Temperature variability alters the stability and thresholds for collapse of interacting species.
Temperature variability and extremes can have profound impacts on populations and ecological communities. Predicting impacts of thermal variability poses a challenge, because it has both direct physiological effects and indirect effects through species interactions. In addition, differences in thermal performance between predators and prey and nonlinear averaging of temperature-dependent performance can result in complex and counterintuitive population dynamics in response to climate change. Yet the combined consequences of these effects remain underexplored. Here, modelling temperature-dependent predator-prey dynamics, we study how changes in temperature variability affect population size, collapse and stable coexistence of both predator and prey, relative to under constant environments or warming alone. We find that the effects of temperature variation on interacting species can lead to a diversity of outcomes, from predator collapse to stable coexistence, depending on interaction strengths and differences in species' thermal performance. Temperature variability also alters predictions about population collapse-in some cases allowing predators to persist for longer than predicted when considering warming alone, and in others accelerating collapse. To inform management responses that are robust to future climates with increasing temperature variability and extremes, we need to incorporate the consequences of temperature variation in complex ecosystems. This article is part of the theme issue 'Integrative research perspectives on marine conservation'.


Identification of adducts derived from reactions of (1-chloroethenyl)oxirane with nucleosides and calf thymus DNA.
(1-Chloroethenyl)oxirane is a major mutagenic metabolite of chloroprene, an important large-scale petrochemical used in the manufacture of synthetic rubbers. The reactions of (1-chloroethenyl)oxirane with 2'-deoxyguanosine, 2'-deoxyadenosine, 2'-deoxycytidine, thymidine, and calf thymus DNA have been studied in aqueous buffered solutions. The adducts from the nucleosides were isolated by reversed-phase HPLC, and characterized by their UV absorbance and (1)H and (13)C NMR spectroscopic and mass spectrometric features. The reaction with 2'-deoxyguanosine gave one major adduct, N7-(3-chloro-2-hydroxy-3-buten-1-yl)-guanine (dGI), and eight minor adducts which were identified as diastereoisomeric pairs of N1-(3-chloro-2-hydroxy-3-buten-1-yl)-2'-deoxyguanosine (dGII, dGIII), N3,N7-bis(3-chloro-2-hydroxy-3-buten-1-yl)-guanine (dGIV, dGV), N7,N9-bis(3-chloro-2-hydroxy-3-buten-1-yl)-guanine (dGVI, dGVII), and N1,N7-bis(3-chloro-2-hydroxy-3-buten-1-yl)-guanine (dGVIII, dGIX). The reaction of 2'-deoxyadenosine with (1-chloroethenyl)oxirane gave two adducts: N1-(3-chloro-2-hydroxy-3-buten-1-yl)-2'-deoxyadenosine (dAI) and N(6)-(3-chloro-2-hydroxy-3-buten-1-yl)-2'-deoxyadenosine (dAII). The adduct dAII was shown to arise via a Dimroth rearrangement of adduct dAI. The HPLC analyses of the reaction mixtures of (1-chloroethenyl)oxirane with 2'-deoxycytidine and thymidine showed the formation of one major product in each reaction. The adduct from 2'-deoxycytidine was identified as N3-(3-chloro-2-hydroxy-3-buten-1-yl)-2'-deoxyuridine (dCI) derived by alkylation at N-3 followed by deamination. The adduct from thymidine was identified as N3-(3-chloro-2-hydroxy-3-buten-1-yl)-thymidine (TI). Reaction of (1-chloroethenyl)oxirane with calf thymus DNA gave all of the adducts observed from the individual nucleosides except dGII and dGIII. However, there was selectivity for the formation of dGI and dCI. The adduct levels in DNA were 9,630 (dGI), 240 (dCI), 83 (dAI), 6 (dAII), and 28 (TI) pmol/mg DNA, respectively. The preferred formation of dCI may be relevant to chloroprene mutagenesis.


GABA depolarizes immature neurons and inhibits network activity in the neonatal neocortex in vivo.
A large body of evidence from in vitro studies suggests that GABA is depolarizing during early postnatal development. However, the mode of GABA action in the intact developing brain is unknown. Here we examine the in vivo effects of GABA in cells of the upper cortical plate using a combination of electrophysiological and Ca(2+)-imaging techniques. We report that at postnatal days (P) 3-4, GABA depolarizes the majority of immature neurons in the occipital cortex of anaesthetized mice. At the same time, GABA does not efficiently activate voltage-gated Ca(2+) channels and fails to induce action potential firing. Blocking GABA(A) receptors disinhibits spontaneous network activity, whereas allosteric activation of GABA(A) receptors has the opposite effect. In summary, our data provide evidence that in vivo GABA acts as a depolarizing neurotransmitter imposing an inhibitory control on network activity in the neonatal (P3-4) neocortex.


The activity of granulocyte alpha-amylase in acute appendicitis.
The activity of alpha-amylase was measured in isolated granulocytes, serum and urine of 35 patients with acute appendicitis. The measurements were performed before operation and on the 7th day after operation. Slightly increased activity of alpha-amylase was found in the serum and urine of 15 patients. On the 7th day after operation the activity of this enzyme reached normal value. The activity of granulocyte alpha-amylase was elevated in 22 patients. In 2 of them the increased activity still maintained on the 7th day after operation. Positive correlation between the serum and granulocyte alpha-amylase activities was found. These observations allow to conclude that granulocytes are the source of increased alpha-amylase activity in the serum of patients with acute appendicitis.


Regulation of lysozyme activity based on thermotolerant protein/smart polymer complex formation.
Proteins have evolved to acquire highly specialized biological functions and are ideal for various applications in both medicine and biotechnology, although denaturation is one of the major problems in protein chemistry. Here, we show a novel strategy for the regulation and preservation of the enzymatic activity even after heat treatment by the complex formation with a cationic smart copolymer, poly(N,N-diethylaminoethyl methacrylate)-graft-poly(ethylene glycol) (PEAMA-g-PEG). PEAMA-g-PEG suppressed the enzymatic activity of lysozyme completely without any conformational change, indicating complex formation and the capping of the active site of lysozyme by PEAMA-g-PEG. The addition of an anionic polymer, poly(acrylic acid) (PAAc), recovered the inhibited enzymatic activity of the lysozyme/PEAMA-g-PEG complex completely. Surprisingly, even after heating the lysozyme with PEAMA-g-PEG for 20 min at 98 degrees C, the addition of PAAc recovered 80% enzymatic activity of lysozyme. Circular dichroism (CD) spectral analysis clearly indicated that the irreversible inactivation of lysozyme induced by the heat treatment was suppressed by the complex formation with PEAMA-g-PEG.


Cognitive Impairment Induced by Lead Exposure during Lifespan: Mechanisms of Lead Neurotoxicity.
Lead (Pb) is considered a strong environmental toxin with human health repercussions. Due to its widespread use and the number of people potentially exposed to different sources of this heavy metal, Pb intoxication is recognized as a public health problem in many countries. Exposure to Pb can occur through ingestion, inhalation, dermal, and transplacental routes. The magnitude of its effects depends on several toxicity conditions: lead speciation, doses, time, and age of exposure, among others. It has been demonstrated that Pb exposure induces stronger effects during early life. The central nervous system is especially vulnerable to Pb toxicity; Pb exposure is linked to cognitive impairment, executive function alterations, abnormal social behavior, and fine motor control perturbations. This review aims to provide a general view of the cognitive consequences associated with Pb exposure during early life as well as during adulthood. Additionally, it describes the neurotoxic mechanisms associated with cognitive impairment induced by Pb, which include neurochemical, molecular, and morphological changes that jointly could have a synergic effect on the cognitive performance.


Potential candidate genomic biomarkers of drug induced vascular injury in the rat.
Drug-induced vascular injury is frequently observed in rats but the relevance and translation to humans present a hurdle for drug development. Numerous structurally diverse pharmacologic agents have been shown to induce mesenteric arterial medial necrosis in rats, but no consistent biomarkers have been identified. To address this need, a novel strategy was developed in rats to identify genes associated with the development of drug-induced mesenteric arterial medial necrosis. Separate groups (n=6/group) of male rats were given 28 different toxicants (30 different treatments) for 1 or 4 days with each toxicant given at 3 different doses (low, mid and high) plus corresponding vehicle (912 total rats). Mesentery was collected, frozen and endothelial and vascular smooth muscle cells were microdissected from each artery. RNA was isolated, amplified and Affymetrix GeneChip® analysis was performed on selectively enriched samples and a novel panel of genes representing those which showed a dose responsive pattern for all treatments in which mesenteric arterial medial necrosis was histologically observed, was developed and verified in individual endothelial cell- and vascular smooth muscle cell-enriched samples. Data were confirmed in samples containing mesentery using quantitative real-time RT-PCR (TaqMan™) gene expression profiling. In addition, the performance of the panel was also confirmed using similarly collected samples obtained from a timecourse study in rats given a well established vascular toxicant (Fenoldopam). Although further validation is still required, a novel gene panel has been developed that represents a strategic opportunity that can potentially be used to help predict the occurrence of drug-induced mesenteric arterial medial necrosis in rats at an early stage in drug development.


Cytotoxic clerodane diterpenoids from Casearia membranacea.
Bioassay-guided fractionation of the EtOAc extract of Casearia membranacea leaves and twigs afforded three new clerodane diterpenes, caseamembrins M-O (1-3), and the known rel-(2S,5R,6R,8S,9S,10R,18S,19R)-2-(2-methylbutyryloxy)-6-hydroxy-18,19-di-O-acetyl-18,19-epoxycleroda-3,13(16),14-triene (4) and caseamembrin D (5). The structures of 1-3, including the relative configurations, were established by extensive NMR spectroscopic analyses. The cytotoxic activities of the isolated diterpenoids against human oral epidermoid (KB), medulla (Med), and colon (DLD-1) cancer cell lines were evaluated.


