Symbiotic microalgal diversity within lichenicolous lichens and crustose hosts on Iberian Peninsula gypsum biocrusts.
This study analyses the interactions among crustose and lichenicolous lichens growing on gypsum biocrusts. The selected community was composed of Acarospora nodulosa, Acarospora placodiiformis, Diploschistes diacapsis, Rhizocarpon malenconianum and Diplotomma rivas-martinezii. These species represent an optimal system for investigating the strategies used to share phycobionts because Acarospora spp. are parasites of D. diacapsis during their first growth stages, while in mature stages, they can develop independently. R. malenconianum is an obligate lichenicolous lichen on D. diacapsis, and D. rivas-martinezii occurs physically close to D. diacapsis. Microalgal diversity was studied by Sanger sequencing and 454-pyrosequencing of the nrITS region, and the microalgae were characterized ultrastructurally. Mycobionts were studied by performing phylogenetic analyses. Mineralogical and macro- and micro-element patterns were analysed to evaluate their influence on the microalgal pool available in the substrate. The intrathalline coexistence of various microalgal lineages was confirmed in all mycobionts. D. diacapsis was confirmed as an algal donor, and the associated lichenicolous lichens acquired their phycobionts in two ways: maintenance of the hosts' microalgae and algal switching. Fe and Sr were the most abundant microelements in the substrates but no significant relationship was found with the microalgal diversity. The range of associated phycobionts are influenced by thallus morphology.


Comparison of the efficacy and drying times of liquid, gel and foam formats of alcohol-based hand rubs.
Hand rubs containing alcohols such as isopropanol (IPA) or ethanol (EtOH) are widely used for hygienic hand disinfection, and are presented in different formats (i.e. liquid, gel or foam). To determine if there is any difference in efficacy between these two active ingredients in the three formats. In addition, an assessment of the drying time was undertaken. Two non-commercial, 'standard' formulations were tested in each format: one containing 60% IPA, and the other containing 80% EtOH. EN 1500 tests were performed with 20 volunteers to assess efficacy. The reference product was 2 x 3 mL of 60% IPA for 60 s, as described in EN 1500 (2013). The test products were 3 mL of liquid, gel or foam format; one full EN 1500 test was performed for each formulation (60% IPA and 80% EtOH). To assess drying time, two different volumes (1.5 and 3.0 mL) of the test formulations in liquid, gel or foam format were applied to the hands of 15 volunteers. Volunteers self-reported when their hands were dry; at the end of the test, the volunteers were asked to rate the time taken to dry on a three-point scale (too short, OK, too long). This study found no difference in antibacterial efficacy attributable to formulation or format for the two 'standard' ABHR formulations, as assessed by EN 1500. When measured objectively, the EtOH-based formulations dried more rapidly than the IPA-based formulations, and for both formulations, gels took longer to dry than other formats. User perception of drying time broadly agreed with objective measurement. Given that there was no difference in efficacy and only moderate difference in drying time, it is proposed that ABHR in liquid, foam or gel format may be appropriate, provided that the specific product passes the required efficacy and safety standards.


Sample-size calculations for studies with correlated ordinal outcomes.
Correlated ordinal response data often arise in public health studies. Sample-size (power) calculations are a crucial step in designing such studies to ensure an adequate sample to detect a significant effect. Here we extend Rochon's method of sample-size estimation with a repeated binary response to the ordinal case. The proposed sample-size calculations are based on an analysis with generalized estimating equations (GEE) and inference with the Wald test. Simulation results demonstrate the merit of the proposed power calculations. Analysis of an arthritis clinical trial is used for illustration.


Influence of monoclonal IgM cold agglutinins on adhesiveness, phagocytosis, and bactericidal activity on human granulocytes and monocytes.
Monoclonal IgM cold agglutinins (CA) bind and, in the presence of complement, are cytotoxic to various mammalian cells. The impact of these autoantibodies on functional capacity of phagocytes has not been studied until now. Herein we report that sera with monoclonal IgM anti-I and anti-i CA significantly reduce adhesiveness, phagocytosis, phagocytic index, and intracellular bactericidal activity of human peripheral blood polymorphonuclear cells (PMNs) at 37 degrees C and 24 degrees C. Anti-i CA were more active than anti-I. Sera with monoclonal IgMs without CA activity reduced the total number of ingested bacteria but otherwise had no effect on phagocytic functions. There was no difference in the degree of inhibition when anti-i and anti-I CA were tested against cord, maternal, and adult PMNs. Chromatographically purified a-I and a-i CA inhibited markedly phagocytosis in concentrations as low as 1 mg/ml. Phagocytic activity of peripheral blood monocytes was inhibited by CA at 18 degrees C but not at 24 degrees C or 37 degrees C. Pepsin digestion or reduction and alkylation of chromatographically pure IgM CA abolished completely their inhibitory activity. Thus, in physiological temperatures, monoclonal IgM cold agglutinins impair various phagocytic functions of human phagocytes. It may add to the susceptibility to infections in patients in which such autoantibodies are synthesized.


Diastolic blood pressure as a determinant of Doppler left ventricular filling indexes in normotensive adolescents.
Alterations in left ventricular filling can occur with aging and in patients with hypertension, ischemic heart disease, congestive and hypertrophic cardiomyopathy and congenital heart disease. This study examines the effects of blood pressure on left ventricular diastolic filling indexes measured by Doppler ultrasound technique in 47 young normotensive adolescents (mean age 13 years). Left ventricular filling was assessed by Doppler peak early and late diastolic transmitral flow velocities, early and late diastolic flow velocity integrals and early diastolic deceleration. Systolic blood pressure did not correlate with any of the Doppler filling indexes, although it was related to echocardiographic left ventricular mass (r = 0.44, p less than 0.005). Diastolic blood pressure did not correlate with left ventricular mass; however, it was inversely related to peak early diastolic flow velocity (r = -0.44, p less than 0.005), early diastolic flow velocity integral (r = -0.40, p less than 0.01) and early diastolic deceleration (r = -0.32, p less than 0.05). The ratio of late to early peak filling (A/E) was directly related to diastolic blood pressure (r = 0.48, p less than 0.001). Examination of electrocardiograms showed that there was a stronger correlation between A/E ratio and diastolic blood pressure (r = 0.63) in 22 subjects with bimodal P waves in lead V1 than in subjects with unimodal P waves (r = 0.45).(ABSTRACT TRUNCATED AT 250 WORDS)


Some bonding characteristics of a HEMA/maleic acid adhesion promoter.
A recently released dentine adhesion promoter, based on a HEMA/maleic acid primer, was found to bond exceptionally well to dentine (14.1 MPa) if the adhesion promoter layer was applied thickly enough. Air inhibition of the promoter layer during its initial cure was seen to reduce the bond strength by a half if the promoter layer was air-thinned prior to curing. The adhesion promoter was found to greatly enhance the bond strength of composite to glass ionomer, removing the necessity to acid etch the glass ionomer prior to applying the composite. The failure of the composite/glass ionomer bond was always within the glass-ionomer cement itself, with the higher bond strengths resulting in a greater incidence of oblique cracks at 45 degrees to the bond surface than had been previously observed.


Induction of experimental epidermolysis bullosa acquisita by immunization with murine collagen VII.
Epidermolysis bullosa acquisita (EBA) is an autoimmune subepidermal blistering disease caused by an autoreactive response against collagen VII, the major constituent of the anchoring fibrils at the epidermal basement membrane. The pathogenic relevance of collagen VII-specific autoantibodies has been conclusively demonstrated ex vivo and in experimental animals using antibody passive transfer models. To study the mechanisms of autoantibody production and tissue damage an animal model reproducing both the autoimmune response and the active skin disease is needed. In the present protocol, we describe the induction of an autoimmune response and active disease by immunizing mice with recombinant murine collagen VII and the analysis of the induced disease phenotype. The humoral and cellular immune response elicited in mice by immunization with the autoantigen, as well as the induced skin pathology replicate the features of the human disease at the clinical, histo- and immunopathological levels. Thus, this model is an excellent tool for investigating the mechanisms underlying pathogenic autoantibody production, the autoantibody-mediated tissue injury, and for the development of more effective therapeutic strategies in autoimmune diseases.


Efavirenz and 8-hydroxyefavirenz induce cell death via a JNK- and BimEL-dependent mechanism in primary human hepatocytes.
Chronic use of efavirenz (EFV) has been linked to incidences of hepatotoxicity in patients receiving EFV to treat HIV-1. While recent studies have demonstrated that EFV stimulates hepatic cell death a role for the metabolites of efavirenz in this process has yet to be examined. In the present study, incubation of primary human hepatocytes with synthetic 8-hydroxyEFV (8-OHEFV), which is the primary metabolite of EFV, resulted in cell death, caspase-3 activation and reactive oxygen species formation. The metabolite exerted these effects at earlier time points and using lower concentrations than were required for the parent compound. In addition, pharmacological inhibition of cytochrome P450-dependent metabolism of EFV using 1-aminobenzotriazole markedly decreased reactive oxygen species formation and cell death. Treatment of primary human hepatocytes with EFV and 8-OHEFV also stimulated phosphorylation of c-Jun N-terminal kinase (JNK) as well as phosphorylation of the JNK substrate c-Jun. Further, the mRNA and protein expression of an isoform of Bim (Bcl-2 interacting mediator of cell death) denoted as BimEL, which is proapoptotic and has been shown to be modulated by JNK, was increased. Inhibition of JNK using SP600125 prevented the EFV- and 8-OHEFV-mediated cell death. Silencing of Bim using siRNA transfected into hepatocytes also prevented cell death resulting from 8-OHEFV-treatment. These data suggest that the oxidative metabolite 8-OHEFV is a more potent inducer of hepatic cell death than the parent compound EFV. Further, activation of the JNK signaling pathway and BimEL mRNA expression appear to be required for EFV- and 8-OHEFV-mediated hepatocyte death.


[Clinical and diagnostic value of heart rate variabilities in workers exposed to noise and vibration].
Noise and vibration cause disorders of vegetative regulation of cardiovascular system. Daily ECG monitoring with heart rate variabilities analysis enables quanitative evaluation of disordered vegetative control over heart rate and diagnosis of cardioneuropathy caused by long occupational exposure to noise and vibration.


Theodor Meynert: foreshadowing modern concepts of neuropsychiatric pathophysiology.
Theodor Meynert's neuroanatomic studies contributed to the development of the nineteenth-century "brain psychiatry" movement. His speculations--that certain cognitive impairments resulted from an imbalance in blood flow between cortical and subcortical structures--parallel modern controversies concerning the role of these brain regions in the pathophysiology of dementia. Meynert described a subcortical nucleus in the basal forebrain, the nucleus basalis of Meynert, which has recently been shown to provide cholinergic innervation to the cortex. Loss of cells in this structure in Alzheimer's disease, a so-called "cortical" dementia, and in the dementia of Parkinson's disease, a so-called "subcortical" dementia, probably accounts for the loss of cortical cholinergic markers in these diseases. An understanding of Meynert's contributions may avoid unproductive speculation in attempts to study the interactions between cortical and subcortical structures in neuropsychiatric diseases.


