A novel automatic release cage increases survival of Atlantic salmon (Salmo salar) smolts released at night.
Trap-and-transport of migratory fish is commonly used to bypass in-river obstructions. On the River Conon in Scotland, Atlantic salmon (Salmo salar) smolts are transported around two hydropower facilities. Smolt release occurs during daylight, when predation rates can be high. A novel automatic release cage (ARC) was designed to release smolts at night. Smolts were fitted with acoustic tags (n = 99) to compare survival. High post-release mortality was identified in the day-release group, with night-release survival >40% higher. ARCs can provide fishery managers with a cost-effective and reliable method of improving smolt survival.


Long-term effects of payment for performance on maternal and child health outcomes: evidence from Tanzania.
The success of payment for performance (P4P) schemes relies on their ability to generate sustainable changes in the behaviour of healthcare providers. This paper examines short-term and longer-term effects of P4P in Tanzania and the reasons for these changes. We conducted a controlled before and after study and an embedded process evaluation. Three rounds of facility, patient and household survey data (at baseline, after 13 months and at 36 months) measured programme effects in seven intervention districts and four comparison districts. We used linear difference-in-difference regression analysis to determine programme effects, and differential effects over time. Four rounds of qualitative data examined evolution in programme design, implementation and mechanisms of change. Programme effects on the rate of institutional deliveries and antimalarial treatment during antenatal care reduced overtime, with stock out rates of antimalarials increasing over time to baseline levels. P4P led to sustained improvements in kindness during deliveries, with a wider set of improvements in patient experience of care in the longer term. A change in programme management and funding delayed incentive payments affecting performance on some indicators. The verification system became more integrated within routine systems over time, reducing the time burden on managers and health workers. Ongoing financial autonomy and supervision sustained motivational effects in those aspects of care giving not reliant on funding. Our study adds to limited and mixed evidence documenting how P4P effects evolve over time. Our findings highlight the importance of undertaking ongoing assessment of effects over time.


SinEx DB 2.0 update 2020: database for eukaryotic single-exon coding sequences.
Single-exon coding sequences (CDSs), also known as 'single-exon genes' (SEGs), are defined as nuclear, protein-coding genes that lack introns in their CDSs. They have been studied not only to determine their origin and evolution but also because their expression has been linked to several types of human cancers and neurological/developmental disorders, and many exhibit tissue-specific transcription. We developed SinEx DB that houses DNA and protein sequence information of SEGs from 10 mammalian genomes including human. SinEx DB includes their functional predictions (KOG (euKaryotic Orthologous Groups)) and the relative distribution of these functions within species. Here, we report SinEx 2.0, a major update of SinEx DB that includes information of the occurrence, distribution and functional prediction of SEGs from 60 completely sequenced eukaryotic genomes, representing animals, fungi, protists and plants. The information is stored in a relational database built with MySQL Server 5.7, and the complete dataset of SEG sequences and their GO (Gene Ontology) functional assignations are available for downloading. SinEx DB 2.0 was built with a novel pipeline that helps disambiguate single-exon isoforms from SEGs. SinEx DB 2.0 is the largest available database for SEGs and provides a rich source of information for advancing our understanding of the evolution, function of SEGs and their associations with disorders including cancers and neurological and developmental diseases. Database URL: http://v2.sinex.cl/.


From monomers to π stacks, from nonconductive to conductive: syntheses, characterization, and crystal structures of benzidine radical cations.
Salts that contain radical cations of benzidine (BZ), 3,3',5,5'-tetramethylbenzidine (TMB), 2,2',6,6'-tetraisopropylbenzidine (TPB), and 4,4'-terphenyldiamine (DATP) have been isolated with weakly coordinating anions [Al(OR(F))(4)](-) (OR(F) = OC(CF(3))(3)) or SbF(6)(-). They were prepared by reaction of the respective silver(I) salts with stoichiometric amounts of benzidine or its alkyl-substituted derivatives in CH(2)Cl(2). The salts were characterized by UV absorption and EPR spectroscopy as well as by their single-crystal X-ray structures. Variable-temperature UV/Vis absorption spectra of BZ(·)(+)[Al(OR(F))(4)](-) and TMB(·)(+)[Al(OR(F))(4)](-) in acetonitrile indicate an equilibrium between monomeric free radical cations and a radical-cation dimer. In contrast, the absorption spectrum of TPB(·)(+)SbF(6)(-) in acetonitrile indicates that the oxidation of TPB only resulted in a monomeric radical cation. Single-crystal X-ray diffraction studies show that in the solid state BZ and its methylation derivative (TMB) form radical-cation π dimers upon oxidation, whereas that modified with isopropyl groups (TPB) becomes a monomeric free radical cation. By increasing the chain length, π stacks of π dimers are obtained for the radical cation of DATP. The single-crystal conductivity measurements show that monomerized or π-dimerized radicals (BZ(·)(+), TMB(·)(+), and TPB(·)(+)) are nonconductive, whereas the π-stacked radical (DATP(·)(+)) is conductive. A conduction mechanism between chains through π stacks is proposed.


Characterization of the effects of the new inotropic agent BDF 9148 in isolated papillary muscles and myocytes of the guinea-pig heart.
1. The cardiotonic agent BDF 9148 (4-[3'-(1''-benzhydryl-azetidine-3''-oxy)-2'-hydroxypropoxy]-1H-indole- 2-carbonitrile) is structurally related to DPI 201-106 (4-[3'-(4''-benzhydryl-1''-piperazinyl) -2'-hydroxypropoxy]-1H-indole-2-carbonitrile) which is known to modify cardiac sodium channels. In guinea-pig papillary muscles, both compounds increase force of contraction with similar concentration-response curves. Like DPI 201-106, BDF 9148 prolongs the action potential duration in a tetrodotoxin-sensitive manner. With high concentrations (greater than 3 microM), however, the action potential duration shortens again. In order to elucidate the underlying changes in membrane currents, we have investigated the effects of BDF 9148 in isolated ventricular myocytes of the guinea-pig heart. 2. In isolated cells, a concentration of 1 microM BDF 9148 prolonged the action potential duration and markedly enhanced unloaded cell shortening, indicating that the procedure of cell isolation does not abolish the effect of the drug. 3. Membrane currents were studied with the single electrode voltage clamp technique. With clamp steps from -80 mV to -40 mV, BDF 9148 (1 microM) induced a slowly decaying inward current which was suppressed by tetrodotoxin. Therefore, like DPI 201-106, BDF 9148 slows the inactivation of the sodium channels. 4. In order to quantify the effects of BDF 9148 and DPI 201-106 on sodium current inactivation, we have measured the inward current amplitude still present at 100 ms after a depolarizing clamp step from -80 mV to -30 mV. Both drugs increased this current component in a concentration-dependent manner; however, BDF 9148 had a larger effect in the low concentration range.5. The calcium current was inhibited by BDF 9148 and DPI 201-106 in a concentration-dependent manner; the pD2 values were 5.70 and 5.95, respectively.6. The two compounds are thought to produce similar positive inotropic effects by imposing a sodium load on the muscle cells via modification of the sodium channels. The differences in action potential duration could be due to different contributions of ionic currents other than sodium or calcium currents and of pump and exchange currents. At present, there is not sufficient data to identify clearly distinct current components responsible for the differences in action potential prolongation.


Soluble Toll-Like Receptor 4 Impairs the Interaction of Shiga Toxin 2a with Human Serum Amyloid P Component.
Shiga toxin 2a (Stx2a) is the main virulence factor produced by pathogenic Escherichia coli strains (Stx-producing E. coli, STEC) responsible for hemorrhagic colitis and the life-threatening sequela hemolytic uremic syndrome in children. The toxin released in the intestine by STEC targets the globotriaosylceramide receptor (Gb3Cer) present on the endothelial cells of the brain and the kidney after a transient blood phase during which Stx2a interacts with blood components, such as neutrophils, which, conversely, recognize Stx through Toll-like receptor 4 (TLR4). Among non-cellular blood constituents, human amyloid P component (HuSAP) is considered a negative modulating factor that specifically binds Stx2a and impairs its toxic action. Here, we show that the soluble extracellular domain of TLR4 inhibits the binding of Stx2a to neutrophils, assessed by indirect flow cytometric analysis. Moreover, by using human sensitive Gb3Cer-expressing cells (Raji cells) we found that the complex Stx2a/soluble TLR4 escaped from capture by HuSAP allowing the toxin to target and damage human cells, as assayed by measuring translation inhibition, the typical Stx-induced functional impairment. Thus, soluble TLR4 stood out as a positive modulating factor for Stx2a. In the paper, these findings have been discussed in the context of the pathogenesis of hemolytic uremic syndrome.


Influence of ligand distribution on uptake efficiency.
Cellular uptake is a crucial process in nanomedicine and drug-delivery; however, the factors that affect its efficiency/speed are not well understood. We report computer simulations on passive uptake via receptor-mediated endocytosis of nanoparticle coated with ligands. In particular, we study how the distribution of ligands on the nanoparticle surface influences the uptake rate. The speed of membrane wrapping and uptake was found to be the fastest for nanoparticles with homogeneous ligand distributions, where ligands are spread evenly on the surface. We show that the diffusion of the ligands on the nanoparticle can hinder its uptake, since upon the interaction with the membrane the ligand distribution becomes extremely inhomogeneous, with a large ligand-free patch. When the ligand-free-area was more than 20% of the surface, we did not observe uptake within the scale of our simulations.


[Modification of the simplified Cobb-Radge and Raz techniques in the treatment of stress urinary incontinence. Description and results].
Various surgical procedures have been described for correction of stress urinary incontinence (SUI) which have afforded different results. Modifications to these procedures have been made in an attempt to reduce morbidity and the operating time without detriment to the efficacy of the procedures. Herein we describe two procedures, the modified Cobb-Radge and Raz techniques, and report on the results achieved. In patients with no cystocele that had been submitted to the modified Cobb-Radge technique, we achieved 80.4% good results. In patients with significant cystocele, our modified Cobb-Radge technique and anterior colporrhaphy achieved a success rate of 80%, and we achieved good results in 88.3% of these cases with our modified Raz procedure.


The "Ethics Rupture" Summit, Fredericton, New Brunswick, Canada, October 25-28, 2012.
This report explains the background of the "Ethics Rupture" Summit held in New Brunswick, Canada, October 2012, focusing on the disconnect between research-ethics policies and the nature and purpose of social-science research-an unintended "rupture" in ethics governance. Ethics is about human relationships, and the governance of ethics must reflect that fact rather than function as a bureaucratic, self-legitimating system of control. The themes that emerged from the Summit point to: structural problems with the current system; an undermining of the original, historical mission of some social-science disciplines; a discomfort with new methodologies; ethics committees and the well-being and education of social-science students; the possibilities of reform and renewal; and the next steps. Finally, the report refers in broad outlines to a "New Brunswick Declaration," which is currently being considered by participants of the Summit.