Impact of protease inhibitors on the outcome of human immunodeficiency virus-infected patients with chronic diarrhea.
The effect of protease inhibitors on the outcome of chronic HIV-related diarrhea is unknown. The aim of this study was to compare the response to treatment of chronic HIV-related diarrhea, recurrence of diarrhea, and survival in a large cohort of individuals taking protease inhibitors to the outcome in similar patients not receiving protease inhibitors. We reviewed the medical records of all patients referred between October 1993 and October 1996 at Bellevue Hospital for endoscopic evaluation of chronic HIV-related diarrhea after negative stool examination. Only patients presenting after December 1995 received protease inhibitor therapy. Follow-up data were obtained from chart review and direct telephone contact. The success of antidiarrheal therapy was compared between protease inhibitor and nonprotease inhibitor groups for patients receiving pathogen-specific therapy and for those with no pathogens found on endoscopy. Two hundred eighty-two of 307 patients evaluated for chronic diarrhea were followed for a mean of 69.9+/-34.1 weeks. Patients receiving protease inhibitors had a significantly higher rate of successful response to antidiarrheal therapy (62.0% vs 33.5%, p < 0.001). Protease inhibitors were associated with a significant decrease in stool frequency (4.8+/-4.5 vs 3.4+/-4.6 bowel movements per day, p = 0.01), an increase in weight (2.4+/-5.9 vs -1.6+/-6.2 kg, p < 0.001), a decrease in recurrence of diarrhea (34.8% vs 15.3%, p = 0.02), and a longer mean survival (148 vs 118 weeks, p = 0.002). Protease inhibitors significantly improve the outcome of antidiarrheal therapy and survival in patients with chronic HIV-associated diarrhea.


A mouse line expressing Sall1-driven inducible Cre recombinase in the kidney mesenchyme.
Sall1 is expressed in the metanephric mesenchyme in the developing kidney, and mice deficient in Sall1 show kidney agenesis or dysgenesis. Sall1 is also expressed elsewhere, including in the limb buds, anus, heart, and central nervous system. Dominant-negative mutations of Sall1 in mice and humans lead to developmental defects in these organs. Here, we generated a mouse line expressing tamoxifen-inducible Cre recombinase (CreER(T2)) under the control of the endogenous Sall1 promoter. Upon tamoxifen treatment, these mice showed genomic recombination in the tissues where endogenous Sall1 is expressed. When CreER(T2) mice were crossed with the floxed Sall1 allele, tamoxifen administration during gestation led to a significant decrease in Sall1 expression and small kidneys at birth, suggesting that Sall1 functions were disrupted. Furthermore, Sall1 expression in the kidney was significantly reduced by neonatal tamoxifen treatment. The Sall1CreER(T2) mouse is a valuable tool for in vivo time-dependent and region-specific knockout and overexpression studies.


Preparation of core-shell biodegradable microfibers for long-term drug delivery.
A coaxial electrospun technique to fabricate core-shell microfibers (MFs) for drug delivery application is described. In one-step, Paclitaxel (PTX)-loaded poly(L-lactic acid-co-epsilon-caprolactone) (75:25) (P(LLA-CL)(core/shell)) was electrospun into MFs using 2,2,2-trifluoroethanol as the solvent. The physical and chemical properties of electrospun fibers were characterized by various techniques, such as scanning electron microscopy, transmission electron microscopy, X-ray diffractometry, and Fourier-transform infrared. The fiber diameter depended on both the polymer concentration and the flow ratio of PTX to P(LLA-CL). The encapsulation efficiency and in vitro release profile were measured using high performance liquid chromatography methods. PTX released from the MFs in a short burst over 24 h followed by very slow release over the following 60 days. In addition, the cytotoxicity of PTX-loaded P(LLA-CL) MFs was evaluated using 3-[4,5-dimehyl-2-thiazolyl]-2, 5-diphenyl-2H-tetrazolium bromide assay on HeLa cell lines. These results indicate that PTX could be released from P(LLA-CL) fibers in a steady manner and effectively inhibit the activity of HeLa cells.


Enterovirus D68 - The New Polio?
Enterovirus D68 (EV-D68) has emerged over the recent years, with large outbreaks worldwide. Increased occurrence has coincided with improved clinical awareness and surveillance of non-polio enteroviruses. Studies showing its neurotropic nature and the change in pathogenicity have established EV-D68 as a probable cause of Acute Flaccid Myelitis (AFM). The EV-D68 storyline shows many similarities with poliovirus a century ago, stimulating discussion whether EV-D68 could be ascertaining itself as the "new polio." Increasing awareness amongst clinicians, incorporating proper diagnostics and integrating EV-D68 into accessible surveillance systems in a way that promotes data sharing, will be essential to reveal the burden of disease. This will be a necessary step in preventing EV-D68 from becoming a threat to public health.


Ability of laser fluorescence device associated with fluorescent dyes in detecting and quantifying early smooth surface caries lesions.
A laser fluorescence (LF) device is a portable tool, but it does not measure minor mineral changes. Our in vitro study aim is to propose the association of an LF with two fluorescent dyes and to evaluate the performance in detecting and quantifying early demineralization. Artificial caries lesions are created in 40 primary canine teeth using a demineralizing solution (pH=4.8) for 12, 24, 48, and 96 h. LF measurements are performed with DIAGNOdent after demineralization in these samples and in 20 sound primary teeth. Measurements with LF with 0.2-mM tetrakis(N-methylpyridyl)porphyrin (LF TMPyP) and with 4-mM protoporphyrin IX (LF PPIX) are made. The amount of calcium loss is determined by atomic emission spectrometry. A correlation between LF and LF with dyes and mineral loss and receiver operating characteristics analysis are performed, as well as comparisons of sensitivity, specificity, and accuracy values. Significant correlation is obtained with LF TMPyP and mineral loss of lesions demineralized for 24, 48, and 96 h. Better performance is achieved with LF TMPyP for all parameters than with LF alone. LF PPIX does not present good results. In conclusion, LF TMPyP provides good performance in detecting and quantifying very early enamel caries lesions.


Alterations of the endocannabinoid system and its therapeutic potential in autism spectrum disorder.
Autism spectrum disorder (ASD) is a group of developmental disabilities, the aetiology of which remains elusive. The endocannabinoid (eCB) system modulates neurotransmission and neuronal plasticity. Evidence points to the involvement of this neuromodulatory system in the pathophysiology of ASD. We investigated whether there is a disruption to the eCB system in ASD and whether pharmacological modulation of the eCB system might offer therapeutic potential. We examined three major components of the eCB system-endogenous cannabinoids, their receptors and associated enzymes-in ASD children as well as in the valproic acid (VPA) induced animal model in autism. Furthermore, we specifically increased 2-arachidonoylglycerol (2-AG) levels by administering JZL184, a selective inhibitor of monoacylglycerol lipase which is the hydrolytic enzyme for 2-AG, to examine ASD-like behaviours in VPA-induced rats. Results showed that autistic children and VPA-induced rats exhibited reduced eCB content, increased degradation of enzymes and upregulation of CBRs. We found that repetitive and stereotypical behaviours, hyperactivity, sociability, social preference and cognitive functioning improved after acute and chronic JZL184 treatment. The major efficacy of JZL184 was observed after administration of a dosage regimen of 3 mg kg-1, which affected both the eCB system and ASD-like behaviours. In conclusion, a reduced eCB signalling was observed in autistic children and in the ASD animal model, and boosting 2-AG could ameliorate ASD-like phenotypes in animals. Collectively, the results suggested a novel approach to ASD treatment.


Time-correlation analysis of simulated water motion in flexible and rigid gramicidin channels.
Molecular dynamics simulations have been done on a system consisting of the polypeptide membrane channel former gramicidin, plus water molecules in the channel and caps of waters at the two ends of the channel. In the absence of explicit simulation of the surrounding membrane, the helical form of the channel was maintained by artificial restraints on the peptide motion. The characteristic time constant of the artificial restraint was varied to assess the effect of the restraints on the channel structure and water motions. Time-correlation analysis was done on the motions of individual channel waters and on the motions of the center of mass of the channel waters. It is found that individual water molecules confined in the channel execute higher frequency motions than bulk water, for all degrees of channel peptide restraint. The center-of-mass motion of the chain of channel waters (which is the motion that is critical for transmembrane transport, due to the mandatory single filing of water in the channel) does not exhibit these higher frequency motions. The mobility of the water chain is dramatically reduced by holding the channel rigid. Thus permeation through the channel is not like flow through a rigid pipe; rather permeation is facilitated by peptide motion. For the looser restraints we used, the mobility of the water chain was not very much affected by the degree of restraint. Depending on which set of experiments is considered, the computed mobility of our water chain in the flexible channel is four to twenty times too high to account for the experimentally measured resistance of the gramicidin channel to water flow. From this result it appears likely that the peptide motions of an actual gramicidin channel embedded in a lipid membrane may be more restrained than in our flexible channel model, and that these restraints may be a significant modulator of channel permeability. For the completely rigid channel model the "trapping" of the water molecules in preferred positions throughout the molecular dynamics run precludes a reasonable assessment of mobility, but it seems to be quite low.


Brain region-specific lipid alterations in the PLB4 hBACE1 knock-in mouse model of Alzheimer's disease.
Lipid dysregulation is associated with several key characteristics of Alzheimer's disease (AD), including amyloid-β and tau neuropathology, neurodegeneration, glucose hypometabolism, as well as synaptic and mitochondrial dysfunction. The β-site amyloid precursor protein cleavage enzyme 1 (BACE1) is associated with increased amyloidogenesis, and has been affiliated with diabetes via its role in metabolic regulation. The research presented herein investigates the role of hBACE1 in lipid metabolism and whether specific brain regions show increased vulnerability to lipid dysregulation. By utilising advanced mass spectrometry techniques, a comprehensive, quantitative lipidomics analysis was performed to investigate the phospholipid, sterol, and fatty acid profiles of the brain from the well-known PLB4 hBACE1 knock-in mouse model of AD, which also shows a diabetic phenotype, to provide insight into regional alterations in lipid metabolism. Results show extensive region - specific lipid alterations in the PLB4 brain compared to the wild-type, with decreases in the phosphatidylethanolamine content of the cortex and triacylglycerol content of the hippocampus and hypothalamus, but increases in the phosphatidylcholine, phosphatidylinositol, and diacylglycerol content of the hippocampus. Several sterol and fatty acids were also specifically decreased in the PLB4 hippocampus. Collectively, the lipid alterations observed in the PLB4 hBACE1 knock-in AD mouse model highlights the regional vulnerability of the brain, in particular the hippocampus and hypothalamus, to lipid dysregulation, hence supports the premise that metabolic abnormalities have a central role in both AD and diabetes.


