Synthesis and enhanced NO2 gas sensing properties of ZnO nanorods/TiO2 nanoparticles heterojunction composites.
ZnO nanorods/TiO2 nanoparticles composites were synthesized and the effects of TiO2 concentrations on the NO2 sensing properties were studied in detail. The as-prepared composites were characterized by XRD, SEM, TEM, PL, I-V and gas sensing measurements. The gas sensing results demonstrated that all the sensors based on ZnO/TiO2 nanocomposites exhibited much higher response than that of sensors based on pure ZnO nanorods. At the optimum operating temperature of 180°C, the response values of the sensors based on ZnO/TiO2 nanocomposites decorated with TiO2 concentrations of 0, 3, 5, 8 and 10wt% were 50, 140, 310, 350 and 258, respectively. The PL and I-V results indicated that the increased charge transfer between the ZnO nanorods mediated by TiO2 nanoparticles enhanced the conductivity of the ZnO/TiO2 nanocomposites. The gas sensing mechanism was also carefully analyzed. The attachment of TiO2 nanoparticles onto ZnO nanorods induced more active sites for the adsorption of oxygen molecules (O(2)) and O(2) which can be more easily adsorbed on the surface of ZnO nanorods. Furthermore, the conduction channel of ZnO/TiO2 was much narrower as a result of the formation of heterojunction which may further contribute to the enhanced NO2 sensing properties.


Neuroendocrine regulation of long-term pair maintenance in the monogamous zebra finch.
This article is part of a Special Issue "SBN 2014". Understanding affiliative behavior is critical to understanding social organisms. While affiliative behaviors are present across a wide range of taxa and contexts, much of what is known about the neuroendocrine regulation of affiliation comes from studies of pair-bond formation in prairie voles. This leaves at least three gaps in our current knowledge. First, little is known about long-term pair-bond maintenance. Second, few studies have examined non-mammalian systems, even though monogamy is much more common in birds than in mammals. Third, the influence of breeding condition on affiliation is largely unknown. The zebra finch (Taeniopygia guttata) is an excellent model system for examining the neuroendocrine regulation of affiliative behaviors, including the formation and maintenance of a long-term pair bond. Zebra finches form genetically monogamous pair bonds, which they actively maintain throughout the year. The genomic and neuroanatomical resources, combined with the wealth of knowledge on the ecology and ethology of wild zebra finches, give this model system unique advantages to study the neuroendocrine regulation of pair bonding. Here, we review the endocrinology of opportunistic breeding in zebra finches, the sex steroid profiles of breeding and non-breeding zebra finches (domesticated and wild), and the roles of sex steroids and other signaling molecules in pair-maintenance behaviors in the zebra finch and other monogamous species. Studies of zebra finches and other songbirds will be useful for broadly understanding the neuroendocrine regulation of affiliative behaviors, including pair bonding and monogamy.


Low-scale expression and purification of an active putative iduronate 2-sulfate sulfatase-Like enzyme from Escherichia coli K12.
The sulfatase family involves a group of enzymes with a large degree of similarity. Until now, sixteen human sulfatases have been identified, most of them found in lysosomes. Human deficiency of sulfatases generates various genetic disorders characterized by abnormal accumulation of sulfated intermediate compounds. Mucopolysaccharidosis type II is characterized by the deficiency of iduronate 2-sulfate sulfatase (IDS), causing the lysosomal accumulation of heparan and dermatan sulfates. Currently, there are several cases of genetic diseases treated with enzyme replacement therapy, which have generated a great interest in the development of systems for recombinant protein expression. In this work we expressed the human recombinant IDS-Like enzyme (hrIDS-Like) in Escherichia coli DH5α. The enzyme concentration revealed by ELISA varied from 78.13 to 94.35 ng/ml and the specific activity varied from 34.20 to 25.97 nmol/h/mg. Western blotting done after affinity chromatography purification showed a single band of approximately 40 kDa, which was recognized by an IgY polyclonal antibody that was developed against the specific peptide of the native protein. Our 100 ml-shake-flask assays allowed us to improve the enzyme activity seven fold, compared to the E. coli JM109/pUC13-hrIDS-Like system. Additionally, the results obtained in the present study were equal to those obtained with the Pichia pastoris GS1115/pPIC-9-hrIDS-Like system (3 L bioreactor scale). The system used in this work (E. coli DH5α/pGEX-3X-hrIDS-Like) emerges as a strategy for improving protein expression and purification, aimed at recombinant protein chemical characterization, future laboratory assays for enzyme replacement therapy, and as new evidence of active putative sulfatase production in E. coli.


Studies on compound I formation of the lignin peroxidase from Phanerochaete chrysosporium.
Ligninase, isolated from the wood-destroying fungus Phanerochaete chrysosporium, catalyzes the oxidation of lignin and lignin-related compounds. Ligninase reacts with H2O2 to form the classical peroxidase intermediates Compounds I and II. We have determined the activation energy of ligninase Compound I formation to be 5.9 kcal/mol. The effect of pH and ionic strength on the rate of ligninase Compound I formation was studied. In contrast to all other peroxidases, no pH effect was observed. This is despite homology of active-site amino acids residues (Tien, M., and Tu, C.-P. D. (1987) Nature 326, 520-523) which are proposed to affect the pH profile of Compound I formation. Ligninase Compound I formation can also be supported by organic peroxides. The second-order rate constants with the organic peroxides are lower, suggesting that H2O2 is the preferred substrate.


Communication skills training in undergraduate nursing programs in Spain.
of the present cross sectional study were to analyze the offer of subjects with communication skills in the nursing degree in Spain and to describe the distribution of these subjects. Documentary, systematic and independent search of web pages from Spanish universities was carried out to collect the following variables: subjects with communication skills, course in which the subject is taught, type of teaching (exclusive or combined), type of subject (compulsory or optional) and number of credits on communication skills. Although an average of 3.6 subjects per center was offered, most of the subjects were combined and with little communication content load. In one third of the centers, the offer was below 2.3 credits. Only 1 in 6 centers had exclusive communication skills subjects, and a quarter of them were optional. The teaching load of communication contents was highest in optional subjects. The offer of communication skills contents in Spanish Nursing Schools was scarce and very heterogeneous between centers and between courses in a center, with excessive presence of combined and optional subjects. Our results may be useful when developing the teaching guides for subjects with communication skills, as well as when defining communication competencies in the different Nursing Schools.


The management of Japanese quail and their use in virological research: a review.
Since the domestication of Japanese quail during the last few decades, they are extensively used as table birds and pet birds. These birds, because of their physiological resemblance to chickens, inexpensive maintenance and rapid generation turnover are increasingly used in biomedical research including virology. In the present review the life cycle of birds, care and incubation of eggs, rearing, nutrition and naturally occurring diseases are described. The use of Japanese quail, their embryos and cell cultures derived from them in virological research are also discussed.


Interactions between prostaglandins, leukotrienes and HIV-1: possible implications for the central nervous system.
In HIV-1-infected individuals, there is often discordance between viremia in peripheral blood and viral load found in the central nervous system (CNS). Although the viral burden is often lower in the CNS compartment than in the plasma, neuroinflammation is present in most infected individuals, albeit attenuated by the current combined antiretroviral therapy. The HIV-1-associated neurological complications are thought to result not only from direct viral replication, but also from the subsequent neuroinflammatory processes. The eicosanoids - prostanoids and leukotrienes - are known as potent inflammatory lipid mediators. They are often present in neuroinflammatory diseases, notably HIV-1 infection. Their exact modulatory role in HIV-1 infection is, however, still poorly understood, especially in the CNS compartment. Nonetheless, a handful of studies have provided evidence as to how these lipid mediators can modulate HIV-1 infection. This review summarizes findings indicating how eicosanoids may influence the progression of neuroAIDS.


Functional expression and display of an antibody Fab fragment in Escherichia coli: study of vector designs and culture conditions.
Several different vector designs are currently being used to display and express Fab molecules in Escherichia coli, but their relative efficiency in phage display and protein expression cannot be compared from the published data. We systematically investigated which vector design most effectively displays and expresses Fab molecules in E. coli using, as a model system, a human Fab against tetanus toxoid (tt). Three different vectors were used in this study: pFab1 where the VL-CL and VH-CH1 genes were driven by two promoters in two separate expression cassettes, and pFab2 and pFab3 that both contain one dicistronic expression cassette with two translation initiation sites and either VH-CH1 before VL-CL or VL-CL before VH-CH1, respectively. The display of tt-Fab on the surface of phage and the expression of tt-Fab protein in E. coli were compared for the aforementioned vectors. Our results showed that the pFab3 vector was most effective in Fab display. A 10-fold increase in the expression of secreted Fab was observed in pFab3 when compared with vectors pFab1 and pFab2. Further experiments were conducted using pFab3 to optimize expression levels using different strains of E. coli and various culture conditions. The highest expression of tt-Fab was obtained using the pFab3 vector in host strain JM105 with an induction temperature at 37 degrees C and IPTG concentration of 0.1 mM.


Evaluating trainee doctors' educational use of a personal digital assistant: a pilot study.
In recent times, health-care providers in the western world have embraced modern technology to advance patient care. Ease and speed of access to modern technologies has enhanced the quality of medical education and provided a valuable new adjunct to workplace-based learning.


Metkephamid and meperidine analgesia after episiotomy.
Metkephamid is an analog of methionine enkephalin. The efficacy, safety, and time course of analgesia with 70 or 140 mg metkephamid were compared with those of 100 mg meperidine and placebo in 59 hospitalized women with severe postpartum episiotomy pain. There were two separate trials with single intramuscular doses and identical designs, including parallel groups, randomized blocks, and double-blind conditions. Using subjective reports as indexes of response, patients rated pain intensity, pain relief, and side effects at periodic interviews for 6 hr. Almost all measures of summed and peak analgesia exhibited important differences among the three treatments in both trials. Metkephamid at the 140-mg dose was the most effective and meperidine, 100 mg, was next, whereas metkephamid, 70 mg, and placebo were least effective. Only metkephamid, 140 mg, and meperidine were measurably superior to placebo. Both treatments took effect within 30 min and peaked at 1 to 2 hr; with 140 mg metkephamid, maximum analgesia was sustained 6 hr, i.e., 2 hr longer than with meperidine. Metkephamid, 70 mg, could not be distinguished from placebo throughout its entire time course. Although dizziness was experienced with meperidine, the two metkephamid doses induced other side effects, including sensation of heavy limbs, dry mouth, eye redness, and nasal stuffiness. None were distressing. Our results suggest that 140 mg metkephamid compares favorably with 100 mg meperidine for analgesia after episiotomy, but it induces minor side effects more frequently.