Population Attributable Fraction of Anemia Associated with Plasmodium falciparum Infection in Children in Southern Malawi.
Anemia is a leading cause of morbidity in sub-Saharan Africa. The etiologies of anemia are multifactorial, and it is unclear what proportion of anemia is attributable to malaria in children of different ages in Malawi. We evaluated the population attributable fraction (PAF) of anemia due to malaria using multiple cross-sectional surveys in southern Malawi. We found a high prevalence of anemia, with the greatest proportion attributable to malaria among school-age children (5-15 years) in the rainy season (PAF = 18.8% [95% CI: 16.3, 21.0], compared with PAF = 5.2% [95% CI: 4.0, 6.2] among young children pooled across season [< 5 years] and PAF = 9.7% [95% CI: 6.5, 12.4] among school-age children in the dry season). Malaria control interventions will likely lead to decreases in anemia, especially among school-age children.


Localized T3 production modifies the transcriptome and promotes the hepatocyte-like lineage in iPSC-derived hepatic organoids.
Thyroid hormone (TH) levels are low during development, and the deiodinases control TH signaling through tissue-specific activation or inactivation of TH. Here, we studied human induced pluripotent stem cell-derived (iPSC-derived) hepatic organoids and identified a robust induction of DIO2 expression (the deiodinase that activates T4 to T3) that occurs in hepatoblasts. The surge in DIO2-T3 (the deiodinase that activates thyroxine [T4] to triiodothyronine [T3]) persists until the hepatoblasts differentiate into hepatocyte- or cholangiocyte-like cells, neither of which expresses DIO2. Preventing the induction of the DIO2-T3 signaling modified the expression of key transcription factors, decreased the number of hepatocyte-like cells by ~60%, and increased the number of cholangiocyte-like cells by ~55% without affecting the growth or the size of the mature liver organoid. Physiological levels of T3 could not fully restore the transition from hepatoblasts to mature cells. This indicates that the timed surge in DIO2-T3 signaling critically determines the fate of developing human hepatoblasts and the transcriptome of the maturing hepatocytes, with physiological and clinical implications for how the liver handles energy substrates.


A maximum-likelihood approach to fitting equilibrium models of microsatellite evolution.
Here, we develop a new approach to Markov chain modeling of microsatellite evolution through polymerase slippage and introduce new models: a "constant-slippage-rate" model, in which there is no dependence of slippage rate on microsatellite length, as envisaged by Moran; and a "linear-with-constant" model, in which slippage rate increases linearly with microsatellite length, but the line of best fit is not constrained to go through the origin. We show how these and a linear no-constant model can be fitted to data hierarchically using maximum likelihood. This has advantages over previous methods in allowing statistical comparisons between models. When applied to a previously analyzed data set, the method allowed us to statistically establish that slippage rate increases with microsatellite length for dinucleotide microsatellites in humans, mice, and fruit flies, and suggested that no slippage occurs in very short microsatellites of one to four repeats. The suggestion that slippage rates are zero or close to zero for very short microsatellites of one to four repeats has important implications for understanding the mechanism of polymerase slippage.


Alveolar macrophages rely on GM-CSF from alveolar epithelial type 2 cells before and after birth.
Programs defining tissue-resident macrophage identity depend on local environmental cues. For alveolar macrophages (AMs), these signals are provided by immune and nonimmune cells and include GM-CSF (CSF2). However, evidence to functionally link components of this intercellular cross talk remains scarce. We thus developed new transgenic mice to profile pulmonary GM-CSF expression, which we detected in both immune cells, including group 2 innate lymphoid cells and γδ T cells, as well as AT2s. AMs were unaffected by constitutive deletion of hematopoietic Csf2 and basophil depletion. Instead, AT2 lineage-specific constitutive and inducible Csf2 deletion revealed the nonredundant function of AT2-derived GM-CSF in instructing AM fate, establishing the postnatal AM compartment, and maintaining AMs in adult lungs. This AT2-AM relationship begins during embryogenesis, where nascent AT2s timely induce GM-CSF expression to support the proliferation and differentiation of fetal monocytes contemporaneously seeding the tissue, and persists into adulthood, when epithelial GM-CSF remains restricted to AT2s.


Phenotypic characterization of an intestinal subepithelial myofibroblast cell line.
Subepithelial myofibroblasts are located at the interface between the epithelium and lamina propria in most mucosal tissues. Their biological functions are largely unknown because a long-term cell culture model for these cells has not been available. In this report, we define the phenotypic properties of a human colonic cell line (18Co) that exhibits most of the known characteristics of intestinal subepithelial myofibroblasts in situ. These characteristics include 1) a cell shape that can be reversibly interconverted between a flattened discoid and stellate morphology, 2) intracellular organelles reminiscent of myofibroblasts and smooth muscle cells in situ, 3) expression of alpha-smooth muscle actin, 4) plasma membrane receptors for endothelins and natriuretic peptides, and 5) regulation of epithelial sensitivity to calcium-dependent secretagogues by paracrine secretion of prostaglandins. 18Co cells provide an exploitable model to begin defining the physiological and pathophysiological functions of intestinal subepithelial myofibroblasts at the molecular level.


Alcohol-free red wine enhances plasma antioxidant capacity in humans.
Moderate wine consumption is reputed to exert a protective effect against coronary heart disease (CHD). The nature of the protective compounds is unclear and the mechanisms are incompletely understood. We studied whether the nonalcoholic component of wine increases plasma antioxidant capacity measured as total radical-trapping antioxidant parameter (TRAP), and whether such an effect is associated with the presence of phenolic compounds in plasma. The TRAP and plasma levels of phenolic compounds were measured in 10 healthy subjects after the ingestion of 113 mL of tap water (control) and alcohol-free red and white wine at 1-wk intervals. Both alcohol-free wines possessed an in vitro dose-dependent peroxyl-radical activity, but red wine, with a polyphenol concentration of 363 +/- 48.0 mg/L quercetin equivalent (QE), was 20 times more active (40.0 +/- 0.1 mmol/L) than white wine (1.9 +/- 0.1 mmol/L), which has a polyphenol concentration of 31 +/- 1 mg QE/L. The ingestion of alcohol-free red wine caused significant increases in plasma TRAP values and polyphenol concentrations 50 min after ingestion. Alcohol-free white wine and water had no effects on either of the plasma values. The parallel and prompt increase of antioxidant status and of circulating levels of polyphenols in fasting subjects after bolus ingestion of a moderate amount of alcohol-free red wine suggests that polyphenols are absorbed in the upper gastrointestinal tract and might be directly involved in the in vivo antioxidant defenses.


Nickel hexacyanoferrate modified screen-printed carbon electrode for sensitive detection of ascorbic acid and hydrogen peroxide.
Electrochemically modified screen-printed carbon electrode (SPCE) has been prepared by electrodepositing nickel hexacyanoferrate(III) (NiHCF) onto the electrode surface using cyclic voltammetry (CV). The performance of NiHCF-SPCE sensor was characterized and optimized by controlling several operational parameters. The NiHCF film has been proven to remain stable after CV scanning from 0 to +1.0 V vs. Ag/AgCl in the pH range of 3 to 10 and is re-useable. The most favourable supporting electrolyte solution exhibiting the optimum electroanalytical performance of the NiHCF-SPCE sensor was found to be 0.2 mol/L sodium nitrate. The electrochemical response toward ascorbic acid (AA) and H2O2 in 0.2 mol/L sodium nitrate solution was studied by using CV and the results showed that both analytes were electrocatalytically oxidized at approximately +0.4 V, while H2O2 also revealed a reduction signal at -0.8 V vs. Ag/AgCl. The NiHCF-SPCE sensor exhibited highly linear response for AA and H2O2 in the examined concentration range from 5.0x10-5 to 1.5x10-3 mol/L and from 2.0x10-5 to 1.0x10-3 mol/L (at +0.4 V), with the correlation coefficients of 0.999 and 0.998, respectively. The reproducibility of the NiHCF-SPCE sensor was followed for the determination of AA by using four individual electrodes, and the relative standard deviation of CV peak currents varied between 0.9 % and 2.2 %. The proposed NiHCF-SPCE has been shown to be a very attractive electrochemical sensor for AA and H2O2, also in a view of inexpensive mass production of disposable single-use sensors. The NiHCF-SPCE sensor was tested by measuring AA in multivitamin tablets, with recoveries obtained between 94.4 % and 108.2 % (n=5).


Local flicker stimulation evokes local retinal blood velocity changes.
We investigated the effect of localized visual stimulation on human retinal blood velocity using an adaptive optics scanning laser ophthalmoscope (AOSLO). To measure the blood velocity response, the AOSLO scanning raster was moved over the target arteries and red blood cell velocity was measured. Localized visual stimuli were delivered by projecting flicker patterns inside or outside the target artery's downstream region. The blood velocity increased in the presence of a flicker stimulus in the downstream region but not when outside the downstream region. The blood velocity increased more with larger area of stimulation. This increase was significant even when the stimulus was smaller than 600 μm × 600 μm. These findings suggest that when the retina regulates its blood flow to metabolic demands, it regulates blood velocity in the vascular system selectively, according to activity of neurons within its field of influence.


Extraction of lotus fibres from lotus stems under microwave irradiation.
An efficient technology for preparing lotus fibres under microwave irradiation was developed. The lotus fibres were characterized by scanning electron microscopy, Fourier transform infrared spectrometry, X-ray diffraction and thermogravimetry. Lotus fibres prepared are a kind of hollow fibres which are composed of a superfine fibre and an external shell. The effect of the treatment time with hydrogen peroxide under microwave irradiation on components, whiteness, moisture regain, removal rate of impurities, fineness, tensile strength and breaking elongation of lotus fibres was investigated. The results show that the cellulose content in lotus fibres increases with increase in treatment time. Whiteness and moisture regain of lotus fibres increase with increase in treatment time with hydrogen peroxide. The removal rate of impurities and the fineness of lotus fibres are improved after they are treated with hydrogen peroxide. Microwave irradiation is supposed to be an efficient method for producing lotus fibres.