[Simultaneous determination of adrenaline, noradrenaline, cortisone and cortisol in plasma with HPLC/MS/MS].
To develop a method for simultaneous determination of adrenaline, noradrenaline, cortisone and cortisol in plasma using HPLC/MS/MS. Sample proteins were precipitated with acetonitrile and the sample solution was injected into HPLC/MS/MS after centrifugation at 15,000 r/min for 5 min. Electrospray ionization (ESI) and the positive ion detection were applied with a multiple reaction monitoring (MRM) mode for quantitative analyses. Under the optimal conditions, good linearity (r > 0.999) was observed in the range of 0.02-200.00 ng/mL of target compounds. The detection limit reached 4.13 pg/mL, 4.64 pg/mL, 4.29 pg/mL and 4.52 pg/mL for adrenaline, noradrenaline, cortisone and cortisol respectively. The inter-day and intra-day precisions ranged from 1.19%-5.42% and 2.16%-6.04% respectively. Satisfied results were achieved using human plasma samples, with a spiked recovery in the range of 80.0%-109.0% and a relative standard deviation of 3.93%-7.57%. The proposed method is quick, sensitive and suitable for batch analyses of plasma samples.


Penile injuries with particular reference to injury to the erectile tissue.
A retrospective study of 56 patients with penile injuries showed that 28 injuries were sustained during coitus and a further 12 in other sexual practices. Four different types of injury to the erectile mechanism are described and the management of each discussed. A modified phalloplasty technique is described for patients who have sustained a complete loss of the phallus.


Cellulose Tailored Anatase TiO2 Nanospindles in Three-Dimensional Graphene Composites for High-Performance Supercapacitors.
The morphologies of transition metal oxides have decisive impact on the performance of their applications. Here, we report a new and facile strategy for in situ preparation of anatase TiO2 nanospindles in three-dimensional reduced graphene oxide (RGO) structure (3D TiO2@RGO) using cellulose as both an intermediate agent eliminating the negative effect of graphene oxide (GO) on the growth of TiO2 crystals and as a structure-directing agent for the shape-controlled synthesis of TiO2 crystals. High-resolution transmission electron microscopy and X-ray diffractometer analysis indicated that the spindle shape of TiO2 crystals was formed through the restriction of the growth of high energy {010} facets due to preferential adsorption of cellulose on these facets. Because of the 3D structure of the composite, the large aspect ratio of the TiO2 nanospindles, and the exposed high-energy {010} facets of the TiO2 crystals, the 3D TiO2@RGO(Ce 1.7) exhibited excellent capacitive performance as an electrode material for supercapacitors, with a high specific capacitance (ca. 397 F g(-1)), a high energy density (55.7 Wh kg(-1)), and a high power density (1327 W kg(-1)) on the basis of the masses of RGO and TiO2. These levels of capacitive performance far exceed those of previously reported TiO2-based composites.


On the Impact of Public Housing on Income Segregation in France.
This article provides a geographic analysis of the contribution of public housing to income segregation in France from 1999 to 2015. The analysis is conducted with several segregation indices and at different geographic scales. Surprisingly, it appears that while home tenure (public vs. private housing) segregation has been decreasing, income segregation has been rising. With segregation decomposition techniques, we provide evidence that this is partly due to an increasing concentration of low-income households in public housing, which cancels out the effect of the spatial dispersion of public housing. Indeed, while public housing has become more homogeneously distributed geographically, which should help to reduce income segregation, the distribution of income within public (and private) housing has changed: households living in public housing were poorer in 2015 than in 1999. We also provide evidence of a sorting effect-the process of allocating public housing that is not random-so that the richest neighborhoods or municipalities receive wealthier-than-average public tenants.


Hierarchy of susceptibility of dendritic cell subsets to infection by Leishmania major: inverse relationship to interleukin-12 production.
Dendritic cells (DCs) are professional antigen-presenting cells which initiate and regulate T-cell immune responses. Here we show that murine splenic DCs can be ranked on the basis of their ability to phagocytose and harbor the obligately intracellular parasite Leishmania major. CD4(+) CD8(-) DCs are the most permissive host cells for L. major amastigotes, followed by CD4(-) CD8(-) DCs; CD4(-) CD8(+) cells are the least permissive. However, the least susceptible CD4(-) CD8(+) DC subset was the best interleukin-12 producer in response to infection. Infection did not induce in any DC subset production of the proinflammatory cytokine gamma interferon and nitric oxide associated with the induction of Th1 responses. The number of parasites phagocytosed by DCs was low, no more than 3 organisms per cell, compared to more than 10 organisms per macrophage. In infected DCs, the parasites are located in a parasitophorous vacuole containing both major histocompatibility complex (MHC) class II and lysosome-associated membrane protein 1 molecules, similar to their location in the infected macrophage. The parasite-driven redistribution of MHC class II to this compartment indicates that infected DCs should be able to present parasite antigen.


Randomized controlled trial: targeted neck cooling in the treatment of the migraine patient.
Cold therapy has long been the number one self-care treatment employed for migraine without aura and the second most common for migraine with aura, yet its mechanism remains elusive. In this study, a mechanism by which this time-tested therapy works is proposed (by cooling the blood passing through intracranial vessels) in an attempt to further elucidate its beneficial effects. The study is designed as a randomized, controlled, crossover clinical trial utilizing an adjustable wrap containing two freezable ice packs targeting the carotid arteries at the neck, where they come close to the skin surface. Fifty-five participants successfully completed the study. Pain at onset, as recorded on a visual analog scale, was similar between the two treatment arms. Maximum pain reduction was observed at the 30 minute time point with a 31.8% ± 15.2% decrease in pain in the treatment arm compared to a 31.5% ± 20.0% increase in pain at the same time interval in the control arm. These findings confirm the application of a frozen neck wrap at onset of migraine headache targeting the carotid arteries at the neck significantly reduced recorded pain in participants with migraine headaches (P<.001).


[Homeostatic model of aging: state and perspectives].
The homeostatic model of aging formalizing the concept of oxidative damage to the body was proposed in 2001. This formalization led to extensive opportunities for using the model to analyze reproduction and longevity of living organisms. Currently, the simulation of life processes in fruit flies gives much attention to the distribution of resources, taking into account the action of genetic noise. The result is arising of individual heterogeneity, in which unbalanced allocation of resources ends with the death from reproductive overload. The article considers the model of the mechanism of individual reproduction of stochasticity and possibility of its use to assess the maximally tolerated changes in the external environment.


Depth of sedation during drug induced sedation endoscopy monitored by BiSpectral Index® and Cerebral State Index®.
Drug induced sedation endoscopy (DISE) is performed to investigate patterns and sites of obstruction in patients with sleep-disordered breathing (SDB). During DISE the patients are sedated to obtain a muscular relaxation of the upper airway which mimics the relaxation during natural sleep. Different sleep stages are intended to be simulated by drug induced sedation, and it is helpful to measure the depth of sedation. The BiSpectral Index® (BIS) is often used for this procedure. Besides the BIS, other means of sedation depth monitoring exist in anaesthesiology but have not yet been investigated with respect to DISE. Monitoring of the Cerebral State Index® (CSI) is one of these methods. The aim of the study was to compare the BIS and CSI for sedation depth monitoring during DISE. Sixty patients underwent DISE monitored by the BIS and CSI in parallel. The BIS and CSI values were compared using the Bland-Altman analysis. The BIS and CSI values differed during the course of sedation during DISE by a mean of - 6.07. At light sedation (BIS 60-80), lower values by 10 scale points of CSI compared with BIS were detectable. At deeper sedation levels (BIS 40-50), the CSI turned to present equal and even higher values compared with the BIS. Sedation depth measurement during DISE can be performed by the BIS or CSI, but the differences should be interpreted carefully as comparable data for sleep stages in natural sleep are available only for BIS.


Cyst detection and viability assessment of Balantioides coli in environmental samples: Current status and future needs.
The ciliate Balantioides coli is a human enteric parasite that can cause life-threatening infections. It is a food- and waterborne parasite, with cysts being the infective stage. Despite its importance as a potential pathogen, few reports have investigated its presence in environmental samples, and some issues need attention including i) The accuracy of B. coli identification. In most cases, the protozoa is identified only by its morphological traits, which can be identical to those from other parasitic ciliates of animals. Genetic analysis of cysts recovered from environmental samples is necessary for species confirmation. In addition, genetic methods used with faecal samples need to be adequately validated with environmental matrices. ii) The methodology for searching this parasite in environmental samples. The protocols include an initial phase to isolate the cysts from the matrix followed by a second phase in which concentration procedures are usually applied. The methods may be valid but are not standardised and differences between studies could affect the results obtained. iii) The areas that needs further research. The development of genetic identification methods and standardised analytical protocols in environmental samples are required, as well as the assessment of viability and infectivity of B. coli cysts. The development of axenic culture systems will boost research on this parasite.


A benzindole substituted carbazole cyanine dye: a novel targeting fluorescent probe for parallel c-myc G-quadruplexes.
Many organic ligands were synthesized to recognize G-quadruplexes. However, different kinds of G-quadruplexes (G4s) possess different structures and functions. Therefore, selective recognition of certain types of G4s is important for the study of G4s. In this paper, a novel cyanine dye, 3-(2-(4-vinylpyridine))-6-(2-((1-(4-sulfobutyl))-3,3-dimethyl-2-vinylbenz[e]indole)-9-ethyl-carbazole (9E PBIC), composed of benzindole and carbazole was designed and synthesised. The studies on UV-vis and fluorescence properties of the dye with different DNA forms showed that the dye exhibits almost no fluorescence under aqueous buffer conditions, but it increased over 100 fold in the presence of c-myc G4 and 10-30 fold in the presence of other G4s, while little in the presence of single/double-stranded DNA, indicating that it has excellent selectivity to c-myc 2345 G4. For the binding studies the dye is interacted with the c-myc 2345 G-quadruplex by using the end-stack binding model. It can be said that the dye is an excellent targeting fluorescent probe for c-myc G-quadruplexes.


Shewanella canadensis sp. nov. and Shewanella atlantica sp. nov., manganese dioxide- and hexahydro-1,3,5-trinitro-1,3,5-triazine-reducing, psychrophilic marine bacteria.
Two strains belonging to the genus Shewanella, HAW-EB2(T) and HAW-EB5(T), were isolated previously from marine sediment sampled from the Atlantic Ocean, near Halifax harbour in Canada, for their potential to degrade explosive hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX). In the present study, strains HAW-EB2(T) and HAW-EB5(T) were found to display high 16S rRNA gene sequence similarity (90-99.5 %) to species of Shewanella, but their gyrB sequences were significantly different from each other and from species of Shewanella (79-87.6 %). Furthermore, DNA-DNA hybridization showed that the genomic DNA of the two strains was only 22 % related and showed less than 41 % relatedness to closely related species of Shewanella. In comparison to other species of Shewanella, strains HAW-EB2(T) and HAW-EB5(T) were also unique in some phenotypic properties such as activities of beta-galactosidase and tyrosine arylamidase and the ability to metabolize certain organic acids and sugars. Both strains HAW-EB2(T) and HAW-EB5(T) utilize malate, valerate, peptone and yeast extract as sole carbon and energy sources. The major membrane fatty acids of the two strains were C(14 : 0), iso-C(15 : 0), C(16 : 0), C(16 : 1)omega7, C(18 : 1)omega7 and C(20 : 5)omega3 and their major quinones were Q-7, Q-8 and MK-7. On the basis of these results, strain HAW-EB2(T) (=NCIMB 14238(T) =CCUG 54553(T)) is proposed as the type strain of Shewanella canadensis sp. nov. and strain HAW-EB5(T) (=NCIMB 14239(T) =CCUG 54554(T)) is proposed as the type strain of Shewanella atlantica sp. nov.