Denoising Autoencoder Normalization for Large-Scale Untargeted Metabolomics by Gas Chromatography-Mass Spectrometry.
Large-scale metabolomics assays are widely used in epidemiology for biomarker discovery and risk assessments. However, systematic errors introduced by instrumental signal drifting pose a big challenge in large-scale assays, especially for derivatization-based gas chromatography-mass spectrometry (GC-MS). Here, we compare the results of different normalization methods for a study with more than 4000 human plasma samples involved in a type 2 diabetes cohort study, in addition to 413 pooled quality control (QC) samples, 413 commercial pooled plasma samples, and a set of 25 stable isotope-labeled internal standards used for every sample. Data acquisition was conducted across 1.2 years, including seven column changes. In total, 413 pooled QC (training) and 413 BioIVT samples (validation) were used for normalization comparisons. Surprisingly, neither internal standards nor sum-based normalizations yielded median precision of less than 30% across all 563 metabolite annotations. While the machine-learning-based SERRF algorithm gave 19% median precision based on the pooled quality control samples, external cross-validation with BioIVT plasma pools yielded a median 34% relative standard deviation (RSD). We developed a new method: systematic error reduction by denoising autoencoder (SERDA). SERDA lowered the median standard deviations of the training QC samples down to 16% RSD, yielding an overall error of 19% RSD when applied to the independent BioIVT validation QC samples. This is the largest study on GC-MS metabolomics ever reported, demonstrating that technical errors can be normalized and handled effectively for this assay. SERDA was further validated on two additional large-scale GC-MS-based human plasma metabolomics studies, confirming the superior performance of SERDA over SERRF or sum normalizations.


Intergenerational Ambivalence and Dyadic Strain: Understanding Stress in Family Care Partners of Older Adults.
The present study used Pearlin, Mullan, Semple & Skaff's (1990) caregiving stress process model as a framework to examine the comparative influence of two stressors: (a) intergenerational ambivalence as a unified construct and (b) dyadic strain, which is one isolated component of intergenerational ambivalence. Participants were 120 women providing healthcare and medication assistance to an earlier generation family member with physical and/or cognitive impairments. Hierarchical regression confirmed that intergenerational ambivalence explained perceived stress in family care partners, beyond the variance accounted for by other commonly reported stressors such as length of caregiving experience, memory/cognitive and functional impairments of the care recipient, caregiver overload, family conflict and financial strain. Further analyses revealed that examining dyadic strain apart from intergenerational ambivalence may more accurately explain the influence of ambivalence scores on care partners' perceived stress. The comparative influence of dyadic strain versus ambivalence suggests that stress-reducing interventions may benefit from a focus on reducing care partners' experiences of negative strain in the dyadic relationship rather than managing ambivalence.


Adolescents' and adults' perceptions of 'natural', 'organic' and 'additive-free' cigarettes, and the required disclaimers.
We sought to investigate adolescents' and adults' perceptions of an American Spirit advertisement with 'natural', 'organic' and 'additive-free' descriptors and related disclaimers. We conducted nine focus group discussions in the Southern USA, with 59 participants aged 13-64 years (30 male, 29 female), stratified by age, smoking status and susceptibility to smoking. We conducted thematic content analysis of the transcripts. Many participants were sceptical or confused about the 'natural', 'organic' and 'additive-free' descriptors. Many participants viewed American Spirit cigarettes as being less, or possibly less harmful than other cigarettes, even though the ad contained disclaimers explicitly stating that these cigarettes are not safer. Some participants said that people tend to ignore disclaimers, a few expressed doubt that the disclaimers were fully true, and others did not notice the disclaimers. A few smokers said they smoke American Spirit cigarettes because they think they are not as bad for them as other cigarettes. Disclaimers intended to prevent consumers from attributing a health benefit to cigarettes labelled as 'natural', 'additive-free', or 'organic' may be insufficient. A ban on these descriptors may be a more appropriate remedy than disclaimers.


Ocular delivery of felodipine for the management of intraocular pressure and inflammation: Effect of film plasticizer and in vitro in vivo evaluation.
Glaucoma may cause irreversible eyesight loss and damage to the optic nerve. Trabecular meshwork obstruction may raise intraocular pressure (IOP) in open-angle and/or closed-angle type inflammatory glaucoma. Ocular delivery of felodipine (FEL) has been undertaken for the management of intraocular pressure and inflammation. FEL film was formulated using different plasticizers, and IOP has been assessed using a normotensive rabbit eye model. Ocular acute inflammation induced by carrageenan has also been monitored. Drug release has been enhanced significantly (93.9 % in 7 h) in the presence of DMSO (FDM) as a plasticizer in the film compared to others (59.8 to 86.2 % in 7 h). The same film also exhibited the highest ocular permeation of 75.5 % rather than others (50.5 to 61.0 %) in 7 h. Decreased IOP was maintained up to 8 h after ocular application of FDM compared to the solution of FEL only up to 5 h. Ocular inflammation has almost been disappeared within 2 h of using the film (FDM), whereas inflammation has been continued even after 3 h of the induced rabbit without film. DMSO plasticized felodipine film could be used for the better management of IOP and associated inflammation.


Studies on electrochemical behaviors of acyclovir and its voltammetric determination with nano-structured film electrode.
A multi-wall carbon nanotubes (MWNTs)-dihexadecyl hydrogen phosphate (DHP) film-coated glassy carbon electrode (GCE) was fabricated, and the electrochemical behaviors of acyclovir on the MWNTs-DHP film-coated GCE were investigated by using cyclic voltammetry (CV), linear sweep voltammetry (LSV), electrochemical impedance spectroscopy (EIS) and chronocoulometry (CC). The oxidation peak current of acyclovir increased significantly and the peak potential shifted negatively at the MWNTs-DHP film-modified GCE, compared with that at a bare GCE. The results showed that this nano-structured film electrode exhibited excellent enhancement effects on the electrochemical oxidation of acyclovir. Consequently, a simple and sensitive electroanalytical method was developed for the determination of acyclovir. The oxidation peak current was proportional to the concentration of acyclovir from 8.0 x 10(-8) to 1.0 x 10(-5) mol/L. The detection limit was about 3.0 x 10(-8) mol/L for 60s accumulation at 0.00 V. The proposed method was demonstrated by using acyclovir tablets and the result was satisfying.


The orientation of the ligands in iron(III)-bleomycin intercalated with DNA.
EPR data show that Fe(III)-bleomycin intercalates with DNA, or that the Fe(III) coordination sphere has a fixed geometrical configuration with respect to the DNA helical axis. An analysis of the data from oriented DNA fibers, drawn from a viscous gel, shows that the angle between the fiber axis and the normal to a plane containing the Fe(III) ion and ligands ranges between 15 and 30 degrees. The principal g values for the low-spin Fe(III)-bleomycin-DNA complex at pH 7.5 are 2.45, 2.18 and 1.87.


Primary hyperparathyroidism in the geriatric population: A case report and mini literature review.
We report a case of a 93-year-old woman with PHPT secondary to a left inferior parathyroid adenoma. The patient met criteria to be a surgical candidate; however, literature about parathyroidectomy in the elderly was limited and controversial. The patient remained stable through medical management for the next 5 years.


New insight into the mechanism of in vivo fibroin self-assembly and secretion in the silkworm, Bombyx mori.
Fibroin of the silkworm consists of fibroin heavy chain (Fib-H) with hydrophobic intermediate repeats flanked by hydrophilic N and C terminal domains (NTD and CTD, respectively), fibroin light chain (Fib-L), and P25. However, the respective roles of each polypeptide in silk processing remain largely unknown. Here, a series of transgenic silkworms with different fusion gene expression cassettes were created in order to selectively express different fluorescent fusion proteins in silk glands. The roles of different components in silk processing were investigated via observing and analyzing the movement and distribution of these proteins in the silk gland and in cocoon silk. The data showed that hydrophilic NTDs were distributed on the surface of micelles, providing sufficient electrostatic repulsion to prevent premature crystallization of silk proteins. Hydrophilic CTD==Ls ("==" represents the disulfide bond) were located on the inner layer of micelles to control the solubility of large micelles. The results presented here elucidated the underlying mechanisms of silkworm silk processing in vivo. This is significant for the development of artificial spinning technology, novel silk biomaterials, and silk gland expression systems.


Urine concentrations of selected trace metals in a cohort of Irish adults.
Human biomonitoring studies are of increasing importance in regulatory toxicology; however, there is a paucity of human biomonitoring data for the Irish population. In this study, we provide new data for urinary biomarker concentrations of aluminium, arsenic, cadmium, chromium, copper, mercury, manganese, lead and selenium. One hundred urine samples, collected between 2011 and 2014 from healthy participants of the EuroMOTOR project, were randomly selected. Metal concentrations were measured via ICPMS. Descriptive statistics for each of the metals stratified by gender were performed. There were 58 male and 42 female participants and metals were detectable for all samples. Geometric mean urinary concentrations for each metal in males were as follows: aluminium 8.5 μg/L, arsenic 8.1 μg/L, cadmium 0.3 μg/L, chromium 0.5 μg/L, copper 5.1 μg/L, mercury 0.4 μg/L, manganese 0.3 μg/L, lead 1.3 μg/L and selenium 10.8 μg/L; and in females: aluminium 8.5 μg/L, arsenic 10.2 μg/L, cadmium 0.4 μg/L, chromium 0.6 μg/L, copper 5.6 μg/L, mercury 0.3 μg/L, manganese 0.2 μg/L, lead 1.6 μg/L and selenium 13.7 μg/L. We observed higher geometric mean concentrations in women for arsenic, cadmium, chromium, copper, lead and selenium, with equal geometric mean concentrations for aluminium and manganese, leaving only mercury with lower geometric mean concentrations in women. Aluminium, cadmium, chromium, lead and urinary concentrations of metals were slightly elevated compared to European data, while for arsenic, copper, manganese and selenium, Irish levels were lower. Our findings highlight that there are differences in urinary metal concentrations between European populations.


