace element essential for normal plant life activities and is involved in various metabolic pathways such as chlorophyll synthesis, photosynthesis, and respiration. Although iron is highly abundant in the earth's crust, the amount that can be absorbed and utilized by plants is very low. Therefore, plants have developed a series of systems for absorption, transport, and utilization in the course of long-term evolution. This review focuses on the findings of current studies of the Fe2+ absorption mechanism I, Fe3+ chelate absorption mechanism II and plant-microbial interaction iron absorption mechanism, particularly effective measures for artificially regulating plant iron absorption and transportation to promote plant growth and development. According to the available literature, the beneficial effects of using microbial fertilizers as iron fertilizers are promising but further evidence of the interaction mechanism between microorganisms and plants is required.


<Editors' Choice> Learning curve of robotic lobectomy for lung malignancies by certified thoracic surgeons.
Video-assisted thoracic surgery (VATS) has become widespread in the last 20 years, followed by robot-assisted thoracic surgery (RATS). Few studies compared the learning curve between RATS lobectomy and conventional VATS. This study included 79 RATS lobectomy cases performed in our hospital from November 2015 to October 2019. To estimate the required number for learning, the cumulative sum method, which is to plot a value obtained by sequentially accumulating a difference from a mean value was applied. As a result, the median total operative time and the median console time for all cases were 167 minutes and 138 minutes, respectively. Firstly, for our team, 28 cases were estimated to be required for learning curve for RATS lobectomy. For individual, each surgeon might be learned in only 5 to 6 cases. By contrast, the number of cases for learning VATS lobectomy which was underwent by a 'single' surgeon from 2009 was estimated to be 35 cases. The time to dock from start operation (median 14 minutes) reached plateau in 18 cases, but the time after rollout was median of 18 minutes and there was no significant change from the beginning. In conclusion, RATS lobectomy might be a technique that could be learned in a small number of cases compared to VATS. The results of this study might be helpful for certified surgeons who tried to get started with RATS and for establishing a learning program.


The effects of ingestion of hormonal host factors on the longevity and insecticide resistance phenotype of the major malaria vector Anopheles arabiensis (Diptera: Culicidae).
Exogenous vertebrate-derived factors circulating in the blood have the capacity to modulate the biology of haematophagous insects. These include insulin, insulin growth factor 1 (IGF) and transforming growth factor β1 (TGFβ). The effects of the consumption of these three proteins were examined on laboratory strains of Anopheles arabiensis. SENN, an insecticide susceptible strain and SENN DDT, a resistant strain selected from SENN, were fed with host factor-supplemented sucrose. Adult longevity was measured and insecticide resistance phenotype over time was assessed by WHO bioassay. Detoxification and oxidative stress defence enzyme activity was assessed calorimetrically. Insulin supplementation augmented insecticide resistance in young adult mosquitoes. This effect was due to the hormonal nature of the protein, as heat-denatured insulin did not elicit the same response. In contrast, IGF and TGFβ consumption generally reduced the expression of insecticide resistance. Insulin ingestion significantly reduced longevity in the insecticide susceptible strain. IGF elicited the same response in the susceptible strain, while TGF consumption had no effect on either strain. Consumption of all factors significantly decreased Glutathione S-transferase activity and increased cytochrome P450 and superoxide dismutase activity. This suggests that the altered detoxification phenotype is mediated primarily by cytochrome P450 activity, which would result in an increase in oxidative stress. The increased superoxide dismutase activity suggests that this enzyme class alleviates the oxidative stress as opposed to glutathione-based redox systems. Oxidative stress responses play a crucial role in insecticide resistance and longevity. These data show that ingested hormonal factors can affect mosquito longevity and insecticide susceptibility, both of which are important characteristics in terms of malaria transmission and control.