[Expression of Raf kinase inhibitor protein and its significance in invasion and metastasis of hepatocellular carcinoma].
To investigate the expression of RKIP, p65 and pERK in hepatocellular carcinoma (HCC) and theIr correlation with invasion and metastasis of HCC. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of RKIP mRNA. The expression levels of RKIP, p65 and pERK proteins in HCC tumor and peritumoral tissues were determined by immunohistochemistry and Western blot analysis. Statistical analysis was performed to determine the relationship between their expression and clinicopathological parameters. RKIP protein expression level (RKIP/actin) was 0.579 ± 0.380 in HCCs, 1.178 ± 0.659 in peritumoral tissues and 1.115 ± 0.442 in normal liver tissues. The pERK protein level was 1.023 ± 0.478, 0.605 ± 0.367 and 0.461 ± 0.293, p65 protein level was 0.83 ± 0.376, 0.63 ± 0.337 and 0.466 ± 0.345, respectively. Immunohistochemistry analysis showed that the RKIP positive rates in HCCs, peritumoral tissues and normal liver tissues, were 22.2%, 86.0%, and 93.8%, positive rates of p65 were 73.6%, 56.0% and 37.5%, positive rates of pERK were 65.3%, 38.0% and 31.3%, respectively. Statistical analysis revealed that there was a significant difference in RKIP protein expression levels (P < 0.05), but no significant difference in RKIP mRNA expression levels (P > 0.05) among HCC tumors, peritumoral tissues and normal liver tissues. The p65-positive and pERK-positive rates were higher in tumor tissues than that in peritumoral tissues and in normal liver tissues (P < 0.05), but RKIP-positive rates were lower in tumor tissues than that in paritumoral tissues and normal liver tissues (P < 0.05). RKIP protein expression levels were significantly lower in HCCs with intrahepatic or lymphatic metastasis than that in without. The RKIP positive rates in moderately and well differentiated HCCs were significantly higher than that in poorly differentiated HCCs. There was a relationship between RKIP and pERK expressions (P = 0.04), but RKIP expression was not correlated with p65 expression in HCCs (P = 0.143). Our findings indicate that the down-regulation of RKIP expression may serve as a predictive marker for HCC development, progression and metastasis, which may contribute to the elevated ERK activity. The inhibiting effect of RKIP on invasion and metastasis of liver cancer cells may be due to the down-regulation of pERK expression rather than p65 expression.


Musculoskeletal Adverse Events Associated with PCSK9 Inhibitors: Disproportionality Analysis of the FDA Adverse Event Reporting System.
Some studies suggest that potential safety issues about PCSK9 inhibitors have not been sufficiently explored in clinical trials, including musculoskeletal adverse events (MAEs). To examine the association between use of PCSK9 inhibitors with and without concurrent statins and risk of MAEs. Patients and Methods. FDA Adverse Event Reporting System (FAERS) dataset of PCSK9 inhibitors and statins from October 2015 to June 2021 was queried. The reporting odds ratio (ROR) with relevant 95% confidence interval (95% CI) was calculated as the index of disproportionality. Outcome of MAEs of different PCSK9 inhibitors regimens was also investigated. 3,185 cases of PCSK9 inhibitor-associated MAEs were recorded. PCSK9 inhibitor class alone demonstrated a strong link to MAEs (ROR 5.92; 95% CI 5.70-6.15), and evolocumab was associated with more reports of MAEs than alirocumab. Concomitant use with statins leaded to an increased occurrence of MAEs (ROR 32.15 (25.55-40.46)), and the risk differed among different statins. The PCSK9 inhibitors were safer than statins in terms of hospitalization rate and death rate (15.64% vs. 36.83%; 0.72% vs. 3.53%). This pharmacovigilance investigation suggests that PCSK9 inhibitors are associated with MAEs. The risk significantly increases when combined with statins. Increased laboratory and clinical monitoring are required to timely diagnose and manage MAEs.


[Theoretical analysis of ecological diversity models and their application in Fukang of Xinjiang Uygur Autonomous Region].
Ecological diversity refers to a combination of the richness and evenness of an investigation object. Based on this, the widely used model, Shannon model, and a recently developed model, Scaling ecological diversity model, were theoretically analyzed in this paper. It was indicated that Shannon model had many limitations, e. g., it could be available only when the number of each type of investigation object was more than 100, did not include any information of scale, and could not express the richness of diversity. In other words, Shannon model could only express the evenness of diversity. A case-study in Fukang of Xinjiang Uygur Autonomous Region showed that the richness and Shannon evenness were always resolution-dependent, while the ecotope diversity calculated by Scaling ecological diversity model was resolution-independent when the spatial resolution ranged from 30 m x 30 m to 150 m x 150 m, and strictly increased when the spatial resolution ranged from 150 m x 150 m to 480 m x 480 m.


Stem cell homing factor, CCL7, expression in mouse models of stress urinary incontinence.
Animal models of vaginal distention (VD) have demonstrated increased expression of chemokine (C-C motif) ligand 7 (CCL7) In this study, we investigated the expression of CCL7 in mice models of simulated birth trauma-induced urinary incontinence using VD and pudendal nerve transection (PNT). Forty-nine mice were divided into 6 groups: VD, sham VD, PNT, sham PNT, anesthesia, and age-matched controls. The urethra, vagina, and rectum were harvested for the expression of CCL7 immediately or 24 hours after assigned procedure. Venous sampling for quantification of serum CCL7 was also performed. An analysis of variance model was used to compare the relative expression of CCL7 in each group. Urethral CCL7 expression in the VD group was significantly higher than control group after 24 hours (P < 0.01). There was no difference in the urethral CCL7 expression in PNT, sham PNT, sham VD, or anesthesia groups compared with the controls. No statistically significant difference was noted in the vaginal and rectal expression of CCL7 between any of the groups except for sham PNT. Statistically significant differences were noted in the serum CCL7 expression in the VD, PNT, and sham PNT (P < 0.01 in all) groups after 24 hours compared with the control group. This study demonstrates overexpression of urethral CCL7 after VD but not PNT. This suggests that nerve injury does not contribute to the CCL7 overexpression. The overexpression of CCL7 in the serum of mice after VD suggests a translational potential where CCL7 measurement could be used as a surrogate for injury after delivery.


Correction of partial-volume effect for PET striatal imaging: fast implementation and study of robustness.
PET imaging of D(2) receptors or (18)F-L-dopa metabolism are reference protocols to follow and study neurodegenerative diseases, but the accuracy of striatal PET imaging is limited by the partial-volume effect (PVE). For such studies, the geometric transfer matrix (GTM) method has been proposed to correct the regional mean values for PVE and is now widely used. The GTM method models the geometric interactions induced by the PET system between the anatomic regions in which PVE correction is performed. This implies estimation of the corresponding regional spread function (RSF). The literature describes 2 implementations for the RSF calculation; they differ in the way the point spread function (PSF) of the imaging system is modeled, but no comparison or discussion has been given. The first and reference implementation uses an accurate intrinsic detector PSF that is applied in the sinogram space. The second uses a global PSF that is applied in the image space. In this work, we compared the 2 GTM implementations for 3-dimensional (3D) PET striatal imaging using Monte Carlo simulations and a phantom study. We studied the robustness of the GTM correction with respect to residual registration errors between PET and anatomy and with respect to residual segmentation errors. Despite the differences in RSF calculation and computation cost between the 2 implementations, similar recovery results were obtained (between 95% and 100%). The study of robustness of the GTM correction yielded 2 results. A realistic residual misregistration between the anatomic and PET images did not modify the algorithm accuracy but decreased its precision. Conversely, a realistic residual missegmentation of the anatomic regions submitted to GTM correction decreased the correction accuracy. A simple but efficient implementation in the image space of the GTM method yields accurate PVE correction in striatal regions in studies with 3D PET and enables clinical use. The method is less sensitive to residual misregistration errors between PET and anatomy than to residual missegmentation of the anatomy. Special care should be taken with segmentation of the regions to correct for PVE.


In vitro evaluation of bond strength and surface roughness of a resin-paint material.
This study investigated the stability of a resin-paint material (Master Palette)--which was developed for chairside shade modification of composite restorations--by evaluating its bond strength to indirect resin composite and surface degradation. Bond strength was evaluated with four surface treatments including an application of methylene chloride, airborne particle abrasion with 50 microm aluminum oxide, and additional applications of bonding agents after air-abrasion. The surface roughness (Rz value) of both the resin-paint and indirect resin composite before and after thermo-cycling (4-60 degrees C, 50,000 cycles) was also evaluated. All data were statistically analyzed by two-way ANOVA and Boneferroni's test (p=0.05). It was found that bond strength was improved by bonding agent application (14.9+/-1.9 MPa to 18.6+/-2.2 MPa, p<0.0054) after thermo-cycling. As for surface roughness, its results after thermo-cycling (2.7+/-0.2 microm, p<0.001) demonstrated that the resin-paint needed further improvements to maintain the original surface texture.


Nutrients and pheromones promote insulin release to inhibit courtship drive.
Food and reproduction are the fundamental needs for all animals. However, the neural mechanisms that orchestrate nutrient intake and sexual behaviors are not well understood. Here, we find that sugar feeding immediately suppresses sexual drive of male Drosophila, a regulation mediated by insulin that acts on insulin receptors on the courtship-promoting P1 neurons. The same pathway was co-opted by anaphrodisiac pheromones to suppress sexual hyperactivity to suboptimal mates. Activated by repulsive pheromones, male-specific PPK23 neurons on the leg tarsus release crustacean cardioactive peptide (CCAP) that acts on CCAP receptor on the insulin-producing cells in the brain to trigger insulin release, which then inhibits P1 neurons. Our results reveal how male flies avoid promiscuity by balancing the weight between aphrodisiac and anaphrodisiac inputs from multiple peripheral sensory pathways and nutritional states. Such a regulation enables male animals to make an appropriate mating decision under fluctuating feeding conditions.


