Network of the sympathetic nervous system: focus on the input and output of the cervical sympathetic ganglion.
Unlike the thoracic and lumbar sympathetic nervous systems with paravertebral ganglions in individual spinal segments, the cervical sympathetic nervous system lacks segmental structures corresponding to the spinal segments and only three ganglions, namely the upper and middle cervical ganglions and the stellate ganglion, are present. Single axons have been observed in the ganglions using an anterograde-labeling method to analyze their expansion in order to investigate the relationship between the cervical sympathetic ganglions and the spinal cord in rats. Although segmental structures were not confirmed in the upper cervical ganglion, segmental structures were demonstrated in the stellate ganglion. Next, it was determined that some sympathetic preganglionic neurons, nitric oxide synthetase-positive preganglionic neurons, form dense nerve endings on the upper cervical ganglion neurons that project onto organs closely related to glandular secretion in the head and neck region. Finally, the relationship between the cell body size of upper cervical ganglion neurons and the size of the target was investigated for the three major salivary glands in rats and it was determined that no direct relationship was present.


Consensus Clustering of temporal profiles for the identification of metabolic markers of pre-diabetes in childhood (EarlyBird 73).
In longitudinal clinical studies, methodologies available for the analysis of multivariate data with multivariate methods are relatively limited. Here, we present Consensus Clustering (CClust) a new computational method based on clustering of time profiles and posterior identification of correlation between clusters and predictors. Subjects are first clustered in groups according to a response variable temporal profile, using a robust consensus-based strategy. To discover which of the remaining variables are associated with the resulting groups, a non-parametric hypothesis test is performed between groups at every time point, and then the results are aggregated according to the Fisher method. Our approach is tested through its application to the EarlyBird cohort database, which contains temporal variations of clinical, metabolic, and anthropometric profiles in a population of 150 children followed-up annually from age 5 to age 16. Our results show that our consensus-based method is able to overcome the problem of the approach-dependent results produced by current clustering algorithms, producing groups defined according to Insulin Resistance (IR) and biological age (Tanner Score). Moreover, it provides meaningful biological results confirmed by hypothesis testing with most of the main clinical variables. These results position CClust as a valid alternative for the analysis of multivariate longitudinal data.


Enhancement of gentamicin nephrotoxicity by magnesium depletion in the rat.
This study examined the possible enhancement of gentamicin-induced nephrotoxicity by coexisting magnesium depletion. The effect of concurrent magnesium depletion on enhancing gentamicin-induced nephrotoxicity was measured by azotemia and mortality contrasted to magnesium repleted control rats also receiving gentamicin. After 28 days of dietary preparation, magnesium depleted rats and their magnesium repleted controls were each subdivided into 3 groups: (1) saline injection (NS); (2) gentamicin 80 mg/kg/day, and (3) gentamicin 120 mg/kg/day. Injections were continued for 14 days. All rats receiving gentamicin had proteinuria, increased mortality and significant renal morphological abnormalities. However, those rats which were concurrently magnesium depleted had statistically significant increments in BUN levels, more apparent renal tubular damage, and earlier mortality than the magnesium repleted controls. These observations support the view that concurrent magnesium deficiency in the rat enhanced gentamicin nephrotoxicity.


Inhibition of LPS-stimulated NO production in mouse macrophage-like cells by benzocycloheptoxazines.
Twenty-six benzocycloheptoxazine derivatives were investigated for their effect on nitric oxide (NO) production by lipopolysaccharide (LPS)-stimulated mouse macrophage-like RAW 264.7 cells. Benzo[b]cyclohepta[e][1,4]thiazine most effectively inhibited the LPS-stimulated NO production at noncytotoxic concentrations. 6H-Benzo[b]cyclohepta[e][1,4]-diazine cation, and benzo[b]cyclohepta[e][1,4]oxazine and its 6-bromo derivative also efficiently inhibited the LPS-stimulated NO production. Another sixteen benzo[b]cyclohepta[e]-[1,4]oxazine derivatives, 14H-[1,4]benzoxazino[3',2' :3,4]-cyclohepta[1,2-b][1,4]benzoxazine and its 7-bromo- and 7-isopropyl derivatives were slightly less active (selectivity index (SI)=83-66). Bromination of benzo[b]cyclohepta[e][1,4]-thiazine, benzo[b]cyclohepta[e][1,4]oxazine and 2-methylbenzo[b]cyclohepta[e][1,4]oxazine at C-6, C-8 or C-10 positions resulted in the significant reduction of the inhibitory activity. The observed inhibitory activity of benzo[b]cyclohepta-[e][1,4]thiazine and its 6,8-dibromo derivatives were not due to the reduction of the intracellular level of inducible NO synthase protein (based on Western blot analysis), nor to NO scavenging activity (based on ESR spectroscopy). These results suggest the possible anti-inflammatory action of benzocyclo-heptoxazines via inhibition of LPS-activated macrophages.


Direct Catalytic Desaturation of Lactams Enabled by Soft Enolization.
A direct catalytic method is described for the α,β-desaturation of N-protected lactams to their conjugated unsaturated counterparts under mildly acidic conditions. The reaction is consistently operated at room temperature and tolerates a wide range of functional groups, showing reactivity complementary to that of prior desaturation methods. Lactams with various ring sizes and substituents at different positions all reacted smoothly. The synthetic utility of this method is demonstrated in a concise synthesis of Rolipram. In addition, linear amides also prove to be competent substrates, and the phthaloyl-protected product serves as a convenient precursor to access various conjugated carboxylic acid derivatives. Strong bases are avoided in this desaturation approach, and the key is to merge soft enolization with a Pd-catalyzed oxidation process.


Lessons Learned from the COVID-19 Pandemic: Emphasizing the Emerging Role and Perspectives from Artificial Intelligence, Mobile Health, and Digital Laboratory Medicine.
SARS-CoV-2, the new coronavirus causing COVID-19, is one of the most contagious disease of past decades. COVID-19 is different only in that everyone is encountering it for the first time during this pandemic. The world has gone from complete ignorance to a blitz of details in a matter of months. The foremost challenge that the scientific community faces is to understand the growth and transmission capability of the virus. As the world grapples with the global pandemic, people are spending more time than ever before living and working in the digital milieu, and the adoption of Artificial Intelligence (AI) is propelled to an unprecedented level especially as AI has already proven to play an important role in counteracting COVID-19. AI and Data Science are rapidly becoming important tools in clinical research, precision medicine, biomedical discovery and medical diagnostics. Machine learning (ML) and their subsets, such as deep learning, are also referred to as cognitive computing due to their foundational basis and relationship to cognition. To date, AI based techniques are helping epidemiologists in projecting the spread of virus, contact tracing, early detection, monitoring, social distancing, compiling data and training of healthcare workers. Beside AI, the use of telemedicine, mobile health or mHealth and the Internet of Things (IOT) is also emerging. These techniques have proven to be powerful tools in fighting against the pandemic because they provide strong support in pandemic prevention and control. The present study highlights applications and evaluations of these technologies, practices, and health delivery services as well as regulatory and ethical challenges regarding AI/ML-based medical products.


Does dextran 40 reduce early graft thrombogenicity? An experimental investigation on patency and platelet deposition on prosthetic graft materials in sheep.
The mechanism by which dextran 40 reduces early graft thrombogenicity has not been fully elucidated. Dextran improves haemaodynamics, reduces platelet aggregation, alters fibrin formation and enhances thrombus lysis. In this experimental investigation on sheep using a low flow model, the thrombogenicity of various grafts was studied when either a dextran or saline infusion was given. Bilateral carotid interposition grafts with expanded polytetrafluorethylene (ePTFE) on one side and dacron on the other (random allocation) were inserted in 12 sheep. The sheep were randomly divided into two groups, one given a dextran infusion and the other saline. A tendency for improved graft patency was seen in the dextran 40 treated animals (P less than 0.05 at 3 h). However, platelet accumulation did not differ markedly between the dextran 40 and saline treated groups. On the other hand there was a clear reduction of platelet accumulation on ePTFE grafts compared to dacron grafts (P less than 0.01). A large part of the radioactivity measured from the dacron graft was located within the graft wall. Further studies to clarify the mechanism of action of dextran are needed.


Simulation of absorption spectra of molecular aggregates: A hierarchy of stochastic pure state approach.
Simulation of spectroscopic observables for molecular aggregates with strong and structured coupling of electronic excitation to vibrational degrees of freedom is an important but challenging task. The Hierarchy of Pure States (HOPS) provides a formally exact solution based on local, stochastic trajectories. Exploiting the localization of HOPS for the simulation of absorption spectra in large aggregates requires a formulation in terms of normalized trajectories. Here, we provide a normalized dyadic equation where the ket- and bra-states are propagated in different electronic Hilbert spaces. This work opens the door to applying adaptive HOPS methods for the simulation of absorption spectra.


The Rhodobacter capsulatus genome.
The genome of Rhodobacter capsulatus has been completely sequenced. It consists of a single chromosome containing 3.5 Mb and a circular plasmid of 134 kb. This effort, started in 1992, began with a fine-structure restriction map of an overlapping set of cosmids that covered the genome. Cosmid sequencing led to a gapped genome that was filled by primer walking on the chromosome and by using lambda clones. Methods had to be developed to handle strong stops in the high GC (68%) inserts. Annotation was done with the ERGO system at Integrated Genomics, as was the reconstruction of the cell's metabolism. It was possible to recognize 3709 orfs of which functional assignments could be made with high confidence to 2392 (65%). Unusual features include the presence of numerous cryptic phage genomes embedded in the chromosome.