Two-step colocalization of MORC3 with PML nuclear bodies.
Many functional subdomains, including promyelocytic leukemia nuclear bodies (PML NBs), are formed in the mammalian nucleus. Various proteins are constitutively or transiently accumulated in PML NBs in a PML-dependent manner. MORC3 (microrchidia family CW-type zinc-finger 3), also known as NXP2, which consists of GHL-ATPase, a CW-type zinc-finger and coiled-coil domains, is localized in PML NBs, where it recruits and activates p53 to induce cellular senescence. Interestingly, we found that MORC3 can form PML-independent nuclear domains (NDs) in mouse hematopoietic cells and even in Pml-deficient cells. Here, we show that MORC3 colocalizes with PML by a two-step molecular mechanism: the PML-independent formation of MORC3 NDs by the ATPase cycle, and the association of MORC3 with PML via the SUMO1-SUMO-interacting motif (SIM). Similarly to other members of the GHL-ATPase family, MORC3 functions as a 'molecular clamp'. ATP binding induces conformational changes in MORC3, leading to the formation of MORC3 NDs, and subsequent ATP hydrolysis mediates the diffusion and binding of MORC3 to the nuclear matrix. MORC3 might clamp DNA or nucleosomes in MORC3 NDs via the CW domain. Furthermore, the SUMOylation of MORC3 at five sites was involved in the association of MORC3 with PML, and SUMO1-unmodified MORC3 formed NDs independently of PML.


[Regulation of yeast gene Leu 2 expression in Escherichia coli by IS1 element].
Expression of the yeast LEU2 gene in Escherichia coli is not sufficiently high. That is why the growth rate of leuB E. coli transformants slowed down on media lacking leucine. The mutations leading to the increase in yeast gene expression in bacteria were found. It has been shown that mutations are connected with insertion of the bacterial IS1 element into the regulatory region of LEU2. The increase in the yeast gene expression does not depend on orientation of the inserted IS1 element. The IS1 element insertion seems to control the attenuation of transcription of LEU2.


[Factors that increasing tendency to smoking cessation].
Cigarette smoking is just important problem of public health. In the present study, our aim; was to determine to factors that increasing tendency to smoking cessation, the cases who are involved to policlinic of smoking cessation. Two hundred-forty five cigarette smokers were included in this study. It was recorded demographic signs, the novel of cigarette smoking, the degree of knowledge about the harmful of smoking in their opinion, the reason of starting to cigarette. It was evaluated that the principle reason to come to policlinic of smoking cessation and the other reasons. There were 53.9% male, 46.1% female in our study. Median (min-max) age was 45 (21-73) in females, 42 (20-75) in males. When evaluating the state of education; there was 35.9% primary school, 31.4% high school, 7.3% academy, 25.3% university graduates. 97.1% in all participants have used only cigarette smoking from tobacco products. Primarily reasons were 44% the fear of deterioration of health, 16.3% to be better model for their children, 9.8% to have disease at the time and 6.9% breathlessness for smoking cessation. Secondary reasons were of smoking harm to the environment, economic reasons, bad smell, being a good example of the environment and recommended by a physician. The most of cases are want to quit smoking because of smoking harm to their health. Specially, parents wish to quit smoking because of they don't want to be bad model for their children. As a result; it is given to necessary support to participants who are this awareness in policlinics of smoking cessation. However, we think that it was necessity that should be continue increase of the therapy to growing to these awareness for the smokers who couldn't be enough awareness and who didn't think of quit smoking.


Molecular characterization and expression analysis of the dextransucrase DsrD of Leuconostoc mesenteroides Lcc4 in homologous and heterologous Lactococcus lactis cultures.
The gene encoding the dextransucrase DsrD from the industrial strain Leuconostoc mesenteroides Lcc4 was isolated by PCR using degenerate primers recognizing conserved regions present in other dextransucrase-encoding genes from Leuconostoc spp. and Southern blot analyses on total genomic DNA. N-terminal sequence analysis of the active protein recovered in the culture showed that the secreted protein of 165 kDa is devoid of a 42 aa prepeptide which is removed post-translationally, most likely by signal peptidase cleavage. Primer extension and Northern blot analysis identified a monocistronic dsrD mRNA with two transcription initiation sites. Expression of the dextransucrase DsrD was investigated in pH-controlled fed-batch cultures via Northern blot analysis and enzyme activity measurement during the experiments. Sucrose levels of 20 g l(-1) were shown to induce the DsrD biosynthesis around 10-fold. The combination of pH-controlled fed-batch fermentation and Northern analysis clearly showed that dsrD expression was related to the growth of the bacteria. dsrD was transferred to and expressed in Lactococcus lactis MG1363. Controlled fed-batch cultures revealed that active dextransucrase was produced and secreted by the recombinant L. lactis strain. The expression was independent of sucrose levels. These results show that dextransucrase can be efficiently expressed and secreted in a non-Leuconostoc, heterologous host and is able to drive dextran synthesis.


Evolutionary Conservation of pou5f3 Genomic Organization and Its Dynamic Distribution during Embryogenesis and in Adult Gonads in Japanese Flounder Paralichthys olivaceus.
Octamer-binding transcription factor 4 (Oct4) is a member of POU (Pit-Oct-Unc) transcription factor family Class V that plays a crucial role in maintaining the pluripotency and self-renewal of stem cells. Though it has been deeply investigated in mammals, its lower vertebrate homologue, especially in the marine fish, is poorly studied. In this study, we isolated the full-length sequence of Paralichthys olivaceus pou5f3 (Popou5f3), and we found that it is homologous to mammalian Oct4. We identified two transcript variants with different lengths of 3'-untranslated regions (UTRs) generated by alternative polyadenylation (APA). Quantitative real-time RT-PCR (qRT-PCR), in situ hybridization (ISH) and immunohistochemistry (IHC) were implemented to characterize the spatial and temporal expression pattern of Popou5f3 during early development and in adult tissues. Our results show that Popou5f3 is maternally inherited, abundantly expressed at the blastula and early gastrula stages, then greatly diminishes at the end of gastrulation. It is hardly detectable from the heart-beating stage onward. We found that Popou5f3 expression is restricted to the adult gonads, and continuously expresses during oogenesis while its dynamics are downregulated during spermatogenesis. Additionally, numerous cis-regulatory elements (CRE) on both sides of the flanking regions show potential roles in regulating the expression of Popou5f3. Taken together, these findings could further our understanding of the functions and evolution of pou5f3 in lower vertebrates, and also provides fundamental information for stem cell tracing and genetic manipulation in Paralichthys olivaceus.


Estimation of the size of genetic bottlenecks in cell-to-cell movement of soil-borne wheat mosaic virus and the possible role of the bottlenecks in speeding up selection of variations in trans-acting genes or elements.
Genetic bottlenecks facilitate the fixation and extinction of variants in populations, and viral populations are no exception to this theory. To examine the existence of genetic bottlenecks in cell-to-cell movement of plant RNA viruses, we prepared constructs for Soil-borne wheat mosaic virus RNA2 vectors carrying two different fluorescent proteins, yellow fluorescent protein (YFP) and cyan fluorescent protein (CFP). Coinoculation of host plant leaves with the two RNA2 vectors and the wild-type RNA1 showed separation of the two vector RNA2s, mostly within seven to nine cell-to-cell movements from individual initially coinfected cells. Our statistical analysis showed that the number of viral RNA genomes establishing infection in adjacent cells after the first cell-to-cell movement from an initially infected cell was 5.97 +/- 0.22 on average and 5.02 +/- 0.29 after the second cell-to-cell movement. These results indicate that plant RNA viruses may generally face narrow genetic bottlenecks in every cell-to-cell movement. Furthermore, our model suggests that, rather than suffering from fitness losses caused by the bottlenecks, the plant RNA viruses are utilizing the repeated genetic bottlenecks as an essential element of rapid selection of their adaptive variants in trans-acting genes or elements to respond to host shifting and changes in the growth conditions of the hosts.


A retrospective analysis of oral and maxillofacial pathology in an Australian adult population.
The prevalence of oral and maxillofacial pathology has not previously been reported in the Australian adult population. This study aimed to audit a large pathology service to provide insight into the prevalence of head and neck pathologies. Written records of a major Australian oral pathology service were imported into an electronic database. Age, gender and histological diagnosis were assessed. Prevalence of histological diagnoses as a percentage of the major diagnostic categories and of the whole sample were calculated, as well as gender predilections and mean age of presentation of disease. A total of 6344 oral pathology specimens, collected from adults aged 17 years and over were included in the analysis. Mucosal pathology was the most common pathology (37.2%), followed by odontogenic cysts (16.3%) and dental pathology (14.5%). The three most common histological diagnoses were fibrous hyperplasia (15.2%), chronic periapical granuloma (9.6%) and radicular cyst (9.5%). The male:female ratio of the entire sample was 0.74. This is the first study to describe the prevalence of oral and maxillofacial pathology among adult patients in an Australian population. The trends seen in this study are repeated in studies from other parts of the world, and are of diagnostic importance.


Critical tumor suppressor function mediated by epithelial Mig-6 in endometrial cancer.
Endometrial cancer is preceded by endometrial hyperplasia, unopposed estrogen exposure, and genetic alterations, but the precise causes of endometrial cancer remain uncertain. Mig-6, mainly known as a negative regulator of the EGF receptor, is an important mediator of progesterone signaling in the uterus, where it mediates tumor suppression by modulating endometrial stromal-epithelial communications. In this study, we investigated the function of Mig-6 in the uterine epithelium using a tissue-specific gene knockout strategy, in which floxed Mig-6 (Mig-6(f/f)) mice were crossed to Wnt7a-Cre mice (Wnt7a(cre+)Mig-6(f/f)). Wnt7a(cre+)Mig-6(f/f) mice developed endometrial hyperplasia and estrogen-dependent endometrial cancer, exhibiting increased proliferation in epithelial cells as well as apoptosis in subepithelial stromal cells. We documented increased expression of NOTCH1 and BIRC3 in epithelial cells of Wnt7a(cre+)Mig-6(f/f) mice and decreased expression of the progesterone receptor (PR) in stromal cells. Progesterone therapy controls endometrial growth and prevents endometrial cancer, but the effectiveness of progesterone as a treatment for women with endometrial cancer is less clear. We noted that the hyperplasic phenotype of Wnt7a(cre+)Mig-6(f/f) mice was prevented by progesterone treatment, whereas this treatment had no effect in PR(cre/+)Mig-6(f/f) mice where Mig-6 was deleted in both the epithelial and stromal compartments of the uterus. In contrast, activation of progesterone signaling in the stroma regulated proliferation and apoptosis in the epithelium via suppression of ERα signaling. In summary, our results establish that epithelial Mig-6 functions as a critical tumor suppressor that mediates the ability of progesterone to prevent the development of endometrial cancer.