Mining Symptom-Herb Patterns from Patient Records Using Tripartite Graph.
Unlike the western medical approach where a drug is prescribed against specific symptoms of patients, traditional Chinese medicine (TCM) treatment has a unique step, which is called syndrome differentiation (SD). It is argued that SD is considered as patient classification because prior to the selection of the most appropriate formula from a set of relevant formulae for personalization, a practitioner has to label a patient belonging to a particular class (syndrome) first. Hence, to detect the patterns between herbs and symptoms via syndrome is a challenging problem; finding these patterns can help prepare a prescription that contributes to the efficacy of a treatment. In order to highlight this unique triangular relationship of symptom, syndrome, and herb, we propose a novel three-step mining approach. It first starts with the construction of a heterogeneous tripartite information network, which carries richer information. The second step is to systematically extract path-based topological features from this tripartite network. Finally, an unsupervised method is used to learn the best parameters associated with different features in deciding the symptom-herb relationships. Experiments have been carried out on four real-world patient records (Insomnia, Diabetes, Infertility, and Tourette syndrome) with comprehensive measurements. Interesting and insightful experimental results are noted and discussed.


Identification of factor H-like protein 1 as the predominant complement regulator in Bruch's membrane: implications for age-related macular degeneration.
The tight regulation of innate immunity on extracellular matrix (ECM) is a vital part of immune homeostasis throughout the human body, and disruption to this regulation in the eye is thought to contribute directly to the progression of age-related macular degeneration (AMD). The plasma complement regulator factor H (FH) is thought to be the main regulator that protects ECM against damaging complement activation. However, in the present study we demonstrate that a truncated form of FH, called FH-like protein 1 (FHL-1), is the main regulatory protein in the layer of ECM under human retina, called Bruch's membrane. Bruch's membrane is a major site of AMD disease pathogenesis and where drusen, the hallmark lesions of AMD, form. We show that FHL-1 can passively diffuse through Bruch's membrane, whereas the full sized, glycosylated, FH cannot. FHL-1 is largely bound to Bruch's membrane through interactions with heparan sulfate, and we show that the common Y402H polymorphism in the CFH gene, associated with an increased risk of AMD, reduces the binding of FHL-1 to this heparan sulfate. We also show that FHL-1 is retained in drusen whereas FH coats the periphery of the lesions, perhaps inhibiting their clearance. Our results identify a novel mechanism of complement regulation in the human eye, which highlights potential new avenues for therapeutic strategies.


MALIGNANT TRANSFORMATION OF A CHOROIDAL NEVUS IN AN EYE TREATED FOR CHOROIDAL MELANOMA.
To report a case of a choroidal melanoma and a discrete choroidal nevus that has transformed into a malignant melanoma 5 years after initial diagnosis. Retrospective case report. A diffuse macular choroidal melanoma and a discrete choroidal nevus located superonasal to the optic disk were diagnosed in the right eye of a 63-year-old woman in 2009. The patient was treated by ruthenium plaque radiotherapy for the choroidal melanoma, which consequently flattened and scarred. On a routine eye check in 2014, the nevus was found to have been transformed into a choroidal melanoma. It was treated with ruthenium plaque radiotherapy. Although extremely rare, patients with a uveal melanoma can develop an additional discrete uveal melanoma. This case highlights the importance of monitoring benign choroidal nevi in patients with a history of choroidal melanoma.


[Continuous medical education of general practitioners/family doctors in chronic wound care].
A number of healthcare professionals, specialists in different fields and with different levels of education, as well as non-healthcare professionals, are involved in the care of chronic wound patients, thus forming a multidisciplinary team that is not only responsible for the course and outcome of treatment, but also for the patient quality of life. Family doctor is also member of the team the task of which is to prevent, diagnose, monitor and anticipate complications and relapses, as well as complete recovery of chronic wound patients, with the overall care continuing even after the wound has healed, or is involved in palliative care. A family medicine practitioner with specialized education and their team of associates in the primary health care, along with material conditions and equipment improvement, can provide quality care for patients with peripheral cardiovascular diseases and chronic wounds, organized according to the holistic approach. It is essential that all professional associations of family medicine as well as professional associations of other specialties - fields that are involved in wound prevention and treatment - be included in developing the continuous medical education program. The benefits of modern information technology should be used to good advantage. The education should be adapted to the needs of family practitioners in terms of the form, place, time, volume, financial affordability and choice of topic. The interest shown in team education should be transformed into specialized programs in the creation of which it is essential to include both physicians and nurses and their respective professional associations. Special attention should be paid to education and training of young doctors/nurses, those with less work experience, those that have not yet been part of such education, those that lack experience in working with wound patients, those whose teams deal mostly with elderly patients, and also residents in family medicine and Nursing College students.


A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose, Multiple Ascending Dose and Food Effect Study to Evaluate the Tolerance, Pharmacokinetics of Jaktinib, a New Selective Janus Kinase Inhibitor in Healthy Chinese Volunteers.
Background: Jaktinib is a novel selective janus kinase 1/2 inhibitor. The phase I first-in-human study evaluated the tolerance and pharmacokinetics of jaktinib in healthy Chinese subjects. Methods: A randomized, double-blind, placebo-controlled study were designed. A total of 126 healthy subjects were enrolled into the single ascending dose, multiple ascending dose and food effect study. Safety endpoints included adverse events, abnormal vital signs, 12-lead ECGs, abdominal ultrasound, chest x-ray, physical examination and clinical laboratory tests. Blood, urine and feces samples were collected at predetermined time points for pharmacokinetic analysis of jaktinib, the metabolites ZG0244 and ZG0245, which are formed by oxidation or hydrolysis metabolic pathway, respectively. Results: Jaktinib was absorbed with a median time to peak plasma concentration of 1.25-3.5 h and was eliminated with a half-life of 2.952-9.040 h. Linear pharmacokinetic characteristic was presented over the dose range from 25 to 400 mg. No obvious accumulation was observed after multiple doses for 10 days. Administration after a high-fat breakfast significantly increased the absorption of jaktinib. The accumulated fraction of jaktinib and the determined metabolites excreted in urine and feces was 19.478%. Jaktinib was well tolerated in all single dose cohorts. In multiple dose cohorts, 200 mg q24 h method was evaluated as maximally tolerated dose. Neutropenia, diarrhea, dizziness and headache were the most frequently reported treatment related adverse events. No deaths, serious or Grade ≥4 adverse events was developed. Conclusion: Jaktinib was well tolerated when single dose ranging from 25 to 400 mg and multiple dose up to 200 mg q24 h. The safety and pharmacokinetic characteristics support the next trial in myelofibrosis patients.


Statistical learning as a predictor of attention bias modification outcome: A preliminary study among socially anxious patients.
Attention bias modification (ABM) is a novel therapy designed to modulate attentional biases towards threat typically observed among anxious individuals. Bias modification is allegedly achieved via extraction of a statistical regularity embedded within the treatment task. However, no prior study examined prediction of ABM therapeutic response in relation to patients' capacity to extract statistical properties from the environment, a capacity known as "statistical learning". Here, 30 treatment-seeking patients with social anxiety disorder completed a gold-standard statistical learning task at baseline and then received six sessions of ABM therapy. Results indicate that baseline statistical learning capacity predicts treatment outcome: the better patients' statistical learning capacity, the greater their reduction in clinician-rated and self-reported social anxiety symptoms. Restricted capacities for statistical learning could account for the moderate effect sizes of ABM therapy in clinical trials. Poor response may occur in patients who fail to extract the underlying contingency embedded in ABM.


Stable High-Sensitivity Cardiac Troponin T Levels and Outcomes in Patients With Chest Pain.
There is a paucity of data on the association between high-sensitivity cardiac troponin (hs-cTn) levels and outcomes in patients with chest pain but no myocardial infarction (MI), or any other condition that may lead to acutely elevated troponin levels. The authors hypothesized that any detectable high-sensitivity cardiac troponin T (hs-cTnT) level is associated with adverse outcomes. All patients (N = 22,589) >25 years of age with chest pain and hs-cTnT analyzed concurrently in the emergency department of Karolinska University Hospital, Stockholm, Sweden from 2011 to 2014 were eligible for inclusion. After excluding all patients with acute conditions that may have affected hs-cTnT, or MI associated with the visit, or insufficient information to determine whether troponin levels were stable, Cox regression was used to estimate risks for all-cause, cardiovascular, and noncardiovascular mortality, MI, and heart failure at different levels of troponins. A total of 19,460 patients with a mean age of 54 ± 17 years were included. During a mean follow-up of 3.3 ± 1.2 years, 1,349 (6.9%) patients died. Adjusted hazard ratios (with 95% confidence intervals) for all-cause mortality were 2.00 (1.66 to 2.42), 2.92 (2.38 to 3.59), 4.07 (3.28 to 5.05), 6.77 (5.22 to 8.78), and 9.68 (7.18 to 13.00) in patients with hs-cTnT levels of 5 to 9, 10 to 14, 15 to 29, 30 to 49, and ≥50 ng/l, respectively, compared with patients with hs-cTnT levels <5 ng/l. There was a strong and graded association between all detectable levels of hs-cTnT and risk for MI, heart failure, and cardiovascular and noncardiovascular mortality. Among patients with chest pain and stable troponin levels, any detectable level of hs-cTnT is associated with an increased risk of death and cardiovascular outcomes and should merit further attention.


Quantitative proteomic analyses of influenza virus-infected cultured human lung cells.
Because they are obligate intracellular parasites, all viruses are exclusively and intimately dependent upon host cells for replication. Viruses, in turn, induce profound changes within cells, including apoptosis, morphological changes, and activation of signaling pathways. Many of these alterations have been analyzed by gene arrays, which measure the cellular "transcriptome." Until recently, it has not been possible to extend comparable types of studies to globally examine all the host cellular proteins, which are the actual effector molecules. We have used stable isotope labeling by amino acids in cell culture (SILAC), combined with high-throughput two-dimensional (2-D) high-performance liquid chromatography (HPLC)/mass spectrometry, to determine quantitative differences in host proteins after infection of human lung A549 cells with human influenza virus A/PR/8/34 (H1N1) for 24 h. Of the 4,689 identified and measured cytosolic protein pairs, 127 were significantly upregulated at >95% confidence, 153 were significantly downregulated at >95% confidence, and a total of 87 proteins were upregulated or downregulated more than 5-fold at >99% confidence. Gene ontology and pathway analyses indicated differentially regulated proteins and included those involved in host cell immunity and antigen presentation, cell adhesion, metabolism, protein function, signal transduction, and transcription pathways.