Impact of breast MRI in women eligible for breast conservation surgery and intra-operative radiation therapy.
The current standard of care for women diagnosed with early stage breast cancer is breast-conserving surgery (BCS) followed by external beam radiation therapy, commonly delivered over 3-6 weeks. As an alternative, select patients can undergo intra-operative radiation therapy (IORT) at the time of BCT. This technique delivers a single fraction of radiation at the time of surgery, enabling patients to undergo both surgery and radiation in a single session. Our current study analyzed the value of incorporating breast MRI into the routine work-up of patients deemed eligible for IORT, to quantify the impact on patient eligibility and requirement for additional work-up. We retrospectively identified patients treated by a single surgeon who were eligible for IORT based on institutional eligibility criteria which included: women age ≥55, grades 1-2, size <3 cm, estrogen receptor (ER) positive, Her-2 neu non-amplified and low/intermediate Ki-67, unifocal invasive ductal/mixed histology carcinomas. All patients must have undergone a physical exam and bilateral diagnostic mammography with ultrasound. From this population, we identified all patients who had undergone bilateral breast MRI as part of pre-operative evaluation. A total of 215 women were identified who met all eligibility criteria. MRI detected additional abnormalities in the breast in 89 patients (41%). Sixty-eight women underwent additional biopsies, with a total of 117 separate lesions biopsied. Of these, pathology was benign in 61 (52.1%), atypical ductal hyperplasia (ADH) in 21 (18%), ductal carcinoma in-situ (DCIS) in 17 (14.5%) and invasive disease in 18 (15.4%). Six patients had MRI-detected abnormalities in the contralateral breast only, with biopsies identifying invasive disease (3), DCIS (1) and benign (2) findings. MRI showed abnormalities in both breasts in 6 patients and 18 additional lesions were biopsied which reveled invasive carcinoma (6), DCIS (7), ADH (3) and benign findings (2). Fifteen patients had either multifocal/multicentric disease or index lesion >3 cm on MRI and were deemed ineligible for IORT. Based on either MRI size or biopsy results, management was ultimately changed for 27 patients (12.5%). Extramammary findings were observed in 17 patients and 11 of these patients underwent further imaging studies all of which returned negative results. Preoperative bilateral breast MRI is a valuable tool in the proper selection of patients best suited for IORT. Even in highly selected, favorable risk patients, MRI detected additional lesions that changed surgical and radiation therapy recommendations in 12.5% of patients. However, the cost/benefit ratio needs to be taken into consideration given the high frequency of benign biopsies and additional radiological work-up.


Water quality assessment of the Sinchun stream based on epilithic diatom communities.
Water quality was assessed 11 sites on the Sinchun Stream, in the region of Daegu City (South Korea), from May 2007 to March 2008 using Diatom Assemblage Index to Organic Water Pollution (DAIpo) and Trophic Diatom Index (TDI). The reference sites were unaffected by effluent from a closed mine or treated sewage and had, epilithic diatom communities that were dominated by saproxenous taxa such as Achnanthes convergens and Cocconeisplacentula var. lineata. The water quality of these sites had DAIpo values ranging between 77.5-93.8 and TDI values between 51.3-67.6, indicating β-oligosaprobic and mesotrophic environments, respectively. Study sites affected by effluent from the closed mine had epilithic diatom communities that were dominated by acidobiontic diatoms, such as Eunotia exigua and Achnanthidium minutissimum. The water quality of these sites had DAlpo values of 45.9-70.8, indicating β-mesosaprobic to α-oligosaprobic environments, whereas TDI ranged between 1.7-66.9, indicating an oligotrophic to mesotrophic environment. Downstream sites affected by the influx of mine effluent and treated sewage had many species and a high percentage of saprophilous taxa, including Fragilaria construens var. venter and Nitzschia amphibia. The water quality of these regions had DAIpo values ranging between 21.8-33.1 and TDI values between 67.5-76.7, indicating α-mesosaprobic and eutrophic environments, respectively.


Inhibition by colchicine of changes in amino acid transport and initiation of DNA synthesis in regenerating rat liver.
The uptake of amino acids (measured with alpha-aminoisobutyric acid) by hepatocytes stimulated to proliferate by partial hepatectomy followed a biphasic pattern, with an initial peak 8-10 hr after surgery followed by a release of amino acids between 10 and 16 hr and a further increase between 16 and 20 hr after the operation. The second period of increased uptake coincided with the increase in DNA synthesis by the hepatocytes. Colchicine, and other microtubule disrupters administered at the time of partial hepatectomy, abolished the first period of increased amino acid uptake and prevented the cells from initiating DNA synthesis. Pulse-labeling experiments with alpha-aminoisobutyric acid revealed that colchicine did not inhibit amino acid transport per se, but prevented the increased capacity for amino acid transport induced by partial hepatectomy. An injection of colchicine 14 hr after hepatectomy prevented the release of amino acids by the liver and also substantially reduced the initiation of DNA synthesis. The data suggest that the microtubules may play a role in proliferative activation and also in the initiation of DNA synthesis of hepatocytes in vivo and that changes in amino acid transport are linked to these microtubule-requiring processes.


A novel nonobese diabetic/severe combined immunodeficient xenograft model for chronic lymphocytic leukemia reflects important clinical characteristics of the disease.
We here describe a novel xenograft model of chronic lymphocytic leukemia (CLL) generated by infusion of human primary CLL cells into immunodeficient nonobese/severe combined immunodeficient (NOD/SCID) mice. Combined i.v. and i.p. injection of peripheral blood mononuclear cells (PBMC) from 39 patients with CLL resulted in highly reproducible splenic (37 of 39) and peritoneal (35 of 39) engraftment, which remained stable over a time span of 4 to 8 weeks. By comparison, recovery of leukemic cells from bone marrow (21 of 39) or peripheral blood (8 of 22) was substantially lower. The engraftment pattern of CLL PBMC 4 weeks posttransplant was correlated with clinical disease activity: infusion of PBMC from donors with Binet stage A, lymphocyte doubling time of >12 months, and normal lactate dehydrogenase (LDH) serum levels led to marked engraftment of T cells whereas comparably few tumor cells could be detected. In contrast, NOD/SCID mice receiving PBMC from donors with advanced stage Binet C, lymphocyte doubling time of <12 months, and elevated LDH serum levels exhibited predominant engraftment of tumor cells and comparably low numbers of T cells. These results suggest that this model reflects the heterogeneity and important clinical characteristics of the disease, and thus may serve as a tool for preclinical drug testing and investigation of the pathophysiology of CLL.


[Penile adenoma: clinical case].
Penile melanoma is a very uncommon neoplasm, being reported less than 60 cases. Event yet it outlines not few doubts about its diagnosis and treatment, and in advanced stages represents a challenge for the future since it prognosis is awful at short time. In the present article, its presented a glans melanoma diagnosed and treated at our Service. We make a brief revision of the literature and some basic issues on the management of this entity when it's localized in penis, since in the cases in which it extends far from this organ is yet oncological field.


3D MR angiography of renal arteries: comparison of volume rendering and maximum intensity projection algorithms.
To compare volume rendering (VR) and maximum intensity projection (MIP) as postprocessing techniques of magnetic resonance (MR) angiography for detection and quantification of renal artery stenosis. Twenty-seven patients underwent three-dimensional contrast material-enhanced MR angiography of the renal arteries with a 1.5-T imager. For each renal artery, targeted MIP and VR images were reconstructed in oblique coronal and transverse orientations. For each modality, image generation and evaluation were performed interactively by two independent radiologists blinded to angiographic results. In comparison with digital subtraction angiography (DSA) findings, stenosis quantification and detection by using MIP and VR were evaluated with the use of 50% and 70% cutoff points by using linear regression analysis and 2 x 2 tables. Overall image quality and vascular delineation on MIP and VR images were also compared. All main and accessory renal arteries depicted at DSA were also demonstrated on MIP and VR images. VR performed slightly better than MIP for quantification of stenoses greater than 50% (VR: r(2) = 0.84, P <.001; MIP: r(2) = 0.38, P =.001) and significantly better for severe stenoses (VR: r(2) = 0.83, P <.001; MIP: r(2) = 0.21, P =.1). For detection of stenosis, VR yielded a substantial improvement in positive predictive value (VR: 95% and 90%; MIP: 86% and 68% for stenoses greater than 50% and 70%, respectively). Image quality obtained with VR was not significantly better than that with MIP; however, vascular delineation on VR images was significantly better. The VR technique of renal MR angiography enabled more accurate detection and quantification of renal artery stenosis than did MIP, with significantly improved vascular delineation.


Recovery and phylogenetic analysis of archaeal rRNA sequences from continental shelf sediments.
Phylogenetic analyses of archaeal 16S rRNA genes (rDNA) from DNA extracted from continental shelf sediments revealed the presence of two major lineages, belonging to the kingdoms Crenarchaeota and Euryarchacota, respectively. Our analyses indicate that the benthic Archaea belong to a new group, divergent from the marine low-temperature planktonic Archaea. This is the first report showing the existence of Archaea, unrelated to methanogens, specifically associated with low-temperature anoxic marine sediments.


A late-phase, long-term memory trace forms in the γ neurons of Drosophila mushroom bodies after olfactory classical conditioning.
Using functional optical imaging in vivo, we demonstrate that the γ mushroom body (MB) neurons of Drosophila melanogaster respond with axonal calcium influx when odors or electric shock stimuli are presented to the fly. Pairing of odor and electric shock stimuli in a single training trial or multiple, massed training trials failed to modify the odor-evoked calcium signal when flies were tested at several different times after training. In contrast, animals that received multiple but spaced odor-shock pairings exhibited a robust increase in calcium influx into the MB axons when tested between 18 and 48 h after training. This time window for the γ neuron memory trace is displaced relative to the modifications that occur between 9 and 24 h after training in the α branch of the α/β MB neurons. The α/β and the γ neuron long-term memory traces were both blocked by expressing a repressor of the transcription factor cAMP response element-binding protein or a calcium/calmodulin-dependent kinase II hairpin RNA. These results demonstrate that behavioral long-term olfactory memory is encoded as modifications of calcium influx into distinct MB neurons during overlapping but different windows of time after training.


Two analytical approaches quantifying the electron donating capacities of dissolved organic matter to monitor its oxidation during chlorination and ozonation.
Electron-donating activated aromatic moieties, including phenols, in dissolved organic matter (DOM) partially control its reactivity with the chemical oxidants ozone and chlorine. This comparative study introduces two sensitive analytical systems to directly and selectively quantify the electron-donating capacity (EDC) of DOM, which corresponds to the number of electrons transferred from activated aromatic moieties, including phenols, to the added chemical oxidant 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonate) radical cation (i.e., ABTS•+). The first system separates DOM by size exclusion chromatography (SEC) followed by a post-column reaction with ABTS•+ and a spectrophotometric quantification of the reduction of ABTS•+ by DOM. The second system employs flow-injection analysis (FIA) coupled to electrochemical detection to quantify ABTS•+ reduction by DOM. Both systems have very low limits of quantification, allowing determination of EDC values of dilute DOM samples with <1 mg carbon per liter. When applied to ozonated and chlorinated model DOM isolates and real water samples, the two analytical systems showed that EDC values of the treated DOM decrease with increasing specific oxidant doses. The EDC decreases detected by the two systems were in overall good agreement except for one sample containing DOM with a very low EDC. The combination of EDC with UV-absorbance measurements gives further insights into the chemical reaction pathways of DOM with chemical oxidants such as ozone or chlorine. We propose the use of EDC in water treatment facilities as a readily measurable parameter to determine the content of electron-donating aromatic moieties in DOM and thereby its reactivity with added chemical oxidants.