Atorvastatin Inhibits Ferroptosis of H9C2 Cells by regulatingSMAD7/Hepcidin Expression to Improve Ischemia-Reperfusion Injury.
Ferroptosis plays a key role in cardiomyopathy. Atorvastatin (ATV) has a protective effect on ischemia-reperfusion (I/R) cardiomyopathy. The purpose of this study is to elucidate the mechanism of ATV in I/R injury. H9C2 cells and cardiomyopathy rats were induced by hypoxia/reoxygenation (H/R) and I/R to construct in vitro and in vivo models. Cell viability was determined by CCK8. Cardiac histopathology was observed by HE staining. Transmission electron microscope (TEM) was used to observe the mitochondrial morphology. The reactive oxygen species (ROS) content in cells was analyzed by the biochemical method. ELISA was conducted to calculate the concentrations of total iron/Fe2+ and hepcidin. The expression of ferroptosis and SMAD pathway-related genes were detected by qPCR. Western blot was performed to detect the expression levels of ferroptosis and SMAD pathway-related proteins. In H9C2 cells, ATV reversed the decline in cell viability, mitochondrial shrinkage, and ROS elevation induced by erastin or H/R. The concentration of total iron and Fe2+ in H/R-induced H9C2 cells increased, and the protein expression of FPN1 decreased. After ATV treatment, the concentration of total iron and Fe2+ decreased, and the protein expression of FPN1 increased. The expression of the SMAD7 gene in H/R-induced H9C2 cells decreased, and the expression of the hepcidin gene increased, which were reversed by ATV. When SMAD7 was knocked down, ATV treatment failed to produce the above effect. ATV also improved ferroptosis in I/R rat myocardium through the SMAD7/hepcidin pathway. ATV reversed the decline in H9C2 cell viability, mitochondrial shrinkage, and ROS elevation, and improved the myocardium ferroptosis through the SMAD7/hepcidin pathway in I/R rat.


Correlation of in situ detection of infectious agents in the placenta with neonatal outcome.
To determine if infections involving the placenta are associated with unexplained systemic illness in the newborn infant and subsequent poor neonatal outcome (death or significant neurodevelopmental abnormalities). Placental tissue from 33 newborn infants with systemic illness and poor neonatal outcome were tested by in situ hybridization or reverse transcriptase-polymerase chain reaction for infectious pathogens. Control placentas came from mothers delivering infants with poor neonatal outcome of known cause (ie, cord prolapse, uterine rupture), mothers with known infections, and normal births (n=21). There were 5 deaths among the newborn infants, and all survivors had poor neonatal outcome. Placentas from 24 of 33 cases (73%) had positive test results for Coxsackie virus (46%), bacteria (38%), herpes (8%), and parvovirus (4%) and picornavirus (4%). At autopsy, multiple organs from the newborn infant had positive test results for the same organism isolated from the placenta. No infectious agents were detected in the control infants, except those from mothers with known infections. In utero infection of the placenta is associated with systemic illness in the newborn infant and poor neonatal outcome. These results emphasize the importance of pathologic and molecular examination of the placenta in critically ill newborn infants.


Molecular cloning of cellular apoptosis susceptibility (CAS) gene in Oreochromis niloticus and its proposed role in regulation of non-specific cytotoxic cell (NCC) functions.
Cellular apoptosis susceptibility (CAS) gene is a homologue of the chromosome segregation gene (CSE) in yeast, involved in multiple cellular mechanisms associated with cell proliferation as well as cell death. CAS is highly expressed in proliferating cells but at a lower level in quiescent cells and tissues. Therefore it appears that CAS may play an important role in cancer development. We have previously identified CAS in tilapia non-specific cytotoxic cells (NCC) with a cross-reacting monoclonal antibody. Its expression was up-regulated in NCC in response to apoptosis regulatory factors. In the present report, the molecular cloning and expression of CAS in NCC is described, suggesting the importance of this protein in regulation of teleost immune functions. Furthermore, CAS expression is proposed as one of the mechanisms of regulation of activation induced programmed cell death (AIPCD) in these cytotoxic cells. As CAS expression is ubiquitous, we expect that these studies will help identify proliferating cells protected from apoptosis in additional tissues.


Quantitative phase contrast optimised cancerous cell differentiation via ptychography.
This paper shows that visible-light ptychography can be used to distinguish quantitatively between healthy and tumorous unstained cells. Advantages of ptychography in comparison to conventional phase-sensitive imaging techniques are highlighted. A novel procedure to automatically refocus ptychographic reconstructions is also presented, which improves quantitative analysis.


Hyperactivity. Overview and new directions.
An enormous number of articles have been published in recent years on this most researched and best known of the childhood behavior disorders. This article discusses the syndrome of hyperactivity in terms of postdictive, concurrent, and predictive validity. Future research is considered and follow-up studies are reviewed.


Cimetidine modulates the antigen presenting capacity of dendritic cells from colorectal cancer patients.
Cimetidine, a H(2) receptor antagonist, has been reported to improve survival in gastrointestinal cancer patients. These effects have largely been attributed to the enhancing effects of cimetidine on the host's antitumour cell-mediated immune response, such as inhibition of suppressor T lymphocyte activity, stimulation of natural killer cell activity and increase of interleukin-2 production from helper T lymphocytes. We conducted an in vitro study on the effects of cimetidine on differentiation and antigen presenting capacity of monocyte-derived dendritic cells from advanced colorectal cancer patients and normal controls. As a result, an investigation of expression of surface molecules associated with dendritic cells by flow cytometric analyses showed that cimetidine had no enhancing effect on differentiation of dendritic cells from cancer patients and normal controls. An investigation of [(3)H]thymidine incorporation by allogeneic mixed lymphocyte reactions revealed that cimetidine increased the antigen presenting capacity of dendritic cells from both materials. Moreover, a higher antigen presenting capacity was observed in advanced cancer patients compared to normal controls. These effects might be mediated via specific action of cimetidine and not via H(2) receptors because famotidine did not show similar effects. Our results suggest that cimetidine may enhance the host's antitumour cell-mediated immunity by improving the suppressed dendritic cells function of advanced cancer patients.


The FMO2 analysis of the ligand-receptor binding energy: the Biscarbene-Gold(I)/DNA G-Quadruplex case study.
In this work, the ab initio fragment molecular orbital (FMO) method was applied to calculate and analyze the binding energy of two biscarbene-Au(I) derivatives, [Au(9-methylcaffein-8-ylidene)2]+ and [Au(1,3-dimethylbenzimidazol-2-ylidene)2]+, to the DNA G-Quadruplex structure. The FMO2 binding energy considers the ligand-receptor complex as well as the isolated forms of energy-minimum state of ligand and receptor, providing a better description of ligand-receptor affinity compared with simple pair interaction energies (PIE). Our results highlight important features of the binding process of biscarbene-Au(I) derivatives to DNA G-Quadruplex, indicating that the total deformation-polarization energy and desolvation penalty of the ligands are the main terms destabilizing the binding. The pair interaction energy decomposition analysis (PIEDA) between ligand and nucleobases suggest that the main interaction terms are electrostatic and charge-transfer energies supporting the hypothesis that Au(I) ion can be involved in π-cation interactions further stabilizing the ligand-receptor complex. Moreover, the presence of polar groups on the carbene ring, as C = O, can improve the charge-transfer interaction with K+ ion. These findings can be employed to design new powerful biscarbene-Au(I) DNA-G quadruplex binders as promising anticancer drugs. The procedure described in this work can be applied to investigate any ligand-receptor system and is particularly useful when the binding process is strongly characterized by polarization, charge-transfer and dispersion interactions, properly evaluated by ab initio methods.


Synthesis, dielectric, magnetic, and photoluminescence properties of two new hybrid rare-earth double perovskites.
Two new organic-inorganic hybrid double perovskites (R3HQ)4CsSm(NO3)8 (1) (R3HQ = (R)-(-)-3-quinuclidinol) and (R3HQ)4CsEu(NO3)8 (2) were synthesized and characterized. Compounds 1 and 2 exhibit obvious phase transitions at 379 and 375 K, respectively, confirmed by differential scanning calorimetry (DSC) and variable temperature powder X-ray diffraction. The rapid switching between high- and low-dielectric states makes it a typical dielectric material with a switchable dielectric constant for thermal stimulus response. Furthermore, 1 and 2 show attractive photoluminescence and paramagnetic behavior, and the fluorescence quantum yield of 2 reached 14.6%. These results show that compounds 1 and 2 can be used as excellent candidates for multifunctional intelligent materials, which also provides a new way for development of multifunctional materials.


Low adiponectin levels in primary hypertriglyceridemic male patients.
Adiponectin is an adipokine highly and specifically expressed by adipose cells with antiatherogenic and antiinflammatory activities. The aim of the present study was to evaluate plasma adiponectin concentration in patients with primary hypertriglyceridemia and its relationship with metabolic parameters. Male patients with primary hypertriglyceridemia and without the metabolic syndrome (n=22) were compared with normotriglyceridemic individuals (n=25). Plasma adiponectin concentration was measured by standardised enzyme-linked immunosorbent assay. Body mass index, waist circumference, glucose, insulin and non-esterified fatty acid levels, lipoprotein profile, and CETP activity were evaluated. Adiponectin levels were significantly decreased in hypertriglyceridemic patients in comparison with normotriglyceridemic subjects (4292+/-1717 vs. 6939+/-3249 ng/ml, p<0.005, respectively). Adiponectin was negatively associated with glucose (r=-0.44, p<0.01), insulin (r=-0.37, p<0.01), HOMA (r=-0.40, p<0.01), triglycerides (r=-0.36, p<0.01), VLDL-C (r=-0.34, p<0.05), and CETP (r=-0.47, p<0.001). Positive and significant correlations were observed with QUICKI (r=0.49, p<0.001) and HDL-C (r=0.33, p<0.05). In the multiple linear regression analysis, considering waist circumference, QUICKI, Log-triglycerides, HDL-C, and CETP as independent variables, Log-adiponectin showed a positive correlation with QUICKI, with an r(2)=0.229 and p<0.001. Therefore, the independent variable QUICKI explained the 23% of the variance in Log-adiponectin concentration. We found low adiponectin levels in a population of primary hypertriglyceridemic men without the metabolic syndrome and an independent relationship between adiponectin concentration and insulin resistance. A reduction in insulin sensitivity and its impact on adiponectin concentration could be linked to high non-esterified fatty acid levels, increased triglyceride synthesis in the liver and impaired catabolism of triglyceride-rich lipoproteins.