A vast repertoire of Dscam binding specificities arises from modular interactions of variable Ig domains.
Dscam encodes a family of cell surface proteins required for establishing neural circuits in Drosophila. Alternative splicing of Drosophila Dscam can generate 19,008 distinct extracellular domains containing different combinations of three variable immunoglobulin domains. To test the binding properties of many Dscam isoforms, we developed a high-throughput ELISA-based binding assay. We provide evidence that 95% (>18,000) of Dscam isoforms exhibit striking isoform-specific homophilic binding. We demonstrate that each of the three variable domains binds to the same variable domain in an opposing isoform and identify the structural elements that mediate this self-binding of each domain. These studies demonstrate that self-binding domains can assemble in different combinations to generate an enormous family of homophilic binding proteins. We propose that this vast repertoire of Dscam recognition molecules is sufficient to provide each neuron with a unique identity and homotypic binding specificity, thereby allowing neuronal processes to distinguish between self and nonself.


Histamine content of the digestive tract of a catfish Clarias batrachus (Linn.) in relation to spawning, sex and seasonal variation.
Histamine content of the digestive tract of a catfish Clarias batrachus has been estimated biologically on the atropinized guineapig ileum. A significant decrease of histamine content has been observed with the decrease of gonosomatic index (G.S.I.) during breeding season in female fishes, while no such type of change in histamine content of male fishes during breeding season has been noted. In the summer histamine content of both the sexes was signivicantly lowered in comparison with the histamine content during breeding season in both the sexes. It is concluded that higher histamine content in prespawing female fishes during breeding season may be due to the inhibition of the enzyme histaminase by gonadotrophines. It is also suggested that the route of inactivation of histamine during breeding season may be different in both the sexes, while in summer a common factor may be involved in depletion of histamine content of both the sexes.


Doublesex establishes sexual dimorphism in the Drosophila central nervous system in an isoform-dependent manner by directing cell number.
doublesex (dsx) encodes sex-specific transcription factors (DSX(F) in females and DSX(M) in males) that act at the bottom of the Drosophila somatic sex determination hierarchy. dsx, which is conserved among diverse taxa, is responsible for directing all aspects of Drosophila somatic sexual differentiation outside the nervous system. The role of dsx in the nervous system remainsminimally understood. Here, the mechanisms by which DSX acts to establish dimorphism in the central nervous system were examined. This study shows that the number of DSX-expressing cells in the central nervous system is sexually dimorphic during both pupal and adult stages. Additionally, the number of DSX-expressing cells depends on both the amount of DSX and the isoform present. One cluster of DSX-expressing neurons in the ventral nerve cord undergoes female-specific cell death that is DSX(F)-dependent. Another DSX-expressing cluster in the posterior brain undergoes more cell divisions in males than in females. Additionally, early in development, DSX(M) is present in a portion of the neural circuitry in which the male-specific product of fruitless (fru) is produced, in a region that has been shown to be critical for sex-specific behaviors. This study demonstrates that DSX(M) and FRU(M) expression patterns are established independent of each other in the regions of the central nervous system examined. In addition to the known role of dsx in establishing sexual dimorphism outside the central nervous system, the results demonstrate that DSX establishes sex-specific differences in neural circuitry by regulating the number of neurons using distinct mechanisms.


Engineering reactions in crystalline solids: predicting photochemical decarbonylation from calculated thermochemical parameters.
A detailed thermochemical analysis of the alpha-cleavage and decarbonylation reactions of acetone and several ketodiesters was carried out with the B3LYP/6-31G* density functional method. The heats of formation of several ground-state ketones and radicals were calculated at 298 K to determine bond dissociation energies (BDE) and radical stabilization energies (RSE) as a function of substituents. Results show that the radical-stabilizing abilities of the ketone substituents play a very important role on the thermodynamics of the alpha-cleavage and decarbonylation steps. An excellent correlation between calculated values and previous experimental observations suggests that photochemical alpha-cleavage and decarbonylation in crystals should be predictable from knowledge of excitation energies and the RSE of the substituent.