INITIAL EXPERIENCE OF THE ENZALUTAMIDE TREATMENT FOR CASTRATION-RESISTANT PROSTATE CANCER.
(Objective) Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with castration-resistant prostate cancer (CRPC). We retrospectively evaluated clinical efficacy and safety of enzalutamide in CRPC. (Patients and methods) We reviewed clinical records of 73 patients who had received enzalutamide for the CRPC at Showa University and affiliated 7 hospitals. Enzalutamide was given at a dose of 160 mg/day, but some patients were treated at lower dose because of there age or poor performance status. Prostrate-specific antigen (PSA) response, prior docetaxel use and the previously administered agents were evaluated retrospectively. (Results) The median patients age was 77 years, the median Gleason score was 9 and the median PSA level at baseline was 26.9 ng/ml. The patients who had prior docetaxel use were 29 (39.7%) and the median of total docetaxel dose was 460 mg/body. The median number of total prior treatments (anti-androgens, Estramustine and steroid) was 3. Twenty seven (61.4%) patients with docetaxel-naïve achieved over 50% reduction of PSA level from baseline, but only 7 (24.1%) in patients previously treated with docetaxel. The most common adverse events included fatigue (24.7%), anorexia (24.7%) and the nausea (16.4%). We found a small proportion of responders to enzalutamide experienced a PSA flare. (Conclusion) Our results of the use of Enzaltamide for CRPC were similar with previous reports. PSA flare was found in some patients with CRPC who responded to enzaltamide. It should be noted that this possible PSA flare phenomenon.


A Phospho-SIM in the Antiviral Protein PML is Required for Its Recruitment to HSV-1 Genomes.
Herpes simplex virus type 1 (HSV-1) is a significant human pathogen that infects a large portion of the human population. Cells deploy a variety of defenses to limit the extent to which the virus can replicate. One such factor is the promyelocytic leukemia (PML) protein, the nucleating and organizing factor of nuclear domain 10 (ND10). PML responds to a number of stimuli and is implicated in intrinsic and innate cellular antiviral defenses against HSV-1. While the role of PML in a number of cellular pathways is controlled by post-translational modifications, the effects of phosphorylation on its antiviral activity toward HSV-1 have been largely unexplored. Consequently, we mapped phosphorylation sites on PML, mutated these and other known phosphorylation sites on PML isoform I (PML-I), and examined their effects on a number of PML's activities. Our results show that phosphorylation at most sites on PML-I is dispensable for the formation of ND10s and colocalization between PML-I and the HSV-1 regulatory protein, ICP0, which antagonizes PML-I function. However, inhibiting phosphorylation at sites near the SUMO-interaction motif (SIM) of PML-I impairs its ability to respond to HSV-1 infection. Overall, our data suggest that PML phosphorylation regulates its antiviral activity against HSV-1.


Toward deformation densities for intramolecular interactions without radical reference states using the fragment, atom, localized, delocalized, and interatomic (FALDI) charge density decomposition scheme.
A novel approach for calculating deformation densities is presented, which enables to calculate the deformation density resulting from a change between two chemical states, typically conformers, without the need for radical fragments. The Fragment, Atom, Localized, Delocalized, and Interatomic (FALDI) charge density decomposition scheme is introduced, which is applicable to static electron densities (FALDI-ED), conformational deformation densities (FALDI-DD) as well as orthodox fragment-based deformation densities. The formation of an intramolecular NH⋅⋅⋅N interaction in protonated ethylene diamine is used as a case study where the FALDI-based conformational deformation densities (with atomic or fragment resolution) are compared with an orthodox EDA-based approach. Atomic and fragment deformation densities revealed in real-space details that (i) pointed at the origin of density changes associated with the intramolecular H-bond formation and (ii) fully support the IUPAC H-bond representation. The FALDI scheme is equally applicable to intra- and intermolecular interactions. © 2017 Wiley Periodicals, Inc.


Caffeic acid derivatives, analogs and applications: a patent review (2009-2013).
Caffeic acid (CA) is broadly distributed in several species of the plant kingdom and is widely consumed in human diet. CA and derivatives have been extensively studied in the past years, which unveiled a broad spectrum of biological activities and potential therapeutic applications. As a result, there has been an upsurge in the development of new chemical entities based on the CA scaffold. The scope of this review is to revisit the therapeutic potential of CA and derivatives. It provides an overview of patented processes and applications thereof between 2009 and 2013. The phenylpropanoid framework is currently considered a valid structure for drug discovery programs. Actually, CA has been widely used as a template for the development of new chemical entities with potential therapeutic interest in human diseases associated with oxidative stress. Additionally, the applicability of CA derivatives expands to the realms of cosmetic industry due to its stabilizing properties. The synthesis of esters, amides and hybrids with currently marketed drugs is a trending strategy for the development of derivatives with therapeutic application. It is our opinion that the innovative artwork currently being developed involving this chemical scaffold will yield new and effective therapeutic agents in a foreseeable future.


Old Photo Restoration via Deep Latent Space Translation.
We propose to restore old photos that suffer from severe degradation through a deep learning approach. Unlike conventional restoration tasks that can be solved through supervised learning, the degradation in real photos is complex and the domain gap between synthetic images and real old photos makes the network fail to generalize. Therefore, we propose a novel triplet domain translation network by leveraging real photos along with massive synthetic image pairs. Specifically, we train two variational autoencoders (VAEs) to respectively transform old photos and clean photos into two latent spaces. And the translation between these two latent spaces is learned with synthetic paired data. This translation generalizes well to real photos because the domain gap is closed in the compact latent space. Besides, to address multiple degradations mixed in one old photo, we design a global branch with a partial nonlocal block targeting the structured defects, such as scratches and dust spots, and a local branch targeting the unstructured defects, such as noises and blurriness. We also extend the global branch with a more memory-efficient scheme, named multi-scale patch-based attention to processing high-resolution photos. Two branches are fused in the latent space, leading to improved capability to restore old photos from multiple defects. Furthermore, we apply another face refinement network to recover fine details of faces in the old photos, thus ultimately generating photos with enhanced perceptual quality. With comprehensive experiments, the proposed pipeline demonstrates superior performance over state-of-the-art methods as well as existing commercial tools in terms of visual quality for old photos restoration. Both code and models could be found at https://github.com/microsoft/Bringing-Old-Photos-Back-to-Life.


Human gammadelta T cells modulate the mite allergen-specific T-helper type 2-skewed immunity.
Gammadelta T cells have been described as one of immune regulators in patients with infection, malignancy, and allergy. To elucidate the ability of gammadelta T cells as an allergen immunotherapy candidate, the effectiveness of human gammadelta T cells in allergen-specific T-helper type 2 (Th2)-type T cells was evaluated in vitro. House dust mite-specific Th2-type T cell clones, Bacillus Calmette-Guerin (BCG)-specific Th1-type T cell clones, and gammadelta T cell lines were established from the peripheral blood mononuclear cells of two patients with allergic rhinitis. The effectiveness of gammadelta T cells and BCG-specific Th1-type T cell clones in the modulation of allergen-specific Th2 cells in terms of their cytokine productions was evaluated. In response to cognate antigens, the gammadelta T cell lines demonstrated a proliferation and production of IFN-gamma that exceeded that of BCG-specific Th1-type T cell clones (mean stimulation index: 14.5 vs. 2.8, mean IFN-gamma: 130.5 vs. 10.0 pg/mL). When the gammadelta T cell lines and mite-allergen-specific Th2 clones were co-cultured with each other, only the levels of IL-4 (mean, -87%) decreased, but not the levels of IL-5 and IL-13, with an increasing concentration of gammadelta T cell antigen and IFN-gamma production (mean, +730%). These results demonstrated that gammadelta T cells derived from allergic patients might thus have a partial ability to modulate allergen-specific Th2-skewed immunity.


Lead poisoning: case studies.
Early clinical features of lead toxicity are non-specific and an occupational history is particularly valuable. Lead in the body comprises 2% in the blood (t1/2 35 days) and 95% in bone and dentine (t1/2 20-30 years). Blood lead may remain elevated for years after cessation from long exposure, due to redistribution from bone. Blood lead concentration is the most widely used marker for inorganic lead exposure. Zinc protoporphyrin (ZPP) concentration in blood usefully reflects lead exposure over the prior 3 months. Symptomatic patients with blood lead concentration >2.4 micromol l-1 (50 microg dl-1) or in any event >3.8 micromol l-1 (80 microg dl-1) should receive sodium calciumedetate i.v., followed by succimer by mouth for 19 days. Asymptomatic patients with blood lead concentration >2.4 micromol l-1 (50 microg dl-1) may be treated with succimer alone. Sodium calciumedetate should be given with dimercaprol to treat lead encephalopathy.


[Pulse signal processing based on continuous wavelet transform].
Using the common algorithm and the Mellin algorithm of a continuous wavelet transform, we analyzed the pulse signals of 15 heroin addicts and 15 normal persons. With the use of two algorithms, every pulse signal was processed under 4 scales. From the analyzed results, we found that there was significant difference of wavelet transform coefficients in the time interval 0.2 to approximately 0.4 seconds between the heroin addicts and normal persons. In this paper, the critical parameter used to classify heroin addicts and normal persons is given to every algorithm. The research result of this paper shows that the continuous wavelet transform is really an effective method for processing pulse signals.


Gender-specific problems and needs of family caregivers during specialist inpatient palliative care: a qualitative study on experiences of family caregivers and healthcare professionals.
Previous studies have demonstrated gender-specific impacts on symptoms and problems of patients receiving palliative care; however, there is limited knowledge about the impact of gender on the problems and needs of their family caregivers (FCs). Using a qualitative design, semi-structured interviews with FCs and healthcare professionals (HCPs) of a specialist palliative care inpatient ward were conducted. Themes and categories were identified using qualitative content analysis, with data coded using MAXQDA. Ten FCs (6 female, 4 male) and 16 HCPs (8 female, 8 male) were interviewed. Analysis revealed seven main categories of gendered problems and needs: role as FC, physical and emotional burden, self-care and coping strategies, adaptation to new life circumstances, interaction with the palliative care team, use of psychosocial or care-related support, as well as advance care planning and caregiving after inpatient palliative care. Stronger identification with the caregiver role, less consideration of own needs, and more active utilization of professional and informal support were ascribed to female FCs. With regard to male FCs, respondents had the impression of better self-caring strategies, less expressiveness of emotions, less involvement in care and more target-oriented interactions with the palliative care team. Gender has a relevant impact on roles, coping, communication and support as well as psychosocial needs of FCs of patients receiving palliative care. These gender-related aspects have to be taken into account during palliative care including care for FCs.