Divalent cations in native and reaggregated mycoplasma membranes.
The Mg(2+) content of membranes of several Mycoplasma and Acholeplasma species varied between 0.88 and 1.98 mug of Mg(2+) per mg of protein, depending on the species and on growth conditions. Ca(2+) could be detected only when it was added to the growth medium. The Mg(2+) content of isolated A. laidlawii membranes could be increased almost threefold by dialysis against 20 mm Mg(2+), whereas aggregated A. laidlawii membranes contained about six to eight times more Mg(2+) per mg of protein than the native membranes. This was taken to indicate that the molecular organization of the lipid and protein in the reaggregated membranes differs from that of the native membranes. Between 60 and 83% of the Mg(2+) in native and reaggregated A. laidlawii membranes was associated with the lipid fraction extracted with chloroform-methanol. The removal of over 80% of membrane protein by Pronase digestion did not release any significant amount of Mg(2+). Hence, most of the divalent cation appears to be bound to membrane lipids, most probably to phospholipids. Ethylenediaminetetraacetic acid released the bulk of Mg(2+) bound to the native and reaggregated A. laidlawii membranes, except for about 0.5 mug of Mg(2+) per mg of protein which was too tightly bound. Hence, a small but fairly constant amount of Mg(2+) is unavailable for chelation.


Vaccinia virus F1L interacts with Bak using highly divergent Bcl-2 homology domains and replaces the function of Mcl-1.
The Bcl-2 family regulates induction of apoptosis at the mitochondria. Essential to this regulation are the interactions between Bcl-2 family members, which are mediated by Bcl-2 homology (BH) domains. Vaccinia virus F1L is a unique inhibitor of apoptosis that lacks significant sequence similarity with the Bcl-2 family and does not contain obvious BH domains. Despite this, F1L inhibits cytochrome c release from mitochondria by preventing Bak and Bax activation. Although F1L constitutively interacts with Bak to prevent Bak activation, the precise mechanism of this interaction remains elusive. We have identified highly divergent BH domains in F1L that were verified by the recent crystal structure of F1L (Kvansakul, M., Yang, H., Fairlie, W. D., Czabotar, P. E., Fischer, S. F., Perugini, M. A., Huang, D. C., and Colman, P. M. (2008) Cell Death Differ. 15, 1564-1571). Here we show that F1L required these BH domains to interact with ectopically expressed and endogenous Bak. The interaction between F1L and Bak was conserved across species, and both F1L and the cellular antiapoptotic protein Mcl-1 required the Bak BH3 domain for interaction. Moreover, F1L replaced Mcl-1 during infection, as the Bak x Mcl-1 complex was disrupted during vaccinia virus infection. In contrast to UV irradiation, vaccinia virus infection did not result in rapid degradation of Mcl-1, consistent with our observation that vaccinia virus did not initiate a DNA damage response. Additionally, Mcl-1 expression prevented Bak activation and apoptosis during infection with a proapoptotic vaccinia virus devoid of F1L. Our data suggest that F1L replaces the antiapoptotic activity of Mcl-1 during vaccinia virus infection by interacting with Bak using highly divergent BH domains.


The challenges posed by radiation and radionuclide releases to the environment.
The recent accident at the Fukushima I nuclear power plant in Japan (also known as Fukushima Daiichi) captured the world's attention and re-invigorated concerns about the safety of nuclear power technology. The Editors of Integrated Environmental Assessment and Management invited experts in the field to describe the primary issues associated with the control and release of radioactive materials to the environment, particularly those that are of importance to the health of the human populations and the ecological systems that populate our planet. This collection of invited short commentaries aims to inform on the safety of nuclear power plants damaged by natural disasters and provide a primer on the potential environmental impacts. The intent of these invited commentaries is not to fuel the excitement and fears about the Fukushima Daiichi incident; rather, it is to collect views and comments from some of the world's experts on the broad science and policy challenges raised by this event, and to provide high-level views on the science issues that surround this situation in order to improve our collective ability to avoid or at least minimize the consequences of future events.


The effects of a combination of hyaluronic and amniotic membrane on the formation of peritendinous adhesions after flexor tendon surgery in chickens.
We have investigated the effects of the intra-operative application of a combination of hyaluronic acid and amniotic membrane on adhesions in the flexor tendons of a chicken model. We used 144 tendons which were partially divided and then repaired by a modified Kessler technique. There were four test groups: group 1, simple tendon repair, group 2, repair site wrapped with amniotic membrane, group 3, hyaluronic acid injected around the repair site, and group 4, repair site wrapped with amniotic membrane and hyaluronic acid injected within it. At three and six weeks, the extent of the adhesions and the healing of the tendon were evaluated macroscopically and histologically. The range of movement of the toe and tensile strength of the repaired tendons were measured at 20 weeks. The least adhesions were observed in group 4 but no significant difference was found in the healing of the tendons. Overall, the intra-operative application of a combination of hyaluronic acid and amniotic membrane appears to be effective in preventing adhesions of the flexor tendon.


Valgus Osteotomy with DHS Fixation in the Management of Malunited Intertrochanteric Fractures in a Rural Population.
Malunited intertrochanteric fractures are frequently seen in rural populations as they tend to go in for native treatment with traditional bone setters. The resulting Coxa vara is associated with shortening, abductor weakness, limp and decreased range of movement of the affected hip. The aim of this study was to evaluate the role of Valgus osteotomy with Dynamic hip screw (DHS) fixation in the management of these fractures and to evaluate the functional outcome using the Harris hip score. Fifteen patients with malunited intertrochanteric fractures who presented between January 2011 to January 2013 were managed by Valgus osteotomy with DHS fixation and were followed-up for a minimum period of three years. There was a male preponderance seen in our study with the right hip being more commonly affected. The most common mode of injury was slip and fall followed by road traffic accidents. The duration of native treatment ranged from seven to 12 weeks and the time of presentation to the hospital ranged from four to nine months following injury. Pre-operative mean neck shaft angle was 94.73° while it was 134.6° post-operatively. The mean pre-operative Harris hip score was 72.33 and it was 91 at follow-up. All patients were happy with the procedure and the functional outcome. Valgus osteotomy with DHS fixation is an effective procedure in the management of malunited intertrochanteric fractures. It corrects the limb length discrepancy, restores the decreased neck shaft angle, improves range of movement, restores the integrity of the abductor mechanism of the hip and gives good functional results.


Advancing probabilistic risk assessment by integrating human biomonitoring, new approach methods, and Bayesian modeling: A case study with the mycotoxin deoxynivalenol.
Deoxynivalenol (DON) is a mycotoxin frequently observed in cereals and cereal-based foods, with reported toxicological effects including reduced body weight, immunotoxicity and reproductive defects. The European Food Safety Authority used traditional risk assessment approaches to derive a deterministic Tolerable Daily Intake (TDI) of 1 μg/kg-day, however data from human biomarkers studies indicate widespread and variable exposure worldwide, necessitating more sophisticated and advanced methods to quantify population risk. The World Health Organization/International Programme on Chemical Safety (WHO/IPCS) has previously used DON as a case example in replacing the TDI with a probabilistic toxicity value, using default uncertainty and variability distributions to derive the Human Dose corresponding to an effect size M in the Ith percentile of the population (HDMI) for M = 5 % decrease in body weight and I = 1 %. In this study, we extend this case study by incorporating (1) Bayesian modeling approaches, (2) using both in vivo data and in vitro population new approach methods to replace default distributions for interspecies toxicokinetic (TK) differences and intraspecies TK and toxicodynamic (TD) variability, and (3) integrating biomonitoring data and probabilistic dose-response functions to characterize population risk distributions. We first derive an HDMI of 5.5 [1.4-24] μg/kg-day, also using TK modeling to converted the HDMI to Biomonitoring Equivalents, BEMI for comparison with biomonitoring data, with a blood BEMI of 0.53 [0.17-1.6] μg/L and a urinary excretion BEMI of 3.9 [1.0-16] μg/kg-day. We then illustrate how this integrative approach can advance quantitative risk characterization using two human biomonitoring datasets, estimating both the fraction of population with an effect size M ≥ 5 % as well as the distribution of effect sizes. Overall, we demonstrate that integration of Bayesian modeling, human biomonitoring data, and in vitro population-based TD data within the WHO/IPCS probabilistic framework yields more accurate, precise, and comprehensive risk characterization.


[Surgical treatment of the acute thrombosis of superficial veins].
Treatment results of 53 patients with acute thrombosis of superficial veins are presented. Carrying-out of radical one-stage cross-ectomy with combined phlebectomy in the saphena magna system at the height of inflammation period is proposed. Radical one-stage cross-ectomy with phlebectomy in case of phlebothrombosis gives good therapeutic effect, improves the status of a patient. Given treatment mode allows to reduce the period of temporary disability and rehospitalization in order to move off the trunk and inflows left after cross-ectomy.


Hematopoietic recovery after allogeneic blood stem-cell transplantation compared with bone marrow transplantation in patients with hematologic malignancies.
To compare hematopoietic recovery, duration of hospitalization, and 100-day survival in patients who received allogeneic-blood stem cells (BSC) or conventional allogeneic bone marrow transplantation (BMT). From December 1994 to August 1995, 21 patients participated in a phase II study of allogeneic BSC transplantation. Cells mobilized with granulocyte colony-stimulating factor (G-CSF; 5 micrograms/kg/ d) were collected from human leukocyte antigen (HLA)-matched related donors and cryopreserved. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate. G-CSF (10 micrograms/kg/d) was administered posttransplant. The outcomes were compared with 22 identically treated historical patients who received allogeneic BMT. The median infused CD34+ cell and granulocyte-macrophage colony-forming unit (CFU-GM) content were 7.73 x 10(4)/kg and 41.6 x 10(4)/kg, respectively. The median time to a neutrophil count greater than 500/ microL was 11 days after BSC and 16.5 days after BMT (P = .0003). A trend toward faster platelet and RBC recovery after BSC was observed. BSC patients received fewer platelet transfusions: 10 versus 19 (P = .015). The median length of hospitalization was shorter after BSC transplantation: 25 versus 31.5 days (P = .0243). The 100-day survival rates were similar: 83% after BSC and 75% after BMT (P = .3585). The incidence of acute GVHD grade II to IV was 57% and 45% for BSC and BMT, respectively (P = .4654). In comparison to BMT, allogeneic BSC transplantation may result in faster hematopoietic recovery, shorter hospital stay, and similar early survival. Whether allogeneic BSC are superior to bone marrow needs to be determined in randomized trials.