[Nontuberculous mycobacteriosis; the present status and in the future. 3-(2) Long-term prognosis of Mycobacterium avium complex disease].
This paper shows long-term course of 71 patients with Mycobacterium avium complex (MAC) disease treated in National Hiroshima Hospital between 1977 and 1991 and were observed for more than 5 years or died between 6 months and years from the onset. In the patients who were not treated with chemotherapeutic agent or treated with less than 3 drugs, about 60 per cent deteriorated and few obtained persistent negativity of bacteria. In patients treated with at least 3 drugs out of isoniazid, rifampicin, ethambutol, ethionamide, cycloserine, clarithromycin and new-quinolones for more than 12 months, 59.2 per cent deteriorated, while 29.6 per cent obtained negative conversion of bacteria by initial chemotherapy. However only 18.5 per cent remained negative during long term observation. In patients treated with at least 3 drugs including one aminoglycoside such as streptomycin for more than 12 months, 64.7 per cent obtained negative conversion and 35.5 per cent remained negative bacteriologically, while 23.5 per cent deteriorated. In twelve patients who were operated, only one patient deteriorated. The long-term prognosis of MAC disease under the chemotherapy mainly by antituberculous agents up to this time was still poor compared to that by short-term observation. Anticipated new regimens for MAC should be multidrug, to prevent secondary drug resistance.


Optimizing Outcomes in 2-Stage Prepectoral Breast Reconstruction Utilizing Round Form-Stable Implants.
Prepectoral breast reconstruction carries many benefits to patients, including its minimally invasive (muscle-sparing) nature, and its reduction in symptoms such as pain and animation deformity, relative to subpectoral reconstruction. However, without the traditional use of the pectoralis major muscle to mask the upper pole of the implant, and dictate the shape of the upper pole, certain steps must be taken to ensure the optimal aesthetic outcome in prepectoral reconstruction. Surgeons have utilized acellular dermal matrices, fat grafting, and highly cohesive implants to improve outcomes. Among the most important steps is the proper implant selection. To this end, the authors routinely utilize round form-stable gel implants, when performing prepectoral breast reconstruction. These implants offer improved aesthetic outcomes, given their ability to reduce rates of rippling and edge visibility. Furthermore, the characteristics of a soft and naturally shaped breast are achieved despite the lack of muscle coverage. The authors believe that reproducibly successful prepectoral reconstruction is dependent on proper technique. In this article, we present the proper techniques necessary for optimizing outcomes when using these implants in 2-stage prepectoral breast reconstruction.


How will I be when I will grow up? The importance of psychological intervention in pediatric patients to prevent symptoms from becoming chronical.
Psychological discomforts in pediatric patients, if not identified, and considered as personality traits can lead to abnormalities in the development. Identifying psychological problems and treating them with psychological intervention could avoid the raise of psychological disease in adulthood. The aim of this study is to evaluate the perception of self-image and interpersonal relationships of children affected by juvenile idiopathic arthritis (chronic pathology); to compare those data with those published in a previous research about enuretic children (functional pathology) and children affected by cleft palate (organic pathology). Forty children were tested using two Graphic Projective Tests: Machover test (Human Figure Drawing Test) and Corman test (Family Drawing Test) in order to assess specific disorders of their personality through the self-image perception and the emotional relationships with other members of family. Children affected by juvenile idiopathic arthritis show problems about the contact with the external world, underestimation of himself and inadequate perception of himself, exactly like children affected by enuresis and cleft lip and palate. Situation of discomfort, if not taken in consideration and seen as personality traits could easily become an emotional and behavioral chronic psychological disease.


Early failure of surgical angioplasty with tissue glue: a word of caution.
A 43-year-old woman with critical stenosis of the left main stem was managed with saphenous vein angioplasty using BioGlue. She developed severe myocardial ischemia postoperatively, probably due to external compression exerted on the patch by the adhesive material, and required emergency coronary artery bypass grafting.