Detection of Epstein-Barr virus genome and latent infection gene expression in normal epithelia, epithelial dysplasia, and squamous cell carcinoma of the oral cavity.
A relationship between Epstein-Barr virus (EBV) infection and cancer of lymphoid and epithelial tissues such as Burkitt's lymphoma, Hodgkin's disease, nasopharyngeal carcinoma (NPC), gastric carcinoma, and oral cancer has been reported. EBV is transmitted orally and infects B cells and epithelial cells. However, it has remained uncertain whether EBV plays a role in carcinogenesis of oral mucosal tissue. In the present study, we detected the EBV genome and latent EBV gene expression in normal mucosal epithelia, epithelial dysplasia, and oral squamous cell carcinoma (OSCC) to clarify whether EBV is involved in carcinogenesis of the oral cavity. We examined 333 formalin-fixed, paraffin-embedded tissue samples (morphologically normal oral mucosa 30 samples, gingivitis 32, tonsillitis 17, oral epithelial dysplasia 83, OSCC 150, and NPC 21). EBV latent infection genes (EBNA-2, LMP-1) were detected not only in OSCC (50.2 %, 10.7 %) but also in severe epithelial dysplasia (66.7 %, 44.4 %), mild to moderate epithelial dysplasia (43.1 %, 18.5 %), gingivitis (78.1 %, 21.9 %), and normal mucosa (83.3 %, 23.3 %). Furthermore, the intensity of EBV latent infection gene expression (EBER, LMP-1) was significantly higher in severe epithelial dysplasia (94.4 %, 72.2 %) than in OSCC (34.7 %, 38.7 %). These results suggest that EBV latent infection genes and their increased expression in severe epithelial dysplasia might play an important role in the dysplasia-carcinoma sequence in the oral cavity.


Determination of a reference value for N(G), N(G)-dimethyl-L-arginine in 500 subjects.
Asymmetric dimethylarginine (ADMA) acts as an endogenous inhibitor of NO-synthase. In the last years ADMA has emerged as a cardiovascular risk factor. The aim of this study was to determine a reference value for ADMA. Plasma samples of 500 healthy subjects in the 19-75 year age group were analyzed. Exclusion criteria from this study were smoking, any known significant disease, body-mass-index (BMI) above 30 kg m(-2), elevated plasma lipid levels, impaired renal function, hypertension, and intake of any medication. The ADMA levels were determined by ELISA, (DLD Diagnostics, Hamburg, Germany). Mean ADMA plasma concentration of the total population was 0.69 micromol L(-1) (SD 0.20) and 95% of the measured values were in the range from 0.36 micromol L(-1) to 1.17 micromol L(-1). Women below 50 years of age had lower ADMA levels than men below 50 years of age [0.62 (0.17) micromol L(-1) vs. 0.69 (0.19) micromol L(-1); P = 0.001] and woman above 50 years of age had higher ADMA levels than men above 50 years of age [0.80 (0.22) micromol L(-1) vs. 0.73 (0.20) micromol L(-1); P = 0.036]. A regression analysis of ADMA levels and age was performed for each sex. The regression factor was r = 0.444 for women in a squared regression model (P < 0.001) and r = 0.212 for men in a linear regression model (P < 0.001). The study was able to define a reference value for ADMA plasma levels with 0.36-1.17 micromol L(-1) and found sex dependent correlations between ADMA and age. Women showed a significant increase in ADMA plasma levels with onset of menopause.


Excitotoxin lesion of nucleus basalis causes a specific decrease in Go mRNA in cerebral cortex. Sensitivity to MK-801.
Lesions of the ascending cholinergic pathway from nucleus basalis are known to have profound effects on cortical function. In particular, a substantial potentiation of carbachol-stimulated polyphosphoinositide turnover is detected from 1 day after lesion and is maintained for several days before returning to normal by 1 month. In this study the effect of this lesion was investigated on levels of three G-protein alpha-subunit mRNAs. Excitotoxin lesion of the nucleus basalis caused a selective reduction in the levels of Go alpha mRNA in cerebral cortex ipsilateral to the lesion, Gs alpha and Gi alpha mRNA being unaffected. The maximal effect was obtained at 3 days after lesion where levels of Go alpha mRNA were decreased by 40% compared to sham-operated animals. Levels of Go alpha mRNA returned to normal values by 28 days. Treatment with MK-801 caused a significant attenuation of the decrease in Go alpha mRNA, indicating the involvement of NMDA receptors in this response.


Complete genome sequence of a novel bacteriophage vB_Pci_PCMW57 infecting phytobacteria pseudomonas cichorii.
A novel virulent bacteriophage infecting phytobacteria Pseudomonas cichorii (P. cichorii) was isolated from leafy vegetables in Brazil. P. cichorii is a Gram-negative soil phytobacterium, the causal agent of a number of economically important plant diseases worldwide. In this study, a new phage specific for P. cichorii was isolated from solid samples (lettuce, chicory and cabbage), designated vB_Pci_PCMW57. Electron microscopy revealed a small virion (~ 50-nm-diameter icosahedral capsid) with a short, non-contractile tail. The genome of vB_Pci_PCMW57 is 40,117 bp in size, with a GC content of 57.6% and encodes 49 open reading frames. The phage is genetically similar to P. syringae phages Pst_GM1 and Pst_GIL1, and the P. fluorescens phages WRT and KNP. According to electron microscopy and whole-genome sequence analysis, vB_Pci_PCMW57 should be classified as a Caudoviticetes, family Autographiviridae, subfamily Studiervirinae. The complete phage genome was annotated, and the sequence identity of the virus with other Pseudomonas viruses was higher than 95%. To our knowledge, this is the first report of a bacteriophage infecting Pseudomonas cichorii.


Fertile homozygous transgenic mice expressing a functional truncated herpes simplex thymidine kinase delta TK gene.
Dividing cells expressing the Herpes simplex type 1 thymidine kinase (TK) can be killed upon ganciclovir treatment. Likewise, conditional cell knock-out can be obtained in transgenic mice expressing a TK gene placed under the control of tissue-specific regulatory sequences. Such animals provide powerful experimental systems for assessing the functional role of specific cell populations through their time-controlled ablation. However, whatever the regulatory sequences used, a leaky toxic overexpression of TK in testis renders male TK-transgenic mice sterile and prevents the generation of homozygous TK-expressing animals. To solve this problem, we designed a truncated TK variant (delta TK) not expressed in the testis. We generated transgenic mice expressing delta TK under the control of lymphocyte-specific regulatory sequences derived from the CD4 gene. The delta TK protein expressed in T-lymphocytes allowed the conditional ablation of activated T-cells in vitro and in vivo. Importantly, for one transgenic line we could generate fertile homozygous mice harboring a functional delta TK transgene. delta TK should thus dramatically facilitate the development of transgenic mice expressing a conditional suicide gene.


Molecular memory of Flavescence dorée phytoplasma in recovering grapevines.
Flavescence dorée (FD) is a destructive phytoplasma disease of European grapevines. Spontaneous and cultivar-dependent recovery (REC) may occur in the field in FD-infected vines starting the year following the first symptoms. However, the biological underpinnings of this process are still largely unexplored. In this study, transcriptome sequencing (RNAseq), whole-genome bisulphite sequencing (WGBS) and metabolite analysis were combined to dissect molecular and metabolic changes associated to FD and REC in leaf veins collected in the field from healthy (H), FD and REC plants of the highly susceptible Vitis vinifera 'Barbera'. Genes involved in flavonoid biosynthesis, carbohydrate metabolism and stress responses were overexpressed in FD conditions, whereas transcripts linked to hormone and stilbene metabolisms were upregulated in REC vines. Accumulation patterns of abscisic acid and stilbenoid compounds analysed in the same samples confirmed the RNAseq data. In recovery conditions, we also observed the persistence of some FD-induced expression changes concerning inhibition of photosynthetic processes and stress responses. Several differentially expressed genes tied to those pathways also underwent post-transcriptional regulation by microRNAs, as outlined by merging our transcriptomic data set with a previously conducted smallRNAseq analysis. Investigations by WGBS analysis also revealed different DNA methylation marks between REC and H leaves, occurring within the promoters of genes tied to photosynthesis and secondary metabolism. The results allowed us to advance the existence of a "molecular memory" of FDp infection, involving alterations in the DNA methylation status of REC plants potentially related to transcriptional reprogramming events, in turn triggering changes in hormonal and secondary metabolite profiles.


Ovarian regulation of kisspeptin neurones in the arcuate nucleus of the rhesus monkey (macaca mulatta).
Tonic gonadotrophin secretion throughout the menstrual cycle is regulated by the negative-feedback actions of ovarian oestradiol (E₂) and progesterone. Although kisspeptin neurones in the arcuate nucleus (ARC) of the hypothalamus appear to play a major role in mediating these feedback actions of the steroids in nonprimate species, this issue has been less well studied in the monkey. In the present study, we used immunohistochemistry and in situ hybridisation to examine kisspeptin and KISS1 expression, respectively, in the mediobasal hypothalamus (MBH) of adult ovariectomised (OVX) rhesus monkeys. We also examined kisspeptin expression in the MBH of ovarian intact females, and the effect of E₂, progesterone and E₂ + progesterone replacement on KISS1 expression in OVX animals. Kisspeptin or KISS1 expressing neurones and pronounced kisspeptin fibres were readily identified throughout the ARC of ovariectomised monkeys but, on the other hand, in intact animals, kisspeptin cell bodies were small in size and number and only fine fibres were observed. Replacement of OVX monkeys with physiological levels of E₂, either alone or with luteal phase levels of progesterone, abolished KISS1 expression in the ARC. Interestingly, progesterone replacement alone for 14 days also resulted in a significant down-regulation of KISS1 expression. These findings support the view that, in primates, as in rodents and sheep, kisspeptin signalling in ARC neurones appears to play an important role in mediating the negative-feedback action of E₂ on gonadotrophin secretion, and also indicate the need to study further their regulation by progesterone.


The antidiuretic effect of pneumadin requires a functional arginine vasopressin system.
Pneumadin is an antidiuretic decapeptide, recently isolated from rat and human lung. Bolus intravenous injection of 5 nmol of pneumadin into water-loaded rats caused a rapid and significant antidiuresis and a reduction in Na+ and Cl- excretion. Pneumadin administration did not alter mean arterial pressure, right atrial pressure, heart rate or haematocrit. Bolus intravenous injection of 20 nmol of pneumadin into non-water-loaded rats caused a significant increase in arginine vasopressin (AVP) within 10 min. Pneumadin administration also increased circulating atrial natriuretic peptide (ANP) but did not alter aldosterone or plasma renin activity levels. Injection of pneumadin into water-loaded Brattleboro rats, which genetically lack circulating AVP, did not change urine flow, confirming that the pneumadin induced antidiuresis is AVP dependent. Radioactive pneumadin was cleared from the circulation with a t1/2 beta of 480.3 s. Radioactive pneumadin, isolated from plasma, eluted at an altered position on reverse phase HPLC, which indicated that the peptide was modified in vivo. This modification was also observed when synthetic pneumadin was incubated in rat plasma in vitro. Purification and sequencing of the modified synthetic peptide indicated that the modification is not a proteolytic cleavage. These results indicate that pneumadin injected into the rat caused an antidiuresis by altering circulating AVP levels.