Nebivolol treatment increases splanchnic blood flow and portal pressure in cirrhotic rats via modulation of nitric oxide signalling.
We evaluated the effects of nebivolol, a third generation beta-blocker capable of increasing NO-bioavailability on portal pressure, and on splachnic and systemic haemodynamics in a cirrhotic portal hypertensive rat model. Male Sprague-Dawley rats underwent sham operation (SO) or bile duct ligation (BDL). When cirrhosis was fully developed, the animals were orally treated with low-dose (5 mg/kg) or high-dose (10 mg/kg) nebivolol (NEBI) or vehicle (VEH) for 7 days. Heart rate (HR), mean arterial pressure (MAP), portal pressure (PP) and superior mesenteric artery blood flow (SMABF) were measured. Portosystemic collateral blood flow (PSCBF) was quantified using radioactive microspheres. Hepatic and splanchnic NOx levels and GSH/GSSG ratios (RedOx state) were determined using commercially available kits. BDL-VEH rats showed increased HR, PP and PSCBF, whereas MAP was decreased compared to SO-VEH rats. Nebivolol significantly reduced HR both in SO (P < 0.001) and BDL (P < 0.001) rats. BDL-NEBI animals had significantly higher PP (15.5 vs. 12.6 mmHg; P = 0.006) and SMABF (5.3 vs. 3.7 ml/min/100g; P = 0.016) than BDL-VEH animals. The increase in PP and SMABF was noted both in low-dose and high-dose BDL-NEBI rats. While no beneficial effects on hepatic RedOx state were observed, splanchnic NOx levels were significantly increased by NEBI treatment in a dose-dependent manner. Nebivolol treatment did not affect PSCBF in SO and BDL animals. Nebivolol increases portal pressure in cirrhotic animals by increasing splanchnic blood flow via modulation of NO signalling. Portosystemic collateral blood flow remained unchanged. These data do not support the use of nebivolol for treatment of cirrhotic patients with portal hypertension.


The cost of healthy food in rural Victoria.
The cost of healthy food has been associated previously with the degree of remoteness and socioeconomic status. This study aimed to investigate the factors that influence the cost of food in rural Victoria, Australia. It also aimed to compare the cost of nutritious foods with less healthy foods, and to identify the population sub-groups most vulnerable to economic food insecurity. A cross-sectional survey of the cost of food was undertaken in 2007 in a convenience sample of 34 supermarkets in rural areas across Victoria using the Victorian Healthy Food Basket (VHFB). The VHFB was designed to meet the nutritional needs of four different family types for a fortnight. The cost of the VHFB for a 'typical family' (2 adults, 2 children) was (mean [interquartile range]) AU $402.81 ($26.36). No association was evident between food cost and remoteness as indicated by the Accessibility/Remoteness Index for Australia (ARIA) score, socioeconomic status as indicated by the Socio-Economic Indices for Areas (SEIFA), population size or density, or distance of the town from the state capital, Melbourne. It was more expensive to purchase the VHFB at an independent store (median cost $406.66 [$29.39]) than at a supermarket chain (median cost $394.93 [$26.64]), p<0.05. Vegetables and legumes were the most expensive component of the VHFB to purchase and this food group showed significantly greater variation in food price than cereals (p<0.05), non-core foods (p<0.05) and unhealthy foods (p<0.001). The median cost of the VHFB was most expensive for a typical family and 'single parent family' (40% and 37% of welfare income) and least expensive for a single man (29% of income) and elderly pensioner (19% income). The VHFB is an effective tool for assessing economic food security for different population groups. The cost of food in rural Victoria varies in a manner that appears unrelated to remoteness, population, socioeconomic status or distance from the metropolitan centre. Purchase of healthy food requires a considerable proportion of welfare income and may thus be unaffordable for some groups. Food cost must be monitored at a national level to provide a knowledge base to inform development of food and nutrition policies for improved population health.


Life Cycle Assessment of Titania Perovskite Solar Cell Technology for Sustainable Design and Manufacturing.
Perovskite solar cells have attracted enormous attention in recent years due to their low cost and superior technical performance. However, the use of toxic metals, such as lead, in the perovskite dye and toxic chemicals in perovskite solar cell manufacturing causes grave concerns for its environmental performance. To understand and facilitate the sustainable development of perovskite solar cell technology from its design to manufacturing, a comprehensive environmental impact assessment has been conducted on titanium dioxide nanotube based perovskite solar cells by using an attributional life cycle assessment approach, from cradle to gate, with manufacturing data from our laboratory-scale experiments and upstream data collected from professional databases and the literature. The results indicate that the perovskite dye is the primary source of environmental impact, associated with 64.77% total embodied energy and 31.38% embodied materials consumption, contributing to more than 50% of the life cycle impact in almost all impact categories, although lead used in the perovskite dye only contributes to about 1.14% of the human toxicity potential. A comparison of perovskite solar cells with commercial silicon and cadmium-tellurium solar cells reveals that perovskite solar cells could be a promising alternative technology for future large-scale industrial applications.


[Calcified cerebral metastasis].
A hyperdense intraparenchymal lesion on a cerebral computed tomography (CT) usually corresponds to an acute hematoma; however, it is sometimes necessary to rule out a metastatic cause. Focal calcifications in the brain are common and are most often due to granulomas (tuberculosis, cysticercosis...), hamartomas, and primary brain tumors. Cerebral metastases are the most common intracranial neoplasm; however, their rate of calcification in classic series is only approximately 1%. We report the case of a completely calcified cerebral metastasis studied by CT and magnetic resonance imaging (MRI) that was interpreted as acute hemorrhage on the first CT examination.


Rapid quantification of live/dead lactic acid bacteria in probiotic products using high-sensitivity flow cytometry.
A laboratory-built high-sensitivity flow cytometer (HSFCM) was employed for the rapid and accurate detection of lactic acid bacteria (LAB) and their viability in probiotic products. LAB were stained with both the cell membrane-permeable SYTO 9 green-fluorescent nucleic acid stain and the red-fluorescent nucleic acid stain, propidium iodide, which penetrates only bacteria with compromised membranes. The side scatter and dual-color fluorescence signals of single bacteria were detected simultaneously by the HSFCM. Ultra-high temperature processing milk and skim milk spiked with Lactobacillus casei were used as the model systems for the optimization of sample pretreatment and staining. The viable LAB counts measured by the HSFCM were in good agreement with those of the plate count method, and the measured ratios between the live and dead LAB matched well with the theoretical ratios. The established method was successfully applied to the rapid quantification of live/dead LAB in yogurts and fermented milk beverages of different brands. Moreover, the concentration and viability status of LAB in ambient yogurt, a relatively new yet popular milk product in China, are also reported.


Environmental script affects lateral asymmetry of word recognition: A study of French-Hebrew bilinguals tested in Israel and in France.
A written word is identified more easily when it is presented in the right than in the left visual field. This right visual field superiority (RVFS) may be explained by the left hemisphere's role in reading and by reading direction in left-to-right scripts. However, the comparison of left-to-right and right-to-left scripts had not resulted in systematic differences. It had also been found that the linguistic environment has an effect on visuospatial bias. We hypothesized that the linguistic environment might also affect RVFS. In an identification task, French and Hebrew words were presented in each visual field to four groups of 24 neurologically healthy participants, all of whom read French and Hebrew as a first or second language: native French speakers in France, native French speakers in Israel, native Hebrew speakers in Israel, and native Hebrew speakers in France. Results showed a greater RVFS with French than with Hebrew words in all groups except the native Hebrew speakers in Israel. Thus, at least for native Hebrew speakers, the country where participants lived also had an effect on the differential RVFS between languages, suggesting an effect of environmental script or reading practice.


Theoretical studies on the electronic states and liquid structures of ferrocenium-based ionic liquids.
The solvation effects on the electronic structures and magnetic properties were computed for a series of ferrocenium cations in the ferrocenium-based ionic liquids using RISM-SCF-SEDD calculations coupled with CASSCF. The spin-orbit coupling was calculated to get insight into the spin anisotropy. The values were on the order of 100 cm(-1), exhibiting strong spin anisotropy parallel to the angular momentum. The computed results show that the magnetic properties of the ferrocenium cations are similar both in the isolated state and in ionic liquids. We also carried out molecular dynamics and RISM calculations to investigate the liquid structures. The radial and spatial distribution functions around the cations indicate that the cations are surrounded by about seven TFSA anions above and below the cyclopentadienyl rings and from the side of the ferrocenium cations. The nearest-neighbor cations exist in the oblique directions. The introduction of a butyl group to the ring disturbs the solvation structures, and butyl groups in different cations tend to attract each other like those observed in alkylimidazolium ionic liquids.


Combined light and electron microscope in routine histopathology.
We report our experience with a prototype combined light and electron microscope (the LEM 2000) with particular reference to its application to routine surgical histopathology. We found its major advantages over conventional transmission electron microscopies were due to the large grid size (7 mm diameter), low magnification capacity (x 250), and the built-in microprocessor for recording areas of interest. These features combine to reduce sampling errors and greatly facilitate orientation and relocation of fields of diagnostic importance.


Elevated motility-related transmucosal potential difference in the upper small intestine in the irritable bowel syndrome.
The pathophysiology of irritable bowel syndrome (IBS) is complex and incompletely known. Very little has been studied regarding the role of submucous neuronal activity. We therefore measured small intestinal transmural potential difference (PD, reflecting mainly electrogenic chloride secretion), and its linkage with fasting motor activity [migrating motor complex (MMC)] in controls (n = 16) and patients with IBS [n = 23, 14 diarrhoea predominant (d-IBS) and nine constipation predominant (c-IBS)]. Transmural-PD and its relation to MMC phase III was measured by modified multilumen manometry for 3 h in the fasting state using one jejunal and one duodenal infusion line as flowing electrodes. The amplitude and duration of motor phase III was similar in controls and IBS patients, but the propagation speed of phase III was higher in IBS patients. In IBS patients, maximal PD during MMC phase III was significantly elevated in both the duodenum and jejunum (P < 0.05) and the PD decline after phase III was significantly prolonged in the jejunum (P < 0.01). The PD elevation was seen in both duodenum and jejunum in d-IBS patients, but only in the jejunum in the c-IBS patients. On the basis of previous modelling studies, we propose that the enhanced secretion may reflect disturbed enteric network behaviour in some patients with IBS.