Metal-organic framework interface engineering for highly efficient oxygen evolution reaction.
Metal-organic frameworks (MOFs) with intrinsically porous structures and well-dispersed metal sites are promising candidates for the oxygen evolution reaction (OER). However, the practical applications of MOFs for OER are significantly constrained due to their poor charge transfer property and insufficient inherent activity. Herein, we utilized caffeic acid as a bridging agent to covalently bond FeNi-MOF with NiMoO4 in order to tune the charge transfer properties for efficient OER. The optimized organic-inorganic heterocatalyst demonstrates superior OER performance with a low overpotential of 256 mV at a current density of 10 mA cm-2 and long-term stability, outperforming the benchmark IrO2 catalyst and single counterparts. Both experimental and theoretical results indicate that electrons can be transferred from FeNi-MOF to NiMoO4 via a caffeic acid bridging agent, which improves not only the electrical conductivity but also the adsorption capacity of OH- intermediates on MOFs. Therefore, the enhanced OER activity of the heterocatalyst is attributed to the synergistic effects of the multi-components. This study paves the way for the rational design of MOFs-based heterostructures towards efficient electrocatalytic oxygen evolution.


A peptide isolated from a random phage peptide library is a structural mimic to the P1, P4-diadenosine 5'-tetraphosphate binding site on its receptor.
We have previously demonstrated that a monoclonal antibody (mAb TL4), which inhibits P1, P4-diadenosine 5'-tetraphosphate (Ap4A) binding to its receptor, selected a consensus RGS tripeptide from a random phage hexapeptide library. RGS interfered with Ap4A binding to its membrane receptor [Liu, G., Bryant, R. T. & Hilderman, R. H. (1996) Biochemistry 35, 197-201]. However the mechanism by which RGS interfered with Ap4A binding to its receptor was not determined. In this communication, we demonstrate that RGS interacts with Ap4A to prevent [3H]Ap4A binding to the Ap4A membrane receptor. To further characterize the mechanism by which RGS inhibits Ap4A binding to its receptor, we used mAb TL4 to screen a 15-residue random peptide phage library and DNAs from 24 clones were sequenced. 20 clones contain a RGSSS sequence while 17 of these clones contained an identical 15-amino-acid insert (clone A). Gel-filtration studies of previously equilibrated clone A phage and [3H]Ap4A support the idea that [3H]Ap4A interacts specifically with clone A phage while RGS effectively competes for [3H]Ap4A interaction on clone A phage. These data are consistent with RGS mimicking a sequence on the receptor essential for Ap4A binding.


Mice genetically inactivated in interleukin-17A receptor are defective in long-term control of Mycobacterium tuberculosis infection.
Interleukin-17A (IL-17A), a pro-inflammatory cytokine acting on neutrophil recruitment, is known to play an important role during Mycobacterium tuberculosis infection, but the role of IL-17A receptor signalling in immune defence against this intracellular pathogen remains poorly documented. Here we have analysed this signalling using C57BL/6 mice genetically inactivated in the IL-17 receptor A subunit (IL-17RA(-/-) ). Although early after infection bacterial growth was controlled to the same extent as in wild-type mice, IL-17RA(-/-) mice were defective in exerting long-term control of M. tuberculosis infection, as demonstrated by a progressively increasing pulmonary bacterial burden and shortened survival time. Compared with infected wild-type mice, IL-17RA(-/-) mice showed impaired recruitment of neutrophils to the lungs at the early but not the late stage of infection. Pulmonary tumour necrosis factor-α, IL-6 and particularly IL-10 levels were decreased in the absence of IL-17RA signalling, whereas IL-1β was increased. CD4(+) -mediated and γδ-mediated IL-17A production was dramatically increased in IL-17RA(-/-) mice (confirming part of their phenotype), whereas production of interferon-γ and expression of the bactericidal enzyme inducible nitric oxide synthase were not affected. Collectively, our data suggest that early but not late neutrophil recruitment is essential for IL-17A-mediated long-term control of M. tuberculosis infection and that a functional interferon-γ response is not sufficient to control M. tuberculosis growth when the IL-17RA pathway is deficient. As treatment of auto-immune diseases with anti-IL-17A antibodies is actually being tested in clinical studies, our data suggest that caution should be taken with respect to possible reactivation of tuberculosis.


Optimizing dietary lipid use to improve essential fatty acid status and reproductive performance of the modern lactating sow: a review.
Dietary lipid supplementation benefits the prolific and high-producing modern lactating sow. A comprehensive review of recent studies showed that lipid supplementation increases average daily energy intake, which is partitioned for lactation as indicated by greater milk fat output and improved litter growth rate. Recent compelling findings showed that addition of particular lipids during lactation improved the subsequent reproductive outcome of sows. Such benefits were related to the level of dietary essential fatty acids (EFA, linoleic acid, C18:2n-6; and α-linolenic acid, C18:3n-3) during lactation. Lactation diets without supplemental EFA resulted in a pronounced negative balance (intake minus milk output) of linoleic (-25.49 g/d) and α-linolenic acid (-2.75 g/d); which compromised sow fertility (farrowing rate < 75 % and culling rates > 25 % of weaned sows). This phenomenon seems to be increasingly important with advancing sow age because of a progressive reduction of body EFA pool over successive lactations. The net effect of supplemental EFA during lactation was to create a positive EFA balance, which improved the subsequent reproduction of sows. Adequate linoleic acid intake improved the proportion of sows that farrowed in the subsequent cycle (Farrowing rate (%) = [(-1.5 × 10(-3) × linoleic acid intake (g/d)(2)) + (0.53 × linoleic acid intake (g/d)) + (45.2)]; quadratic P = 0.002, R(2) = 0.997, RMSE = 0.031). In addition, increasing linoleic acid intake increased the number of pigs born in the subsequent cycle (total pigs born (n) = [(9.4 × 10(-5) × linoleic acid intake (g/d)(2)) + (0.04 × linoleic acid intake (g/d)) + (10.94)]; quadratic P = 0.002, R(2) = 0.997, RMSE = 0.031). Supplemental α-linolenic acid resulted in a rapid return to estrus (sows bred: sows weaned = 94.2 %; wean-to-estrus interval = 4.0 d) and achieved a high retention of pregnancy (sows pregnant: sows bred = 98 %). Collectively, we conclude that a minimum dietary intake of 10 g/d of α-linolenic acid, simultaneous with a minimum of 125 g/d of linoleic acid should be provided to ≥ 95 % of the sows; thereby, achieving a maximum sow reproductive efficiency through multiple mechanisms that include rapid return to estrus, high maintenance of pregnancy and large subsequent litter size in mature sows, that appear to be susceptible to EFA deficiency.


The Effects of N Enrichment on Microbial Cycling of Non-CO2 Greenhouse Gases in Soils-a Review and a Meta-analysis.
Terrestrial ecosystems are typically nitrogen (N) limited, but recent years have witnessed N enrichment in various soil ecosystems caused by human activities such as fossil fuel combustion and fertilizer application. This enrichment may alter microbial processes in soils in a way that would increase the emissions of methane (CH4) and nitrous oxide (N2O), thereby aggravating global climate change. This review focuses on the effects of N enrichment on methanogens and methanotrophs, which play a central role in the dynamics of CH4 at the global scale. We also address the effects of N enrichment on N2O, which is produced in soils mainly by nitrification and denitrification. Overall, N enrichment inhibits methanogenesis in pure culture experiments, while its effects on CH4 oxidation are more complicated. The majority of previous studies reported that N enrichment, especially NH4+ enrichment, inhibits CH4 oxidation, resulting in higher CH4 emissions from soils. However, both activation and neutral responses have also been reported, particularly in rice paddies and landfill sites, which is well reflected in our meta-analysis. In contrast, N enrichment substantially increases N2O emission by both nitrification and denitrification, which increases proportionally to the amount of N amended. Future studies should address the effects of N enrichment on the active microbes of those functional groups at multiple scales along with parameterization of microbial communities for the application to climate models at the global scale.


Fundamentality from grounding trees.
I provide and defend two natural accounts of (both relative and absolute) fundamentality for facts that do justice to the idea that the "degree of fundamentality" enjoyed by a fact is a matter of how far, from a ground-theoretic perspective, the fact is from the ungrounded facts.


Derepression of a neuronal inhibitor due to miRNA dysregulation in a schizophrenia-related microdeletion.
22q11.2 microdeletions result in specific cognitive deficits and schizophrenia. Analysis of Df(16)A(+/-) mice, which model this microdeletion, revealed abnormalities in the formation of neuronal dendrites and spines, as well as altered brain microRNAs. Here, we show a drastic reduction of miR-185, which resides within the 22q11.2 locus, to levels more than expected by a hemizygous deletion, and we demonstrate that this reduction alters dendritic and spine development. miR-185 represses, through an evolutionarily conserved target site, a previously unknown inhibitor of these processes that resides in the Golgi apparatus and shows higher prenatal brain expression. Sustained derepression of this inhibitor after birth represents the most robust transcriptional disturbance in the brains of Df(16)A(+/-) mice and results in structural alterations in the hippocampus. Reduction of miR-185 also has milder age- and region-specific effects on the expression of some Golgi-related genes. Our findings illuminate the contribution of microRNAs in psychiatric disorders and cognitive dysfunction.


Transitioning intravenous epoprostenol to oral selexipag in idiopathic pulmonary arterial hypertension: a case report.
Intravenous (i.v.) prostacyclin is the cornerstone treatment in high-risk pulmonary arterial hypertension (PAH) patients. Selexipag is an orally available prostacyclin receptor agonist. Limited data are available regarding the feasibility of transitioning from i.v. epoprostenol to selexipag. A 50-year-old woman with idiopathic PAH was diagnosed in a World Health Organization (WHO) Functional Class (FC) IV. She improved with upfront triple combination therapy, including i.v. epoprostenol. Over 2 years of follow-up, the patient remained at low risk and expressed strong preference towards oral therapies. After careful risk-benefit clinical consideration, she was transitioned from i.v. epoprostenol to selexipag. Selexipag was started at dosage of 200 μg twice daily (b.i.d.) and titrated up to 1600 μg b.i.d. over 8 weeks (up-titration of 200 μg b.i.d. every week). Simultaneously, i.v. epoprostenol was down-titrated 3.0 ng/kg/min every week from a dosage of 27.5 ng/kg/min. The transition occurred under strict medical surveillance and was well tolerated. One year after discontinuation of epoprostenol, the patient remains in WHO FC I and has no signs of clinical deterioration. Although not generalizable to most PAH patients, this case highlights that a carefully planned transition from epoprostenol to selexipag is feasible in selected low-risk patients within a shared medical decision-making framework.