[How much food for a soul? Psychosomatic treatment of infantile feeding disorders].
Severe feeding disorders often require inpatient treatment and need a holistic assessment and treatment approach. This article introduces some of the current literature concerning feeding disorders in infants and toddlers. The philosophy of the Department of Infant Psychosomatics at the University Children's Hospital Zürich emphasizes interdisciplinary teamwork, the application of psychodyamic tools in pediatric liaison psychiatry and utilization of group settings. Clinical approach and course of treatment are illustrated by three case reports, highlighting specific psychotherapeutic interventions with the parent-infant relationship in the context of a paediatric clinic.


Multiple sized europium(III) chelate-dyed polystyrene particles as donors in FRET - an application for sensitive protein quantification utilizing competitive adsorption.
A variety of particles have been adopted as solid support in bioaffinity assays, and the ability to modify the particle properties makes them a versatile tool in assay development. In separation-free fluorescence resonance energy transfer (FRET) assays, fluorescent particles have been used as donors and acceptors due to their high binding capacity and high specific activity. The availability of multiple fluorophores within the FRET range renders the orientation of individual donors and acceptors a non-factor enabling efficient sensitization. The high specific activity, being proportional to the particle size, may also inflict background fluorescence due to distance dependency of FRET, if the donor emission and detection wavelengths overlap. This is the first study to evaluate the impact of differently sized (47, 68, 92 and 202 nm in diameter) europium(III) chelate-doped polystyrene/acrylic acid donor particles on the core-related background fluorescence in a separation-free FRET-based assay utilizing competitive adsorption of acceptor-labelled protein. Within the particle size range studied, the particle core size-related background fluorescence showed no significant effect on the assay performance at the detection wavelength, which was selected on account of donor emission minimum. The assay sensitivity and dynamics showed compliancy with the rules of competitive assay. The results can be used in designing a competitive separation-free FRET-based assay utilizing particles as donors. In accordance, we applied the method for protein quantification. Sample protein prevented the adsorption of acceptor-labelled protein on the nanoparticle reducing energy transfer. Using this approach, a 100- to 1000-fold lower protein concentration was measured in comparison to traditional photometric protein assays suggesting that a high sensitivity assay can be constructed using FRET-based nanoparticle assay concepts.


Effects of oligomycin on transient currents carried by Na+ translocation of Bufo Na+/K(+)-ATPase expressed in Xenopus oocytes.
Na(+)/K(+)-ATPase (NKA) exports 3Na(+) and imports 2K(+) at the expense of the hydrolysis of 1ATP under physiological conditions. In the absence of K(+), it can mediate electroneutral Na(+)/Na(+) exchange. In the electroneutral Na(+)/Na(+) exchange mode, NKA produces a transient current containing fast, medium and slow components in response to a sudden voltage step. These three components of the transient current demonstrate the sequential release of Na(+) ions from three binding sites. Our data from oocytes provide further experimental support for the existence of these components. Oligomycin is an NKA inhibitor that favors the 2Na(+)-occluded state without affecting the conformational state of the NKA. We studied the effects of oligomycin on both K(+)-activated currents and transient currents in wild-type Bufo NKA and a mutant form of Bufo NKA, NKA: G813A. Oligomycin blocked almost all of the K(+)-activated current, although the three components of the transient current showed different sensitivities to oligomycin. The oligomycin-inhibited charge movement measured using a P/4 protocol had a rate coefficient similar to the medium transient component. The fast component of the transient current elicited by a short voltage step also showed sensitivity to oligomycin. However, the slow component was not totally inhibited by oligomycin. Our results indicate that the second and third sodium ions might be released to the extracellular medium by a mechanism that is not shared by the first sodium ion.


Stilbene levels in grape cane of different cultivars in southern Chile: determination by HPLC-DAD-MS/MS method.
Health benefits of trans-resveratrol and other stilbenes in grapes, must, and wine have been pointed out by numerous authors. Less attention has been paid to the presence of stilbene derivatives in viticultural residues, such as grape canes. The present work reports the first results of a systematic study of stilbene levels in different grape varieties and cultivation areas in Chile, to evaluate their potential as an alternative source of bioactive stilbenes. In all cane samples, the predominant stilbene is trans-resveratrol, followed by ε-viniferin and piceatannol. In canes of Pinot noir up to 5590 ± 172 mg kg(-1) of trans-resveratrol and up to 6915 ± 175 mg kg(-1) of total stilbenes were detected. The observed concentrations of stilbenes in canes of Pinot noir from southern Chile until now are higher than those reported previously for this red variety. However, the highest concentration of total stilbenes observed in the analyzed samples was in the canes of white variety Gewürztraminer with 7857 ± 498 mg kg(-1). Preliminary results indicate that these levels can evolve if canes are left for some months on the vineyard after pruning, observing an increase during the first 2 months and a decrease after this period.


LRRK2 affects vesicle trafficking, neurotransmitter extracellular level and membrane receptor localization.
The leucine-rich repeat kinase 2 (LRRK2) gene was found to play a role in the pathogenesis of both familial and sporadic Parkinson's disease (PD). LRRK2 encodes a large multi-domain protein that is expressed in different tissues. To date, the physiological and pathological functions of LRRK2 are not clearly defined. In this study we have explored the role of LRRK2 in controlling vesicle trafficking in different cellular or animal models and using various readouts. In neuronal cells, the presence of LRRK2(G2019S) pathological mutant determines increased extracellular dopamine levels either under basal conditions or upon nicotine stimulation. Moreover, mutant LRRK2 affects the levels of dopamine receptor D1 on the membrane surface in neuronal cells or animal models. Ultrastructural analysis of PC12-derived cells expressing mutant LRRK2(G2019S) shows an altered intracellular vesicle distribution. Taken together, our results point to the key role of LRRK2 to control vesicle trafficking in neuronal cells.


The Arabidopsis homolog of human minor spliceosomal protein U11-48K plays a crucial role in U12 intron splicing and plant development.
The minor U12 introns are removed from precursor mRNAs by the U12 intron-specific minor spliceosome. Among the seven ribonucleoproteins unique to the minor spliceosome, denoted as U11/U12-20K, U11/U12-25K, U11/U12-31K, U11/U12-65K, U11-35K, U11-48K, and U11-59K, the roles of only U11/U12-31K and U11/U12-65K have been demonstrated in U12 intron splicing and plant development. Here, the functional role of the Arabidopsis homolog of human U11-48K in U12 intron splicing and the development of Arabidopsis thaliana was examined using transgenic knockdown plants. The u11-48k mutants exhibited several defects in growth and development, such as severely arrested primary inflorescence stems, formation of serrated leaves, production of many rosette leaves after bolting, and delayed senescence. The splicing of most U12 introns analyzed was impaired in the u11-48k mutants. Comparative analysis of the splicing defects and phenotypes among the u11/u12-31k, u11-48k, and u11/12-65k mutants showed that the severity of abnormal development was closely correlated with the degree of impairment in U12 intron splicing. Taken together, these results provide compelling evidence that the Arabidopsis homolog of human U11-48K protein, as well as U11/U12-31K and U11/U12-65K proteins, is necessary for correct splicing of U12 introns and normal plant growth and development.


[Haikou issues circular on planned parenthood].
The Organization Department of the Haikou Municipal CCP Committee, the municipal grain, finance, commerce, education bureau, personnel, public security, labor, civil affairs, public health, and housing bureaus, supply and marketing cooperative, and planned parenthood office recently issued a joint circular on implementing the provincial planned parenthood regulations. The circular demanded that the marriage registration and census system be seriously implemented. When people are registering for marriage, we must teach them to have only 1 child. We must give priority in housing and employment to an only child and his parents. When commercial, supply, and marketing departments are distributing coupons for fuel, and nonstaple food, they should supply a double amount to the only child. We must carry out serious health care for an only child and give them regular physical check-ups. When they are ill, hospitals should give them priority in registration, treatment, reservation of beds and medicines. The circular reiterated: We must seriously implement the stipulations on rewards and punishments contained in the provincial planned parenthood regulations. Cadres, staff, or workers who apply to have only 1 child must be given lump sums in addition to enjoying the relevant rewards stipulated by the regulations. Cadres, staff, workers, inhabitants, and commune workers who depend on state grain who violate the regulations must be punished according to the regulation. As for those who have 3 or more than 3 children, a 2nd child without planning, or an illegitimate child, the child's grain ration will be sold at negotiated price up to the age of 14. The grain department will distribute to them a supply ticket for negotiated price grain to buy grain in assigned grain shops.


Oscillatory properties of the central pattern generator for locomotion in neonatal rats.
1. The oscillatory properties of the lumbar spinal networks that generate locomotor activity in mammals were studied. These experiments were performed on an in vitro isolated spinal cord preparation from newborn rats. Adding to the saline serotonin (5-HT) and N-methyl-D-aspartate (NMDA) excitatory amino acid receptor agonist (N-methyl-D,L-aspartate, NMA) induced rhythmic locomotor-like activity that was recorded in the ventral roots. 2. The period of the rhythmic locomotor-like activity could be set by combining the neurotransmitters at various concentrations. The combined transmitters also acted on the instantaneous variations of the period value. The stability of the period from one cycle to another increased when 5-HT was mixed with NMA compared with the activity induced by bath application of the compound alone. 3. K(+)-induced depolarizations were used to set the neuron membrane potential. These systematic changes in the K+ concentration resulted in a change in the period value. 4. Stimulation of the dorsal roots reset the ongoing rhythm. Phase-response curves were drawn up that showed that the spinal networks exhibit a differential sensitivity to the same stimulus depending on the phase at which the stimulus is applied. The free-running activity could be entrained by the cyclic volleys of sensory discharges. Entrainment occurred, on average, between -28 and 36% of the rest period. Because the lumbar segments were completely isolated by means of a sucrose blockade of all descending neuronal activity, the entrainment of the locomotor activity must take place directly at the lumbar level. 5. In conclusion, our data show that, at birth, the rhythmic activity produced by the spinal networks is based on a neuronal architecture that displays oscillatory properties. At this early age, the peripheral sensory afferents have already established connections with the central pattern generator. These sensory inputs are able to control the cycling activity of the spinal networks step by step.