Pulmonary Exacerbations in Adults With Cystic Fibrosis: A Grown-up Issue in a Changing Cystic Fibrosis Landscape.
Pulmonary exacerbations (PExs) are significant life events in people with cystic fibrosis (CF), associated with declining lung function, reduced quality of life, hospitalizations, and decreased survival. The adult CF population is increasing worldwide, with many patients surviving prolonged periods with severe multimorbid disease. In many countries, the number of adults with CF exceeds the number of children, and PExs are particularly burdensome for adults as they tend to require longer courses and more IV treatment than children. The approach to managing PExs is multifactorial and needs to evolve to reflect this changing adult population. This review discusses PEx definitions, precipitants, treatments, and the wider implications to health-care resources. It reviews current management strategies, their relevance in particular to adults with CF, and highlights some of the gaps in our knowledge. A number of studies are underway to try to answer some of the unmet needs, such as the optimal length of treatment and the use of nonantimicrobial agents alongside antibiotics. An overview of these issues is provided, concluding that with the changing landscape of adult CF care, the definitions and management of PExs may need to evolve to enable continued improvements in outcomes across the age spectrum of CF.


Frequency and mechanism of neonatal thrombocytopenia.
We performed a 1-year prospective study of 807 consecutive infants admitted to a regional neonatal intensive care unit to determine the frequency, natural history, mechanism(s), and cause of thrombocytopenia. Thrombocytopenia developed in 22% of the infants. The platelet count nadir usually occurred by day 4 and resolved by day 10. Possible mechanisms responsible for the thrombocytopenia were assessed by comparing mean platelet volume, platelet-associated IgG (PAIgG), and coagulation test results in those infants whose platelet count fell below 100 X 10(9)/L (n = 97) with values in age-, weight-, and disease-matched control infants without thrombocytopenia (n = 80). In some thrombocytopenic infants, 111In-labeled-platelet survival, an estimate of megakaryocyte number in bone marrow biopsy specimens obtained at autopsy, and response to platelet infusions were also assessed. The thrombocytopenia was caused by increased platelet destruction, as shown by short 111In-labeled-platelet survival (12 to 128 hours), a rising mean platelet volume during the first week of life, normal numbers of megakaryocytes, and a poorer than predicted response to platelet infusions. A potential cause for the thrombocytopenia could be found in the majority of infants: 52% had elevated levels of PAIgG, 21% had laboratory evidence of disseminated intravascular coagulation, and 12% had had exchange transfusions. In contrast, the control infants had normal coagulation assay results, and only 15% had elevated levels of PAIgG. Birth asphyxia was identified as an associated risk factor for thrombocytopenia. This study demonstrates that transient, destructive thrombocytopenia develops in a large proportion (22%) of infants admitted to a neonatal intensive care unit, and that birth asphyxia is an important risk factor.


GLM-beamformer method demonstrates stationary field, alpha ERD and gamma ERS co-localisation with fMRI BOLD response in visual cortex.
Recently, we introduced a new 'GLM-beamformer' technique for MEG analysis that enables accurate localisation of both phase-locked and non-phase-locked neuromagnetic effects, and their representation as statistical parametric maps (SPMs). This provides a useful framework for comparison of the full range of MEG responses with fMRI BOLD results. This paper reports a 'proof of principle' study using a simple visual paradigm (static checkerboard). The five subjects each underwent both MEG and fMRI paradigms. We demonstrate, for the first time, the presence of a sustained (DC) field in the visual cortex, and its co-localisation with the visual BOLD response. The GLM-beamformer analysis method is also used to investigate the main non-phase-locked oscillatory effects: an event-related desynchronisation (ERD) in the alpha band (8-13 Hz) and an event-related synchronisation (ERS) in the gamma band (55-70 Hz). We show, using SPMs and virtual electrode traces, the spatio-temporal covariance of these effects with the visual BOLD response. Comparisons between MEG and fMRI data sets generally focus on the relationship between the BOLD response and the transient evoked response. Here, we show that the stationary field and changes in oscillatory power are also important contributors to the BOLD response, and should be included in future studies on the relationship between neuronal activation and the haemodynamic response.


Survival of Theileria parva-infected adult Rhipicephalus appendiculatus under laboratory and quasi-natural conditions.
Adult Rhipicephalus appendiculatus Muguga, having high or low intensities of Theileria parva Muguga infection in their salivary glands, were exposed to 20 degrees C and 85% relative humidity in the laboratory or quasi-natural conditions. Survival of the ticks and T. parva infections in their salivary glands was then monitored over a two year period. Ticks, having an average infection level of 2 infected acini per female, survived for up to 70 or 106 weeks after moulting under the laboratory or quasi-natural conditions respectively. Those having an infection level of 26 infected acini per female, survived for a similar duration except that those under quasi-natural conditions survived for a slightly shorter duration (102 weeks). Similarly, T. parva parasites survived for much longer periods under quasi-natural conditions than under the laboratory conditions. They survived for up to 38 or 78 weeks post salivary gland infection under the laboratory or quasi-natural conditions respectively in both categories of infection levels. There was apparently a density dependent relationship in T. parva survival, with a dramatic fall in infection occurring in ticks with high levels of infection between weeks 10 and 18 or weeks 38 and 46 post salivary gland infection in those exposed to laboratory or quasi-natural conditions before levelling off.


Pathogenicity of three genetically distinct and highly pathogenic Egyptian H5N8 avian influenza viruses in chickens.
In late 2016, Egypt encountered multiple cases of the highly pathogenic avian influenza (HPAI) virus of the H5N8 subtype. In a previous study, three distinct genotypes, including A/common-coot/Egypt/CA285/2016 (H5N8) (CA285), A/duck/Egypt/SS19/2017 (H5N8) (SS19), and A/duck/Egypt/F446/2017 (H5N8) (F446), were isolated from wild birds, a backyard, and a commercial farm, respectively, during the first wave of infection. In this current study, we investigated the differences in the pathogenicity, replication and transmissibility of the three genotypes and A/chicken/Egypt/15S75/2015 (H5N1) (S75) was used as the control. The intravenous pathogenicity index was between 2.68 and 2.9. The chicken lethal dose 50 values of F446, SS19 and CA285 were 103.7, 103.7, an 104 with a natural route of infection, respectively. These strains took longer than S75 to cause death when infection was carried out through the natural route (HPAI H5N1). After inoculation with the original concentration of 105 and 106 egg infective dose 50 (EID50), F446 had a higher mortality rate with short mean death times of 4, and 7 days, respectively compared with the other H5N8 viruses. Chickens inoculated with F446 and contacted exposed chickens infected with F446 showed the highest viral titer with remarkable differences in all H5N8 tested swabs at 2-4 days postinfection (dpi) compared to S75 at 2 dpi. This indicates that F446 had a more efficient transmission and spread from contact exposed birds to other birds. All H5N8 viruses were able to replicate systematically in all organs (trachea, brain, lung, and spleen) of the chicken with high viral titer with significantly different and more pathological changes observed in F446 than in other H5N8 viruses at 2 and 4 dpi. Compared with H5N1, we recorded a significantly high viral titer in the samples obtained from the lung, brain and both cloacal and tracheal swabs at 2 and 4 dpi, respectively and in the samples obtained from the spleen at 2 and 4 dpi among the experimental chicken. The comparative pathogenesis study revealed that in comparison with the other HPAI H5N8 viruses, the genotype F446 was more pathogenic, and showed more efficient viral replication and transmissibility in chickens in Egypt. The genotype F446 also showed a high viral titer than HPAI H5N1 and short mean death time at the third day after inoculation with 106 and 105 EID50, which revealed a conservation of certain H5N8 genotypes and a decrease in the incidence of H5N1.


Profile of an accident flying squad.
An analysis of 184 accident flying squad calls and of 280 patients injured in road accidents and treated by a flying squad based on an accident department inclusive from 1967 to 1971 has shown that such a service can provide an efficient system without disrupting the routine work of the hospital.


A new locus for non-syndromal, autosomal recessive, sensorineural hearing loss (DFNB16) maps to human chromosome 15q21-q22.
Non-syndromal, recessive deafness (NSRD) is the most common form of inherited deafness or hearing impairment in humans. NSRD is genetically heterogeneous and it has been estimated that as many as 35 different loci may be involved. We report the mapping of a novel locus for autosomal recessive, non-syndromal deafness (DFNB16) in three consanguineous families originating from Pakistan and the Middle East. Using multipoint analysis (HOMOZ/MAPMAKER) a maximum combined lod score of 6.5 was obtained for the interval D15S1039-D15S123. Recombination events and haplotype analysis define a 12-14 cM critical region between the markers D15S1039 and D15S155 on chromosome 15q15-q21.


Prophylactic positive end-expiratory pressure and postintubation hemodynamics: an interventional, randomized study.
To investigate the hemodynamic and outcome effects of implementing prophylactic positive end-expiratory pressure (PEEP) versus zero end-expiratory pressure (ZEEP) in patients during the postintubation period in the emergency setting. The present study was a prospective, single-centre, interventional, single-blinded randomized trial performed in a 16-bed medical intensive care unit. The study cohort consisted of consecutive patients who urgently required intubation. During the postintubation period, patients received either 5 cmH2O PEEP or ZEEP. The primary aim was to assess the variation in mean arterial pressure (MAP) from baseline up to 90 min postintubation. The secondary aim was to determine the mean duration of intubation, level of MAP support after intubation and 28-day mortality. Seventy-five consecutive patients with similar mean (+/- SD) baseline characteristics and preintubation MAP (76+/-18 mmHg in the ZEEP group and 78.5+/-23 mmHg in the PEEP group, P=Not significant [NS]) were studied. The final analysis was performed in 33 patients in the ZEEP group and 30 patients in the PEEP group. Regarding outcome measures following intubation, delta MAP (ie, the difference between the lowest MAP values from baseline) was not differentially affected in either group (P=NS); the mean durations of intubation were similar (ZEEP 9.2+/-8.5 days versus PEEP 9.2+/-8.8 days, P=NS); 28-day mortality was not discriminative (ZEEP 14 of 33, PEEP nine of 30; P=NS); and levels of MAP support after intubation were comparable between the two groups. In the present trial, there was no evidence that implementing a prophylactic PEEP of 5 cmH2O adversely affects short-term hemodynamics or outcome in medical intensive care patients during the postintubation period.


Solving large scale phylogenetic problems using DCM2.
In an earlier paper, we described a new method for phylogenetic tree reconstruction called the Disk Covering Method, or DCM. This is a general method which can be used with any existing phylogenetic method in order to improve its performance. We showed analytically and experimentally that when DCM is used in conjunction with polynomial time distance-based methods, it improves the accuracy of the trees reconstructed. In this paper, we discuss a variant on DCM, that we call DCM2. DCM2 is designed to be used with phylogenetic methods whose objective is the solution of NP-hard optimization problems. We show that DCM2 can be used to accelerate searches for Maximum Parsimony trees. We also motivate the need for solutions to NP-hard optimization problems by showing that on some very large and important datasets, the most popular (and presumably best performing) polynomial time distance methods have poor accuracy.