Application of the forensic Luminol for blood in infection control.
Transmission of hepatitis C virus occurs frequently in haemodialysis units. A possible route of transmission is indirectly via the hospital environment although this has never been recorded. We investigated the haemodialysis unit in Deventer Hospital, Deventer, The Netherlands, with the forensic Luminol test. With this test, invisible traces of blood can be visualised based on the principle of biochemiluminescence. We demonstrated extensive contamination of the environment with traces of blood. The aim of this article is to introduce this method to infection control professionals, so it can be used to monitor cleaning and disinfection procedures, and alert healthcare workers to the possibility of contamination of the hospital environment with blood.


Exposure to Gambling and Alcohol Marketing in Soccer Matchday Programmes.
The UK's Premier League and Championship are two of the most well attended soccer leagues worldwide; however, little is known regarding exposure to gambling marketing through the matchday experience. The current study sought to quantify exposure to gambling and alcohol marketing, and responsible gambling messages within matchday programmes. Programmes for each team in the English Premier League and Championship were analysed across consecutive matchday weekends, made available to 1,269,404 match-going fans. Direct adverts for, and incidental exposure to, gambling, alcohol, and responsible gambling marketing or messages were coded. Direct adverts were counted, as were absolute counts and percentage of pages with incidental exposure. Programmes averaged 2.3 direct gambling adverts and 37.8 instances of incidental gambling marketing exposure. Incidental gambling marketing was found on 22.2% of pages. There was more gambling marketing than either alcohol marketing or responsible gambling messages. This was observed across: number of direct adverts (p < .001), incidents of exposure (p < .001) and the percentage of pages with exposure (p < .001). Teams with gambling shirt sponsors had more incidental marketing exposure, in both absolute count (p < .001) and percentage of pages (p < .001) but did not have more direct gambling adverts (p = .63). Incidental exposure to gambling marketing was present in 59.0% of children's specific sections of programmes. There was greater exposure to gambling marketing in soccer matchday programmes. Gambling marketing was frequently evident in child specific sections of matchday programmes. Attending soccer matches and reading the matchday programme increases exposure to gambling.


A fluorescent histochemical study of changes in noradrenergic neurons following experimental cerebral infarction in the rat.
Following surgical ligation of the middle cerebral artery in the rat, central catecholamine containing neurons were studied using the glyoxylic acid histochemical technique. By 5 days after the ischemic lesion, the density of fluorescent varicosities decreased in both uninjured cerebral cortex and the cerebellar cortex and the intensity of fluorescence of somata in the ipsilateral and contralateral locus coeruleus decreased as compared with controls. At 20 days afer lesioning, catecholamine containing neurons looked normal under fluorescence microscopic examination, except fine varicose fluorescent axons were present for the first time among the cellular debris of the lesion and appeared to have sprouted into the lesion site. However, by 40 days after surgery, there was a marked increase in the density of fluorescent varicosities in the uninjured ipsilateral cerebral cortex, in the contralateral cerebral cortex, and in the cerebellum. These observations confirm the view that an ischemic cortical lesion can lead to profound changes in cetecholamine containing neurons in distant areas of the brain which are uninjured by the local infarction.


Capillary gas chromatographic analysis of illicit diamorphine preparations.
An improved capillary gas chromatographic method for the analysis of illicit diamorphine preparation is reported. The method was able to resolve the impurities and more frequent adulterants and contaminants present in street heroin preparations with a diamorphine detection limit of 0.2 ng in split-less mode.


The effect of refined nursing education on improving the urination of patients after renal biopsy.
To investigate the clinical effect of better nursing education on patients' postoperative urination after renal biopsy. In this study, patients who underwent renal biopsy in the Department of Nephrology at our hospital were selected as the observation group (July-December 2018, n = 120) and control group (January-June 2018, n = 110) and received refined nursing education and routine nursing education, respectively. Postoperatively, the causes of dysuria after puncture, the degree of postoperative pain, and the urination mode were compared between the two groups. Six patients in the observation group and 23 patients in the control group needed urethral catheterization, accounting for about 5% and 15.2%, respectively. Therefore, the postoperative catheterization rate in the observation group was significantly lower than the control group, with a statistically significant difference. The refined nursing education proposed in this study can effectively improve urinary dysfunction after renal biopsy and has a clinical promotional value.


Persistent perfluorinated acids in seafood collected from two cities of China.
As an initial survey of human exposure to perfluorinated acids through food consumption in China, seven types of seafood collected from fish markets in two coastal cities were analyzed. Nine perfluorinated compounds were determined using HPLC coupled with ESI-MS/MS. Perfluorooctane sulfonate (PFOS) was the predominant fluorochemical and was found in all 27 seafood samples, including fish, molluscs, crabs, shrimp, oysters, mussels, and clams. Concentrations of PFOS in seafood samples ranged from 0.3 to 13.9 ng/g wet weight, with the highest concentration in mantis shrimp. The hazard ratios of noncancer risk through seafood consumption based on PFOS and perfluorooctanoic acid concentrations were calculated and were less than unity.


Metal oxide monolithic columns.
Metal oxide monoliths composed of ZrO2 and HfO2 have been synthesized in situ inside capillary columns. The material shows globular-like structure and through pores. Capillary electrochromatography and capillary liquid chromatography were performed in a monolithic column with the HfO2 material. Separation of a simple sample mixture showed the potential of the new metal oxide monolithic columns.


Haloketone transition state analog inhibitors of cholesterol esterase.
The cholesterol esterase-catalyzed hydrolysis of p-nitro-phenyl butyrate is reversibly inhibited by four phenyl haloalkyl ketones. Inhibitor potency is greatest for halogenated acetophenones and parallels the extent of hydration of the various ketones in buffered D2O. These results are consistent with an inhibition mechanism wherein haloketones reversibly form hemiketal adducts at the active site that structurally mimic tetrahedral intermediates of the cholesterol esterase catalytic cycle.


Unraveling the multi-targeted curative potential of bioactive molecules against cervical cancer through integrated omics and systems pharmacology approach.
Molecular level understanding on the role of viral infections causing cervical cancer is highly essential for therapeutic development. In these instances, systems pharmacology along with multi omics approach helps in unraveling the multi-targeted mechanisms of novel biologically active compounds to combat cervical cancer. The immuno-transcriptomic dataset of healthy and infected cervical cancer patients was retrieved from the array express. Further, the phytocompounds from medicinal plants were collected from the literature. Network Analyst 3.0 has been used to identify the immune genes around 384 which are differentially expressed and responsible for cervical cancer. Among the 87 compounds reported in plants for treating cervical cancer, only 79 compounds were targeting the identified immune genes of cervical cancer. The significant genes responsible for the domination in cervical cancer are identified in this study. The virogenomic signatures observed from cervical cancer caused by E7 oncoproteins serve as the potential therapeutic targets whereas, the identified compounds can act as anti-HPV drug deliveries. In future, the exploratory rationale of the acquired results will be useful in optimizing small molecules which can be a viable drug candidate.


Highly conserved, but highly specific: Somatic cell-cell fusion in filamentous fungi.
The development of ascomycete fungal colonies involves cell-cell fusion at different growth stages. In the model fungus Neurospora crassa, communication of two fusing cells is mediated by an unusual signaling mechanism, in which the two partners take turns in signal sending and receiving. In recent years, the molecular basis of this unusual cellular behavior has started to unfold, indicating the presence of an excitable signaling network. New evidence suggests that this communication system is highly conserved in ascomycete fungi and, unexpectedly, even mediates interspecies interactions. At the same time, intricate allorecognition mechanisms were identified, which prevent the fusion of genetically unlike individuals. These observations suggest that signal specificity during fungal social behavior has not evolved on the level of signals and receptors, but is achieved at downstream checkpoints. Despite growing insight into the molecular mechanisms controlling self and non-self fungal interactions, their role in natural environments remains largely unknown.


Psychometric testing of the facilitative student-patient relationship scale within six EUROPEAN countries.
The aim of the study was to test the psychometric properties of the Facilitative Student-Patient Relationship (FSPR) Scale in clinical practicum in hospital settings within six European countries. A multi-country, cross-sectional survey design was applied. A convenience sample of graduating nursing students (N = 1,796) completed the FSPR Scale. Psychometric testing was carried out through explorative factor analysis and confirmatory factor analysis. Internal consistency was assessed using Cronbach's alpha. Both validity and reliability of the scale were confirmed. The explorative factor analysis yielded a two-factor construct explaining 47.7% of the total variance, identifying two sub-scales: caring relationship and learning relationship. Confirmatory factor analysis confirmed the two-factor structure. The Cronbach alpha coefficients (0.8-0.9) indicated acceptable reliability of the scale.


Interrogating the configurational stability of atropisomers.
Atropisomers are molecules whose stereogenicity arises from restricted rotation about a single bond. They are of current importance because of their applications in catalysis, medicine and materials science. The defining feature of atropisomeric molecules is that their stereoisomers are related to one another by bond rotation: as a result, evaluating their configurational stability (i.e., the rate at which their stereoisomers interconvert) is central to any work in this area. Important atropisomeric scaffolds include C-C linked biaryls, such as the ligand BINAP and the drug vancomycin, and C-N linked amine derivatives such as the drug telenzepine. This article focuses on the three most widely used experimental methods that are available to measure the rate of racemization in atropisomers, namely: (i) kinetic analysis of the racemization of an enantioenriched sample, (ii) dynamic HPLC and (iii) variable-temperature NMR. For each technique, an explanation of the theory is set out, followed by a detailed experimental procedure. A discussion is also included of which technique to try when confronted with a new molecular structure whose properties are not yet known. None of the three procedures require complex experimental techniques, and all can be performed by using standard analytical equipment (NMR and HPLC). The time taken to determine a racemization rate depends on which experimental method is required, but for a new compound it is generally possible to measure a racemization rate in <1 d.