Sofia Quintero Romero: Protection and Support of Breastfeeding With a Feminist and Social Justice Lens.
Sofia Quintero Romero graduated as a medical doctor at Universidad del Rosario, Bogotà, Colombia, in 1977. She spent a compulsory rural year working in a remote indigenous community in the Sierra Nevada de Santa Marta in Columbia. In 1979 she worked in Bolivia for Terre des Hommes and Oxfam, evaluating their health projects with the Aymara Indians and in the tin mines. She had to leave Colombia for political reasons and went to England, where she obtained, in 1981, an MSc in Community Health at the London School of Hygiene & Tropical Medicine (LSHTM). That's where she met her husband, Adriano Cattaneo. She then worked in Mozambique and Nicaragua where she was in charge of maternal and child health services at the regional level. Since 1990, she devoted her time to the protection, promotion, and support of breastfeeding. Sofia obtained a PhD in Maternal and Child Health at the University of Bologna, Italy, and a Diploma in Breastfeeding Theory and Practice at the Child Health Institute in London UK. She taught hundreds of breastfeeding courses for health professionals and peer counsellors in Italy and in dozens of countries abroad, using the World Health Organization/United Nations Children's Fund (WHO/UNICEF) manuals. In the past 15 years, she changed her approach for breastfeeding education to biological nurturing. Sofia has been a member of the International Baby Food Action Network (IBFAN) since 1992 and coordinated the Nestlé Boycott in Italy. She retired in 2018.


Impact of body mass index on radical cystectomy.
Radical cystectomy has a significant rate of morbidity and it is important to elucidate the factors that contribute to this risk. Obesity is a major problem in the United States and is associated with increased health hazard. Morbid obesity may even preclude definitive surgical treatment. This study examines the impact of body mass index (BMI) on radical cystectomy. Retrospective analysis was performed on 498 patients who underwent radical cystectomy primarily for bladder cancer from July 1, 1990 to May 10, 2002. Patient BMI was defined as normal (less than 25 in 151), overweight (25 to 29.9 in 198), obese (30 to 34.9 in 98) and morbidly obese (35 or greater in 51). The bivariate relationships among BMI categories and clinical parameters were assessed using the chi-square test, the analysis of variance and the log rank test. Multivariate analyses were performed using Cox regression models. Median followup for the cohort was 3.3 years. Mean BMI was 28 and 70 of the study group was above normal weight. Compared to normal BMI, upper weight BMI groups were younger (p <0.0001), and had increased estimated blood loss (p = 0.01) and operative time (p = 0.001). Complication number (p = 0.0004) was increased in these groups but complication severity was similar (p = 0.54). Morbidly obese patients underwent incontinent diversion more often (p = 0.03). In multivariate models increased BMI was independently associated with increased estimated blood loss (p = 0.004), prolonged operative time (p = 0.006) and increased complication rate (p = 0.01). Increased BMI independently poses a greater perioperative risk to the patient and contributes to the technical challenge of the cystectomy. This is most appreciated in the morbidly obese population and likely contributes to a greater use of incontinent diversion in this group. The increased perioperative risk associated with elevated BMI is significant but not prohibitive and should not preclude cystectomy as definitive treatment.


Intensive loading dose of trastuzumab achieves higher-than-steady-state serum concentrations and is well tolerated.
PURPOSE Pharmacokinetics (PKs) and safety results from phase II/III trials suggest that, if high trastuzumab serum concentrations are reached early during treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer, patients will gain clinical benefit, and the synergistic effects of trastuzumab and chemotherapy will be maximized. This phase I/II study evaluated the PKs, efficacy, and safety of a novel, intensive loading regimen of trastuzumab in women with HER2-positive metastatic breast cancer (MBC). PATIENTS AND METHODS An intensive loading regimen of trastuzumab was given (6 mg/kg intravenously on days 1, 8, and 15 followed by 6 mg/kg every 3 weeks from day 22) to women age 18 years or older with HER2-positive MBC who may have received previous surgery, radiotherapy, and/or chemotherapy. Study medication was continued until disease progression or withdrawal occurred. Results All eligible women (N = 72) received at least one dose of trastuzumab. Median estimated trough concentration of trastuzumab at the end of 3 weeks of the intensive loading regimen (total of 18 mg/kg of trastuzumab administered) of cycle 1 was 119 mg/L, which is higher than steady-state trough concentrations with a conventional weekly or every-3-week regimen (64.9 or 47.3 mg/L, respectively). No new or unexpected adverse events or increased cardiotoxicity were reported during the study. In patients with measurable disease (n = 47), response rate was 23.4%. Median time to progression was 7.7 months (in all patients). CONCLUSION An intensive loading regimen of trastuzumab achieved higher-than-steady-state serum concentrations during cycle 1, was well tolerated, and had a good efficacy profile.


Unwinding Induced Melting of Double-Stranded DNA Studied by Free Energy Simulations.
DNA unwinding plays a major role in many biological processes, such as replication, transcription, and repair. It can lead to local melting and strand separation and can serve as a key mechanism to promote access to the separate strands of a double-stranded DNA. While DNA unwinding has been investigated extensively by DNA cyclization and single-molecule studies on a length-scale of kilo base pairs, it is neither fully understood at the base pair level nor at the level of molecular interactions. By employing a torque acting on the termini of DNA oligonucleotides during molecular dynamics free energy simulations, we locally unwind the central part of a DNA beyond an elastic (harmonic) regime. The simulations reproduce experimental results on the twist elasticity in the harmonic regime (characterized by a mostly quadratic free energy change with respect to changes in twist) and a deformation up to 7° was found as a limit of the harmonic response. Beyond this limit the free energy increase per twist change dropped dramatically coupled to local base pair disruptions and significant deformation of the nucleic acid backbone structure. Restriction of the DNA bending flexibility resulted in a stiffer harmonic response and an earlier onset of the anharmonic response. Whereas local melting with a complete disruption of base pairing and flipping of nucleotides was observed in case of an AT rich central segment strong backbone changes and changes in the stacking arrangements were observed in case of a GC rich segment. Unrestrained MD simulations starting from locally melted DNA reformed regular B-DNA after 50-300 ns simulation time. The simulations may have important implications for understanding DNA recognition processes coupled with significant structural alterations.


[Therapeutic management of fracture-induced osteitis].
Fractural osteitis is considered to be exclusively of external origin, being due either to accidental wounds, or to operatory wounds. The infection is usually either with a single strain of germs, or with a small number of strains, most frequently a staphylococcus strain with a necrototizing effect on the bone structure. The prophylaxis has a determinant role, and the authors stress the organisatory measures, as well as the medical attitudes that should prevail in the face of an open fracture. In the case of closed fractures that have been infected as a result of surgery the necessity for an "early reintervention" is stressed. Late postoperative osteitis may develop in a consolidated focus, and is called osteitis of the repaired bone. It may also develop as an osteoarthritis or, and this is more serious, as a suppurated pseudarthrosis. The therapeutic attitude depends on the condition, and may consist in the removal of the osteosynthesis material, removal of the sequestered bone tissue, a so-called: "mis-à-plat" of the cavity with muscular tissue and application of septopal pearls, or a two-stage spongious graft according to Papineau, under protection of the external fixation when the necessity arises.


Stepwise gradient elution of capillary electrochromatography in the analysis of environmental samples.
Two modes of stepwise gradient elution of capillary electrochromatography were developed for the analysis of environmental samples on both a laboratory-made and a commercial CE instrument. Using the laboratory-made apparatus, another mobile phase was dropped directly into the inlet vial with a pipet. By this means, nine 2,4-dinitrophenylhydrazine (DNPH)-derivatized ketones and aldehydes were separated with high resolution. Not only was analysis time shortened by more than one half, but the detection limit was greatly improved compared to that in isocratic elution. The latter was achieved using the P/ACE 5510 system (Beckman Instruments, Fullerton, CA, U.S.A.), which moved the mobile phase vials automatically. The stop-flow technique was utilized during transfer. It had no effect on solute retention. With this method, the concentration and type of organic modifier in the mobile phase could be changed. A mixture of 13 aromatic hydrocarbons was separated completely in 14 min by changing the mobile phase from 80% methanol to 80% acetonitrile and 90% acetonitrile in a sequential step mode. The RSD of the retention time of each component in six consecutive injections was below 0.374%. All of these results demonstrate that stepwise gradient elution of capillary electrochromatography may be useful in the analysis of complex environmental samples.


Testing the sympathetic nervous system of the foot has a high predictive value for early amputation in patients with diabetes with a neuroischemic ulcer.
There is evidence from the literature that dysfunctionality of the sympathetic nervous system of the foot with subsequent loss of local autoregulation could be a predictor of early amputation in patients with diabetes with a neuroischemic ulcer. To confirm this we tested the functionality of the sympathetic nervous system in the foot in a consecutive group of 31 patients with diabetes with critical limb ischemia and non-healing neuroischemic ulcer. Prospective cohort with retrospective analysis after 12 months of routinely acquired clinical data. All patients in the study group underwent angiography of the foot as part of a routine angioplasty procedure. Primary study endpoint was lower extremity amputation-free survival at 12 months. Because of the study design no other endpoints could be analyzed. The functionality of the sympathetic nervous system was tested with perfusion angiography. Thirty-one patients were followed for 12 months. The Capillary Resistance Index (CRI) was used to measure the response of the sympathetic nervous system. CRI≥0.9 is the cut-off point for a non-responsive sympathetic nervous system. All patients (n=11) with a CRI≥0.9 underwent a major amputation before 12 months. Of all patients with a CRI only 15% underwent major amputation. The positive predictive value for major amputation before 12 months for patients with a CRI ≥ 0.9 was 100%. A non-responsive sympathetic nervous system of the foot is a strong predictor of early major amputation (log rank p<0.001; HR 14.22; 95% CI 3.64 to 55.51).


A two process model of burnout and work engagement: distinct implications of demands and values.
A model of job burnout proposes two distinct processes. The first process concerns balance of demands to resources. A poor balance leads to chronic exhaustion, an integral aspect of the burnout syndrome. The second process concerns the congruence of individual and organizational values. The model proposes that value conflicts have implications for all three aspects of burnout. It also proposes that the impact of value conflicts has only minor implications for the exhaustion aspect of burnout; they are more relevant for the cynicism and inefficacy aspects of the syndrome. The model considers distinct processes at work that concern employees' perception of organizational justice and their trust in leadership. With a sample of 725 nurses, the analysis tested one component of the theory: the extent to which value congruence enhances the prediction of burnout beyond the prediction provided by demands and resources. Future directions are discussed.