Relationship of Circulating Fetuin-A Levels with Body Size and Metabolic Phenotypes.
Previous studies have suggested the existence of distinct body size subgroups according to metabolic health referred to as metabolically healthy obesity (MHO) and metabolically abnormal but normal weight (MANW) patients. Although nonalcoholic fatty liver disease (NAFLD) is strongly associated with obesity and metabolic syndrome, the relationship between these phenotypes and fetuin-A, a representative hepatokine, has not been explored. We examined the association between circulating fetuin-A levels, metabolic health phenotypes, cardiometabolic risk parameters, and subclinical atherosclerosis in 290 subjects who were randomly selected from an ongoing cohort study. Fetuin-A concentrations were significantly associated with detrimental anthropometric and laboratory measurements, including increased waist circumference, blood pressure, alanine aminotransferase, fasting plasma glucose, and triglyceride levels. Furthermore, fetuin-A levels were significantly increased in the metabolically abnormal (MA) group compared to the metabolically healthy (MH) group in subjects without obesity (717.1 [632.1, 769.7] vs. 599.5 [502.0, 709.3], P = 0.001) and subjects with obesity (704.1 [595.5-880.9] vs. 612.2 [547.9-802.1], P = 0.016). In addition, brachial-ankle pulse wave velocity (baPWV), which reflects arterial stiffness, was higher in MA individuals compared to MH individuals. Multiple logistic regression analysis revealed that both individuals without obesity (P for trend = 0.017) and with obesity (P for trend = 0.028) in the higher tertiles of fetuin-A had an increased risk of MA than those in the lowest tertile. This study demonstrates that fetuin-A levels are significantly associated with metabolic health phenotypes, such as MHO and MANW, in Korean adults.


The RIM101 signal transduction pathway regulates Candida albicans virulence during experimental keratomycosis.
To examine the role of the fungal RIM101 signal transduction pathway in the pathogenesis of Candida albicans keratitis. C. albicans wild-type strain SC5314, prototrophic mutant control DAY185, and homozygous fungal mutants for the rim8, rim13, rim20, rim101, and phr1 genes were evaluated in vitro using proliferation and filamentation assays. Scarified corneas of BALB/c and C57BL/6J mice were topically inoculated and observed daily for keratitis severity. Corneal adaptation and pathogenicity were assessed ex vivo by maintaining infected porcine corneas for 3 days in an explantation culture system for histologic evaluation of hyphal penetration. All C. albicans strains had similar growth kinetics, and SC5314 and DAY185 demonstrated pH-induced filamentation. Fungal mutants had reduced hyphal formation at alkaline and neutral pH, but normal acidic assays ascertained that mutant strains did not have a generalized filamentation defect. SC5314 and DAY185 caused moderate to severe keratitis in mice, whereas fungal strains lacking constituents of the RIM101 pathway had significantly (P<0.05) attenuated severity in vivo. Three days after inoculation of porcine corneas, SC5314 and DAY185 produced hyphae that penetrated 28% and 25%, respectively, of the corneal thickness, and all five mutant strains showed significantly (P<0.05) less stromal penetration. The RIM101 signal transduction pathway plays an important role in the development of C. albicans keratitis. The fungal pathway intermediates Rim8p, Rim13p, Rim20p, and Rim101p and the downstream cell-wall protein Phr1p are pivotal in the process of corneal invasion by C. albicans.


Coming or going? Un-BLOC-ing delivery and recycling pathways during melanosome maturation.
Melanosome biogenesis requires successive waves of cargo delivery from endosomes to immature melanosomes, coupled with recycling of the trafficking machinery. Dennis et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201605090) report differential roles for BLOC-1 and BLOC-3 complexes in delivery and recycling of melanosomal biogenetic components, supplying directionality to melanosome maturation.


