Effects of pinealectomy, oestradiol and melatonin on plasma prolactin and LH secretion in ovariectomized sheep.
The study examines whether the pineal gland mediates in the seasonal rhythm in the response of the hypothalamo-pituitary axis to oestrogen in the sheep. Five groups of ewes, each comprised of five sham-pinealectomized ewes and five pinealectomized ewes, were maintained under field conditions over a 2-year period. Group I ewes were ovariectomized and treated with two oestradiol capsules in the first year and one oestradiol capsule in the second year; group 2 ewes were ovariectomized and treated with two oestradiol capsules and three melatonin sachets in the first year and one oestradiol capsule and three melatonin sachets in the second year; group 3 ewes were ovariectomized and treated with three melatonin sachets in the first year and one oestradiol capsule in the second year; group 4 ewes were ovariectomized and treated with empty implants; group 5 had intact ovaries. Blood samples were taken at weekly intervals for determination of plasma prolactin, LH and FSH levels. Cyclic ovarian activity, determined by rams fitted with a marking harness, occurred in both sham-pinealectomized and pinealectomized ewes in group 5 during December to May in both years. A circannual rhythm in plasma prolactin levels was apparent in all ten groups of animals. The levels were highest in spring (September to November) and decreased before the onset of breeding activity in midsummer (December). Ovariectomized ewes with intact pineal glands and treated with oestradiol capsules (group 1) exhibited marked changes in LH and FSH concentrations during the study.(ABSTRACT TRUNCATED AT 250 WORDS)


Assessment of ibuprofen-associated nephrotoxicity in renal dysfunction.
Ibuprofen-incurred nephrotoxicity in renal insufficiency was assessed by examining renal functional and pathological changes in rabbits with pre-existing renal failure after receiving consecutive doses of ibuprofen. The pharmacokinetic behavior of ibuprofen enantiomers in rabbits with renal dysfunction appeared to qualitatively parallel that of their human counterparts. Modifications of the pharmacokinetic profile occurred in a stereoselective fashion: (R)-ibuprofen disposition was independent of renal conditions, whereas (S)-ibuprofen clearance was significantly hampered. Pathological damage associated with ibuprofen use in renal dysfunction was evident from the renal necropsy specimens, which was characterized by tubular necrosis and interstitial nephritis. This animal model study indicates clearly that renal insufficiency is a causative factor for ibuprofen-induced interstitial nephritis. Moreover, based on the evidence of interstitial lymphocytic infiltration, this nephrotoxic syndrome is assumed to be a manifestation of a disordered cellular immunity.


AIDS and ethics: an analytic framework.
The acquired immunodeficiency syndrome (AIDS) pandemic has raised difficult ethical issues in public policy formulation and in the care of patients infected with the human immunodeficiency virus (HIV). Many issues relate to measures proposed for the protection of the public from HIV infection. This article presents an analytic framework from which these measures can be rationally evaluated. Specific measures are assessed on the basis of their likelihood of success, in relation to their justification for infringement on individual rights, and with reference to other less intrusive measures that could accomplish the same objective. Case histories are discussed which raise ethical dilemmas in the care of HIV infected and high-risk patients. The application of this framework could assist physicians in analysing public health policy and making judgements in individual clinical situations.


The search for yield predictors for mature field-grown plants from juvenile pot-grown cassava (Manihot esculenta Crantz).
Cassava is the 6th most important source of dietary energy in the world but its root system architecture (RSA) had seldom been quantified. Ability to select superior genotypes at juvenile stages can significantly reduce the cost and time for breeding to bridge the large yield gap. This study adopted a simple approach to phenotyping RSA traits of juvenile and mature cassava plants to identify genotypic differences and the relationships between juvenile traits and harvest index of mature plants. Root classes were categorised and root and shoot traits of eight (8) juvenile pot-grown cassava genotypes, were measured at 30 and 45 days after planting (DAP). The same or related traits were measured at 7 months after planting of the same genotypes grown in the field while yield and yield components were measured in 12-months old field-grown plants. The field experiment was done in 2017 and repeated in 2018. Differences between genotypes for the measured traits were explored using analysis of variance (ANOVA) while traits in juvenile plants were correlated or regressed onto traits measured in 7- and 12-months old plants. The results show significant genotypic variations for most of the traits measured in both juvenile and 7-months old plants. In the 12-months old plants, differences between genotypes were consistent for both 2017 and 2018. Broad-sense heritability was highest for the number of commercial roots (0.87) and shoot fresh weight (0.78) and intermediate for the total number of roots (0.60), harvest index (0.58), fresh weight of roots (0.45). For all the sampling time points or growth stages, there were greater correlations between traits measured at a particular growth stage than between the same traits at different growth stages. However, some juvenile-mature plant trait relationships were significant, positive and consistent for both 2017 and 2018. For example, total root length and the total number of roots in 30 DAP, and branching density of upper nodal roots in 45 DAP, positively correlated with harvest index of 12-months old plants in both 2017 and 2018. Similarly, the diameter of nodal roots, for example, had a negative, significant correlation with fresh shoot biomass of mature plants in both 2017 and 2018. Regression of traits measured in 30 DAP explained up to 22% and 36% of the variation in HI of mature plants in 2017 and 2018, respectively. It is concluded that the simple, rapid, inexpensive phenotyping approach adopted in this study is robust for identifying genotypic variations in juvenile cassava using root system traits. Also, the results provide seminal evidence for the existence of useful relationships between traits of juvenile and mature cassava plants that can be explored to predict yield and yield components.