Chromatographic analysis of salicylic compounds in different species of the genus Salix.
The separation of nine phenol glycosides--salicin, salicortin, 2'-acetylsalicortin, populin, tremulacin, salidroside, triandrin, picein and helicin--by normal phase (NP), reversed phase (RP) HPLC techniques and a coupling of NP and RP monolithic silica columns was studied. Among the above nine compounds only five--salicin, populin, tremulacin, salidroside and triandrin--were resolved in an NP system with a mobile phase comprising hexane/isopropanol/methanol (87:12:1, v/v/v). Optimized separation was performed with two coupled monolithic silica columns of different polarity (bare silica and RP-18). The method was applied to verify the presence of salicylic compounds and other phenolic derivatives in the bark of six species from the genus Salix, namely S. purpurea, S. daphnoides clone 1095, S. alba clone 1100, S. triandra, S. viminalis, and S. herbacea. Gradient elution with a mobile phase composed of acetonitrile and water containing 0.05% of trifluoroacetic acid, with increasing acetonitrile concentration from 3% to 48%, was chosen as optimal. For the selective detection of the salicylic compounds, an evaporative light scattering detector was employed along with a UV detector. The differences in the composition of phenols in the different plant materials were confirmed. Additionally, it must be emphasized that for the first time the presence of 2'-acetylsalicortin was revealed in S. alba clone 1100. Furthermore, an SPE-HPLC method was developed for the rapid analysis of the salicin content, analyzed as free and total fraction, in willow barks. The determined concentrations of total salicin varied from 25.4 mg/g in S. alba clone 1100 to 96.47 mg/g in S. daphnoides clone 1095.


Phosphate solubilization and promotion of maize growth by Penicillium oxalicum P4 and Aspergillus niger P85 in a calcareous soil.
Alternative tactics for improving phosphorus nutrition in crop production are needed in China and elsewhere, as the overapplication of phosphatic fertilizers can adversely impact agricultural sustainability. Penicillium oxalicum P4 and Aspergillus niger P85 were isolated from a calcareous soil in China that had been exposed to excessive application of phosphatic fertilizer for decades. Each isolate excreted a number of organic acids into, acidified, and solubilized phosphorus in a synthetic broth containing insoluble tricalcium phosphate or rock phosphate. Isolate P4, applied as a seed treatment, increased maize fresh mass per plant when rock phosphate was added to the calcareous soil in greenhouse pot studies. Isolate P85 did not increase maize fresh mass per plant but did significantly increase total phosphorus per plant when rock phosphate was added. Significant increases in 7 and 4 organic acids were detected in soil in association with isolates P4 and P85, respectively, relative to the soil-only control. The quantity and (or) number of organic acids produced by these isolates increased when rock phosphate was added to the soil. Both isolates also significantly increased available phosphorus in soil in the presence of added rock phosphate and effectively colonized the maize rhizosphere. Studies reported here indicate that isolate P4 is adapted to and capable of promoting maize growth in a calcareous soil. Plant-growth promotion by this isolate is likely due, at least in part, to increased phosphorus availability resulting from the excretion of organic acids into, and the resulting acidification of, this soil.


[Long-term results with the off-label use of paclitaxel-eluting stents].
Little information is available about the results obtained with the off-label use of drug-eluting stents. Our aim was to investigate clinical findings on long-term follow-up. The study included 604 consecutive patients who received > or = 1 paclitaxel-eluting stents (PES) at our catherization laboratory between June 2003 and February 2005. Patients were divided into two groups according to whether stent use was on-label or off-label as defined by current practice. The primary study endpoints were the combination of death and non-fatal acute myocardial infarction (AMI) and the combination of death, AMI and target-vessel revascularization (TVR). Secondary endpoints were these events individually and late stent thrombosis (ST). During the median follow-up period of 34.3 months (interquartile range 8.6 months), PESs had been used off-label in the majority of patients (i.e., 464, 76.8% of the sample) and their use was associated with an increased risk of death or AMI (hazard ratio [HR]=2.2; 95% confidence interval [CI], 1.2-4) and of death, AMI or TVR (HR=1.8; 95% CI, 1.1-3). There was no significant difference in individual events (i.e., death, AMI or TVR). The group who used stents off-label had poorer clinical characteristics (i.e., older age, and higher likelihoods of previous AMI or previous revascularization and multivessel disease), as well as a higher incidence of ST (5% vs. 0; log-rank test, P=.015). The off-label use of PESs was associated with an increased risk of a combined clinical endpoint during long-term follow-up. Further studies are needed to determine the efficacy and safety of these devices in these settings.


Antifibrotic effect of lung-resident progenitor cells with high aldehyde dehydrogenase activity.
Aldehyde dehydrogenase (ALDH) is highly expressed in stem/progenitor cells in various tissues, and cell populations with high ALDH activity (ALDHbr) are associated with tissue repair. However, little is known about lung-resident ALDHbr. This study was performed to clarify the characteristics of lung-resident ALDHbr cells and to evaluate their possible use as a tool for cell therapy using a mouse model of bleomycin-induced pulmonary fibrosis. The characteristics of lung-resident/nonhematopoietic (CD45-) ALDHbr cells were assessed in control C57BL/6 mice. The kinetics and the potential usage of CD45-/ALDHbr for cell therapy were investigated in bleomycin-induced pulmonary fibrosis. Localization of transferred CD45-/ALDHbr cells was determined using mCherry-expressing mice as donors. The effects of aging on ALDH expression were also assessed using aged mice. Lung CD45-/ALDHbr showed higher proliferative and colony-forming potential than cell populations with low ALDH activity. The CD45-/ALDHbr cell population, and especially its CD45-/ALDHbr/PDGFRα+ subpopulation, was significantly reduced in the lung during bleomycin-induced pulmonary fibrosis. Furthermore, mRNA expression of ALDH isoforms was significantly reduced in the fibrotic lung. When transferred in vivo into bleomycin-pretreated mice, CD45-/ALDHbr cells reached the site of injury, ameliorated pulmonary fibrosis, recovered the reduced expression of ALDH mRNA, and prolonged survival, which was associated with the upregulation of the retinol-metabolizing pathway and the suppression of profibrotic cytokines. The reduction in CD45-/ALDHbr/PDGFRα+ population was more remarkable in aged mice than in young mice. Our results strongly suggest that the lung expression of ALDH and lung-resident CD45-/ALDHbr cells are involved in pulmonary fibrosis. The current study signified the possibility that CD45-/ALDHbr cells could find application as novel and useful cell therapy tools in pulmonary fibrosis treatment.


[Mechanism of prostate cancer invasion and metastasis].
Prostate cancer cells pass through numerous steps during the process of progression and metastasis. Cancer cells from primary site undertake "epithelial-mesenchymal transition (EMT)" and migrate into neighboring site and invade into blood vessels. Migrated cancer cells will detach from extracellular matrix (ECM) and float into distant metastasis site. Those detached cells will go through either "apoptosis" or acquire "anoikis resistance" and, finally, transfer to distant metastasis site. When settle at novel metastasis site, "mesenchymal-epithelial transition (MET)" will take place. Receptor activator of nuclear factor κ-B ligand (RANKL) plays significant role in formation of bone metastasis site.


Impairment of Thyroid Function in Critically Ill Patients in the Intensive Care Units.
Unexplained hypotension in the intensive care unit is commonly attributed to volume depletion, cardiorespiratory failure, sepsis, or relative adrenal insufficiency. In these acute conditions, thyroid hormone levels measured in blood, serum or plasma are often altered and solely attributed to critical illness. We report a series of 3 critically ill patients with prolonged respiratory failure, suppressed mental status and unexplained hypotension. Thyroid stimulating hormone levels ranged from normal to mildly elevated (2.36-7.65IU/mL; normal: 0.27-4.20), but free thyroxin was markedly suppressed (0.239-0.66ng/dL; normal: 0.93-1.70). After initiation of intravenous levothyroxine (75-100μg/day), the patients could be weaned off vasopressors and were successfully extubated shortly thereafter. These cases demonstrate that hypothyroid intensive care unit patients may exhibit even seemingly normal or mildly abnormal thyroid stimulating hormone values. Early recognition and treatment of a hypothyroid state superimposed on critical illness may contribute to recovery from hypotension or the need for mechanical ventilation.


Asymmetric synthesis of α-(1-oxoisoindolin-3-yl)glycine: synthetic and mechanistic challenges.
We report herein that the NaOMe-catalyzed reactions between the chiral glycine Schiff base (S)-4 with 2-cyanobenzaldehyde 3a provide for a convenient preparation of the novel α-(1-oxoisoindolin-3-yl)glycine 1 of high pharmaceutical potential. The reactions involve at least eight synthetic steps and can mechanistically be realized only with application of Ni(II) complexes described in this study.


Down-modulation of EGF receptors in cells transformed by the src oncogene.
The effects of src oncogene expression on epidermal growth factor (EGF) receptors have been investigated in mouse 3T3 and rat-1 fibroblasts. Transformation of both cell types with src resulted in marked reductions in cellular EGF receptor levels, as assayed by either 125I-EGF binding or immunoprecipitation of receptor protein from radiolabeled cell lysates. In contrast to cells transformed by other types of retroviral oncogenes, the loss of EGF receptors in the src-transformed cells did not appear to be due to secreted transforming growth factor-alpha (TGF-alpha), since such factors were undetectable in culture fluids from the src-transformed cells. By several criteria of transformation, an EGF-receptorless cell line infected with src was shown to be transformed, suggesting that EGF receptors themselves are not obligatory to the src transformation process. We suggest that pp60src down-modulates EGF receptors by an intracellular mechanism and that the loss of the receptors is symptomatic of more general effects of pp60src on the machinery of growth regulation.