[Arteriovenous sheathotomy in venous thrombosis].
The pathogenesis of branch retinal vein occlusion (BRVO) seems to differ from that of central retinal vein occlusion (CRVO). Arteriosclerotic and anatomic aspects suggest that arteriovenous crossing of vessels may play a significant role. New procedures like arteriovenous decompression have been proposed to be a suitable form of treatment. In a clinical trial, 12 patients with ischemic BRVO underwent surgical decompression. Strict criteria of inclusion were maintained. Arteriovenous sheathotomy (AVS) was performed 0.5 - 6 months after retinal vein occlusion. Follow up-time was 3 months. Visual acuity and incidence of typical complications after RVO were the main aspects of interest in the scientific evaluation. After surgical AVS, visual acuity increased significantly from logMAR 0.74 (decimal 0.18) to 0.56 (0.32) in EDTRS charts. Surgical or early complications did not occur during the 3-month control period. Improvement of retinal blood flow during angiography was demonstrated in 75 % of the patients. In 50 % of the patients all non-perfusion areas had disappeared. For patients with retinal vein occlusion, AVS seems to be a safe and feasible procedure according to the pathogenesis of branch occlusion. Our results suggest that AVS has the potential to improve visual acuity while typical complications due to surgery or vein occlusion do not occur during the first three months.


Reversible three-state switching of luminescence: a new twist to electro- and photochromic behavior.
The fully reversible three-state blue/red/off emission from photo-/electrochromic substituted bis-thiaxanthylidenes is reported. The blue luminescence of the most stable (anti-folded) conformer of dimethyl- and dimethoxy-bis-thiaxanthylidene can be switched off by photochemical conversion to the meta-stable (syn-folded) conformer and switched on again by thermal reversion to the anti-folded state. The red luminescence of the bis-thiaxanthylium dication can be switched on by oxidation at approximately 1.0 and 1.2 V vs SCE of the syn- and anti-folded conformers respectively and switched off or to blue by reduction at approximately 0.35 V vs SCE.


Surface-bonded amide-functionalized imidazolium ionic liquid as stationary phase for hydrophilic interaction liquid chromatography.
The amide group modified silica materials are popular stationary phases for hydrophilic interaction liquid chromatography (HILIC). Meanwhile, surface-confined imidazolium ionic liquids (ILs) have been proved to be useful HILIC stationary phases and possess many unique properties. In this study, the synthesis of an amide-functionalized imidazolium IL was conducted which was then bonded onto silica surface to obtain a novel imidazolium-embedded amide stationary phase for HILIC. The combination of the amide group and imidazolium IL moiety might bring some advantages in selectivity or retention and therefore extended its applications. After characterizing the prepared IL and the resulting modified silica materials, the chromatographic performance and separation selectivity of the packed column were evaluated and compared with a commercial amide column. Then, the retention behavior was investigated through observing the retention factors at different chromatographic conditions using a wide range of compounds. Exceptionally, the prepared amide IL column exhibited superior separation performance towards complex samples such as flavonoids mixture, soybean flavonoids and human urine. All the results indicated that the novel amide IL column possessed an anion-exchange/HILIC mixed-mode retention mechanism and could be useful in the sample analysis as a promising candidate for HILIC stationary phase.