Pregnancy rates following the exclusive transfer of twice frozen twice thawed embryos using a modified slow cool cryopreservation technique.
To determine the pregnancy rate following the exclusive transfer of twice frozen twice thawed embryos. All day 3 transfers of exclusive twice frozen-twice thawed embryos were retrospectively identified over a 13-year time-period. The cryopreservation technique used a simplified slow cool freezing protocol. Embryos could have been originally cryopreserved at the 2 pronuclear or multi-cell stage. Survival rates were 83.3%. The live delivered pregnancy rate was 18.1% (15/83). The implantation rate was 13.1% (22/168). These data suggest that twice frozen twice thawed embryos should not be discarded but either transferred alone if they are the only embryos left, or mixed with frozen embryos that have never been thawed. Though the live delivered pregnancy rates are inferior to fresh embryo transfer the marked reduction in cost and avoidance of the risk of ovarian hyperstimulation justifies their transfer.


Determination of ganciclovir in human plasma by ultra performance liquid chromatography-UV detection.
Implement a sensitive UHPLC method for the assay of ganciclovir in human plasma. We developed and validated a chromatographic method coupled to ultraviolet detection for quantification of ganciclovir, with a short run time using a small volume of human plasma. Comparison of system performance was made with respect to analysis time, efficiency and sensitivity. Correlation coefficients (r) of the calibration curves ranged from 0.999744 to 0.999784. Within-day and between-day imprecision and inaccuracy, specificity and recovery were also evaluated for validation. The method was precise and accurate and the retention time was 0.7 min. The calibration curves were linear between 0.5 and 30 μg/mL. There was a good correlation between HPLC and UHPLC techniques. We developed a method that is currently applied in a clinical study assessing GCV plasma concentration variability after ganciclovir and valganciclovir administration.


Susceptibility of triticale cultivars to grain fusariosis.
The infestation of triticale grains by Fusaria and responses of four cultivars on artifical infection of three Fusarium species were studied. Mycelium penetration through kernel tissues and its presence in embryo and endosperm were found. In inoculated spikes reduction of grains number and weight in relation to the control was noted. The most resistant triticale cultivar appeared to be Grado and the most susceptible - Salvo.


No effect of a levodopa single dose on motor performance and motor excitability in chronic stroke. A double-blind placebo-controlled cross-over pilot study.
Drugs that modulate neuronal transmission can influence motor recovery after stroke. Here, we tested if a single dose of levodopa could improve motor functions and change motor excitability in a group of chronic stroke patients. Ten patients > 6 months after their stroke participated in a placebo-controlled double-blind trial. On two different occasions, they received either 100 mg levodopa or placebo in a randomized order. After drug intake, they participated in one hour of physiotherapy aimed at an improvement of dexterity. Motor functions were tested by application of the Nine-Hole-Peg Test, a dynamometer measuring grip strength and the Action Research Arm Test. In addition, transcranial magnetic stimulation (TMS) was applied to study intracortical excitability, stimulus response curves and silent periods. TMS studies and motor function measurements were performed before drug intake, 45 minutes after drug ingestion and after the physiotherapy. Compared to placebo, levodopa neither improved motor functions nor changed motor excitability as tested by TMS. These findings suggests that a single levodopa dose is not sufficient to improve motor function in chronic stroke. However, it cannot be excluded that the lack of a beneficial effect is related to the small study sample.


Fourier transform infrared study on the thermotropic behaviour of fully hydrated 1-palmitoyl-2-[10-(pyren-1-y) decanoyl]-sn-glycero-3-phosphatidylcholine.
Fourier transform infrared (FTIR) spectroscopy was used to study the thermotropic behaviour of fully hydrated 1-palmitoyl-2-[10-(pyren-1-yl)-decanoyl]-sn-glycero-3-phosphatidyl choline (PPDPC) in the temperature range of 3-30 degrees C. Several changes in the spectral features of PPDPC were observed. Major alterations analogous to the gel-to-liquid crystalline phase transition of saturated phosphatidylcholines were evident at approximately 16 degrees C in both the wavenumbers and the halfbandwidths of five different vibrational modes of PPDPC, viz. asymmetric and symmetric CH2 stretching, C = O stretching, and CH2 bending. Also the pyrene ring deformation mode changed at this temperature. Using Fourier self-deconvolution technique we resolved the carbonyl stretching mode into two bands at approx. 1741 and 1726 cm-1. These bands are due to conformational differences in the ester linkages of the two acyl chains, and are further assigned on the basis of literature data to the sn-1 and sn-2 carbonyl groups, respectively. The ratio of the relative intensities of these two bands is shown to depend on the phase state of the phospholipid.


Online ANN-based fault diagnosis implementation using an FPGA: Application in the EFI system of a vehicle.
In this research, fault detection and diagnosis (FDD) scheme for isolating the damaged injector of an internal combustion engine is formulated and experimentally applied. The FDD scheme is based on a temporal analysis (statistical methods), as well as in a frequency analysis (fast Fourier transform) of the fuel rail pressure. The arrangement of the scheme consists of three coupled artificial neural networks (ANNs) to classify the faulty injector correctly. The ANNs were trained considering five different scenarios, one scenario without fault in the injection system, and the other four scenarios represent a fault per injector (1 to 4). The Levenberg-Marquardt (LM), BFGS quasi-Newton, gradient descent (GD), and extreme learning machine (ELM) algorithms were tested to select the best training algorithm to classify the faults. Experimental results obtained from the implementation in a VW four-cylinder CBU 2.5L vehicle in idle operating conditions (800 rpm) show the effectiveness of the proposed FDD scheme.


Rare case of metastatic prostate adenocarcinoma to the pituitary.
We report a rare case of metastatic prostate adenocarcinoma to the pituitary gland. The patient had lung and bone metastases when he presented with bitemporal hemianopsia. He was also receiving total androgen blockade at that time. Magnetic resonance imaging showed an intrasellar mass, and biopsy confirmed metastatic prostate cancer. Radiotherapy, in the form of intensity-modulated radiotherapy, was delivered to the intrasellar mass. The patient responded well to radiotherapy. The mechanisms of spread to the pituitary gland and treatment options, including intensity-modulated radiotherapy, are discussed.


Stomatal closure with soil water depletion not associated with changes in Bulk leaf water status.
It has previously been reported that canopy water loss by cowpea (Vigna unguiculata) decreases with small depletions in soil water. In these studies, under field conditions, it was demonstrated that with small changes in soil water status leaf conductance of cowpea decreases in a manner which is consistent with the sensitive regulation of canopy water loss.However, treatments which differed in leaf conductance, and presumably stomatal aperture, had similar leaf water potentials. It is hypothesized that the stomatal closure which results from soil water depletion is mediated by changes in root water status through effects on the flow of information from root to shoot. An efficient mechanism of this type could be partially responsible for the extreme drought avoidance exhibited by this plant.


Optimized Immobilization of Biomolecules on Nonspherical Gold Nanostructures for Efficient Localized Surface Plasmon Resonance Biosensing.
Plasmonic biosensing techniques employ metal nanostructures, commonly gold (Au), often with biomolecules attached to their surfaces either directly or via other linkers. Various surface chemistry methods based on dispersion and covalent interactions are used to attach biomolecules to Au. As a result, when immobilizing a molecule on a metal surface, quantitative estimates of binding efficiency and stability of these surface chemistry methods are needed. Most prior work to compare such methods deals with bulk/thin film configurations or spherical nanoparticles, and very little is known about immobilization of biomolecules on plasmonic nanostructures of different shapes. Besides, due to rapid advancement of modern nanofabrication techniques, there is a growing need to determine an efficient surface chemistry method for immobilization of biomolecules on nonspherical plasmonic nanostructures. Previous comparison of immobilization methods on spherical Au nanoparticles has shown that physical adsorption resulted in the highest concentration of immobilized antibodies. In our work, we conducted a similar study and compared four representative Au surface functionalization methods as well as estimated how efficient these methods are at attaching biomolecules to nonspherical plasmonic Au nanostructures. We estimated the concentration of immobilized antibody that is specific to human C-reactive protein (anti-hCRP) by measuring the localized surface plasmon resonance (LSPR) shifts after exposing the surface of Au nanostructures to the antibody. Our results differ from the previously reported ones since the highest concentration of anti-hCRP was immobilized using 11-mercaptoundecanoic acid (MUA) chemistry. We demonstrated that immobilized antibodies retained their stability and specificity toward hCRP throughout the immunoassay when diluted hCRP or hCRP-spiked human serum samples were used. These findings have important implications for the fields of biosensing and diagnostics that employ nonspherical plasmonic nanostructures since an overall performance of these devices depends on efficient biomolecule immobilization.


Reknitting the injured spinal cord by self-assembling peptide nanofiber scaffold.
In traumatic spinal cord injury, loss of neurological function is due to the inability of damaged axons to regenerate across large, cystic cavities. It has recently been demonstrated that a self-assembled nanofiber scaffold (SAPNS) could repair the injured optical pathway and restore visual function. To demonstrate the possibility of using it to repair spinal cord injury, transplanted neural progenitor cells and Schwann cells were isolated from green fluorescent protein-transgenic rats, cultured within SAPNS, and then transplanted into the transected dorsal column of spinal cord of rats. Here we report the use of SAPNS to bridge the injured spinal cord of rats, demonstrating robust migration of host cells, growth of blood vessels, and axons into the scaffolds, indicating that SAPNS provides a true three-dimensional environment for the migration of living cells.


Deciphering and advancing CAR T-cell therapy with single-cell sequencing technologies.
Chimeric antigen receptor (CAR) T-cell therapy has made remarkable progress in cancer immunotherapy, but several challenges with unclear mechanisms hinder its wide clinical application. Single-cell sequencing technologies, with the powerful unbiased analysis of cellular heterogeneity and molecular patterns at unprecedented resolution, have greatly advanced our understanding of immunology and oncology. In this review, we summarize the recent applications of single-cell sequencing technologies in CAR T-cell therapy, including the biological characteristics, the latest mechanisms of clinical response and adverse events, promising strategies that contribute to the development of CAR T-cell therapy and CAR target selection. Generally, we propose a multi-omics research mode to guide potential future research on CAR T-cell therapy.