[Non-immunologic fetal ascites and anasarca. Apropos of 44 cases].
Between January 1980 and July 1987 there were 44 cases of fetal non-immune ascites and generalised oedema. These are presented. This pathological condition which occurs rarely (1/1,600 to 1/3,500), is considered by most authors to have a very high mortality (80-95%). An aetiological study shows that for the main part the causes are fetal (75%) and among those there is an important place for cardiac abnormalities (20.4%). These are principally faults in fetal cardiac rhythm. The second most common abnormalities are chromosomal (13.6%). These should be sought out by ultrasound. A typical malformation should lead to karyotyping. Idiopathic cases (9%) are fewer comparatively than in old series because of more accurate investigation. 34% survived out of the whole series of all the pathological conditions together. The only way to arrive at accurate antenatal diagnosis is by looking hard for the aetiological causes. These, when found, will show the way to handle the cases both obstetrically and after delivery. It will also help to identify the prognosis and to improve the chances of survival for those fetuses that can be saved.


Medicine and the law.
When a doctor is required to go to court, he does so with some amount of trepidation. The degree of trepidation increases in direct proportion as to whether he is required to be a witness or a defendant. The practice of medicine on the other hand requires the patient to have full confidence and open out his secrets to the doctor. If you hold back vital information, the diagnosis may be entirely different to the disease that you have. Lawyers who enter hospitals may also do so with some trepidation, maybe even more so than doctors who enter courts, as their lives are at stake. There is a perception that medico-legal matters are on the rise. We may put forward a few reasons for this: 1. A better educated and increasingly assertive public with greater awareness of the medical and legal systems; 2. Rising expectations of medical results; 3. Commercialization of medical care with erosion of the doctor-patient trust relationship. This paper will discuss the reasons for and the ways to address medical errors as well as explore the reasons for defensive medicine. The argument is put forward that public education programs on the risks inherent in some of the new advances in treatment modalities and surgery and professional education programs on the need for obtaining the patient's informed consent to such treatment is needed. Public advocacy programs to demonstrate the problems in medicine and the delivery of health care resulting from strict cost containment limitations should be carried out. There is also the need to enhance the level and quality of medical education for all physicians, including improved clinical training experiences. Doctors' must manage their clinical affairs in a professional manner without being dictated to by the legal system. However, it would be wise to take note of the views expressed by learned counsel and judges in their courts. The middle road is always the best and we must never be extreme in our viewpoints. We must always remember the patient is why we are here and the patient must never suffer in the process while we formulate our responses to the medico-legal challenges that lie ahead.


Biliary Mucosal Barrier and Microbiome.
The biliary system is in continuous contact with the complex microbiota of the intestine. Microbial products have recently been proposed as potential triggers for biliary diseases. The aim of this review is to provide a summary of the current knowledge regarding the role of the biliary and intestinal microbiome in biliary inflammatory diseases. Previously, it was suggested that the healthy biliary system is a sterile organ, while acute cholangitis and cholecystitis may occur from ascending infections. Although non-inflammatory biliary colonization by certain bacteria such as Salmonella spp. has been already recognized since several decades, human and animal studies indicated only very recently that the gallbladder harbors a complex microbiota also under non-pathologic conditions. Novel findings suggested that - similar to the situation in the intestine - the biliary mucosa features a chemical, mechanical, and immunological barrier, ensuring immunological tolerance against commensals. However, microbial triggers might influence acute and chronic inflammatory disease of the biliary system and the whole liver. Although yet undefined, dysbiosis of the biliary or intestinal microbiota rather than a single microorganism may influence disease progression.


Determination of an anti-inflammatory methanesulfonanilide in plasma by high-speed liquid chromatography.
A sensitive and chemically specific high-speed liquid chromatographic method was developed for the determination of 4-nitro 2-phenoxymethanesulfonanilide in plasma. The method includes selective extraction of the anti-inflammatory drug and an internal standard, 2-(4'-chlorophenoxy)-4-nitromethanesulfonanilide, into benzene from acidified plasma followed by reextraction into 0.2 N NaOH. The aqueous layer is acidified, and the drug is reextracted into benzene. The benzene is evaporated, and the residue is dissolved in a small volume of acetonitrile. A 10-microliter aliquot is analyzed on a reversed-phase column. The mean overall extraction recovery, after correction for aliquot factors, is 99%. The accuracy, expressed as the relative error, is 4, 0.3, and -3% at 0.60, 1.50, and 3.00 microgram/ml, respectively. Repeated analysis of reference standards indicates that the precision, expressed as the relative standard deviation, is 3% or less. The lower sensitivity limit is 0.2 microgram/ml with a 2-ml plasma sample. The method was applied successfully to the determination of plasma levels of 4-nitro-2-phenoxymethanesulfonanilide in humans and rats in metabolic experiments at pharmacological doses.


Surface relief hologram formed by selective SiO2 deposition on soda-lime silicate glass.
We propose the fabrication of surface relief holograms via selective SiO2 deposition on soda-lime silicate glass substrates. Initially, the original hologram was recorded on an azobenzene photosensitive polymer film coated on the soda-lime silicate glass by irradiation with a conventional continuous wave Ar+ laser with a wavelength of 514.5 nm. The hologram was transferred to the soda-lime silicate glass surface via a corona discharge treatment as an index modulation hologram, which was created by partial substitution of protons for sodium ions during the corona discharge treatment in air. After the corona discharge treatment, the polymer film was removed from the substrate. The diffraction efficiency of the index hologram on the soda-lime silicate glass was estimated to be 5.8 × 10-2% at a wavelength of 532 nm. Finally, the glass substrate was subjected to corona discharge treatment in air with vaporized cyclic siloxane. A surface relief hologram with the diffraction efficiency of 2.3% was successfully fabricated on the soda-lime silicate glass.


Molecular characterization and expression pattern of tripartite motif protein 39 in Gallus gallus with a complete PRY/SPRY domain.
Members of tripartite motif (TRIM) proteins in mammals play important roles in multiple cellular processes in the immune system. In the present study we have obtained the chicken TRIM39 with the insertion of a base A at position 1006 bp, compared to the sequence in the NCBI database (Accession No: NM 001006196), which made TRIM39 fulfill the TRIM rule of domain composition with both PRY, and SPRY domains. The open reading frame consisted of 1392 bp encoding 463 amino acid residues. The amino acid sequences of TRIM39 protein in mammals were highly similar (from 91.48% to 99.61%), while chicken TRIM39 had relatively low homology with mammals (from 29.2% to 39.59%). Real time RT-PCR indicated that the mRNA expression level of TRIM39 was the highest in spleen, with a lower expression in liver, brain, and lung, suggesting it might be an important protein participating in the immune system.


Competing Effects of Hydration and Cation Complexation in Single-Chain Alginate.
Alginic acid, a naturally occurring anionic polyelectrolyte, forms strong physically cross-linked hydrogels in the presence of metal cations. The latter engage in electrostatic interactions that compete with intra- and intermolecular hydrogen bonds, determining the gel structure and properties of the system in aqueous media. In this study, we use all-atom molecular dynamics simulations to systematically analyze the interactions between alginic acid chains and Na+ and Ca2+ counterions. The formed alginates originate from the competition of intramolecular hydrogen bonding and water coordination around the polyelectrolyte. In contrast to the established interpretation, we show that calcium cations strongly bind to alginate by disrupting hydrogen bonds within (1 → 4)-linked β-d-mannuronate (M) residues. On the other hand, Na+ cations enhance intramolecular hydrogen bonds that stabilize a left-hand, fourfold helical chain structure in poly-M alginate, resulting in stiffer chains. Hence, the traditionally accepted flexible flat-chain model for poly-M sequence is not valid in the presence of Na+. The two cations have a distinct effect on water coordination around alginate and therefore on its solubility. While Ca+ disrupts water coordination directly around the alginate chains, mobile Na+ cations significantly disrupt the second hydration layer.


Vimentin acetylation is involved in SIRT5-mediated hepatocellular carcinoma migration.
Sirtuin 5 (SIRT5) belongs to the sirtuin family of protein deacetylases and contributes to tumorigenesis and migration. However, the underlying molecular mechanism of SIRT5 in hepatocellular carcinoma (HCC) migration is not fully understood. Here we report that SIRT5 was significantly downregulated in HCC, based on analysis of RNA-seq data from the liver HCC dataset of The Cancer Genome Atlas (TCGA). In addition, as compared to adjacent non-tumor tissues, SIRT5 was also significantly downregulated in HCC tissues. In vitro, gain and loss-of-function studies were performed to evaluate the role of SIRT5 in epithelial-mesenchymal transition (EMT). Knockdown of SIRT5 promoted EMT, as indicated by the upregulation of Snail and downregulation of E-cadherin, whereas overexpression of SIRT5 decreased Snail and upregulated E-cadherin. Mechanistically, SIRT5 was found to bind to and deacetylate vimentin at lysine 120. Cell migration was enhanced by overexpression of either wild-type vimentin or acetylation mimetic vimentin (K120Q), whereas cell migration was inhibited by overexpression of the non-acetylation vimentin (K120R). Taken together, these findings indicated that downregulated SIRT5-mediated vimentin acetylation may be involved in the EMT in HCC. Better understanding of SIRT5 may lead to its clinical application as a biomarker for prognosis of prediction of prognosis, as well as a novel therapeutic target.


Assessment of muscle mass and its association with protein intake in a multi-ethnic Asian population: relevance in chronic kidney disease.
Clinical practice guidelines recommend objective nutritional assessments in managing chronic kidney disease (CKD) patients but were developed while referencing to a North-American population. Specific recommendations for assessing muscle mass were suggested (mid-arm circumference, MAC; corrected mid-arm muscle area, cAMA; mid-arm muscle circumference, MAMC). This study aimed to assess correlation and association of these assessments with dietary protein intake in a multi-ethnic Asian population of healthy and CKD patients. We analyzed 24-hour urine collections of selected participants to estimate total protein intake (TPI; g/day). Ideal body weight (IDW; kg) was calculated and muscle assessments conducted. Analyses involved correlation and linear regression, taking significance at p<0.05. There were 232 stable CKD patients and 103 healthy participants comprising of 51.0% male, 38.5% Chinese, 29.6% Malay, 23.6% Indian, and 8.4% others. The mean TPI was 58.9 ± 18.4 g/day in healthy participants and 53.6 ± 19.4 g/day in CKD patients. When normalized to ideal body weight, TPI-IDW (g/kg/day) was similar in healthy and CKD participants. Overall, TPI was associated with MAC (r=0.372, p<0.001), cAMA (r=0.337, p<0.001), and MAMC (r=0.351, p<0.001). TPI-IDW was also associated with MAC (r=0.304, p<0.001), cAMA (r=0.202, p<0.001), and MAMC (r=0.200, p<0.001) but not for TPI normalized to actual body weight. When examined separately, TPI was associated with MAC, cAMA, and MAMC in both CKD and healthy participants, but was associated with TPI-IDW only in CKD patients. Total protein intake was associated with muscle assessments in all participants. TPI normalized to IDW should only be used in CKD patients.