Nanotherapeutics for inhibition of atherogenesis and modulation of inflammation in atherosclerotic plaques.
Atherosclerotic development is exacerbated by two coupled pathophysiological phenomena in plaque-resident cells: modified lipid trafficking and inflammation. To address this therapeutic challenge, we designed and investigated the efficacy in vitro and ex vivo of a novel 'composite' nanotherapeutic formulation with dual activity, wherein the nanoparticle core comprises the antioxidant α-tocopherol and the shell is based on sugar-derived amphiphilic polymers that exhibit scavenger receptor binding and counteract atherogenesis. Amphiphilic macromolecules were kinetically fabricated into serum-stable nanoparticles (NPs) using a core/shell configuration. The core of the NPs comprised either of a hydrophobe derived from mucic acid, M12, or the antioxidant α-tocopherol (α-T), while an amphiphile based on PEG-terminated M12 served as the shell. These composite NPs were then tested and validated for inhibition of oxidized lipid accumulation and inflammatory signalling in cultures of primary human macrophages, smooth muscle cells, and endothelial cells. Next, the NPs were evaluated for their athero-inflammatory effects in a novel ex vivo carotid plaque model and showed similar effects within human tissue. Incorporation of α-T into the hydrophobic core of the NPs caused a pronounced reduction in the inflammatory response, while maintaining high levels of anti-atherogenic efficacy. Sugar-based amphiphilic macromolecules can be complexed with α-T to establish new anti-athero-inflammatory nanotherapeutics. These dual efficacy NPs effectively inhibited key features of atherosclerosis (modified lipid uptake and the formation of foam cells) while demonstrating reduction in inflammatory markers based on a disease-mimetic model of human atherosclerotic plaques.


Identification of tanshinones and their metabolites in rat bile after oral administration of TTE-50, a standardized extract of Salvia miltiorrhiza by HPLC-ESI-DAD-MSn.
TTE-50 is a standardized extract of Salvia miltiorrhiza which mainly consisted of tanshinones. A sensitive and specific method using liquid chromatography-diode array detection-electrospray ionization (ESI) ion trap mass spectrometry was established for the study of the constituents and metabolites of TTE-50 in rat bile sample after oral administration. The bile samples were extracted with ethyl acetate (EtOAc) of three-fold volume for three times. The chromatographic separation was carried out on a Zorbax Extend-C18 column with a gradient elution program whereas acetonitrile-water was used as mobile phase. Mass spectra were acquired in positive ionization mode and data-dependant scan was used for the identification of the tanshinones and metabolites in the bile samples. Identification and structural elucidation of the tanshinones and their metabolites in bile samples were performed by comparing their retention-times and full scan MS(n) spectra with those of reference compounds and data in the literatures. Sixteen tanshinones in TTE-50 along with seventeen phase I metabolites were identified simultaneously. The metabolic modification could take place in the C-4 side chain of tanshinone IIA, from methyl to primary alcohol, then to aldehyde group was proposed for the first time. The established method was valuable for the study of the metabolism of complex system such as herbal extracts or traditional Chinese medicine (TCM) formula.


Advances in translational inner ear stem cell research.
Stem cell research is expanding our understanding of developmental biology as well as promising the development of new therapies for a range of different diseases. Within hearing research, the use of stem cells has focused mainly on cell replacement. Stem cells however have a broad range of other potential applications that are just beginning to be explored in the ear. Mesenchymal stem cells are an adult derived stem cell population that have been shown to produce growth factors, modulate the immune system and can differentiate into a wide variety of tissue types. Potential advantages of mesenchymal/adult stem cells are that they have no ethical constraints on their use. However, appropriate regulatory oversight seems necessary in order to protect patients from side effects. Disadvantages may be the lack of efficacy in many preclinical studies. But if proven safe and efficacious, they are easily translatable to clinical trials. The current review will focus on the potential application on mesenchymal stem cells for the treatment of inner ear disorders.


The relationship between non-invasive papillary lesions and invasive bladder carcinoma.
Ten patients with noninvasive papillary lesions who subsequently developed invasive bladder carcinoma were identified. Five of the 10 patients developed an invasive carcinoma in a location distinctly separate from any preceding papillary lesion. The remaining five patients developed an invasive carcinoma in the same general location as a preceding papillary lesion. These findings suggest that invasive bladder carcinomas, which develop in a patient with previous noninvasive papillary lesions, often arise from nonpapillary urothelium adjacent the noninvasive papillary lesion rather than directly from the preceding papillary lesion.