[Brain computed tomography angiography in case of subarachnoid hemorrhage].
Objective was to evaluate sensitivity, specificity and diagnostic accuracy of brain computed tomography (CTA) in patients with subarachnoid hemorrhage (SAH). In the period of January-September, 2001 CTA was performed in 46 patients (with SAH on initial CT) of Clinic of Neurosurgery and Clinic of Neurology clinics, Kaunas University Hospital. CTA was performed at different time from the onset (from several hours to one year). Each patient underwent care bolus procedure (slice thickness 5 mm, rotation time 1.0 s, voltage 140 kV, delay time 11 s, scan plane suspected aneurysm or cavernous sinus, number of scans 15 (each 2 s), volume 20 ml, flow rate 2.8 ml/s) and CTA (slice thickness 1 mm, rotation 2.0, rotation time 1.0 s, voltage 120 kV, increment 1.0, delay time individual, volume 80 ml, flow rate 2.8 ml/s). Axial and 3D (maximum intensity projection (MIP), volume rendering technique (VRT) and surface shaded display (SSD) images were evaluated. Before or after CTA procedure, digital subarachnoid angiography (DSA) was performed in 44 patients. Twenty-three aneurysms of various localization and size were found. There were no findings in 21 patients. One false negative and one false positive result was present. Specificity and sensitivity was 95.8% (23/24), and diagnostic accuracy--95.6% (44/46). Two patients were operated according to CTA results. Two patients had repeat-DSA (according to CTA results), and the aneurysms were finally found. CTA is a quick, noninvasive method to be performed in outpatient and inpatient basis. It gives information about vessels and surrounding tissues. In some cases it can replace DSA. CTA must not be considered as replacement of DSA, instead, it should be considered as method providing more additional information.


Prone whole-breast irradiation using three-dimensional conformal radiotherapy in women undergoing breast conservation for early disease yields high rates of excellent to good cosmetic outcomes in patients with large and/or pendulous breasts.
To report our institution's experience using prone positioning for three-dimensional conformal radiotherapy (3D-CRT) to deliver post-lumpectomy whole breast irradiation (WBI) in a cohort of women with large and/or pendulous breasts, to determine the rate of acute and late toxicities and, more specifically, cosmetic outcomes. We hypothesized that using 3D-CRT for WBI in the prone position would reduce or eliminate patient and breast size as negative prognostic indicators for toxicities associated with WBI. From 1998 to 2006, 110 cases were treated with prone WBI using 3D-CRT. The lumpectomy, breast target volumes, heart, and lung were contoured on all computed tomography scans. A dose of 45-50 Gy was prescribed to the breast volume using standard fractionation schemes. The planning goals were ≥95% of prescription to 95% of the breast volume, and 100% of boost dose to 95% of lumpectomy planning target volume. Toxicities and cosmesis were prospectively scored using the Common Terminology Criteria for Adverse Effects Version 3.0 and the Harvard Scale. The median follow-up was 40 months. The median body mass index (BMI) was 33.6 kg/m(2), and median breast volume was 1396 cm(3). The worst toxicity encountered during radiation was Grade 3 dermatitis in 5% of our patient population. Moist desquamation occurred in 16% of patients, with only 2% of patients with moist desquamation outside the inframammary/axillary folds. Eleven percent of patients had Grade ≥2 late toxicities, including Grade 3 induration/fibrosis in 2%. Excellent to good cosmesis was achieved in 89%. Higher BMI was associated with moist desquamation and breast pain, but BMI and breast volume did not impact fibrosis or excellent to good cosmesis. In patients with higher BMI and/or large-pendulous breasts, delivering prone WBI using 3D-CRT results in favorable toxicity profiles and high excellent to good cosmesis rates. Higher BMI was associated with moist desquamation, but prone positioning removed BMI and breast size as factors for poorer cosmetic outcomes. This series adds to the growing literature demonstrating that prone WBI may be advantageous in select patients.


Expression and cellular distribution of zona pellucida glycoproteins in canine oocytes before and after in vitro maturation.
This study was aimed at investigating zona pellucida glycoproteins (ZP) ZP2, ZP3 mRNA expression as well as ZP3, ZP4 (ZPB) protein distribution before and after in vitro maturation (IVM) in canine oocytes. The cumulus-oocyte complexes (COCs) were recovered from 27 anoestrous mongrel bitches and matured for 72 h in TCM199 medium. The canine COCs were analysed before and after IVM. Using real-time quantitative polymerase chain reaction (RQ-PCR), both groups of oocytes were analysed for detection of ZP2 and ZP3 mRNA profiles as well as using confocal microscopic analysis for observation of ZP3 and ZP4 protein distribution. In post-IVM canine oocytes an increase in transcript content of ZP2 and ZP3 genes as well as a decrease in ZP3 and ZP4 protein levels were observed when compared with pre-IVM oocytes. Moreover, the ZP4 protein before IVM was significantly distributed in the peripheral area of cytoplasm, whereas after IVM it was localized rather than in the entire cytoplasm. In contrast, the ZP3 protein was found both before and after IVM was distributed in the peripheral area of the cytoplasm. In conclusion, we suggest that the expression of ZP2 and ZP3 genes is associated with the maturation stage of canine oocytes, as higher mRNAs levels were found after IVM. However, a decreased expression of ZP3 and ZP4 proteins after IVM suggests maturation-dependent down-regulation of these protein translations, which may result in disturbed fertilization.


Do Hospitalized Premature Infants Benefit from Music Interventions? A Systematic Review of Randomized Controlled Trials.
Neonatal intensive care units (NICU) around the world increasingly use music interventions. The most recent systematic review of randomized controlled trials (RCT) dates from 2009. Since then, 15 new RCTs have been published. We provide an updated systematic review on the possible benefits of music interventions on premature infants' well-being. We searched 13 electronic databases and 12 journals from their first available date until August 2016. Included were all RCTs published in English with at least 10 participants per group, including infants born prematurely and admitted to the NICU. Interventions were either recorded music interventions or live music therapy interventions. All control conditions were accepted as long as the effects of the music intervention could be analysed separately. A meta-analysis was not possible due to incompleteness and heterogeneity of the data. After removal of duplicates the searches retrieved 4893 citations, 20 of which fulfilled the inclusion/exclusion criteria. The 20 included studies encompassed 1128 participants receiving recorded or live music interventions in the NICU between 24 and 40 weeks gestational age. Twenty-six different outcomes were reported which we classified into three categories: physiological parameters; growth and feeding; behavioural state, relaxation outcomes and pain. Live music interventions were shown to improve sleep in three out of the four studies and heart rate in two out of the four studies. Recorded music improved heart rate in two out of six studies. Better feeding and sucking outcomes were reported in one study using live music and in two studies using recorded music. Although music interventions show promising results in some studies, the variation in quality of the studies, age groups, outcome measures and timing of the interventions across the studies makes it difficult to draw strong conclusions on the effects of music in premature infants.


Isolation and propagation of enteric adenoviruses in HEp-2 cells.
Eighty-two stool samples from children with gastroenteritis in Canada, England, and Thailand which had been shown to contain adenovirus antigen (by a group-specific enzyme-linked immunosorbent assay) or adenovirus particles (by electron microscopy) or both, were tested for primary isolation of enteric adenoviruses in HEp-2 and Graham 293 cells. Graham 293 cells are known to support the replication of enteric adenovirus types (Ad40 and Ad41) on primary isolation, whereas HEp-2 cells reportedly do not. Of the 82 adenovirus isolates, 73 could be typed as Ad40 or Ad41 by type-specific monoclonal antibody enzyme-linked immunosorbent assay and by analysis of SmaI endonuclease digests. Of these 73, 30 (41%) could be isolated in HEp-2 cells, which included 43% (9/21) of those typed as Ad40 and 40% (21/52) of those typed as Ad41. On the basis of these results, the growth characteristics of adenoviruses in HEp-2 cell cultures, commonly used to distinguish enteric from nonenteric adenovirus types, are not valid for either diagnosis or epidemiological studies. For the samples studied here, use of these nondefinitive criteria would result in underestimation of the incidence of enteric adenoviruses in viral gastroenteritis.


Venous hemodynamics during impulse foot pumping.
This study was designed to measure the effect of intermittent pneumatic compression of the plantar venous plexus on popliteal vein (PV) and common femoral vein (CFV) velocities measured by duplex ultrasound scanning. Thirty lower limbs in 15 healthy volunteers had venous duplex scanning measurement of PV and CFV velocities before and during foot pumping with an arteriovenous impulse foot pump system. Venous velocities were measured at two pump pressure settings (100 mm Hg, 200 mm Hg) and during two pump impulse durations (short = 1 second, normal = 3 seconds). All limbs were examined with the subjects in the supine position, and then measurements were repeated with subjects in the 15-degree reverse Trendelenburg position. The mean maximum venous velocity (MVV) produced by foot pumping was compared with resting venous velocity at each anatomic location and for each technologic variable. Impulse foot pumping produced a statistically significant increase in MVV in both the PV and the CFV compared with resting velocities. This significant increase was observed for both pressure settings and both impulse durations, and no differences produced by these two individual variables could be detected. The increase in MVV produced by foot pumping was similar for limbs in the supine position and those examined in the reverse Trendelenburg position. The percentage increase in MVV produced by foot pumping was significantly higher in the PV than in the CFV. Intermittent pneumatic compression of the plantar venous plexus produces measurable increases in venous outflow from the lower limbs of normal subjects. This study seems to justify further evaluation of the effectiveness of this technique for mechanical deep venous thrombosis prophylaxis in selected high-risk patient groups.


A novel mechanism of Sarcophaga lectin gene expression. Possible involvement of oxidation of the sulfhydryl group of a fat-body protein.
The Sarcophaga lectin gene, an acute-phase-responsive protein of Sarcophaga, was found to be activated when the fat body was incubated in phosphate-buffered insect saline (10 mM NaH2PO4/Na2HPO4, pH 6.2, 2 mM NaHCO3, 1 mM MgCl2, 5 mM KCl, 1 mM CaCl2 and 120 mM NaCl). This activation was selectively suppressed by addition of 2-mercaptoethanol. 2-Mercaptoethanol did not affect the transcription directly, suggesting that the oxidation of the sulfhydryl group of a fat-body protein is required for activation of the Sarcophaga lectin gene. This oxidation reaction seemed to occur immediately when the fat body was incubated in vitro, and once this reaction was initiated, 2-mercaptoethanol no longer inhibited transcription of the Sarcophaga lectin gene. This gene is known to be activated when the larval-body wall of Sarcophaga is injured. It is suggested that the Sarcophaga lectin gene is activated via this novel mechanism on its acute-phase expression in vivo.