Both striate cortex and superior colliculus contribute to visual properties of neurons in superior temporal polysensory area of macaque monkey.
Although the tectofugal system projects to the primate cerebral cortex by way of the pulvinar, previous studies have failed to find any physiological evidence that the superior colliculus influences visual activity in the cortex. We studied the relative contributions of the tectofugal and geniculostriate systems to the visual properties of neurons in the superior temporal polysensory area (STP) by comparing the effects of unilateral removal of striate cortex, the superior colliculus, or of both structures. In the intact monkey, STP neurons have large, bilateral receptive fields. Complete unilateral removal of striate cortex did not eliminate visual responses of STP neurons in the contralateral visual hemifield; rather, nearly half the cells still responded to visual stimuli in the hemifield contralateral to the lesion. Thus the visual properties of STP neurons are not completely dependent on the geniculostriate system. Unilateral striate lesions did affect the response properties of STP neurons in three ways. Whereas most STP neurons in the intact monkey respond similarly to stimuli in the two visual hemifields, responses to stimuli in the hemifield contralateral to the striate lesion were usually weaker than responses in the ipsilateral hemifield. Whereas the responses of many STP neurons in the intact monkey were selective for the direction of stimulus motion or for stimulus form, responses in the hemifield contralateral to the striate lesion were not selective for either motion or form. Whereas the median receptive field in the intact monkey extended 80 degrees into the contralateral visual field, the receptive fields of cells with responses in the contralateral field that survived the striate lesions had a median border that extended only 50 degrees into the contralateral visual field. Removal of both striate cortex and the superior colliculus in the same hemisphere abolished the responses of STP neurons to visual stimuli in the hemifield contralateral to the combined lesion. Nearly 80% of the cells still responded to visual stimuli in the hemifield ipsilateral to the lesion. Unilateral removal of the superior colliculus alone had only small effects on visual responses in STP. Receptive-field size and visual response strength were slightly reduced in the hemifield contralateral to the collicular lesion. As in the intact monkey, selectivity for stimulus motion or form were similar in the two visual hemifields. We conclude that both striate cortex and the superior colliculus contribute to the visual responses of STP neurons. Striate cortex is crucial for the movement and stimulus specificity of neurons in STP.(ABSTRACT TRUNCATED AT 400 WORDS)


[Synthesis and antimicrobial activities of tetrahydro-2H-1,3,5-thiadiazine-2-thiones].
Ten 3-benzyl-5-substitued tetrahydro-2H-1,3,5-thiadiazine-2-thiones were synthesized and seven of them are reported for the first time. The structures of the compounds have been elucidated by UV, IR, H-NMR and elemental analysis. The in vitro activity of the compounds against 6 kinds of bacteria and 2 kinds of fungi was tested. The antimicrobial activities of all compounds are more potent than sulfadiazine sodium and less potent than norfloxacini. All compounds were found to be more active against gram-negative and less active against gram-positive bacteria and weak against fungi.


[Prevention of hepatic metastases in radically operated colonic cancers].
The prognosis of colon cancer, after curative resection, is mainly related to the outcome of metastases, and especially of liver metastases. It is generally accepted that adjuvant medical therapy is important in order to prevent the incidence of metastatic recurrences. The aim of the present review is to analyse the conclusions of the main recent randomized trials assessing the comparative value of different adjuvant protocols. The results obtained using either systemic infusion, the classical one, or intraportal infusion, which is mainly designed to prevent liver metastases, are reported. On the basis of the review, we can conclude that: adjuvant chemotherapy using combined drugs (MF, MOF) did not prove to be more active than 5-FU alone. The beneficial action of a combined 5-FU + levamisole regimen has been clearly demonstrated for patients with a Dukes C tumour. According to a unique and limited trial, intraportal adjuvant therapy has been shown to be effective for patients with Dukes B tumours, but this remains to be confirmed. On the basis of the present data, new adjuvant programs using combined chemotherapeutic and immunotherapeutic coupounds, and combined systemic and loco-regional infusion, could be developed.


The different activities of RNA G-quadruplex structures are controlled by flanking sequences.
The role of G-quadruplex (G4) RNA structures is multifaceted and controversial. Here, we have used as a model the EBV-encoded EBNA1 and the Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded LANA1 mRNAs. We have compared the G4s in these two messages in terms of nucleolin binding, nuclear mRNA retention, and mRNA translation inhibition and their effects on immune evasion. The G4s in the EBNA1 message are clustered in one repeat sequence and the G4 ligand PhenDH2 prevents all G4-associated activities. The RNA G4s in the LANA1 message take part in similar multiple mRNA functions but are spread throughout the message. The different G4 activities depend on flanking coding and non-coding sequences and, interestingly, can be separated individually. Together, the results illustrate the multifunctional, dynamic and context-dependent nature of G4 RNAs and highlight the possibility to develop ligands targeting specific RNA G4 functions. The data also suggest a common multifunctional repertoire of viral G4 RNA activities for immune evasion.


The role of routine clinical pretreatment 18F-FDG PET/CT in predicting outcome of colorectal liver metastasis.
The aim of this study was to determine the value of SUV-based metabolic parameters derived from pretreatment F-FDG PET/CT of colorectal liver metastases in predicting disease response, progression-free survival (PFS), and overall survival (OS). We retrospectively reviewed 70 colorectal patients with liver metastases who underwent pretreatment F-FDG PET/CT. SUVmean, SUVmax, TLG (total lesion glycolysis), metabolic tumor volume, and metabolic tumor diameter were the metabolic parameters derived from volume of interest analysis of the most FDG-avid liver lesion in each subject. Clinical and laboratory parameters were recorded. Tumor response was assessed by response evaluation criteria in solid tumors 1.1 criteria at 12 weeks after treatment. Associations between tumor response, metabolic parameters, and clinical/laboratory parameters were examined by 1-way analysis of variance. The relationship of the metabolic parameters with PFS and OS was determined by Kaplan-Meier analyses and further confirmed with multivariate Cox regression analyses. SUVmean less than 4.48, SUVmax less than 6.59, TLG less than 75.2, metabolic tumor volume less than 4.49 cm, and hemoglobin level greater than or equal to 11 g/dL were associated with longer PFS (P < 0.05). Prior surgery or radiofrequency ablation to the liver metastases was the only additional factor shown to be associated with longer OS. SUV-based metabolic parameters derived from pretreatment F-FDG PET/CT can predict PFS in colorectal liver metastases.


Effects of breast pumping on the pharmacokinetics and pharmacodynamics of ethanol during lactation.
This study tested two hypotheses. First, that breast pumping contributes to the previously observed decrease in ethanol bioavailability in lactating women. Second, that the effects of breast pumping are more pronounced when ethanol is consumed after a meal. The within-subject factor was test condition (fed or fasted) and the between-subject factor was experimental group (pumped before, PB; pumped after, PA). Those randomly assigned to the PB group (N = 8) breast pumped 1 h before drinking, whereas those assigned to the PA group (N = 8) breast pumped 0.6 h after drinking. Pumping before drinking significantly decreased blood ethanol concentration (P < 0.05) and ethanol bioavailability (P = 0.05). Pumping after drinking sped up elimination (P = 0.008), attenuated ethanol-induced hypothermia (P = 0.002), and increased feelings of stimulation (P = 0.03). The effects were more pronounced when ethanol was consumed after a meal. Common neural/hormonal responses to food and suckling may contribute additive effects in altering the pharmacokinetics/pharmacodynamics of ethanol, and perhaps of other drugs, during lactation.


[Spread of salmonellosis in Moscow and the ways of its prophylaxis].
The article deals with the results of the epidemiological analysis of the spread of salmonellosis in Moscow. During the last 15 years the proportion of Salmonella enteritidis was about 80% and more. After salmonellosis morbidity decreased to 19.9 per 100,000 of the population (the minimum level) in 1985 its sharp rise was noted. Morbidity rate increased from 31.7 in 1987 to 55.1 per 100,000 in 1988, then to 93.9 per 100,000 of the population in 1989 (the maximum level). In the subsequent years up to 1996 a decrease in morbidity rate was observed, but in 1997-2002 morbidity rate stabilized within 29.8-35.7 per 100,000 of the population without a perceptible tendency towards decrease. The sharp increase of the etiological role of S. enteritidis which led to a wide spread of Salmonella infections was caused by the "chicken-egg" factor of their transmission. High morbidity rate among children and adults, registered all the year round, is the consequence of the constant epidemic activity of this factor.


Survival Analysis for Patients with ALK Rearrangement-Positive Non-Small Cell Lung Cancer and a Poor Performance Status Treated with Alectinib: Updated Results of Lung Oncology Group in Kyushu 1401.
Alectinib confers a pronounced survival benefit in patients with ALK rearrangement-positive non-small cell lung cancer and a poor performance status. Survival benefit of alectinib for patients with a poor performance status was consistent regardless of the presence of central nervous system metastases. We previously reported a marked objective response rate (ORR) and safety for alectinib treatment in patients with ALK rearrangement-positive non-small cell lung cancer (NSCLC) and a poor performance status (PS) in the Lung Oncology Group in Kyushu (LOGiK) 1401 study. It remained unclear, however, whether alectinib might also confer a long-term survival benefit in such patients. Eighteen patients with ALK rearrangement-positive advanced NSCLC and a PS of 2, 3, or 4 (n = 12, 5, and 1, respectively) were enrolled in LOGiK1401 between September 2014 and December 2015 and received alectinib. We have now updated the survival data for the study. The median follow-up time for all patients was 27.3 months. The median progression-free survival (PFS) was 16.2 months (95% confidence interval [CI], 7.1-30.8 months), and the median survival time (MST) and the 3-year overall survival rate were 30.3 months (95% CI, 11.5 months to not reached) and 43.8% (95% CI, 20.8-64.7%), respectively. This survival benefit was similarly manifest in patients with a PS of 2 (MST, 20.5 months) and those with a PS of ≥3 (MST, not reached). PFS did not differ between patients with or without central nervous system (CNS) metastases at baseline (median of 17.5 and 16.2 months, respectively, p = .886). Alectinib showed a pronounced survival benefit for patients with ALK rearrangement-positive NSCLC and a poor PS regardless of the presence of CNS metastases, a patient population for which chemotherapy is not indicated.