High-Throughput Method for Measuring Alcohol Sedation Time of Individual Drosophila melanogaster.
Drosophila melanogaster provides an excellent model to study the genetic underpinnings of alcohol sensitivity. In contrast to studies in human populations, the Drosophila model allows strict control over genetic background, and virtually unlimited numbers of individuals of the same genotype can be reared rapidly under well-controlled environmental conditions without regulatory restrictions and at relatively low cost. Flies exposed to ethanol undergo physiological and behavioral changes that resemble human alcohol intoxication, including loss of postural control, sedation, and development of tolerance. Here, we describe a simple, low-cost, high-throughput assay for assessing alcohol sedation sensitivity in large numbers of single flies. The assay is based on video recording of single flies introduced without anesthesia in 24-well cell culture plates in a set-up that enables synchronous initiation of alcohol exposure. The system enables a single person to collect individual ethanol sedation data on as many as 2,000 flies within an 8 h work period. The assay can, in principle, be extended to assess the effects of exposure to any volatile substance and applied to measure effects of acute toxicity of volatiles on other insects, including other fly species.


Security analysis of discretized polar modulation continuous-variable quantum key distribution.
In experimental setups of Gaussian modulation continuous-variable quantum key distribution (CV-QKD), the amplitude and phase of coherent states will be modulated and discretized due to the finite resolution of voltages that drive electro-optical modulators, resulting in Gaussian modulation discretization. We demonstrate that the impact of discretization on CV-QKD can be described as a multiplicative coefficient experimentally and modeled as a preparation noise imposed on ideal Gaussian modulation theoretically. To obtain an accurate estimation of quadrature fluctuation induced by discretized polar modulation, a data-filtering process named preselection can be applied before state transmission. Numerical results show that when amplitude resolution is 0.25 and phase resolution is 0.02, discretized polar modulation enables a transmission distance of 69 km under homodyne detection, reaching 89% of ideal Gaussian modulation. As for heterodyne detection, 55 km and 80% are achieved.


Novel optometrist-led all Wales primary eye-care services: evaluation of a prospective case series.
To derive an evidence base for the efficacy of two novel optometric primary eye care services in Wales, the Primary Eyecare Acute Referral Scheme (PEARS) and the Welsh Eye Health Examination (WEHE). A Donabedian model using structure, process and outcome was applied to evaluate prospectively 6432 individuals attending 274 optometrists within an 8-month period. Telephone interviews and review of optometric and hospital notes were used to determine management appropriateness for patients either managed in optometric practice or referred to the Hospital Eye Service (HES). A Geographic Information Systems analysis determined distances travelled to the optometrist. A cost analysis was used to determine the net cost of the schemes. 4243 (66%) of the 6432 individuals were managed in optometric practice; inappropriate management was apparent in 1% of individuals. 392 hospital notes were reviewed; 75% exhibited appropriate optometric referrals to the HES. 87% of individuals travelled less than 5 miles to attend an optometrist. The net cost of a PEARS/WEHE consultation was a minimum of pound12. Optometric management within the schemes is acceptable. Good equity of access was achieved at a relatively low net cost per consultation. Agreement on protocols for referral to the HES would enhance the schemes.


Self-assembly and stability of double rosette nanostructures with biological functionalities.
The syntheses of calix[4]arene dimelamines that are functionalized with alkyl, aminoalkyl, ureido, pyridyl, carbohydrate, amino acid and peptide functionalities, and their self-assembly with barbituric acid or cyanuric acid derivatives into well-defined hydrogen-bonded nanostructures are described. The thermodynamic stability of these hydrogen-bonded assemblies was studied by CD spectroscopy in mixtures of CHCl3 and MeOH. The stability of the assemblies depends on several steric factors and the polarity of the functional groups connected to the assembly components.