Image cytometry of insular carcinoma.
To study the morphometric features of insular carcinoma (IC) of thyroid and follicular carcinoma (FC) in fine needle aspiration cytology (FNAC) smear to evaluate the role of the morphometric features to distinguish these two groups. We performed image morphometry in Hematoxyline and Eosin stained FNAC smears of eight each histopathology proven cases of IC and FC of thyroid. Nuclear area, diameter, perimeter, and standard deviation of nuclear area (SDNA) of these two groups were studied and compared. Nuclear area, diameter, perimeter, and SDNA of IC and FC were 30.43 μ(2) , 7.31 μ, 23.01 μ, 8.81 and 38.43 μ(2) , 7.66 μ, 25.63 μ, 10.83, respectively. Student's t-test analysis did not show any significant difference (P > 0.05) in these two groups. Nuclear morphometry data indicate that the nuclear size and shape of IC and FC are essentially similar and it is not possible to differentiate these two entities with the help of image morphometric data.


Intrinsic Muscle Flaps for Coverage of Small Defects in the Foot.
Exposure of critical structures such as joints, bones, ligaments, and tendons necessitates expeditious closure. The longer these structures remain open to the environment, the higher the risk is for that patient developing osteomyelitis and an amputation. Muscle flaps remain often first choice when dealing with bone infections associated with osteomyelitis, soft tissue infections, and large cavities. Foot defects are a challenge especially in the absence of microsurgical expertise. Intrinsic local flaps of the foot can be an option to cover defects. This article describes local intrinsic muscle flaps for coverage of foot defects.


A computational model of organism development and carcinogenesis resulting from cells' bioelectric properties and communication.
A sound theory of biological organization is clearly missing for a better interpretation of observational results and faster progress in understanding life complexity. The availability of such a theory represents a fundamental progress in explaining both normal and pathological organism development. The present work introduces a computational implementation of some principles of a theory of organism development, namely that the default state of cells is proliferation and motility, and includes the principle of variation and organization by closure of constraints. In the present model, the bioelectric context of cells and tissue is the field responsible for organization, as it regulates cell proliferation and the level of communication driving the system's evolution. Starting from a depolarized (proliferative) cell, the organism grows to a certain size, limited by the increasingly polarized state after successive proliferation events. The system reaches homeostasis, with a depolarized core (proliferative cells) surrounded by a rim of polarized cells (non-proliferative in this condition). This state is resilient to cell death (random or due to injure) and to limited depolarization (potentially carcinogenic) events. Carcinogenesis is introduced through a localized event (a spot of depolarized cells) or by random depolarization of cells in the tissue, which returns cells to their initial proliferative state. The normalization of the bioelectric condition can reverse this out-of-equilibrium state to a new homeostatic one. This simplified model of embryogenesis, tissue organization and carcinogenesis, based on non-excitable cells' bioelectric properties, can be made more realistic with the introduction of other components, like biochemical fields and mechanical interactions, which are fundamental for a more faithful representation of reality. However, even a simple model can give insight for new approaches in complex systems and suggest new experimental tests, focused in its predictions and interpreted under a new paradigm.


Enzymes of galactose utilization in the rat tapeworm, Hymenolepis diminuta.
1. Crude enzyme preparations from Hymenolepis diminuta contained galactokinase, galactose 1-phosphate uridyl transferase and UDPgalactose 4-epimerase activity, although their specific activities were low. 2. Galactose 1-phosphate non-competitively inhibited galactose phosphorylation. This inhibition, together with the low specific activities of the enzymes in the pathway of galactose utilization, probably accounts for the inadequacy of galactose as a main nutritive carbohydrate for development of the worm.


Temporal-based Swin Transformer network for workflow recognition of surgical video.
Surgical workflow recognition has emerged as an important part of computer-assisted intervention systems for the modern operating room, which also is a very challenging problem. Although the CNN-based approach achieves excellent performance, it does not learn global and long-range semantic information interactions well due to the inductive bias inherent in convolution. In this paper, we propose a temporal-based Swin Transformer network (TSTNet) for the surgical video workflow recognition task. TSTNet contains two main parts: the Swin Transformer and the LSTM. The Swin Transformer incorporates the attention mechanism to encode remote dependencies and learn highly expressive representations. The LSTM is capable of learning long-range dependencies and is used to extract temporal information. The TSTNet organically combines the two components to extract spatiotemporal features that contain more contextual information. In particular, based on a full understanding of the natural features of the surgical video, we propose a priori revision algorithm (PRA) using a priori information about the sequence of the surgical phase. This strategy optimizes the output of TSTNet and further improves the recognition performance. We conduct extensive experiments using the Cholec80 dataset to validate the effectiveness of the TSTNet-PRA method. Our method achieves excellent performance on the Cholec80 dataset, which accuracy is up to 92.8% and greatly exceeds the state-of-the-art methods. By modelling remote temporal information and multi-scale visual information, we propose the TSTNet-PRA method. It was evaluated on a large public dataset, showing a high recognition capability superior to other spatiotemporal networks.


Organ-Retentive Osmotically Driven System (ORODS): A Novel Expandable Platform for in Situ Drug Delivery.
Drug delivery systems capable of being retained within hollow organs allow the entire drug dose to be delivered locally to the disease site or to absorption windows for improved systemic bioavailability. A novel Organ-Retentive Osmotically Driven System (ORODS) was here proposed, obtained by assembling drug-containing units having prolonged release kinetics with osmotic units used as increasing volume compartments. Particularly, prototypes having H-shape design were conceived, manufactured and evaluated. Such devices were assembled by manually inserting a tube made of regenerated cellulose (osmotic unit) into the holes of two perforated hydrophilic tableted matrices containing paracetamol as a tracer drug. The osmotic unit was obtained by folding and gluing a plain regenerated cellulose membrane and loading sodium chloride inside. When immersed in aqueous fluids, this compartment expanded to approximately 80% of its maximum volume within 30 min of testing, and a plateau was maintained for about 6 h. Subsequently, it slowly shrank to approximately 20% of the maximum volume in 24 h, which would allow for physiological emptying of the device from hollow organs. While expanding, the osmotic unit acquired stiffness. Drug release from H-shaped ORODSs conveyed in hard-gelatin capsules was shown to be prolonged for more than 24 h.


Nationwide analysis of the impact of COVID-19 in patients with a cardiovascular, oncological or chronic pulmonary disease in the context of an Eastern European country with a low vaccination rate, Bulgaria: March 2020-April 2022.
This study focused on Bulgarian patient cohorts harbouring a single documented chronic comorbidity-cardiovascular pathology, an oncological disease or a chronic pulmonary diseases (CPD) comparing the outcomes in fully vaccinated and non-vaccinated populations classified by sex and age groups in ambulatory, hospital and intensive care unit (ICU) settings at the national level. Retrospective analysis SETTINGS, PARTICIPANTS AND OUTCOME MEASURES: In total, 1 126 946 patients with confirmed COVID-19, on a national level, were retrospectively analysed between March 2020 and April 2022, using data from the Ministry of Health's United Information Portal, launched in March 2020. Of all the confirmed 247 441 hospitalised cases of COVID-19, 67 723 (27.3%) had documented cardiovascular disease (CVD), 2140 (0.9%) had confirmed solid malignancy (regardless of stage) and 3243 (1.3%) had established CPD as their only chronic pathology. The number of cumulative deaths in each subgroup was 10 165 (in-hospital=5812 and ICU=4353); 4.0% vaccinated (410/10 165, p<0.001), 344 (in-hospital=196 and ICU=148), 4.9% vaccinated (17/344, p<0.001), 494 (in-hospital=287 and ICU=207) and 5.2% vaccinated (26/494, p<0.001), respectively. Statistical significance (p<0.001) was obtained in favour of reduced ambulatory, hospitalisation and both in-hospital and ICU-related mortality in the vaccinated cohorts, and BNT162b2 was the most effective at preventing mortality in all age groups. This retrospective analysis shows that patients vaccinated against COVID-19 demonstrated trends of reduced hospitalisations and premature mortality in patients with CVD, solid malignancy or CPD as a single comorbidity.


Effect of vitamin B1 supplementation on blood creatinine and lactate levels and clinical outcomes in patients in intensive care units: a systematic review and meta-analysis of randomized controlled trials.
The metabolic response to stress can deplete the remaining thiamine stores, leading to thiamine deficiency. This study is the first meta-analysis of the effectiveness of thiamine supplementation on clinical and biochemical outcomes in adult patients admitted to the intensive care unit (ICU). Scopus, PubMed, and Cochrane databases were searched to select studies up to 20 November 2022. Studies investigating the effect of thiamine supplementation on serum lactate and creatinine levels, the need for renal replacement therapy, length of ICU stay, and mortality rate in ICU patients were selected. After excluding studies based on title and abstract screening, 2 independent investigators reviewed the full texts of the remaining articles. In the next step, a third investigator resolved any discrepancy in the article selection process. Of 1628 retrieved articles, 8 were selected for final analysis. This study showed that thiamine supplementation reduced the serum creatinine level (P = .03) compared with placebo. In addition, according to subgroup analysis, serum creatinine concentration was significantly lower in patients >60 years old (P < .00001). However, there was no statistically significant difference in the lactate level between the thiamine supplementation and placebo groups (P = .26). Thiamine supplementation did not decrease the risk of all-cause mortality (P = .71) or the need for renal replacement therapy (P = .14). The pooled results of eligible randomized controlled trials also showed that thiamine supplementation did not reduce the length of ICU stay in comparison to the placebo group (P = .39). This meta-analysis provides evidence that thiamine supplementation has a protective effect against blood creatinine increase in ICU patients. However, further high-quality trials are needed to discover the effect of thiamine supplementation on clinical and biochemical outcomes in ICU patients. PROSPERO no. CRD42023399710 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=399710).