Practice-based outcomes of dialectical behaviour therapy (DBT) targeting anger and violence, with male forensic patients: a pragmatic and non-contemporaneous comparison.
To examine the effectiveness of an eighteen-month treatment based on dialectical behaviour therapy (DBT) targeting anger and violence, on a group of male forensic patients. Eight male forensic patients in a high security hospital who met the criteria for borderline personality disorder measured by the Personality Assessment Inventory underwent 18 months of treatment. They completed three psychometric tests at pre-, mid- and post-treatment and at a six-month follow up. A comparison group (TAU) of nine patients, assessed as having similar personality disorders, received the usual treatment available in the hospital but excluding DBT. They completed the same tests at the same time intervals corresponding to the pre-, mid- and post-testing of the DBT group. In both groups, all instances behaviours related to anger and violence were monitored for three six-month periods, prior to, during and post-treatment. Overall, patients in the DBT group made greater gains than patients in the TAU group in reducing the seriousness of violence-related incidents, and in self report measures of hostility, cognitive anger, disposition to anger, outward expression of anger and anger experience. The results suggest a potential for DBT to impact positively and lastingly on violent behaviour and components of anger in male forensic patients when compared with standard treatment. The power of the current study to detect group differences was reduced by small ns, large confidence intervals, and a non-contemporaneous comparison group. Cost-effective strategies are proposed to take forward research on DBT with this population.


Military Sexual Trauma As a Risk Factor for Treatment Non-Response from an Online, Self-Management Posttraumatic Stress Disorder Treatment for Women Veterans.
Women veterans are exposed to high rates of trauma, including military sexual trauma (MST), and face unique barriers to posttraumatic stress disorder (PTSD) treatment. Telehealth interventions that are tailored to women veterans' unique lived experiences may improve treatment engagement and outcomes. It is important to ascertain how beneficial new telehealth interventions are in the context of different patient characteristics and trauma types, particularly for lower-intensity telehealth interventions (e.g., web-based programs or apps). This secondary analysis of a randomized clinical trial conducted in a sample of 102 women veterans examines predictors of treatment response to a self-management, telehealth intervention for PTSD: Delivery of Self Training and Education for Stressful Situations-Women Veterans (DESTRESS-WV). In the trial, women veterans with PTSD received either an online cognitive behavioral intervention with phone coaching, or phone monitoring alone. We examined associations between baseline patient characteristics (demographics, trauma types, and clinical symptoms) and treatment outcome at post-treatment, 3 months, and 6 months, focusing on the association between treatment outcome and MST. Our primary outcomes were changes in PTSD (PTSD Symptom Checklist, Version 5, PCL-5) and depression (8-item Patient Health Questionnaire, PHQ-8) in the full sample, adjusting for treatment condition. Women veterans who identified MST as the primary trauma for which they were seeking PTSD treatment experienced a nearly nine-point lesser improvement on the PCL-5 than those seeking PTSD treatment for other trauma types (e.g., childhood abuse, combat trauma; p = .0073). Similar patterns were found for depression symptoms. To our knowledge, this is the first study to examine the association between trauma type and treatment outcomes within the context of a self-management, telehealth treatment for PTSD. While the study was not powered to examine differential treatment response for patient subgroups, our exploratory findings suggest that gaps remain in providing effective PTSD care for women veterans who experienced MST.Trial registration: The trial and analysis plan were preregistered in ClinicalTrials.gov (Identifier: NCT02917447).


IL-25 and IL-25 receptor expression on eosinophils from subjects with allergic asthma.
Allergic asthma is an inflammatory airway disease in which Th2 cytokines play an important role. Epithelial-derived interleukin (IL)-25 has been suggested to be important in the maintenance of Th2-type responses. The effects of IL-25 are mediated by the IL-25 receptor, composed of two subunits, IL-17RA and IL-17RB. Eosinophils are effector cells in allergic asthma. The role of IL-25 in eosinophil function is unknown. This study examined the expression of IL-25 and its receptor on eosinophils in allergic asthmatics compared to atopic nonasthmatics and normal controls. The expression of IL-25, IL-17RA and IL-17RB on eosinophils, and levels of plasma IL-25 were measured in 14 normal control subjects, 15 atopic nonasthmatics and 14 mild allergic asthmatics. The expression of IL-17RB on eosinophils was significantly higher in allergic asthmatics (43.08%, range 33.96-59.98%) than in atopic nonasthmatics (11.98%, range 6.33-27.11%, p = 0.002) and normal controls (17.70%, range 10.97-38.9%, p = 0.01). IL-17RA expression was also significantly higher in the allergic asthmatic group. No differences were observed in the intracellular expression of IL-25. The concentration of IL-25 in plasma was significantly increased in the allergic asthmatics (145 ng/ml, range 64-290 ng/ml) when compared to the normal controls (21 ng/ml, range 0-116 ng/ml, p = 0.012), but not compared to atopic nonasthmatics. There was a significant negative correlation between FEV1 % predicted and the IL-25 level in the plasma (r = -0.443, p = 0.003). The increased IL-25 levels in plasma and the expression of IL-17RA and IL-17RB on eosinophils in allergic asthma patients suggests that IL-25 may activate eosinophils during allergic inflammation.


Self-assessed sleep quality in chronic kidney disease.
Although sleep complaints are commonly reported in persons with end stage renal disease (ESRD), little is known about the prevalence of sleep complaints in chronic kidney disease (CKD), and the relation of sleep quality to the severity of kidney disease. We administered the Kidney Disease Quality of Life (KDQOL) sleep scale to 156 subjects, 78 with ESRD and 78 with CKD. Glomerular filtration rate (GFR) was estimated using the six variable Modification of Diet in Renal Disease (MDRD) equation and used to stratify subjects with CKD as mild-moderate (GFR >25 ml/min/1.73 m(2)) and advanced (GFR <25 ml/min/1.73 m(2)). We used multivariable linear regression to determine independent predictors of KDQOL sleep scale scores. Higher scores indicate higher self-reported quality of sleep. Median scores on the KDQOL sleep scale were 59 (interquartile range 40-80) in subjects with ESRD and 69 (interquartile range 53-80) in subjects with CKD (P=0.04). Thirty-four percent of subjects with ESRD, 27% of subjects with advanced CKD, and 14% of subjects with mild to moderate CKD had sleep maintenance disturbances (P=0.05). Thirteen percent of subjects with ESRD, 11% of subjects with advanced CKD, and no subjects with mild-moderate CKD had complaints of daytime somnolence (P=0.03). There was no significant difference in the prevalence of sleep adequacy complaints in persons with ESRD versus CKD. In multivariable analyses, only age and ESRD status (vs. CKD) were significant predictors of lower KDQOL sleep scores. Among subjects with CKD, there was a significant direct association between estimated GFR and scores on the KDQOL sleep scale in non-African American subjects (P=0.01). Sleep complaints are common in persons with CKD and ESRD and may be associated with the severity of kidney disease.


Do LGBT aging trainings effectuate positive change in mainstream elder service providers?
This study aims to provide empirical evidence regarding whether attitudes, beliefs, and intentions of elder-service providers can be positively affected as a result of attending cultural competency training on the unique challenges of sexual and gender minorities. Stigmatization throughout the lifespan may have a causal influence on barriers to care, social isolation, and concomitant health disparities. Data were collected for this study at 4 Massachusetts training events to pilot a cultural competency workshop on lesbian, gay, bisexual, and transgender (LGBT) aging for mainstream elder service providers. This quasi-experimental study included the analysis of pre- and posttest surveys completed by the service-provider attendees (N = 76). The analytic strategy included descriptive statistics, paired t tests, chi-square analyses, and repeated measures analyses of variance. Findings revealed statistically significant improvement in numerous aspects of providers' knowledge, attitudes, and behavioral intentions subsequent to the training sessions. These included (p = .000) awareness of LGBT resources, policy disparities, spousal benefits for same-sex couples, and the intention to challenge homophobic remarks. This study concludes that mainstream elder-service provider training on LGBT aging issues results in positive change. Recommendations include long-term follow up of participants, the inception of agency-level surveys to appraise institutional culture change, and increased curriculum on transgender older adults.


An examination of the diagnostic efficiency of post-deployment mental health screens.
To conduct a blinded study to examine the diagnostic efficiency of the Department of Defense (DoD) Post-Deployment Health Reassessment (PDHRA) screens for major depressive disorder (MDD), posttraumatic stress disorder (PTSD), and alcohol abuse. Participants were 148 post-deployed soldiers who were completing the PDHRA protocol. Soldiers' mean age was 27.7 (standard deviation = 6.6) years, and 89.0% were male. Mental health professionals blinded to the PDHRA screening results administered the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition directly after the PDHRA assessment protocol. All screens exhibited excellent negative predictive power. Sensitivity metrics were lower, consistent with the relatively low base rates observed for MDD (10.1%), PTSD (8.8%), and alcohol abuse (5.4%). Metrics obtained for the PTSD screen were consistent with previous research with a similar base rate. A two-item screen containing PTSD reexperiencing and hyperarousal symptom items revealed excellent psychometric properties (sensitivity = .92; specificity = .79). The alcohol abuse screen yielded high sensitivity (.86), but very poor precision; these metrics were somewhat improved when the screen was reduced to a single item. The PDHRA MDD, PTSD, and alcohol abuse screens appear to be functioning well in accurately ruling out these diagnoses, consistent with a population-level screening program. Cross validation of the current results is indicated. Additional refinement may yield more sensitive screening measures within constraints imposed by the low base rates in a typically healthy population.


Interplay between circadian clock and viral infection.
The circadian clock underpins most physiological conditions and provides a temporal dimension to our understanding of body and tissue homeostasis. Disruptions of circadian rhythms have been associated with many diseases, including metabolic disorders and cancer. Recent literature highlights a role for the circadian clock to regulate innate and adaptive immune functions that may prime the host response to infectious organisms. Viruses are obligate parasites that rely on host cell synthesis machinery for their own replication, survival and dissemination. Here, we review key findings on how circadian rhythms impact viral infection and how viruses modulate molecular clocks to facilitate their own replication. This emerging area of viral-clock biology research provides a fertile ground for discovering novel anti-viral targets and optimizing immune-based therapies.


Total synthesis and absolute configuration of epicoccamide D, a naturally occurring mannosylated 3-acyltetramic acid.
The endofungal metabolite epicoccamide D was synthesised in eighteen steps and 17 % yield as the first member of the family of natural glycotetramic acids. The modular character of the synthesis opens access also to analogues featuring different sugars and spacers. It comprises several high-yielding key steps. The β-D-mannosyl group was introduced by using an α-D-glucosyl imidate donor with subsequent oxidative-reductive epimerisation at C-2'. The pyrrolidine ring was closed quantitatively by a Lacey-Dieckmann condensation of an N-(β-ketoacyl)-N-methyl alaninate. The resulting 3-[ω-(β-D-mannosyl)octadec-2-enoyl]tetramic acid was hydrogenated in the presence of the rhodium catalyst (R,R)-[Rh(Et-DUPHOS)][BF4 ] to establish the (7S)-stereocentre. This was possible only after blocking the acyltetramic acid as a BF2 -chelate to prevent capture of the metal catalyst. We also assigned the hitherto unknown configuration of the natural product as being 5S,7S by comparison of its (13) C NMR spectroscopic and optical rotation data with those of our two synthetic 5S,7R/S-diasteromers.