Application of capillary electrophoresis-mass spectrometry for the investigation of the binding behavior of oxaliplatin to 5'-GMP in the presence of the sulfur-containing amino acid L-methionine.
Capillary electrophoresis-electrospray ionization-mass spectrometry (CE-ESI-MS) has been used for investigating the influence of the sulfur containing amino acid L-methionine (L-Met) on the binding behavior of oxaliplatin (trans-R,R-diaminocyclohexane-(oxalato)platinum(II)) to 5'-GMP. L-Methionine competes with 5'-GMP for the platinum binding site and forms as well as 5'-GMP adducts with oxaliplatin. The formation of the prognosed complexes [Pt(DACH)(L-Met-S,N)]+ and [Pt(DACH)(5'-GMP)2]2- (DACH = 1,2-diaminocyclohexane) could be proved directly by using CE-ESI-MS. Furthermore, we could now bring forward proofs, that the coordination of 5'-GMP with oxaliplatin is inhibited by L-methionine and could show, that the 5'-GMP ligands of the [Pt(DACH) (5'-GMP)2]2- complex can be replaced slowly by L-methionine whereas methionine can not be replaced by GMP.


A three-year evaluation of metabolic changes in Singaporean Norplant acceptors.
In a longitudinal study involving 100 Singaporean women, the effect of NorplantR on metabolic function was evaluated. With respect to liver function, the results indicate possible hepatocellular dysfunction as evidenced by a significant rise in serum bilirubin and a significant fall in total proteins and globulin during the period under review. As regards lipid metabolism, total triglycerides and total cholesterol still remained significantly decreased at the end of the three years. The LDL, which was significantly decreased in the first year, increased during the subsequent two years to its preinsertion value at the end of three years. The HDL-cholesterol levels continued to decrease in the second and third year after a significant increase in the first year. Despite this, the HDL cholesterol/total cholesterol-HDL cholesterol remained above 0.200. As we have not incorporated a simultaneous non-pill treated control group, the observed changes in lipoprotein lipids could be attributed to extraneous factors such as diet, exercise, or other environmental changes. Nevertheless, the findings at the end of three years, though speculative, still appear to indicate Norplant use to be not directly contributory to cardiovascular risk. The use of Norplant was not associated with any significant effects on carbohydrate metabolism after three years of use.


Survival after minimally invasive radical hysterectomy without using uterine manipulator for early-stage cervical cancer: A systematic review and meta-analysis.
Minimally invasive radical hysterectomy has been reported to increase the risk of cancer relapse and death compared with open surgery in women with early-stage cervical cancer. The use of a uterine manipulator is considered one of the risk factors. To investigate whether women with early-stage cervical cancer treated with minimally invasive radical hysterectomy without using uterine manipulator have oncological outcomes similar to those of open surgery. Searches were performed in MEDLINE, Embase and CENTRAL from their inception until 31 March 2022. Inclusion criteria were: (1) randomised controlled trials or observational cohort studies published in English, (2) studies comparing minimally invasive radical hysterectomy without using a uterine manipulator with open radical hysterectomy in women with early-stage cervical cancer, and (3) studies comparing survival outcomes. Two authors independently conducted data extraction and assessed study quality. We calculated the hazard ratios (HR) and the 95% confidence intervals (CI) using the inverse variance approach for survival outcome. Six observational studies with 2150 women were included. The minimally invasive surgery group had a significantly higher risk of cancer relapse compared with open surgery group (HR 1.55, 95% CI 1.15-2.10). Minimally invasive radical hysterectomy without using a uterine manipulator resulted in an inferior recurrence-free survival compared with open radical hysterectomy in the treatment of women with early-stage cervical cancer.


Characterization of the estrogen receptor transfected MCF10A breast cell line 139B6.
There has been increasing evidence which suggests that abnormal expression of the estrogen receptor (ER) protein in nonmalignant breast tissue may be important in the carcinogenic process. To examine the effects of ER expression in immortalized nonmalignant mammary epithelial cells, an expression vector containing human ER cDNA was transfected into the ER negative human breast cells, MCF10A. Characterization of a clone stably expressing ER, 139B6, provided evidence for the regulated synthesis of a functional ER capable of binding estradiol-17 beta (E2) and undergoing processing. Expression of the ER gene did not enable E2 to stimulate endogenous genes [progesterone receptor (PgR), pS2, cathepsin D and TGF alpha] which normally respond to estrogens in breast cancer cells. The ER in 139B6 cells was, however, capable of inducing expression of an ERE-regulated reporter gene, indicating its ability to interact with transcriptional machinery. Furthermore, cultures in log growth displayed a slight increase in doubling time in the presence of E2. These results indicate that ER expression alone is not sufficient to induce a transformed phenotype. Thus, the 139B6 cell line should provide a new model for determining what additional changes lead to increased growth potential in response to E2 and for exploring how E2 itself may help bring about changes leading to progression of preneoplastic breast epithelial cells.


Enhancement of the conversion of toluene by Pseudomonas putida F-1 using organic cosolvents.
Pseudomonas putida F-1 (ATCC700007) was used as a model organism in stirred tank reactors to study conversion enhancement of poorly soluble substrates by organic cosolvents. After a literature study, silicone oil was used as a solvent system to enhance the mass transfer rate. To study the benefits of the organic solvent addition, batch experiments were conducted in two side-by-side fermentation vessels (experimental and control) at three different levels of silicone oil (10, 30, and 50%). Results showed that the presence of silicone oil resulted in a 100% increase in the toluene mass transfer compared to the control. Experiments in continuous stirred-tank reactors showed that improved conversion could be obtained at higher agitation rates.


Systematic review with meta-analysis: Branched-chain amino acid supplementation in liver disease.
Dietary supplementation with branched-chain amino acids (BCAA) is often used in cirrhotic patients to improve nutritional status. We wanted to explore the evidence for BCAA supplementation in chronic liver disease. We searched MEDLINE and EMBASE for studies with BCAA supplementation with the presence of a disease-control group (placebo or no intervention) using search terms 'liver cirrhosis', 'hepatocellular carcinoma', 'branched chain amino acids' and relevant synonyms. Risk of bias was assessed using ROBINS-I and RoB 2.0 tools. Meta-analyses were performed with a random-effects model. Results were reported following EQUATOR guidelines. Of 3378 studies screened by title and abstract, 54 were included (34 randomized controlled trials, 5 prospective case-control studies, 13 retrospective case-control studies: in total 2308 patients BCAA supplementation, 2876 disease-controls). Risk of bias was high/serious for almost all studies. According to meta-analyses, long-term (at least 6 months) BCAA supplementation in cirrhotic patients significantly improved event-free survival (p = .008; RR .61 95% CI .42-.88) and tended to improve overall survival (p = .05; RR .58 95% CI .34-1.00). Two retrospective studies suggested the beneficial effects during sorafenib for hepatocellular carcinoma. Available studies reported no beneficial effects or contradictory results of BCAA after other specific therapeutic interventions (resection or radiological interventions for hepatocellular carcinoma, liver transplantation, paracentesis or variceal ligation). No convincing beneficial effects of BCAA supplementation on liver function, nutritional status or quality of life were found. No study reported serious side effects of BCAA. Prophylactic BCAA supplementation appears safe and might improve survival in cirrhotic patients.


The Italian hub-and-spoke network for the emergency neurology management.
The aim of the present study was to assess emergency neurology management in Italy by comparing patients admitted to the hub and spoke hospitals. Data obtained from the annual Italian national survey (NEUDay) investigating the activity and facilities of neurology in the emergency room conducted in November 2021 were considered. Information for each patient who received a neurologic consultation after accessing the emergency room was acquired. Data on facilities were also gathered, including hospital classification (hub vs spoke), number of consultations, presence of neurology and stroke unit, number of beds, availability of neurologist, radiologist, neuroradiologist, and instrumental diagnostic accessibility. Overall, 1,111 patients were admitted to the emergency room and had neurological consultation across 153 facilities (out of the 260 Italian ones). Hub hospitals had significantly more beds, availability of neurological staff, and instrumental diagnostic accessibility. Patients admitted to hub hospital had a greater need for assistance (higher number of yellow/red codes at neurologist triage). A higher propensity to be admitted to hub centers for cerebrovascular problems and to receive a diagnosis of stroke was observed. The identification of hub and spoke hospitals is strongly characterized by the presence of beds and instrumentation mainly dedicated to acute cerebrovascular pathologies. Moreover, the similarity in the number and type of accesses between hub and spoke hospitals suggests the need to look for adequate identification of all the neurological pathologies requiring urgent treatment.


Probability of hospitalisation and death among COVID-19 patients with comorbidity during outbreaks occurring in Mexico City.
We compared the probability of hospitalization and death caused by COVID-19 in patients with comorbidities during three periods defined for this study: first-wave (FW), interwave period (IP), and second-wave (SW) observed in Mexico City. In this registry-based study, we included individuals over 20 years of age. During the FW (symptomatic), the IP, and the SW (symptomatic and asymptomatic), participants were diagnosed using nasopharyngeal swabs. Symptomatic individuals with risk factors for serious disease or death were referred to the hospital. SARS-CoV-2 infection was defined by RT-qPCR in all hospitalized patients. All data were added to the SISVER database. Bayesian analysis and False Discovery Rate were used for further evaluation. The study included 2 260 156 persons (mean age of 43.1 years). Of these, 8.6% suffered from DM, 11.6% arterial hypertension, and 9.7% obesity. Of the total, 666 694 persons tested positive (29.5%). Of the infected persons, a total of 85 587 (12.8%) were hospitalized: 24 023 in the FW; 16 935 in the IP, and 44 629 in the SW. Of the hospitalized patients, there were 42 979 deaths (50.2%), in the FW, 11 964 (49.8%), in the IP, 6794 (40.1%), and in the SW 24 221 (54.3%). The probability of death among individuals hospitalized with or without comorbidities increased consistently in all age groups. A significant increase in the Fatality Rate was observed in individuals with comorbidities (1.36E-19< = FDR< = 3.36E-2). A similar trend was also observed in individuals without comorbidities (1.03E-44< = FDR< = 5.58E-4). The data from this study show a considerable increase in the number of detected cases of infection between the FW and SW. In addition, 12.8% of those infected were hospitalized for severe COVID-19. A high mortality rate was observed among hospitalized patients (>50%). An age-dependent probability of death was observed with a positive trend in hospitalized patients with and without comorbidities.


Double-stranded deoxyribonucleic acid binds to HLA class II molecules and inhibits HLA class II-mediated antigen presentation.
CD4+ T cells proliferating in response to purified double-stranded deoxyribonucleic acid (dsDNA) have been recently demonstrated in peripheral blood mononuclear cells of patients with systemic lupus erythematosus. Their activation was inhibited by anti-HLA class II (HLA-II) monoclonal antibodies; thus, the existence of a molecular interaction between dsDNA and HLA-II is conceivable. In this report we show that dsDNA specifically bind to HLA-II. After preincubating cells with purified dsDNA or synthetic oligonucleotides, dsDNA was detected on the cell membrane and in the lysates of HLA-II+ but not of isogenic HLA-II- cell lines. We demonstrate that dsDNA binding inhibits that of a specific peptide to HLA-II. Mixed lymphocyte reaction and antigen-specific T cell proliferation were inhibited by the preincubation of stimulator cells or antigen-presenting cells with dsDNA. These results suggest the existence of a novel mechanism of down-modulation of the CD4+ T cell function generated by lack of stimulation due to the HLA-II presenting molecules being "occupied" by dsDNA.