Electrochemically Exfoliated Graphene and Graphene Oxide for Energy Storage and Electrochemistry Applications.
Top-down methods are of key importance for large-scale graphene and graphene oxide preparation. Electrochemical exfoliation of graphite has lately gained much interest because of the simplicity of execution, the short process time, and the good quality of graphene that can be obtained. Here, we test three different electrolytes, that is, H2 SO4 , Na2 SO4 , and LiClO4 , with a common exfoliation procedure to evaluate the difference in structural and chemical properties that result for the graphene. The properties are analyzed by means of scanning transmission electron microscopy (STEM), Raman spectroscopy, and X-ray photoelectron spectroscopy. We then tested the graphene materials for electrochemical applications, measuring the heterogeneous electron transfer (HET) rates with a Fe(CN)6 (3-/4-) redox probe, and their capacitive behavior in alkaline solutions. We correlate the electrochemical features with the presence of structural defects and oxygen functionalities on the graphene materials. In particular, the use of LiClO4 during the electrochemical exfoliation of graphite allowed the formation of highly oxidized graphene with a C/O ratio close to 4.0 and represents a possible avenue for the mass production of graphene oxide as valid alternative to the current laborious and dangerous chemical procedures, which also have limited scalability.


[Hemangioma of the spleen].
Although the most frequent benign tumors of the spleen, hemangiomas are very rare, much rarer than hemangiomas of the liver. They manifest as localized (either single or multiple) or diffuse lesions, vary from solid to cystic, histologically from capillary to cavernous. Usually, they are small in size (1-3 cm), rarely larger and very rarely of large size. A 67-year old woman admitted to Institute of Hematology, CCS, for investigation of the left upper abdominal pain, loss of appetite, loss in weight and malaise. As the investigation showed a number of hypoechogenic lesions within the enlarged, diffusely non-homogenic spleen, splenectomy was indicated. The spleen weighing 2600 grams was removed, in which the number of lesions histologically corresponded to hemangioma of the spleen. Postoperative recovery was uneventful. The patient has remained symptom free more than two years after surgery.


MATE AVAILABILITY AND FECUNDITY SELECTION IN MULTI-ALLELIC SELF-INCOMPATIBILITY SYSTEMS IN PLANTS.
We investigate mate availability in different models of multiallelic self-incompatibility systems in mutation-selection-drift balance in finite populations. Substantial differences among self-incompatibility systems occur in average mate availability, and in variances of mate availability among individual plants. These differences are most pronounced in small populations in which low mate availability may reduce seed set in some types of sporophytic self-incompatibility. In cases where the pollination system causes a restriction in the number of pollen genotypes available to an individual plant, the fecundity of that plant depends on the availability of compatible pollen, which is determined by its genotype at the incompatibility locus. This leads to an additional component of selection acting on self-incompatibility systems, which we term "fecundity selection." Fecundity selection increases the number of alleles maintained in finite populations and increases mate availability in small populations. The strength of fecundity selection is dependent on the type of self-incompatibility. In some cases, fecundity selection markedly alters the equilibrium dynamics of self-incompatibility alleles. We discuss the population genetic consequences of mate availability and fecundity selection in the contexts of conservation management of self-incompatible plant species and experimental investigations on self-incompatibility in natural populations.


A clinician's artificial organ? Instant messaging applications in medical care.
After the development of the first phone at the end of 19th century, communication technologies took a great leap forward in the 20th century. With the birth of the "smartphone" in the 21st century, communication technologies exponentially evolved and became an important part of our daily routine. Effective communications between clinicians is critical in medical care and miscommunications are a source of errors. Although telecommunication technologies have proliferated dramatically in the last decade, there is scarce evidence-based information on the use of this technology in medical care. For the purposes of medical communication, we can now consult each other about patients individually and within a group via instant messaging applications by using text messages, photos, audio messages and even videos. In this review, we examine the uses and drawbacks of instant messaging applications in medical communications.


Hyperpolarized δ-[1-13 C]gluconolactone as a probe of the pentose phosphate pathway.
The pentose phosphate pathway (PPP) is thought to be upregulated in trauma (to produce excess NADPH) and in cancer (to provide ribose for nucleotide biosynthesis), but simple methods for detecting changes in flux through this pathway are not available. MRI of hyperpolarized 13 C-enriched metabolites offers considerable potential as a rapid, non-invasive tool for detecting changes in metabolic fluxes. In this study, hyperpolarized δ-[1-13 C]gluconolactone was used as a probe to detect flux through the oxidative portion of the pentose phosphate pathway (PPPox ) in isolated perfused mouse livers. The appearance of hyperpolarized (HP) H13 CO3- within seconds after exposure of livers to HP-δ-[1-13 C]gluconolactone demonstrates that this probe rapidly enters hepatocytes, becomes phosphorylated, and enters the PPPox pathway to produce HP-H13 CO3- after three enzyme catalyzed steps (6P-gluconolactonase, 6-phosphogluconate dehydrogenase, and carbonic anhydrase). Livers perfused with octanoate as their sole energy source show no change in production of H13 CO3- after exposure to low levels of H2 O2 , while livers perfused with glucose and insulin showed a twofold increase in H13 CO3- after exposure to peroxide. This indicates that flux through the PPPox is stimulated by H2 O2 in glucose perfused livers but not in livers perfused with octanoate alone. Subsequent perfusion of livers with non-polarized [1,2-13 C]glucose followed by 1 H NMR analysis of lactate in the perfusate verified that flux through the PPPox is indeed low in healthy livers and modestly higher in peroxide damaged livers. We conclude that hyperpolarized δ-[1-13 C]gluconolactone has the potential to serve as a metabolic imaging probe of this important biological pathway.


Plasma and cutaneous drug levels after topical application of piroxicam gel: a study in healthy volunteers.
Two studies in healthy male and female volunteers (aged 18-65 years) were undertaken to determine plasma and cutaneous levels of drug following topical application of piroxicam gel. Twelve subjects applied piroxicam gel to the knee (1 g of 0.5% Feldene gel) at baseline and then after 6, 12 and 24 h. Plasma was collected after 1, 2, 4, 6, 14, 24, 28 and 48 h and piroxicam content determined by high-pressure liquid chromatography (HPLC). For the majority of samples collected, piroxicam levels were below the limit of detection (LOD) of the assay and the maximum recorded plasma level in any subject at any time point was 75.4 ng/ml. A single application of gel was administered to the forearms of four groups each of 6 subjects, and biopsy samples of the stratum corneum (skin surface biopsy, SBB) and epidermis/dermis were taken after 0.5, 1, 2 and 4 h. The levels of piroxicam were again measured in each sample by HPLC. The highest levels of piroxicam were found in the superficial skin surface biopsy with the lowest levels recorded in the skin surface biopsies nearest the viable epidermis. The mean tissue concentrations ranged from 160 to 640 ng per sample (calculated to be 80-320 micrograms/g of tissue). The mean levels of piroxicam in a 4-mm punch biopsy showed an increase with time after application, rising from 60.3 to 94.6 ng per biopsy (calculated to be 2.4 to 3.8 micrograms/g of tissue). It may be concluded that piroxicam rapidly permeates through the stratum corneum into the epidermis/dermis after application of the gel. Low and often undetectable plasma levels of drug were observed after topical application of piroxicam gel in a manner comparable to clinical usage.


[Effect of dehydration and dDAVP on water permeability of basolateral membranes of epithelial cells in the kidney collecting tubules].
Water permeability of the outer medullary collecting duct's (OMCD) basolateral membrane was determined in vitro in the tubules isolated from hyperhydrated or dehydrated Wistar rats. Oil was injected into the lumen to block apical membrane water permeability. OMCD fragments underwent a hypoosmic shock (600/300 mOsm) and epithelial cells volume increased ad recorded with a digital camera. The latter's rate was used to calculate apparent water permeability of the membrane (Pf). Treatment of the tubules with Hg2Cl2 suppressed the water permeability. Water deprivation and dDAVP induced an increase in the basolateral water permeability. The data obtained suggest that the water permeability of the OMCD basolateral membrane may be stimulated by vasopressin and water deprivation.


Maximal oxygen uptake: "classical" versus "contemporary" viewpoints.
The traditional view of VO2max owes a great deal to the work of A. V. Hill, who conducted experiments on exercising man in Manchester, England, in the 1920's. Hill and colleagues proposed that there is an upper limit to oxygen uptake (VO2max), that there are inter-individual differences in this variable, and that VO2max is limited by the circulatory and/or respiratory systems. They demonstrated that oxygen uptake increases linearly with running speed, but in some subjects it eventually "reaches a maximum beyond which no effort can drive it," a phenomenon now referred to as the VO2 plateau. In recent years, Timothy Noakes has strongly criticized Hill's concept of VO2max. He maintains that the absence of a VO2 plateau in some subjects is proof that oxygen delivery is not a limiting factor for VO2max. This view fails to recognize that the plateau is not the principal evidence for a cardiorespiratory limitation. Noakes rejects the VO2max paradigm of A. V. Hill in its entirety. The alternative paradigm he proposes is that endurance performance is limited by "muscle factors." Noakes suggests that the best distance runners have muscle characteristics that allow them to achieve higher running speeds, and since running speed is linearly related to oxygen uptake, an indirect consequence of this is that they will have higher VO2max values. This is exactly the opposite of how the relationship between VO2max and running speed at the end of a maximal exercise test should be viewed. Noakes offers little evidence to support his views, and they conflict with a vast body of scientific evidence showing that oxygen transport is a major determinant of endurance performance. After carefully reviewing the evidence on both sides of the issue, we conclude that the older "classical" VO2max paradigm of A. V. Hill is the correct one.