Double-strand RNAs targeting MaltRelish and MaltSpz reveals potential targets for pest management of Monochamus alternatus.
Overcoming the innate immunity of insects is a key process to improve the efficiency of biological control. Antimicrobial peptides (AMPs) are important effectors in insect innate immunity, usually mediating resistance to pathogenic microorganisms through Toll and IMD signaling pathways. This study investigated the effect of key genes on upstream immune recognition receptor (GNBP3) and downstream effectors (AMPs) by RNAi technology. The transcriptome KEGG enrichment analysis and differential gene annotation results showed that the immune response genes MaltSpz and MaltRelish are important regulators of Toll and IMD signaling pathways, respectively. Both dsSpz and dsRelish could affect AMP gene expression and increase the expression of the immune recognition receptor MaltGNBP3. Moreover, they significantly reduce the survival rate of Monochamus alternatus and promote hyphal growth after Beauveria bassiana infection. This helps to improve the biological control effect of B. bassiana, control the population of vector insects and cut off the transmission route of pine wood nematode. The combined MaltSpz and MaltRelish knockdown increased the infection rate of M. alternatus larvae from 20.69% to 83.93%, achieving the best efficiency in synergistic B. bassiana infection. Our results showed important roles of MaltRelish- and MaltSpz-mediated regulation of AMP genes function in insect entomopathogenic fungi tolerance and induced significant mortality in larvae. Based on this study, MaltSpz and MaltRelish could represent candidate gene targets for the biological control of M. alternatus by RNAi.


[Health care needs of children and adolescents with a traumatic brain injury].
Traumatic brain injury is a leading cause of acquired disability in childhood. Within a project to improve out-patient rehabilitation and aftercare advice, centres for families affected by traumatic brain injuries were implemented in four German cities. The results of two sub-studies are described which aimed on the one hand at a process analysis of the network operation and on the other hand at a prospective analysis of the network interaction. The process analysis was based on a database which was developed for this study. Within a prospective longitudinal study, 103 families could be included. At four project sites, families were questioned with an interview and questionnaire at three different time points. Health-related quality of life, utilisation and health care satisfaction were assessed. In addition, a neuropsychological assessment was conducted with a portion of the sample. Overall, quality of life of the children and adolescents can be described as good. Health care services were scarcely utilised. A childcentred health care was predictive for the health care satisfaction of the parents. The short assessment proved to be a feasible method for identifying children and adolescents with special health care needs.


Pancreas-kidney transplantations with primary bladder drainage followed by enteric conversion: graft survival and outcomes.
In the Leiden University Medical Centre, a two-step approach is routinely used in simultaneous pancreas-kidney (SPK) transplantations: primary bladder drainage (BD) followed by elective enteric conversion. The rationale for this approach is to prevent the short-term disadvantages of primary enteric drainage (intra-abdominal abscesses, pancreas graft loss) and the long-term urological complications related to bladder drainage. Aim of the present study is to evaluate survival and (urological) complications of this approach compared to enteric drainage (ED). Patient records of all 98 SPK transplantations in the period 1997-2004 were reviewed for complications during the initial hospitalization until 30 days after discharge, and to assess urological complications and graft survival until the last hospital visit. Median duration of follow-up was 4.3 years for pancreas graft survival, 4.7 years for kidney graft survival, and 4.8 years for patient survival. Patient survival was significantly better in BD patients than in ED patients (chi2=9.89 P<0.01). Pancreas graft survival was also better in BD patients after adjustment for the longer pancreas warm ischemia time in BD patients (P=0.05). The survival rates in our patient population seem higher than reported by the International Pancreas Transplant Registry, particularly in BD patients. Urological complications occurred in nine BD patients (10.3%), comparable to the rates reported for enteric-drained grafts. This two-step approach of SPK transplantation results in excellent survival rates, with urological complication rates comparable to those reported for enteric-drained grafts, and may thus be viewed as a safe and effective procedure of SPK transplantation.


An updated analysis of the association between CD2-associated protein gene rs9349407 polymorphism and Alzheimer's disease in Chinese population.
Since 2011, three large-scale genome-wide association studies (GWAS) have confirmed that the CD2AP rs9349407 polymorphism is significantly connected with Alzheimer's disease (AD) in individuals of European descent. Subsequently, this association has been replicated in European populations, but is unclear whether it can be replicated in Chinese. Recently, the correlation between rs9349407 and AD in the Chinese population has become a research hotspot. To explore the association between rs9349407 polymorphism and AD in the Chinese population. Firstly, based on the exclusion and inclusion criteria, we selected 11 independent studies from 8 articles exploring the correlation between rs9349407 variation and AD in Chinese. Secondly, we conducted a meta-analysis based on fixed and random effect models and conducted a heterogeneity test. Thirdly, we used the additive model, dominant model, and recessive model for subgroup analysis. We demonstrated that the CD2AP rs9349407 polymorphism increases AD susceptibility in Chinese populations (OR = 1.33, 95% CI = 1.08-1.64, P = 7.45E-03), which is consistent with the effect observed in Caucasian populations. Additionally, subgroup analysis showed that rs9349407 under the additive model (GG + CC vs. GC, OR = 0.76, 95% CI = 0.61-0.97, P = 2.04E-02) and dominant model (GG + GC vs. CC, OR = 0.49, 95% CI = 0.32-0.74, P = 8.51E-04) were also significantly correlated with AD susceptibility, but not under the recessive model (GG vs. GC + CC, OR = 0.77, 95% CI = 0.58-1.03, P = 7.44E-02). These existing data suggest that rs9349307 is significantly correlated with the susceptibility to AD in the Chinese population, but future studies with large samples are needed to confirm our findings.


Perception of speech stress in children with hearing impairment.
The study aimed to test effect of training on the perception of speech stress in children with severe to profound hearing impairment. The first objective was to compare the speech stress perception scores of children with hearing impairment and language age-matched children with normal hearing sensitivity after short term prosody training and the second objective was to correlate between the speech stress perception scores and the language age of the children with hearing impairment. Thirty children with normal hearing (CWNH) in the age range of 3-7 years and thirty children with hearing impairment (CWHI) who had a language age of 3-7 years participated in the study. The authors formulated 24 concrete Malayalam sentences and their picture cognate pairs (stressed and unstressed) for each sentence. The stressed and unstressed version for each sentence was audio recorded separately.The study was carried out in two phases; phase 1 included the training on acoustic cues of speech stress followed by testing in phase 2. Both the phases were attended by all the participants. There was a significant difference between the CWNH and CWHI wherein, children with hearing impairment had lower speech stress perception scores. However, improvements in speech stress perception were observed in children with hearing impairment after the training phase. Also, a positive correlation between the language age and the perception of speech stress scores in CWHI was found indicating that as the language age increased there was an increase in the speech stress perception scores. The pre and post training speech stress perception scores were significantly different, with higher scores on the post-training test, indicating that the short term speech stress training for the children with hearing impairment was beneficial. The positive strong correlation between stress perception scores and language age shows that, prosody perception and language learning facilitate each other. Thereby, the conventional speech-language and auditory training should expand and include prosody training from an early age for children with hearing impairment.


Multi-strain infections and 'relapse' of Leucocytozoon sabrazesi gametocytes in domestic chickens in southern China.
Leucocytozoon parasites infect many species of avian hosts, including domestic chicken, and can inflict heavy economic loss to the poultry industry. Although the prevalence and distribution of two Leucocytozoon species (L. sabrazesi and L. caulleryi) have been reported in China previously, there are many questions related to the parasite infection that remain unanswered, including population diversity and transmission dynamics in domestic chickens. Here we surveyed chicken blood samples from seven sites in four provinces of China to identify Leucocytozoon infection, characterized parasite diversity within individual infected hosts and between sampling sites, and investigated the dynamics of gametocytemia in chickens over time. We found high infection rates in three of the seven sites. Clustering parasite sequences of the mitochondrial cytochrome oxidase III (coxIII) and cytochrome b (cytb) genes showed lack of grouping according to geographic origins and individual hosts carrying large numbers of L. sabrazesi strains. Monitoring gametocytemia in blood samples from infected chickens over time showed 'relapse' or persistence of low-level gametocytemia for 4-5 months, which could be explored as an in vivo model for testing drugs against liver stages of Apicomplexan parasites. This study provides important information on population diversity and transmission dynamics of L. sabrazesi and for disease control.


Discovery of 2H-chromone-4-one based sulfonamide derivatives as potent retinoic acid receptor-related orphan receptor γt inverse agonists.
Retinoic acid receptor related orphan receptor γt (RORγt), identified as the essential functional regulator of IL-17 producing Th17 cells, is an attractive drug target for treating autoimmune diseases. Starting from the reported GSK2981278 (Phase II), we structurally modified and synthesized a series of 2H-chromone-4-one based sulfonamide derivatives as novel RORγt inverse agonists, which significantly improved their human metabolic stabilities while maintaining a potent RORγt inverse agonist profile. Efforts in reducing the lipophilicity and improving the LLE values led to the discovery of c9, which demonstrated potent RORγt inverse agonistic activity and consistent metabolic stability. During in vivo studies, oral administration of compound c9 exhibited a robust and dose-dependent inhibition of IL-17A cytokine expression and significantly lessened the skin inflammatory symptoms in the mouse imiquimod-induced skin inflammation model. Docking analysis of the binding mode revealed that c9 can suitably occupy the active pocket, and the introduction of the morpholine pyridine group can interact with Leu396, His479, and Cys393. Thus, compound c9 was selected as a preclinical compound for treating Th17-driven autoimmune diseases.


The use of nonhomologous scatchard analysis in the evaluation of ligand-protein interactions.
Scatchard plots are widely used for the graphical presentation of receptor-ligand binding data. When a combination of labelled and unlabelled ligand molecules is used in a binding assay, equations for Scatchard plots are readily available if the labelled and unlabelled ligands have similar binding affinities. In this article, Everardus van Zoelen, Roel Kramer, Herman van Moerkerk and Jacques Veerkamp present mathematical equations to obtain the binding characteristics of an unlabelled ligand in a Scatchard plot, which has a dissociation equilibrium constant different from that of the labelled ligand used.


A series of unfortunate events: Long-neglected malpositioned pacemaker and its consequences.
Use of pacemakers has increased in recent years, and they have become the premier treatment option for several arrhythmias. However, they are not without risk; this case report aims to show the importance of follow-up and adherence to guidelines, and methods to diagnose a life-threatening complication.


Immunoreactive leucine-enkephalin content in brains of epileptic E1 mice.
The immunoreactive leucine-enkephalin (IR Leu-E) content in the brains of epileptic E1 mice was determined. E1 mice are mutants from the dd strain of mice and are susceptible to convulsions. Seizures were elicited in E1 mice by repeated postural stimulations. As controls, ddY strain (nonconvulsive) mice and nonstimulated E1 mice (which had not developed convulsions) were used. IR Leu-E content was measured by radioimmuno-assay. Before the convulsion, the IR Leu-E content in the striatum of E1 mice was 60% of the content in the controls. In the hypothalamus, IR Leu-E levels were increased by 85% 45 min after a convulsion. IR Leu-E was also increased in the striatum (176% of preconvulsive state), cortex (121%), medulla oblongata + pons (132%), hypothalamus (180%), and midbrain (159%) 48 h after a convulsion.