Large-scale prediction of microRNA-disease associations by combinatorial prioritization algorithm.
Identification of the associations between microRNA molecules and human diseases from large-scale heterogeneous biological data is an important step for understanding the pathogenesis of diseases in microRNA level. However, experimental verification of microRNA-disease associations is expensive and time-consuming. To overcome the drawbacks of conventional experimental methods, we presented a combinatorial prioritization algorithm to predict the microRNA-disease associations. Importantly, our method can be used to predict microRNAs (diseases) associated with the diseases (microRNAs) without the known associated microRNAs (diseases). The predictive performance of our proposed approach was evaluated and verified by the internal cross-validations and external independent validations based on standard association datasets. The results demonstrate that our proposed method achieves the impressive performance for predicting the microRNA-disease association with the Area Under receiver operation characteristic Curve (AUC), 86.93%, which is indeed outperform the previous prediction methods. Particularly, we observed that the ensemble-based method by integrating the predictions of multiple algorithms can give more reliable and robust prediction than the single algorithm, with the AUC score improved to 92.26%. We applied our combinatorial prioritization algorithm to lung neoplasms and breast neoplasms, and revealed their top 30 microRNA candidates, which are in consistent with the published literatures and databases.


Improving quality of antifungal use through antifungal stewardship interventions.
In recent years antifungal stewardship (AFS) programmes have been increasingly recommended to provide optimal antifungal treatment. In a previous study (study I) in the department of haematology and oncology of a German tertiary care hospital we found areas for improvement concerning antifungal prescription. Subsequently, AFS measures were implemented and their impact on quality of antifungal use was assessed in this study. AFS measures included medical training (two sessions), a pocket card summarising main recommendations for antifungal use, and daily pharmaceutical counselling on the ward. In a 6-month observational study, antifungal prescriptions were analysed and compared to the previously collected data (study I) concerning indication, choice of drug, dosing, duration and drug-drug interactions. The study was approved by the university hospital ethical review board. Antifungal agents were prescribed for 103/1169 inpatients. Compared to study I, a significant increase in dosage accuracy (+ 19.3%; p < 0.05) and correct choice of drug (+ 15.9%; p < 0.05) was noted, as well as a decrease in potential clinically relevant drug-drug interactions with concomitant medication (- 13.9%; p < 0.05). However, no significant improvement in indication and duration of antifungal treatment was identified. 56 recommendations were given to the prescribing physicians (acceptance rate: 66.1%). The implementation of AFS interventions based on pharmaceutical presence on the ward was associated with an improvement in antifungal use; however, indication and duration of therapy need to be communicated by infectious disease specialists. Considering the proportionally short observation period, the long-term effects of our AFS interventions need to be further investigated.


Sacral CSF-Venous Fistulas and Potential Imaging Techniques.
This is the first study to describe CSF-venous fistulas involving the sacrum, a location that may be underrecognized on the basis of current imaging techniques. We describe a delayed decubitus flat CT myelogram technique that may be useful to identify sacral CSF-venous fistulas.


Increased activity of circulating polymorphonuclear leukocytes in acute myocardial infarction.
Acute myocardial infarction results in an increased sensitivity of circulating polymorphonuclear leukocytes to ex vivo aggregation. This increase was prevented by pretreatment of leukocytes with BW755, but not with aspirin, suggesting that the activation of blood leukocytes in infarction is due to a stimulation of cellular lipoxygenase.


Id proteins in development, cell cycle and cancer.
Id proteins are important parts of signaling pathways involved in development, cell cycle and tumorigenesis. They were first shown to act as dominant negative antagonists of the basic helix-loop-helix family of transcription factors, which positively regulate differentiation in many cell lineages. The Id proteins do this by associating with the ubiquitous E proteins and preventing them from binding DNA or other transcription factors. Id proteins also associate with Ets transcription factors and the Rb family of tumor suppressor proteins, and are downstream targets of transforming growth factor beta and bone morphogenic protein signaling. Thus, the Id proteins have become important molecules for understanding basic biological processes as well as targets for potential therapeutic intervention in human disease.


Growth of Escherichia coli at elevated temperatures.
In our studies to develop a simple and reliable method for the generation of recombinant adenoviruses (Fotadar et al . 2003), we noted that the E. coli (BJ5183 and DH5alpha) survived a heat-shock of 45 degrees C for 5 minutes in 0.1 M calcium chloride. As a result, we investigated the growth of E. coli (DH5alpha) at elevated temperatures. We hereby demonstrate that contrary to previous observations (Cooper et al . 2001 and Bronikowski et al . 2001) E. coli can grow consistently at a temperature as high as 49 degrees C, in spite of the fact that growth beyond 40 degrees C can generally be prohibitive. Hence, it is quite likely that these E. coli (DH5alpha) may have acquired mutations which permit them to grow reproducibly at 49 degrees C. Growth of E. coli above 49 degrees C (up to 53 degrees C) was also observed, but this was sporadic and not reproducible. This result could extend the utility of these organisms for cloning and manipulations requiring high temperature.


Protective effect of antioxidant rich aqueous curry leaf (Murraya koenigii) extract against gastro-toxic effects of piroxicam in male Wistar rats.
Piroxicam (chemically 4-hydroxy-2-methyl-N-2-pyridinyl-2H-1,2-benzothiazine-3-carboxamide), a classical non-steroidal anti-inflammatory drug (NSAID) is orally administered to arthritic patients. Inhibition of prostaglandin E2 (PGE2) synthesis and subsequent free hydroxyl radical generation in vivo exert gastro-toxic side effects on piroxicam treatment. Leaves of curry plant are rich in antioxidants with prolific free radical scavenging activities. This led us to investigate the efficiency of the use of curry leaves in ameliorating piroxicam induced gastric damage. Piroxicam was orally (30 mg per kg body weight) administered in male albino Wistar rats to generate gastric ulcers. These rats were orally fed with graded doses of aqueous extract of curry or Murraya koenigii leaves (Cu LE) prior to piroxicam administration. Oxidative stress biomarkers, activities of antioxidant and pro-oxidant enzymes, mucin content and nature, PGE2 level, activities of mitochondrial enzymes and histomorphology of gastric tissues were studied. Piroxicam treatment altered all the above mentioned parameters whereas, curry leaf extract pre-treated animals were protected against piroxicam induced alterations. Hence, the protective action of the antioxidant rich Cu LE was investigated to propose a new combination therapy or dietary management to arthritic patients using piroxicam.


Effects of blood lead on coronary artery disease and its risk factors: a Mendelian Randomization study.
Lead is pervasive, although lead exposure has fallen in response to public health efforts. Observationally, lead is positively associated with cardiovascular disease and hypertension. We used separate-sample instrumental variable analysis with genetic instruments (Mendelian randomization) based on 13 single nucleotide polymorphisms (SNP), from a genome wide association study, strongly (p-value < 5 × 10-6) and independently associated with blood lead. These SNPs were applied to a large extensively genotyped coronary artery disease (CAD) study (cases = <76014, controls = <264785) largely based on CARDIoGRAPMplusC4D 1000 Genomes and the UK Biobank SOFT CAD, to the UK Biobank (n = 361,194) for blood pressure and to the DIAGRAM 1000 genomes diabetes case (n = 26,676)-control (n = 132,532) study. SNP-specific Wald estimates were combined using inverse variance weighting, MR-Egger and MR-PRESSO. Genetically instrumented blood lead was not associated with CAD (odds ratio (OR) 1.01 per effect size of log transformed blood lead, 95% confidence interval (CI) 0.97, 1.05), blood pressure (systolic -0.18 mmHg, 95% CI -0.44 to 0.08 and diastolic -0.03 mmHg, 95% CI -0.09 to 0.15) or diabetes (OR 0.98, 95% CI 0.92 to 1.03) using MR-PRESSO estimates corrected for an outlier SNP (rs550057) from the highly pleiotropic gene ABO. Exogenous lead may have different effects from endogenous lead; nevertheless, this study raises questions about the role of blood lead in CAD.


Degradation of ultrasound probes caused by disinfection with alcohol.
The aim of this study was to clarify the degree of degradation of ultrasonic probes that results from their disinfection with alcohol. No defect in the ultrasound beams was found in any of the probes, but a significant decrease of the brightness was found after a certain period of use of the linear-type probe. Disinfection with alcohol may degrade ultrasound probes despite its high degree of effectiveness in preventing iatrogenic bacterial transmission.


On the occurence and composition of dense particles in mitochondria in ultrathin frozen dry sections.
Clusters of dense particles were observed irregularly in mitochondrial profiles of shock-frozen brown adipose tissue and liver when cryosectioned at a chamber temperature of -80 degrees C and not if sectioning was performed at -110 degrees C. The particles are rich in Ca and P (Ca/P =0.5); they are therefore not any form of tricalcium orthophosphate (e.g. hydroxyapatite). They apparently form by electrolyte diffusion in the section and therefore cannot be considered as representing the in vivo pool of mitochondrial calcium.


Retinyl palmitate labeled intestinally derived lipoproteins accumulate in the circulation of WHHL rabbits.
The behavior of native retinyl palmitate labeled intestinally derived lipoproteins and their remnants was studied in 8 NZW and 8 WHHL (5 homo- and 3 heterozygote) normal-fed rabbits and in 3 cholesterol-fed NZW, after 1 month of cholesterol feeding, and 3 and 5 months after resuming normal feeding. Palmitate labeled lipoproteins were produced by the intestine after administration of 50,000 IU of Vitamin A, together with olive oil via gastric intubation. Blood was drawn before and 3,6,9,12,24, and in some instances, 48 h later. Retinol (R) and retinyl palmitate (RP) were measured in whole serum and in the chylomicron, d less than 1006, d greater than 1006 less than 1019, d greater than 1019 less than 1063, d greater than 1063 less than 1210 g/ml lipoprotein fractions and in the infranatant. The R content of the serum was almost all concentrated in the infranatant, it did not change during the vitamin A test and was similar in WHHL, and normal- or cholesterol-fed NZW rabbits. In the normal-fed NZW the RP content of the serum increased within 6 h after giving the vitamin A fat meal (peak value less than 200 microgram/100 ml) and then decreased. In the WHHL homozygotes, the RP increased to a much greater degree (peak value 600-1820 micrograms) and for a much longer time, as it was still increased in the 5 cases studied after 24 h, and in 3 cases studied after 48 h. Similar RP curves were obtained in NZW rabbits, after 1 month of cholesterol feeding.(ABSTRACT TRUNCATED AT 250 WORDS)


Nuclear receptor antagonists designed based on the helix-folding inhibition hypothesis.
Here we review our studies on the molecular design of nuclear receptor antagonists, including retinoic acid receptor (RAR) antagonists, retinoid X receptor (RXR) antagonists, androgen receptor (AR) antagonists, and vitamin D receptor (VDR) antagonists, based on inhibition of folding of helix 12, which contains a co-activator binding site. Recent progress in structural development studies of peroxisome proliferator-activated receptor (PPAR) ligands is also reviewed.