Assessing quality indicators related to mental health emergency room utilization.
This descriptive study compared 2014-15 to 2005-06 data on the quality of mental health services (MHS) in relation to emergency room (ER) use to assess the impact of the 2005 Quebec MH reform regarding access, continuity and appropriateness of care for patients with mental illnesses (PMI). Data emanated from the Quebec Integrated Chronic Disease Surveillance System (Quebec/Canada). Participants (865,255 for 2014-15; 817,395 for 2005-06) were age 12 or over, with at least one MI, including substance use disorders (SUD), diagnosed during an ER visit, outpatient treatment or hospitalization. Variables included: access (ER use/frequency, hospitalization rates, outpatient consultations preceding an ER visit), care continuity (outpatient consultations following an ER visit/hospitalization, consecutive returns to the ERs), and care appropriateness (high ER use, recurrence of yearly ER visits, length of hospitalization). Frequency distributions were calculated on sex, age and geographic area for ER visits/hospitalizations in 2014-15, and between 2014 and 15 and 2005-06. PMI accounted for 12 % of the Quebec population in 2014-15 (n = 865,255), of whom 39% visited an ER for any reason. Amount and frequency of ER use and number/length of hospitalizations were almost twice as high for PMI versus patients without MI; 17% of PMI were also high/very high ER users and were frequently hospitalized. Among PMI, ER users were also frequent users of outpatient services despite a lack of follow-up appointments after ER visits or hospitalizations. Findings revealed some positive changes over time, such as decreased ER and hospitalization rates; yet overall access, continuity and appropriateness of care, as measured in this study, remained low. This study demonstrated that the Quebec reform did not produce a substantial impact on ER use or substantially improved care, as hypothesized. Better access and continuity of care should be promoted to reduce the high prevalence of ER use among PMI. Quality improvement in MHS may be realized if ERs are supported by substantial and well-integrated community MH networks.


Estimation of ethanol and methanol exposure through jarred fruit purees.
Chemicals in foods enter the human body from early life likely posing chronic toxic health risks in the future. This study aimed to estimate the exposure to ethanol and methanol in children consuming an acceptable daily amount of fruit purees. Different fruit purees were purchased and measured for methanol and ethanol by using HS-GC. The exposure dose of these alcohols was calculated based on a consumption of 125-250 g of fruit purees in children weighing 7, 12 and 16 kg. The highest methanol was found in carrot-apple puree (29.07 mg/dL) and ethanol in peach-banana puree (42.07 mg/dL). Daily methanol exposure was estimated between 4.54 and 6.06, and ethanol between 6.57 and 8.76 mg/kg bw. Our results show higher exposure doses of methanol and ethanol than allowable ones (methanol 2 and ethanol 6 mg/kg/day) in children consuming fruit purees. This should be handled as a public health risk and further comprehensive studies should be enrolled on the chronic toxic effects of food-derived alcohols. Besides, food-derived exposure to toxic chemicals from early life should be more questioned by physicians (in assessing chronic diseases), and related authorities should establish a sustainable, safe, and healthy food production policy.


Neurotropic cutaneous tumors of the head and neck.
To determine the outcomes of patients with neurotropic cutaneous tumors of the head and neck. A retrospective review was conducted of 7852 charts of patients who underwent micrographically controlled excisions of skin cancers of the head and neck between 1984 and 1995, identifying neurotropic tumors and the outcomes of their treatments. Tertiary care center (university hospital). Thirty-seven patients with neurotropic tumors were identified (and confirmed by secondary histological review), constituting 0.47% of all patients. The median age at presentation was 68 years and all except an albino were white. Nine patients had basal cell carcinomas and 28 had squamous cell carcinomas. Twenty-five patients (69%) were referred after at least 1 prior excision was performed a median of 16 months previously. All patients underwent micrographic mapping and excision of the cutaneous portion of the tumor. As necessitated by tumor spread, additional soft tissue, skull base, and/or intracranial surgery and postoperative irradiation were also conducted. Thirty-four patients (3 patients were unavailable for follow-up) were assessed by physician examination a minimum of 19 months after treatment (median, 33 months). Of 25 patients with extracranial disease only, 19 had no evidence of disease during follow-up and 1 died of intercurrent disease at 20 months without evidence of tumor persistence. Of the 9 patients with intracranial neurotropic tumors at the time of presentation, 1 remained with no evidence of disease, 1 died of intercurrent disease at 21 months without evidence of tumor persistence, and the other 7 either died of or are living with an intracranial tumor. Micrographic tissue mapping to detect and then encompass neurotropic cutaneous malignancies, along with conventional surgery for deeper tumor invasions and irradiation in selected cases, was successful in 19 patients (76%) with an extracranial tumor. For those with neurotropic tumors approaching or penetrating the skull base, the prognosis was poor regardless of therapy method.


Day of surgery admission in urology: Patient criteria and the organization required for same-day admission in urology: A retrospective study.
The day of surgery admission (DOSA) has been practiced in surgery for decades, with reports dating as far back as 1909. DOSA policy has potential benefits for the health system and the patient, especially when there is a shortage of health-care resources. This study aims to compare DOSA and standard prior admission (D-1) among patients who underwent major urological operations. This retrospective study enrolled a total of 206 patients who did not meet the criteria for day care surgery admission. The patients were divided into two groups: those admitted on the same day of surgery and those admitted the day before surgery. Among the participants, 111 (53.8%) were admitted on the same day, while 95 (46.2%) were admitted the day before surgery. We collected data from the electronic health records of these patients, documenting various variables, including patient demographics, type of surgery, admission type and date, intervention date, length of stay, complications, Clavien-Dindo score, and American Society of Anesthesiologists (ASA) score. We included a total of 206 patients who were admitted for operations in the urology department. The mean age was 70.5 years, and the majority was males (83.5%). Endoscopic procedures were the most common interventions (68%). The most ASA score for the enrolled patients was 2 (56.2%). DOSA was done for 53.8% of the patients, whereas the remaining patients were admitted 1 day before elective surgery. DOSA patients were significantly younger (P = 0.025), had a higher proportion of ASA score 1 (12.7%) and ASA score 3 (26.4%), had significantly fewer postoperative complications (P = 0.002), and had statistically significantly a shorter length of stay (P < 0.001) compared to D-1 admission patients. In our study, DOSA patients were younger, had a lower prevalence of comorbidities, utilized anticoagulants less frequently, experienced fewer complications, and had significantly shorter hospital stays. Since the DOSA policy is safe and has a lower financial and economic burden on the health-care system, we recommend more urological and surgical centers to implement it.


Clusters of hyperactive neurons near amyloid plaques in a mouse model of Alzheimer's disease.
The neurodegeneration observed in Alzheimer's disease has been associated with synaptic dismantling and progressive decrease in neuronal activity. We tested this hypothesis in vivo by using two-photon Ca2+ imaging in a mouse model of Alzheimer's disease. Although a decrease in neuronal activity was seen in 29% of layer 2/3 cortical neurons, 21% of neurons displayed an unexpected increase in the frequency of spontaneous Ca2+ transients. These "hyperactive" neurons were found exclusively near the plaques of amyloid beta-depositing mice. The hyperactivity appeared to be due to a relative decrease in synaptic inhibition. Thus, we suggest that a redistribution of synaptic drive between silent and hyperactive neurons, rather than an overall decrease in synaptic activity, provides a mechanism for the disturbed cortical function in Alzheimer's disease.


Paradigms of public policies for licit and illicit drugs in Brazil.
Brazil is a country of continental dimensions that, over the last 3 decades, has been making increased efforts to develop effective public policies for controlling the use of both licit and illicit psychoactive substances. In the case of licit drugs, Brazil was a pioneer in following the guidance of the World Health Organization for tobacco control and has witnessed surprising results relating to reduction of smoking prevalence and correlated morbidity and mortality. Today, Brazil has a national structure for organizing, applying, and monitoring laws relating to tobacco. However, in the field of illicit drugs, with crack consumption as a paradigm, the situation is the opposite: its use has been increasing year by year and is being consumed at increasingly young ages and by all social classes. Thus, it is becoming an enormous challenge for public policies relating to prevention and treatment. In this context, the aim of this article is to present a review of the epidemiological data relating to tobacco and crack use in Brazil, with an analysis on the impact of public policies for controlling consumption over recent years. Despite the efforts made over the last 3 decades, Brazil still has a long way to go in order to construct a consistent and effective national drugs policy.


Anaerobic Treatment of Palm Oil Mill Effluent in Pilot-Scale Anaerobic EGSB Reactor.
Large volumes of untreated palm oil mill effluent (POME) pose threat to aquatic environment due to the presence of very high organic content. The present investigation involved two pilot-scale anaerobic expanded granular sludge bed (EGSB) reactors, continuously operated for 1 year to treat POME. Setting HRT at 9.8 d, the anaerobic EGSB reactors reduced COD from 71179 mg/L to 12341 mg/L and recycled half of sludge by a dissolved air flotation (DAF). The average effluent COD was 3587 mg/L with the consistent COD removal efficiency of 94.89%. Adding cationic polymer (PAM) dose of 30 mg/L to DAF unit and recycling its half of sludge caused granulation of anaerobic sludge. Bacilli and small coccid bacteria were the dominant microbial species of the reactor. The reactor produced 27.65 m(3) of biogas per m(3) of POME which was utilized for electricity generation.


High-resolution imaging reveals indirect coordination of opposite motors and a role for LIS1 in high-load axonal transport.
The specific physiological roles of dynein regulatory factors remain poorly understood as a result of their functional complexity and the interdependence of dynein and kinesin motor activities. We used a novel approach to overcome these challenges, combining acute in vivo inhibition with automated high temporal and spatial resolution particle tracking. Acute dynein inhibition in nonneuronal cells caused an immediate dispersal of diverse forms of cargo, resulting from a sharp decrease in microtubule minus-end run length followed by a gradual decrease in plus-end runs. Acute LIS1 inhibition or LIS1 RNA interference had little effect on lysosomes/late endosomes but severely inhibited axonal transport of large, but not small, vesicular structures. Our acute inhibition results argue against direct mechanical activation of opposite-directed motors and offer a novel approach of potential broad utility in the study of motor protein function in vivo. Our data also reveal a specific but cell type-restricted role for LIS1 in large vesicular transport and provide the first quantitative support for a general role for LIS1 in high-load dynein functions.