The microbiome, HLA, and the pathogenesis of uveitis.
An understanding of the microbiome is emerging as an exciting and novel way to elucidate the regulation of the immune system. Since the immune system plays a major role in the pathogenesis of many diseases including most forms of uveitis, it is critical to clarify the relationship between our immune system and the commensal bacteria that coexist in every human being.


A Review of Current State-of-the-Art Control Methods for Lower-Limb Powered Prostheses.
Lower-limb prostheses aim to restore ambulatory function for individuals with lower-limb amputations. While the design of lower-limb prostheses is important, this paper focuses on the complementary challenge - the control of lower-limb prostheses. Specifically, we focus on powered prostheses, a subset of lower-limb prostheses, which utilize actuators to inject mechanical power into the walking gait of a human user. In this paper, we present a review of existing control strategies for lower-limb powered prostheses, including the control objectives, sensing capabilities, and control methodologies. We separate the various control methods into three main tiers of prosthesis control: high-level control for task and gait phase estimation, mid-level control for desired torque computation (both with and without the use of reference trajectories), and low-level control for enforcing the computed torque commands on the prosthesis. In particular, we focus on the high- and mid-level control approaches in this review. Additionally, we outline existing methods for customizing the prosthetic behavior for individual human users. Finally, we conclude with a discussion on future research directions for powered lower-limb prostheses based on the potential of current control methods and open problems in the field.


Synthetic peptide SVVYGLR upregulates cell motility and facilitates oral mucosal wound healing.
Osteopontin-derived SVVYGLR (SV) 7-amino-acid sequence is a multifunctional and synthetic SV peptide implicated in angiogenesis, production of collagen III, and fibroblast differentiation into myofibroblasts. This study investigated the effect of the SV peptide on mucosal wound healing activity. Normal human-derived gingival fibroblasts (NHGF) and human oral mucosa keratinocytes (HOMK) were used for in vitro experiments. In addition, an oral punch wound was prepared at the buccal mucosa in male rats aged 11 weeks, and we evaluated the effect of local injection of SV peptide on wound healing. The synthetic SV peptide showed no influence on the proliferation and adhesion properties of NHGF and HOMK, but it enhanced the cell motility and migration activities. TGF-β1 receptor inhibitor, SB431542 or SB505124, substantially suppressed the SV peptide-induced migration activity, suggesting an involvement of TGF-β1 receptor activation. Furthermore, SV peptide accelerated the healing process of an in vivo oral wound model, compared with control groups. Further immunohistological staining of wound tissue revealed that an increase in capillary growth and the greater number of fibroblasts and myofibroblasts that migrated into the wound area might contribute to the facilitation of the healing process produced by the SV peptide. The SV peptide has beneficial effects on oral wound healing through enhancement of the earlier phase consisting of angiogenesis and remodeling with granulation tissue. The synthetic SV peptide can be a useful treatment option, particularly for intractable mucosal wounds caused by trauma or surgery for progressive lesions such as oral cancer.


Rosiglitazone and imidapril alone or in combination alleviate muscle and adipose depletion in a murine cancer cachexia model.
Rosiglitazone (RGZ) and imidapril improve cancer cachexia via different mechanisms. Therefore, we hypothesized that combination therapy of RGZ+imidapril would further attenuate cancer cachexia in vivo. After injection with colon-26 adenocarcinoma for 9 days, BALB/c mice were randomly divided into the following four treatment groups for 7 days (n = 8 per group): (1) placebo, (2) RGZ, (3) imidapril, and (4) RGZ+imidapril. Eight healthy control animals were also assessed. Body weight, tumor volume, gastrocnemius muscle and epididymal adipose mass, serum metabolic markers and cytokines, and the expression of nuclear factor-κB and two E3 ubiquitin ligases, atrogin-1 and MuRF-1, were measured. From days 14 to 16, all treatments significantly reduced tumor volume (P < 0.05). From days 10 to 16, improvements in the tumor-free body weight were observed in the RGZ and RGZ+imidapril groups. In addition, significant improvements in both gastrocnemius muscle and epididymal adipose mass were observed in all treatment groups (all, P < 0.05). Furthermore, all treatments significantly increased tumor necrosis factor alpha levels as compared to those observed in the healthy control animals (P < 0.001). Insulin levels significantly increased in the placebo group as compared to those in the healthy control group (P < 0.05), which were reduced in all the treatment groups (P < 0.05). Finally, whereas all treatments significantly reduced atrogin-1 levels as compared to the placebo group (all, P < 0.05), significant reductions in MuRF-1 levels were only observed in the RGZ and RGZ+imidapril groups (both, P < 0.05). Thus, all three treatments reduce tumor growth and alleviate cancer cachexia; however, synergistic effects of RGZ+imidapril combination therapy were not observed.


Synaptobrevin-2-like immunoreactivity is associated with vesicles at synapses in rat circumvallate taste buds.
Synaptobrevin is a vesicle-associated membrane protein (VAMP) that is believed to play a critical role with presynaptic membrane proteins (SNAP-25 and syntaxin) during regulated synaptic vesicle docking and exocytosis of neurotransmitter at the central nervous system. Synaptic contacts between taste cells and nerve processes have been found to exist, but little is known about synaptic vesicle docking and neurotransmitter release at taste cell synapses. Previously we demonstrated that immunoreactivity to SNAP-25 is present in taste cells with synapses. Our present results show that synaptobrevin-2-like immunoreactivity (-LIR) is present in approximately 35% of the taste cells in rat circumvallate taste buds. Synaptobrevin-2-LIR colocalizes with SNAP-25-, serotonin-, and protein gene product 9.5-LIR. Synaptobrevin-2-LIR also colocalizes with immunoreactivity for type III inositol 1,4,5-triphosphate receptor (IP3R3), a taste-signaling molecule in taste cells. All IP3R3-LIR taste cells express synaptobrevin-2-LIR. However, approximately 27% of the synaptobrevin-2-LIR taste cells do not display IP3R3-LIR. We believe, based on ultrastructural and biochemical features, that both type II and type III taste cells display synaptobrevin-2-LIR. All of the synapses that we observed from taste cells onto nerve processes express synaptobrevin-2-LIR, as well as some taste cells without synapses. By using colloidal gold immunoelectron microscopy, we found that synaptobrevin-2-LIR is associated with synaptic vesicles at rat taste cell synapses. The results of this study suggest that soluble NSF attachment receptor (SNARE) machinery may control synaptic vesicle fusion and exocytosis at taste cell synapses.


Cardiovascular reactivity of younger and older adults to positive-, negative-, and mixed-emotion cognitive challenge.
Although aging is associated with progressive increases in blood pressure level, previous research has been inconsistent as to whether older adults show greater or lesser cardiovascular reactivity (CVR) to emotion than do younger adults. There is reason to believe that these inconsistencies could be clarified by examining age-related differences in hemodynamic profile revealed by measuring the pattern of cardiac output and total peripheral resistance associated with changes in blood pressure reactivity. Accordingly, the present study examined the performance, CVR, and hemodynamic profile of younger and older adults during encoding and recognition of word pairs involving four valence types: positive, negative, mixed (positive/negative), and neutral word pairs. Results revealed higher baseline blood pressure, increased CVR characterized by a vascular hemodynamic profile, and more rapid recovery (especially during encoding) for older than for younger participants. Results are discussed in light of research and theory on the relationship between aging and cardiovascular health.


Catecholamine stimulation of testosterone production via cyclic AMP in mouse Leydig cells in monolayer culture.
The effects of the beta-adrenergic hormone agonist, isoproterenol, on testosterone and cyclic AMP production in mouse Leydig cells in culture have been investigated. It was found that isoproterenol increased testosterone production on days 1, 2 and 3 of culture but not in freshly cultured cells. Cyclic AMP production was however increased on all days of culture. In subsequent studies carried out on day 2 of culture the amounts of testosterone formed during incubation with isoproterenol were 20-90% of those obtained with maximum stimulating levels of luteinizing hormone. The amounts of cyclic AMP formed were extremely low compared with those obtained with luteinizing hormone (22 +/- 5.3 and 2320 +/- 100 pmoles/10(6) cells/2 h respectively). Isoproterenol (10(-8) -10(-7) M) gave a significant increase in testosterone production and reached a maximum with 10(-6) M. Similar dose-response curves for cyclic AMP production were obtained. The stimulation of cyclic AMP and testosterone by isoproterenol was highly dependent on the presence of the phosphodiesterase inhibitor, methylisobutylxanthine. Propranolol blocked, in a dose-dependent manner, both isoproterenol-stimulated cyclic AMP and testosterone production. In the presence of excess luteinizing hormone no additional effects of isoproterenol were detected. Epinephrine also stimulated testosterone production. It is concluded that catecholamines stimulate testosterone production in mouse Leydig cells in monolayer culture and that this effect if mediated by cyclic AMP.


Characteristics of Youth Presenting to a Canadian Youth Concurrent Disorders Program: Clinical Complexity, Trauma, Adaptive Functioning and Treatment Priorities.
This study describes clinical characteristics of youth presenting for service at a Canadian youth concurrent mental health and substance use disorders (SUD) program. Participants were 100 adolescents and emerging adults (aged 14-25) who attended a Canadian concurrent mental health and substance use disorders outpatient program. SUDs were assigned using the Structured Clinical Interview for DSM-IV. Self-reported mental health symptoms, trauma exposure and adaptive functioning were also assessed. Eighty-three percent of participants scored over the clinical cut-off on at least one mental health scale and 33% reported at least one suicide attempt. Sixty-six percent met criteria for a current SUD; 96% met lifetime criteria. Exposure to adverse events was nearly universal (94%). Almost half of female (46%) and almost a third of male (31%) participants endorsed symptoms consistent with posttraumatic stress disorder (PTSD). Youth reported impairment and need for support in multiple domains of functioning, including school, peer, family and mental health. Substance use was least likely to be identified as a treatment priority. High rates of adverse events and PTSD highlight the need for trauma-informed care when providing services to this vulnerable population. Functional impairment in domains related to developmental transitions and tasks underscores the need for a developmental lens and integrated treatment that goes beyond mental health and SUD symptoms and addresses developmentally relevant domains during this transitional age.