Novel anti-staphylococcal and anti-biofilm properties of two anti-malarial compounds: MMV665953 {1-(3-chloro-4-fluorophenyl)-3-(3,4-dichlorophenyl)urea} and MMV665807 {5-chloro-2-hydroxy-N-[3-(trifluoromethyl)phenyl]benzamide}.
The treatment of device-related infections is challenging and current anti-microbial compounds have poor anti-biofilm activity. We aimed to identify and characterize novel compounds effective in the eradication of Staphylococcus aureus biofilms. Two novel compounds, MMV665953 {1-(3-chloro-4-fluorophenyl)-3-(3,4-dichlorophenyl)urea} and MMV665807{5-chloro-2-hydroxy-N-[3-(trifluoromethyl)phenyl]benzamide}, effective in killing S. aureus biofilms, were identified by screening of the open access 'malaria box' chemical library. The minimum bactericidal concentrations, half-maximal inhibition concentration (IC50) values and minimal biofilm killing concentrations effective in the killing of biofilm were determined against meticillin-resistant S. aureus and meticillin-sensitive S. aureus. Fibrin-embedded biofilms were grown under in vivo-relevant conditions, and viability was measured using a resazurin-conversion assay and confocal microscopy. The potential for the development of resistance and cytotoxicity was also assessed. MMV665953 and MMV665807 were bactericidal against S. aureus isolates. The IC50 against S. aureus biofilms was at 0.15-0.58 mg l-1 after 24 h treatment, whereas the concentration required to eradicate all tested biofilms was 4 mg l-1, making the compounds more bactericidal than conventional antibiotics. The cytotoxicity against human keratinocytes and primary endothelial cells was determined as IC50 7.47 and 0.18 mg l-1 for MMV665953, and as 1.895 and 0.076 mg l-1 for MMV665807. Neither compound was haemolytic nor caused platelet activation. MMV665953 and MMV665807 derivatives with reduced cytotoxicity exhibited a concomitant loss in anti-staphylococcal activity. MMV665953 and MMV665807 are more bactericidal against S. aureus biofilms than currently used anti-staphylococcal antibiotics and represent a valuable structural basis for further investigation in the treatment of staphylococcal biofilm-related infections.


Diagnosis, Staging, Radiation Treatment Response Assessment, and Outcome Prognostication of Head and Neck Cancers Using PET Imaging: A Systematic Review.
This systematic review summarizes the current applications of 18F-FDG PET imaging in the diagnosis, staging, radiation treatment response assessment, and outcome prognostication of head and neck cancers. For head and neck cancers of unknown primary origin, 18F-FDG PET/CT increases the likelihood of identifying the primary tumor and establishing the diagnosis. 18F-FDG PET/CT is important in the accurate staging of locoregionally advanced cases of HNSCC, which can greatly affect recommendations for treatment. Following definitive chemoradiation, 18F-FDG PET/CT is validated as a means of treatment response assessment. Emerging PET tracers of hypoxia and their potential applications are reviewed.


Developmental changes of plasma inhibin, gonadotropins, steroid hormones, and thyroid hormones in male and female Shao ducks.
Plasma samples from developing male and female Shao ducks were assayed for immunoreactive (ir-) inhibin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), steroid hormones, and thyroid hormones. In the male, plasma ir-inhibin significantly increased between 75 and 155 days posthatch, and then decreased slightly at day 165. Plasma FSH of male ducks decreased from day 35 to day 55, followed by progressive elevation until day 95. Plasma FSH of male ducks fell significantly at days 135 and 165, while plasma ir-inhibin rose to high level. In female ducks, plasma ir-inhibin remained low until the start of lay, and thereafter significantly increased at day 135. Plasma FSH fluctuated before day 95 and significantly rose at day 115, and decreased thereafter. In males, plasma LH did not vary significantly before day 135, however, plasma testosterone significantly increased from day 95 onwards. No changes in plasma LH were observed during development of female ducks. Plasma estradiol-17beta gradually increased reaching a peak level at day 135. Plasma progesterone did not vary significantly before day 135 and thereafter significantly increased. Both sexes showed a similar pattern in changes of plasma thyroid hormones during sexual development. There was a significant increase in plasma thyroxine (T4) at day 95, thereafter decreased. Plasma triiodothyronine (T3) was at high level at the earlier stage of development and significantly decreased at day 55. Significant increase in plasma T3 in male and female ducks was observed at 135 and 115 days, respectively. In conclusion, these results demonstrated that the rise in inhibin is correlated with age of sexual maturity in the female while the rise in inhibin significantly precedes sexual maturity in the male. There was a progressive increase in plasma steroid hormones towards sexual maturity, and there was no sex difference in the time course of thyroid hormones.


Combined transcriptomic and proteomic analysis of the response to bile stress in a centenarian-originated probiotic Lactobacillus salivarius Ren.
Tolerance to bile stress is a crucial property for probiotics to survive in the gastrointestinal tract and exert their beneficial effects. In this work, transcriptomic analysis combined with two-dimensional electrophoresis revealed that the transcript levels of 129 genes and the abundance of 34 proteins were significantly changed in Lactobacillus salivarius Ren when exposed to 0.75 g/L ox-bile. Notably, carbohydrate metabolism shifted to the utilization of maltose and glycerol for energy production, suggesting that L. salivarius Ren expanded carbon sources profile for gut adaptation in response to bile. Moreover, the enzymes involved in cell surface charge modification and the cell envelope-located hemolysin-like protein were overproduced, which was supposed to hinder the penetration of bile. Then, the up-regulated ABC transporters could contribute to the extrusion of bile accumulated in the cytoplasm. Additionally, proteolytic system was activated to provide more amino acids for the synthesis and repair of proteins damaged by bile. Finally, γ-glutamylcysteine with antioxidant activity and oxidoreductases for redox homeostasis were increased to cope with the bile-induced oxidative stress. These findings provide new insights into the molecular mechanisms involved in bile stress response and adaptation in L. salivarius.


Are Adewale and Ngochi more employable than Jamal and Lakeisha? The influence of nationality and ethnicity cues on employment-related evaluations of Blacks in the United States.
Previous research has consistently shown that racial bias can influence employers' perceptions and evaluations of Black individuals in hiring and promotion decisions. However, within-race differences (e.g., skin tone, Afrocentric features) can lead to variation in these decisions. In addition to phenotypical variation, ethnicity cues (e.g., perceived country of origin, name) may be important within-race factors influencing the perception and evaluations of Black job applicants. Using a resume evaluation paradigm, participants evaluated one of three resumes in which the target applicant's name provided cues about ethnicity (either Black American, Black African, or White American). Results suggest that Black Americans may experience more discrimination in hiring and are generally perceived less positively across several employment-related domains than both White and Black African applicants. Specifically, we find that Black Americans are less likely to be selected for an interview or offered a job and are evaluated more negatively overall relative to Black Africans.


Noncompliance in neurologic patients.
Patient compliance is essential for optimal therapeutic outcome. However, medical noncompliance remains a significant issue in the treatment of many neurologic disorders. Neurologic patients are particularly vulnerable to poor treatment adherence. The chronic and often relapsing and remitting course of neurologic illness creates challenges in maintaining treatment compliance. In addition, comorbid psychiatric conditions can contribute to noncompliance. Decreasing the complexity of dosing schedules, addressing side effect concerns, recognizing financial impact of treatment, and addressing comorbid psychiatric illness all can help to improve compliance. Potentially, the most effective methods to improve compliance include improving the doctor patient relationship, increasing a patient's social support system, and maximizing patient education.


[Microbiological Surveillance Network in the Valencian community].
Computerization of microbiological laboratories generates an enormous amount of data that has not been fully exploited due to the heterogeneity of the information systems used. The aim of this paper is to present the Microbiological Surveillance Network of the Valencian Community, which provides real-time detection of circulating microorganisms and resistance patterns, and enables microbiological surveillance in the public health setting. We describe the Microbiological Surveillance Network of the Valencian Community, an information system that gathers, analyzes and disseminates the results of microbiological testing to health professionals in our setting. Development of the Microbiological Surveillance Network has made available a centralized system with the results from all the microbiological analyses performed in hospital laboratories of the Valencian Community. This effort provides valuable information for public health, and for studies in research and quality. In addition, it demonstrates the important role of microbiology within the field of medicine and public health.


German physicians' expectations of healthcare management companies: An exploratory study.
Even 20 years after the introduction of managed care (MC) in Germany, many physicians are skeptical of the concept, hindering its acceptance. Based on multivariate statistical methods this exploratory study examines how so-called management companies, that is, administrative service providers within MC contracts, can increase physicians' acceptance of MC by offering, for example, day-to-day coordination and administrative tasks. As a main empirical result, we find support for this hypothesis, that is, that certain physicians evaluate their MC participation according to its prospective administrative support. Based on this, up to four clusters of physicians can be statistically identified in terms of their preferences regarding MC. As a policy recommendation, we derive from our results that a future focus on the administrative support components of MC is essential to attract certain physician groups to participate in MC.