The role of semantic abstractness and perceptual category in processing speech accompanied by gestures.
Space and shape are distinct perceptual categories. In language, perceptual information can also be used to describe abstract semantic concepts like a "rising income" (space) or a "square personality" (shape). Despite being inherently concrete, co-speech gestures depicting space and shape can accompany concrete or abstract utterances. Here, we investigated the way that abstractness influences the neural processing of the perceptual categories of space and shape in gestures. Thus, we tested the hypothesis that the neural processing of perceptual categories is highly dependent on language context. In a two-factorial design, we investigated the neural basis for the processing of gestures containing shape (SH) and spatial information (SP) when accompanying concrete (c) or abstract (a) verbal utterances. During fMRI data acquisition participants were presented with short video clips of the four conditions (cSP, aSP, cSH, aSH) while performing an independent control task. Abstract (a) as opposed to concrete (c) utterances activated temporal lobes bilaterally and the left inferior frontal gyrus (IFG) for both shape-related (SH) and space-related (SP) utterances. An interaction of perceptual category and semantic abstractness in a more anterior part of the left IFG and inferior part of the posterior temporal lobe (pTL) indicates that abstractness strongly influenced the neural processing of space and shape information. Despite the concrete visual input of co-speech gestures in all conditions, space and shape information is processed differently depending on the semantic abstractness of its linguistic context.


Effect of schema-incongruent information on memory for stereotypical attributes.
Two studies were performed to determine the effect of incongruent information on recall of schematic information in the domain of person memory. Subjects heard descriptions of five sterotypical characters, followed by additional information varying in level of relevance to, and congruence with, the initial information. We measured free recall of the initial information establishing the schema, which included a stereotype label and two highly congruent facts. Results showed that the introduction of information that is highly incongruent with a schema makes schematic information more memorable, under both immediate- and delayed-recall conditions. This effect may be one mechanism by which inappropriate schemata persevere in the face of counterevidence. The pattern of results is found to be more consistent with Hastie's (1980) depth of processing-network associational model of schematic processing (with slight modification) than with Smith and Graesser's (1981) schema-pointer + tag model.


Activation, arousal, and neuropsychological rehabilitation.
This paper addresses the concept of arousal and the role of the reticular system in producing the orienting response. For patients with deviant autonomic responses, the use of central neuropharmacological stimulants is considered. Their therapeutic value is discussed in relation to hyperactive children and individual adult cases of the posttraumatic syndrome consequent upon traffic accidents.


Refined Method of Lipofilling following DIEP Breast Reconstruction: 3D Analysis of Graft Survival.
The deep inferior epigastric perforator (DIEP) flap technique gives good clinical results, but aesthetic surgical adjustments are often necessary. Lipofilling represents a good complementary method, but fat resorption within the few months after surgery limits its use. Recently, a new protocol was introduced and successfully evaluated on murine models. This study aims to evaluate this protocol following a DIEP procedure by three-dimensional analysis. Within a period of 4 months, every patient having undergone breast reconstruction with DIEP and who required a lipofilling adjustment was invited to take part in this study. All surgeries were performed using the Adip'sculpt disposable medical device MACROFILL (Laboratoires SEBBIN, Boissy-l'Aillerie, France). Fat resorption was analyzed using a three-dimensional photography system. Twenty-three patients were included, with a total of 25 breasts operated on. Injections were carried out on irradiated breasts in 73% of cases, and average injection volume was 124 mL (SD = 39 mL), whereas average operating time was 68 minutes (44-96 minutes). At an average follow-up of 5 months (4-8 months), 70.9% of projection gain afforded by the lipofilling was still present. It is now clear that particular rules should be respected for an efficient lipofilling, particularly regarding aspiration cannula characteristics, vacuum used, and the necessity of washes and soft centrifugations. We demonstrate here that by following a specific protocol that addresses these precautions, while using material that is specifically adapted, a 70.9% fat survival rate can be achieved, even in the very unfavorable case of postirradiation DIEP breast reconstruction.