Tunable Photoluminescence across the Visible Spectrum and Photocatalytic Activity of Mixed-Valence Rhenium Oxide Nanoparticles.
Materials exhibiting excitation-wavelength-dependent photoluminescence, PL, are useful in a range of biomedical and optoelectronic applications. This paper describes a nanoparticulate material whose PL is tunable across the entire visible range and is achieved without adjusting particle size, any postsynthetic doping, or surface modification. A straightforward thermal decomposition of rhenium (VII) oxide precursor yields nanoparticles that comprise Re atoms at different oxidation states. Studies of time-resolved emission spectra and DFT calculations both indicate that tunable PL of such mixed-valence particles originates from the presence of multiple emissive states that become "active" at different excitation wavelengths. In addition, the nanoparticles exhibit photocatalytic activity that, under visible-light irradiation, is superior to that of TiO2 nanomaterials.


Composition and function of the eukaryotic N-terminal acetyltransferase subunits.
Saccharomyces cerevisiae contains three N-terminal acetyltransferases (NATs), NatA, NatB, and NatC, composed of the following catalytic and auxiliary subunits: Ard1p and Nat1p (NatA); Nat3p and Mdm20p (NatB); and Mak3p, Mak10, and Mak31p (NatC). The overall patterns of N-terminally acetylated proteins and NAT orthologous genes suggest that yeast and higher eukaryotes have similar systems for N-terminal acetylation. The differential expression of certain NAT subunits during development or in carcinomas of higher eukaryotes suggests that the NATs are more highly expressed in cells undergoing rapid protein synthesis. Although Mak3p is functionally the same in yeast and plants, findings with TE2 (a human Ard1p ortholog) and Tbdn100 (a mouse Nat1p ortholog) suggest that certain of the NAT subunits may have functions other than their role in NATs or that these orthologs are not functionally equivalent. Thus, the vertebrate NATs remain to be definitively identified, and, furthermore, it remains to be seen if any of the yeast NATs contribute to other functions.


Prevalence and resistance profile of bacteria isolated from wound infections among a group of patients in upper Egypt: a descriptive cross-sectional study.
This cross-sectional survey aimed to identify aerobic bacteria, antimicrobial resistance, and multi-drug resistance profiles of bacteria isolated from different wound infections among a group of Egyptian patients. Of 120 positive samples, 170 isolates were identified. Polymicrobial infections were determined in 55% of samples. The dominant Gram-positive isolated strains were Staphylococcus aureus, especially from wound infections because of accidents (71.8%). Piperacillin, methicillin, ampicillin/sulbactam, and amoxicillin/clavulanic acid were all highly resistant to S. aureus and Coagulase-negative Staphylococci. The prevalence of methicillin-resistant S. aureus in wound infections was 89.9%. S. aureus showed superior sensitivity to vancomycin (85.3%) and linezolid (81.3%). The highest prevalence of Gram-negative isolates was for Pseudomonas aeruginosa (40%), which was highly sensitive to ciprofloxacin (79.2%) and highly resistant to levofloxacin (83.3%). Several isolates revealed a multi-drug resistance profile (52.4%). The overall MDR rate of Gram-positive and Gram-negative isolates were 50% and 54.9%, respectively. The prevalence of MRSA isolated from various wound infections and MDR is a warning issue in Upper Egypt. It should implement a health education strategy and hygiene measures to prevent the spread of wound infection-causing organisms in the community.


Cutaneous metastases from prostatic carcinoma.
A case of prostatic adenocarcinoma associated with extensive cutaneous metastases and malignant acanthosis nigricans is reported. Pertinent literature is reviewed. The pathogenesis of the possible mechanism of the development of cutaneous metastases in this as well as other related cases is discussed.


Binding of immunoglobulin and activation of complement by asbestos fibers.
Asbestos fibers adsorbed IgG from whole human serum in amounts comparable to that taken up by crystals of calcium pyrophosphate or hydroxyapatite, but less than that adsorbed by crystals of monosodium urate monohydrate. Chrysotile asbestos was much more active in binding IgG than was amphibole asbestos. The electrophoretic mobility of adsorbed IgG was a function of the surface charge of the crystal studied. Negatively charged fibers adsorbed cationic IgG, and positively charged fibers adsorbed anionic IgG. Complement activation by asbestos, as judged by electrophoretic conversion of C3, was similar for all fiber types tested. Properdin factor B was also activated in the presence of asbestos. Activation of both properdin factor B and C3 was only partially inhibited by ethylene glycol tetraacetic acid, demonstrating that activation was occurring through both the classical and alternative pathways.


Brain structure, psychosocial, and physical health in acute and chronic back pain: a UK Biobank study.
Brain structure, psychosocial, and physical factors underpin back pain conditions; however, less is known about how these factors differ based on pain duration and location. We examined, cross-sectionally, 11,106 individuals from the UK Biobank who (1) were pain-free (n = 5616), (2) had acute back pain (n = 1746), (3) had chronic localised back pain (CBP; n = 1872), or (4) had chronic back pain and additional chronic pain sites (CWP; n = 1872). We found differences in structural brain measures in the chronic pain groups alone. Both CBP and CWP groups had lower primary somatosensory cortex {CBP mean difference (MD) (95% confidence interval [CI]): -250 (-393, -107) mm3, P < 0.001; CWP: -170 (-313, -27)mm3, P = 0.011} and higher caudate gray matter volumes (CBP: 127 [38,216]mm3, P = 0.001; CWP: 122 [33,210]mm3, P = 0.002) compared with pain-free controls. The CBP group also had a lower primary motor cortex volume (-215 [-382, -50]mm3, P = 0.005), whereas the CWP group had a lower amygdala gray matter volume (-27 [-52, -3]mm3, P = 0.021) compared with pain-free controls. Differences in gray matter volumes in some regions may be moderated by sex and body mass index. Psychosocial factors and body mass index differed between all groups and affected those with widespread pain the most (all, P < 0.001), whereas grip strength was only compromised in individuals with widespread pain (-1.0 [-1.4, -0.5] kg, P < 0.001) compared with pain-free controls. Longitudinal research is necessary to confirm these interactions to determine the process of pain development in relation to assessed variables and covariates. However, our results suggest that categorised pain duration and the number of pain sites warrant consideration when assessing markers of brain structure, psychosocial, and physical health.


[Syntopical and synchronous leiomyosarcoma and papillary carcinoma of the female breast].
A 61 years old female was treated by total lumpectomy due to a palpable and radiologically demonstrable tumor measuring 22 cm in diameter in the left breast. Two different but directly neighboured malignant tumours were found: a poorly differentiated leiomyosarcoma and a well differentiated invasive papillary carcinoma of the breast. The latter had metastasized in 4 axillary lymph nodes. Three months after surgery the patient died. Post-mortem studies showed many metastases of the leiomyosarcoma in both lungs, the heart, the liver, the left kidney and both adrenals. Cause of death were relapsing pulmonary thrombembolisms. Case reports of leiomyosarcomas following radiotherapy of the breast cancer are published but coincidental occurrence of both metastasizing tumors are so far not known from the literature.


IL-26 inhibits hepatitis C virus replication in hepatocytes.
Interleukin-26 (IL-26) is a proinflammatory cytokine that has properties atypical for a cytokine, such as direct antibacterial activity and DNA-binding capacity. We previously observed an accumulation of IL-26 in fibrotic and inflammatory lesions in the livers of patients with chronic HCV infection and showed that infiltrating CD3+ lymphocytes were the principal source of IL-26. Surprisingly, IL-26 was also detected in the cytoplasm of hepatocytes from HCV-infected patients, even though these cells do not produce IL-26, even when infected with HCV. Based on this observation and possible interactions between IL-26 and nucleic acids, we investigated the possibility that IL-26 controlled HCV infection independently of the immune system. We evaluated the ability of IL-26 to interfere with HCV replication in hepatocytes and investigated the mechanisms by which IL-26 exerts its antiviral activity. We showed that IL-26 penetrated HCV-infected hepatocytes, where it interacted directly with HCV double-stranded RNA replication intermediates, thereby inhibiting viral replication. IL-26 interfered with viral RNA-dependent RNA polymerase activity, preventing the de novo synthesis of viral genomic single-stranded RNA. These findings reveal a new role for IL-26 in direct protection against HCV infection, independently of the immune system, and increase our understanding of the antiviral defense mechanisms controlling HCV infection. Future studies should evaluate the possible use of IL-26 for treating other chronic disorders caused by RNA viruses, for which few treatments are currently available, or emerging RNA viruses. This study sheds new light on the body's arsenal for controlling hepatitis C virus (HCV) infection and identifies interleukin-26 (IL-26) as an antiviral molecule capable of blocking HCV replication. IL-26, which has unique biochemical and structural characteristics, penetrates infected hepatocytes and interacts directly with viral RNA, thereby blocking viral replication. IL-26 is, therefore, a new player in antiviral defenses, operating independently of the immune system. It is of considerable potential interest for treating HCV infection and other chronic disorders caused by RNA viruses for which few treatments are currently available, and for combating emerging RNA viruses.


Changes in serotonin turnover and the brain sensitivity to barbiturates by disulfiram treatment in rats.
The influence of intraperitoneal administration of disulfiram on the serotonin (5HT) turnover and the brain sensitivity to barbiturates were investigated in rats. Treatment of the animals with 200 mg/kg disulfiram resulted in the prolongation of duration of barbiturate-induced hypnosis. This indication and increment of the brain sensitivity to barbiturates after disulfiram treatment. Under the identical condition, disulfiram caused both the reduction of turnover of 5HT and the elevation of 5HT levels, although this effect was less potent than that of phenobarbital. Furthermore, simultaneous administration of disulfiram and phenobarbital resulted in the severe retardation of 5HT metabolism. These results strongly suggest that disulfiram potentiates the hypnotic action of barbiturates by altering 5HT metabolism in rat brain.


Site-directed mutants of human myeloperoxidase. A topological approach to the heme-binding site.
Two site-directed mutants of human promyeloperoxidase, MPO(His416----Ala) and MPO(His502----Ala), have been expressed in Chinese hamster ovary cells and purified. Overall purification yields and apparent molecular masses of the mutant proteins were similar to those of the wild-type enzyme. Both mutant species were analyzed spectroscopically to check the presence of the hemic iron in the proteins and were assayed for peroxidase activity. The data show that substitution of His502 leads to the loss, or to an inappropriate configuration, of the heme together with the loss of activity, suggesting that this residue could be the proximal His involved in the binding to the iron centers. On the other hand, substitution of His416 by alanine had no effect on either of the studied parameters.