Engagement of CD83 ligand induces prolonged expansion of CD8+ T cells and preferential enrichment for antigen specificity.
Following T-cell receptor and CD28 signaling, CD8+ T cells express a receptor for CD83, a molecule up-regulated on functionally mature dendritic cells. Although this expression pattern suggests that CD83 is involved in adaptive immunity, little is known about its function in the periphery, and the existence of its ligand on T cells is controversial. We demonstrate that the engagement of the CD83 ligand (CD83L) preferentially enriches and significantly amplifies the number of antigen-specific CD8+ T cells. Coengagement of the T-cell receptor, CD28, and CD83L supports priming of naive CD8+ T cells that retain antigen specificity and cytotoxic function for more than 6 months. Therefore, engagement of the CD83L provides a unique signal to activated CD8+ T cells that could be exploited to generate long-lived antigen-specific cytotoxic T cells for the treatment of cancer and infection.


Decreased FGF8 signaling causes deficiency of gonadotropin-releasing hormone in humans and mice.
Idiopathic hypogonadotropic hypogonadism (IHH) with anosmia (Kallmann syndrome; KS) or with a normal sense of smell (normosmic IHH; nIHH) are heterogeneous genetic disorders associated with deficiency of gonadotropin-releasing hormone (GnRH). While loss-of-function mutations in FGF receptor 1 (FGFR1) cause human GnRH deficiency, to date no specific ligand for FGFR1 has been identified in GnRH neuron ontogeny. Using a candidate gene approach, we identified 6 missense mutations in FGF8 in IHH probands with variable olfactory phenotypes. These patients exhibited varied degrees of GnRH deficiency, including the rare adult-onset form of hypogonadotropic hypogonadism. Four mutations affected all 4 FGF8 splice isoforms (FGF8a, FGF8b, FGF8e, and FGF8f), while 2 mutations affected FGF8e and FGF8f isoforms only. The mutant FGF8b and FGF8f ligands exhibited decreased biological activity in vitro. Furthermore, mice homozygous for a hypomorphic Fgf8 allele lacked GnRH neurons in the hypothalamus, while heterozygous mice showed substantial decreases in the number of GnRH neurons and hypothalamic GnRH peptide concentration. In conclusion, we identified FGF8 as a gene implicated in GnRH deficiency in both humans and mice and demonstrated an exquisite sensitivity of GnRH neuron development to reductions in FGF8 signaling.


Self-assembly of beta-casein and lysozyme.
The self-assembly of beta-casein and lysozyme, a linear and a globular protein with isoelectric point of pH 5.0 and 10.7, respectively, was studied. Polydisperse electrostatic complex micelles formed when mixing beta-casein and lysozyme aqueous solutions. After the micelle solution was heated, lysozyme gelated and beta-casein was trapped in the gel, producing narrowly dispersed nanoparticles. The nanoparticles were characterized with laser light scattering, zeta-potential, steady state fluorescence, atomic force microscopy, and transmission electron microscopy. The nanoparticles have spherical shape and their sizes depend on the pH of the heat treatment and the molar ratio of beta-casein to lysozyme. The nanoparticles display amphoteric property and are relatively hydrophobic at pH around 5 and around 10. The net charges on the surface stabilize the nanoparticles in the solution.


[Hospital self-management policy in Chile: perceptions of decision-makers].
To learn the perceptions of decision-makers concerning the imple-men-t-ation stage of a hospital self-management policy in two highly complex hospitals in southern Chile. A descriptive, exploratory, qualitative study based on semi-structured in-depth interviews of decision-makers at the Regional Hospital of Valdivia and the Hospital San José de Osorno from August 2010 to December 2011. A convenience sample of 26 decision-makers was selected. The 26 interviews were recorded and transcribed verbatim. The information was analyzed using inductive content analysis. The interviewees consider the concept of self-management to be determined by autonomy in decision-making about resource allocation and the financing of health service delivery in the hospitals. They also stated that human resources and financing policies should be included to improve the implementation stage. They related weaknesses with the lack of organizational capabilities and managerial skills in the health teams implementing the changes. Conceptually, the hospital self-management policy is based on financial autonomy, and implementation is affected by persistent capacity gaps in policy design.


Inference of Gene Regulatory Network Based on Local Bayesian Networks.
The inference of gene regulatory networks (GRNs) from expression data can mine the direct regulations among genes and gain deep insights into biological processes at a network level. During past decades, numerous computational approaches have been introduced for inferring the GRNs. However, many of them still suffer from various problems, e.g., Bayesian network (BN) methods cannot handle large-scale networks due to their high computational complexity, while information theory-based methods cannot identify the directions of regulatory interactions and also suffer from false positive/negative problems. To overcome the limitations, in this work we present a novel algorithm, namely local Bayesian network (LBN), to infer GRNs from gene expression data by using the network decomposition strategy and false-positive edge elimination scheme. Specifically, LBN algorithm first uses conditional mutual information (CMI) to construct an initial network or GRN, which is decomposed into a number of local networks or GRNs. Then, BN method is employed to generate a series of local BNs by selecting the k-nearest neighbors of each gene as its candidate regulatory genes, which significantly reduces the exponential search space from all possible GRN structures. Integrating these local BNs forms a tentative network or GRN by performing CMI, which reduces redundant regulations in the GRN and thus alleviates the false positive problem. The final network or GRN can be obtained by iteratively performing CMI and local BN on the tentative network. In the iterative process, the false or redundant regulations are gradually removed. When tested on the benchmark GRN datasets from DREAM challenge as well as the SOS DNA repair network in E.coli, our results suggest that LBN outperforms other state-of-the-art methods (ARACNE, GENIE3 and NARROMI) significantly, with more accurate and robust performance. In particular, the decomposition strategy with local Bayesian networks not only effectively reduce the computational cost of BN due to much smaller sizes of local GRNs, but also identify the directions of the regulations.


The U Shape of Happiness Across the Life Course: Expanding the Discussion.
The notion of a U shape in happiness-that well-being is highest for people in their 20s, decreases to its nadir in midlife, and then rises into old age-has captured the attention of the media, which often cite it as evidence for a midlife crisis. We argue that support for the purported U shape is not as robust and generalizable as is often assumed and present our case with the following arguments: (a) Cross-sectional studies are inadequate for drawing conclusions about within-person change in happiness across the life span; (b) cross-sectional evidence with respect to the ubiquity and robustness of the U shape in general levels of happiness and life satisfaction is mixed; (c) longitudinal support for the U shape in happiness and life satisfaction is also mixed; (d) longitudinal research on subjective indicators of well-being other than general levels of happiness and life satisfaction challenges the U shape; (e) when asked to reflect on their lives, older adults tend to recall midlife as one of the more positive periods; and (f) a focus on a single trajectory of well-being is of limited scientific and applied value because it obscures the diversity in pathways throughout life as well as its sources. Understanding happiness across the life course and moving the research field forward require a multidisciplinary, collaborative approach.


Occurrence of free fatty acids in the phloem sap of different citrus varieties.
Candidatus Liberibacter asiaticus is a phloem restricted bacterium that causes citrus greening disease or huanglongbing (HLB), a major treat to commercial citrus production in Florida. It is transmitted by the Asian citrus psyllid, a phloem sap-feeding insect. Studies conducted on the composition of citrus phloem sap revealed the presence amino acids, organic acids and sugars and of low amounts of free fatty acids. In the present study, the phloem sap of 12 citrus varieties with different degrees of tolerance to HLB were extracted with ethyl acetate and analyzed by GC-MS after derivatization with boron trifluoride, a fatty acid-specific reagent. Nine free fatty acids were detected in all varieties. Of the 9 fatty acids detected, only capric acid was significantly different among varieties.


Giant pleomorphic adenoma of the submandibular gland. Case report.
Salivary glands are sites for a great variety of tumors. The parotid gland is the most common site followed by the submandibular gland. The pleomorphic adenoma represents the 60-70% of all tumors involving the major salivary glands, while the submandibular gland is involved in 8% of cases. The pleomorphic adenoma of the submandibular gland is rare and can present difficulty in diagnosis. The heterogeneous histology, a possible malignant transformation, an incomplete capsule that can determine a recurrence, are the most important characteristics of pleomorphic adenoma. A complete surgical removal of the tumor is the treatment of choice. In the case presented, the mass showed an unusual vascularization and remarkable dimensions.


Polarization effects in a highly birefringent nonlinear photonic crystal fiber with two-zero dispersion wavelengths.
A theoretical and experimental study is presented on polarized pulsed propagation from a highly birefringent nonlinear photonic crystal fiber with two-zero dispersion wavelengths. Experimental observations show that the input polarization state can maintain its linearity and that the fiber birefringence creates different spectral properties dependent on the input polarization orientation. The most extensive spectra are obtained for a coupling polarization angles aligned with the fast and slow axis, which is created by the high-order dispersion and Kerr nonlinearity.


Turn-On Ratiometric Fluorescent Probe for Selective Discrimination of Cr(3+) from Fe(3+) in Aqueous Media for Living Cell Imaging.
Pyrene-based turn-on ratiometric fluorescent probe 1 demonstrates high sensitivity and exceptional selectivity toward Cr(3+) in the presence of other metals, including Fe(3+) in aqueous media. Interaction of Cr(3+) with probe 1 brings pyrene moieties close enough to have better aligned π-π stacking, thus enhancing the excimer peak many fold. On the other hand, the interaction of Fe(3+) with probe 1 brings forth a negligible difference in stacking, resulting in an insignificant change in fluorescence intensity. Exceptional selectivity of probe 1 with Cr(3+) over Fe(3+) and other metals has been confirmed by theoretical studies in addition to experimental results. Imaging of HeLa cells observed by confocal fluorescence microscopy reveals that probe 1 can be used to monitor Cr(3+) in live cells to map its subcellular distribution.


Noise and autism spectrum disorder in children: An exploratory survey.
With more students being educated in schools for Autism Spectrum Disorder (ASD) than ever before, architects and interior designers need to consider the environmental features that may be modified to enhance the academic and social success of autistic students in school. This study explored existing empirical research on the impact of noise on children with ASD and provides recommendations regarding design features that can contribute to noise reduction. A survey, which addressed the impact of architectural design elements on autism-related behavior, was developed for teachers of children with ASD and distributed to three schools. Most teachers found noise control to be an important issue for students with autism and many observed children using ear defenders. In terms of managing issues related to noise, most teachers agreed that thick or soundproof walls and carpet in the classroom were the most important issues for children with ASD. Suggested future research should address architectural considerations for building an acoustically friendly environment for children with autism, identifying patterns of problematic behaviors in response to acoustical features of the built environment of the classroom setting, and ways to manage maladaptive behaviors in acoustically unfriendly environments.