Economic Burden of Recurrence in Completely Resected Stage IB-IIIA Non-Small Cell Lung Cancer: A Retrospective Study Using Nationwide Claims Data of South Korea.
Although many patients with early stage non-small cell lung cancer (NSCLC) experience recurrence despite complete resection, few studies have reported on the corresponding economic burden. This study aimed to understand the economic impact of recurrence by measuring healthcare costs and resource utilization in patients with recurrent stage IB-IIIA NSCLC. Using Health Insurance Review and Assessment claims data from South Korea, we included patients who underwent complete resection for stage IB-IIIA NSCLC during the index period (January 1, 2012, to October 31, 2018). Patients who experienced recurrence were matched with those who did not using 1:1 propensity score (PS) matching. The mean healthcare costs and resource utilization were analyzed from the date of complete resection to the last claims for cancer treatment. A generalized linear model (GLM) was used to estimate the impact of covariates on healthcare costs. A difference-in-difference (DID) analysis was conducted to analyze the healthcare costs between the two groups before and after recurrence. Patients with recurrence incurred higher healthcare costs, particularly in outpatient settings. The cost of targeted therapy and immune checkpoint inhibitors primarily contributed to cost differences, and medication costs increased over time after complete resection. Patients with recurrence were also hospitalized more frequently (9.3 vs. 5.0, p < 0.0001) for a longer period (74 days vs. 42 days, p < 0.0001) than those without recurrence. GLM analysis showed that the total cost was 2.31-fold higher in patients with recurrence (95% confidence interval: 2.19-2.44). The DID analysis showed significantly increased total costs in patients with recurrence (β = 26,269, p < 0.0001), which was mostly attributed to medication costs (β = 17,951, p < 0.0001). Recurrence of completely resected NSCLC leads to a substantial increase in healthcare costs and resource utilization. The results of this study show the economic burden of recurrence, which may help future economic analyses and resource allocation.


Ileal obstruction caused by transmural endometriosis in a patient with simultaneous C. difficile colitis and Influenza AH1N1. Case report.
Small bowel obstruction secondary to endometriosis is extremely rare. This etiology is reported in 0.10% of cases and diagnosed incidentally. 32-year old female, critically ill patient was diagnosed with small bowel obstruction. After medical stabilization of multiple comorbidities, diagnostic laparoscopy was done and converted to open right ileocolectomy with ileo-transverse anastomosis. Definite diagnosis was ileal obstruction caused by transmural endometriosis. The patient's recovery was uneventful. At one-year follow-up, she remains asymptomatic. We present the uncommon case of ileal obstruction due to transmural endometriosis that was treated surgically. We also present current literature review focusing on diagnostic and treatment methods of this rare disease. Endometriosis should be included in the differential diagnosis of small bowel obstruction. The treatment of choice is bowel resection.


Proprotein processing activity and cleavage site selectivity of the Kex2-like endoprotease PACE4.
Proprotein processing activity of the Kex2-like mammalian endoprotease PACE4 and its cleavage selectivity for sites with basic amino acid residues were determined. Using a recombinant vaccinia virus-based expression system, PACE4 was expressed in pig kidney PK(15) cells and, like two other Kex2-like endoproteases furin and PC6A, shown to correctly process the precursor of von Willebrand factor (pro-vWF). Furthermore, characteristics of the cleavage site selectivity of PACE4 were compared to those of furin and PC6A using the vWF cleavage site mutants vWFR-1G, vWFK-2A, and vWFR-4A as substrates. Cleavage site selectivity of PACE4 and PC6A appeared to be similar but they differed from that of furin.


[Johann Friedrich Dieffenbach (1792-1847) as the founder of plastic surgery. His contribution to maxillofacial surgery].
Johann Friedrich Dieffenbach (1792-1847) is generally known as the founder of modern plastic surgery. One focus of his work, apart from the physiology of transplantation and operative techniques, was reconstructive oral and maxillofacial surgery. This special aspect of plastic surgery as well as Dieffenbach's biography is presented in this historic article.


Identification and characterization of species-specific nanobodies for the detection of Listeria monocytogenes in milk.
Listeria monocytogenes (LM), one of the eight species belonging to the genus Listeria, is pathogenic for both humans and animals. In this study, two novel LM-specific clones, designated L5-78 and L5-79, were isolated from a phage display antibody library that was derived from the variable domain of heavy-chain antibodies (VHHs) of non-immunized alpaca. These two clones were expressed, purified, and characterized. Results showed that both isolated VHHs recognize three serotypes (1/2a, 1/2b, and 4b), which are responsible for more than 95% of documented human listeriosis cases. The recombinant VHHs possess high thermal stability, pH tolerance, and urea resistance. A sandwich enzyme-linked immunosorbent assay (ELISA) based on the VHH clone L5-79 and a monoclonal antibody was developed to detect LM in pasteurized milk, with a detection limit of 1 × 10(4) colony-forming units (CFU)/ml. These findings indicated that the species-specific VHHs could be directly isolated from the non-immunized library with a properly designed panning strategy and VHH could be a new source for possible diagnosis/detection of foodborne pathogens in food because it was shown to be highly specific and stable.


High density lipoproteins, 1978 -- an overview.
High density lipoproteins (HDL) have come of age. For years it has been fashionable to study HDL as an approach to understanding lipoprotein structure and lipid binding. Available in abundant amounts from normal human plasma, readily separable into its individual lipid and soluble apolipoprotein components, HDL has provided much information for lipoprotein model building. Suddenly it has been thrust center stage clinically by a host of convincing epidemiologic studies that clearly establishes an inverse relationship between HDL levels and coronary vascular events. Biochemists, clinicians, cardiologists and epidemiologists are simultaneously focusing attention on HDL. Familial High Density Lipoprotein Deficiency (Tangier Disease) has been well described but is poorly understood as a clinical syndrome complex. We have suddenly become aware of how little we understand about HDL's normal ultracentrifugal and apoprotein heterogeneity, about its functional role(s) or the determinant(s) of its concentration in plasma. The relative contributions of the two sites of HDL origin, the liver and intestine, are yet to be determined as are the site(s) of degradation. Awareness of a problem and its importance is the first step toward the solution(s) of the problem.


Developmental role of GABAB(1) receptors in Drosophila.
Previously, an RNA interference (RNAi) knockdown of GABAB(1) subunit in adult Drosophila was used for behavioral studies. Here we report on developmental deficits caused by embryonic Drosophila GABAB(1) RNAi and drug antagonism. Injecting embryos with CGP54626 (a GABAB receptor antagonist) reduced hatching and caused lethality. Similar effects were produced by injecting embryos with GABAB(1) double-stranded RNA (RNAi). The surviving GABAB(1) RNAi larvae were significantly smaller than controls and showed a peculiar phenotype; their tracheae were folded. Our results suggest that GABAB receptors are required for normal development and that the Drosophila model could be used to investigate the participating molecular mechanisms.


Malaria transmission risk variations derived from different agricultural practices in an irrigated area of northern Tanzania.
Malaria vector Anopheles and other mosquitoes (Diptera: Culicidae) were monitored for 12 months during 1994-95 in villages of Lower Moshi irrigation area (37 degrees 20' E, 3 degrees 21' S; approximately 700 m a.s.l.) south of Mount Kilimanjaro in northern Tanzania. Adult mosquito populations were sampled fortnightly by five methods: human bait collection indoors (18.00-06.00 hours) and outdoors (18.00-24.00 hours); from daytime resting-sites indoors and outdoors; by CDC light-traps over sleepers. Anopheles densities and rates of survival, anthropophily and malaria infection were compared between three villages representing different agro-ecosystems: irrigated sugarcane plantation; smallholder rice irrigation scheme, and savannah with subsistence crops. Respective study villages were Mvuleni (population 2200), Chekereni (population 3200) and Kisangasangeni (population approximately/= 1000), at least 7 km apart. Anopheles arabiensis Patton was found to be the principal malaria vector throughout the study area, with An. funestus Giles sensu lato of secondary importance in the sugarcane and savannah villages. Irrigated sugarcane cultivation resulted in water pooling, but this did not produce more vectors. Anopheles arabiensis densities averaged four-fold higher in the ricefield village, although their human blood-index was significantly less (48%) than in the sugarcane (68%) or savannah (66%) villages, despite similar proportions of humans and cows (ratio 1:1.1-1.4) as the main hosts at all sites. Parous rates, duration of the gonotrophic cycle and survival rates of An. arabiensis were similar in villages of all three agro-ecosystems. The potential risk of malaria, based on measurements of vectorial capacity of An. arabiensis and An.funestus combined, was four-fold higher in the ricefield village than in the sugarcane or savannah villages nearby. However, the more realistic estimate of malaria risk, based on entomological inoculation rates, indicated that exposure to infective vectors was 61-68% less for people in the ricefield village, due to the much lower sporozoite rate in An. arabiensis (ricefield 0.01%, sugarcane 0.1%, savannah 0.12%). This contrast was attributed to better socio-economic conditions of rice farmers, facilitating relatively more use of antimalarials and bednets for their families. Our findings show that, for a combination of reasons, the malaria challenge is lower for villagers associated with an irrigated rice-growing scheme (despite greater malaria vector potential), than for adjacent communities with other agro-ecosystems bringing less socio-economic benefits to health. This encourages the development of agro-irrigation schemes in African savannahs, provided that residents have ready access to antimalaria materials (i.e. effective antimalaria drugs and insecticidal bednets) that they may better afford for protection against the greater vectorial capacity of An. arabiensis from the ricefield agro-ecosystem.


Movement versus focusing of visual attention.
In two experiments, we investigated the idea that attention moves through visual space in an analog fashion. The spatial distribution of attention was determined by presenting a spatially informative cue and comparing reaction times to targets at cued and uncued locations as a function of the interval from cue onset to target onset (SOA). Facilitation and inhibition were measured by reference to a neutral condition in which the cue provided no spatial information. In the first experiment, we used a central cue (an arrow), and in the second experiment, we used a peripheral cue (a 50-msec flash). With central cue, the facilitatory effects of the cuing were initially equal for all locations on the indicated side of the display, and then decreased for all locations except the one that had been specifically cued. These results are interpreted as being more consistent with "focusing" of an initially broad "beam" of attention than with "movement" of a narrow beam from fixation to the cued location. With peripheral cues, strong facilitation specific to the cued location was manifest as early as 50 msec after cue onset, but this effect decreased with increasing SOA. Inhibition for uncued locations increased with increasing SOA at a rate that generally reflected their distance from the cued location. Taken together, these results reveal important differences between peripheral and central cues in the generation of attentional selectivity, not just in the time-course of events, but also in the nature of the processes involved.


Pain Neuroscience Education in cancer survivors with persistent pain: A pilot study.
To describe the Pilot Study: Pain Neuroscience Education in Cancer Survivors and describe the innovative educational component of Pain Neuroscience Education (PNE). Quasi experimental design. The PNE program, encompassing a one-on-one education session and an information leaflet was given to 30 cancer survivors. At baseline and two weeks after the PNE, participants were asked to fill out following outcome measures; pain intensity, pain catastrophizing, and HRQoL. Following PNE, a significant decrease on pain intensity (p = 0.001), on the SF-36 subscale pain (p = 0.003) and for the following PCS subscales: Helplessness (p < 0.001), Rumination (p = 0.002) and Total score (p < 0.001) was found compared to baseline. Although the current results need to be verified in a larger randomized, controlled trial, preliminary evidence shows a decrease in pain intensity and pain catastrophizing following PNE in cancer survivors with persistent pain.