The history of rubella and rubella vaccination leading to elimination.
Congenital rubella syndrome (CRS) was discovered in the 1940s, rubella virus was isolated in the early 1960s, and rubella vaccines became available by the end of the same decade. Systematic vaccination against rubella, usually in combination with measles, has eliminated both the congenital and acquired infection from some developed countries, most recently the United States, as is confirmed by the articles in this supplement. The present article summarizes the clinical syndrome of CRS, the process by which the vaccine was developed, and the history leading up to elimination, as well as the possible extension of elimination on a wider scale.


Anaphylaxis to peanut in a patient predominantly sensitized to Ara h 6.
Diagnosis of peanut allergy has improved thanks to component-resolved diagnostics. Peanut allergen component Ara h 2 is considered to indicate true peanut allergy. The component Ara h 6 is structurally similar to Ara h 2, but the diagnostic value of analyzing IgE antibodies to Ara h 6 is unclear. A boy sensitized (≥0.35 kU(A)/l) to Ara h 8 but not to Ara h 1, Ara h 2 and Ara h 3 was challenged with peanut and developed grade II anaphylaxis. In serum collected at the time of challenge a doubling of IgE to the peanut allergen extract was observed compared to allergy testing 9 months earlier. In contrast, IgE levels to Ara h 1, Ara h 2, Ara h 3 and to Ara h 8 were rather unchanged. After another 2 months, Ara h 6 was analyzed and revealed a level of 24 kU(A)/l whilst Ara h 2 was 0.12 kU(A)/l. We suggest that IgE sensitization to Ara h 6 caused the reaction and conclude that analyses of IgE levels to peanut and peanut components should be performed in connection with a challenge. Furthermore, levels to Ara h 2 below 0.35 kU(A)/l may still indicate a risk of severe reaction at the time of challenge since in rare cases, Ara h 6 IgE antibodies may be present without occurrence of IgE antibodies to Ara h 2.


Should genetic testing be performed in each patient with sporadic pheochromocytoma at presentation?
According to previous studies, around 15% of patients with an apparently sporadic pheochromocytoma and a negative family history had a hereditary disease. This high frequency together with the financial support provided to reference laboratories of molecular genetics by the French government led to a nearly systematic screening in each patient with a pheochromocytoma. To check the efficiency of systematic genetic screening in patients with apparently sporadic pheochromocytoma, by analysing the 6 years experience of a multidisciplinary team in this field. One hundred patients with a pheochromocytoma-only phenotype and no family history were included. Patients with extra-adrenal tumours were excluded. Prevalence of hereditary forms was determined and analyzed according to age at onset, sex. Cost of the genetic analysis was calculated. A germline mutation in one of the five susceptibility genes (VHL, RET, SDHD, SDHC, SDHB) was identified in eight patients (8%) with an age of onset between 13 and 57 years. Among them, six had a bilateral pheochromocytoma and only two had a unilateral tumour. If the guidelines for genetic screening were age of onset less than 50 or bilateral pheochromocytoma, no patients with a hereditary tumour would be missed and a 24% cost reduction would be achieved. According to these data, a genetic predisposition test for hereditary pheochromocytoma seems not recommended in patients with a unilateral adrenal tumour diagnosed after 50 in the absence of familial, clinical, biological or imaging features for a familial disease.


Orthodontic treatment of a patient with severe class II malocclusion, bony fibrous dysplasia, root resorptions, and missing four premolars.
A case of distal occlusion is presented with root resorptions and missing premolars, treated at the end of the growth period with Herbst appliance. Orthodontic treatment in non-progressive fibrous dysplasia is assessed. Anamnesis, results of extraoral and intraoral examinations, typodonts, panoramic view, hand-wrist radiogram, and cephalogram were obtained in a 14-year-old boy with severe distal occlusion, root resorptions resulting from previous orthodontic treatment, fibrous dysplasia of bone, and missing four premolars. Successful treatment was achieved with Herbst appliance followed by fixed appliances. Bands were placed on upper second molars and lower first premolars and the Herbst appliance was positioned forcing the mandible forward. After three months the patient was unable to position the mandible backwards. Canine and Angle Class I were achieved, overjet and overbite were reduced to 2 mm. Lower face height was reduced and the upper lip was retracted, producing lip competence. At this point the fixed appliances were removed, an upper removable retention plate was made, and a lower flexible spiral wire retainer was bonded. Active retreatment lasted 15 months. No hypermobility of any teeth nor progression or neoplastic transformation of fibrous dysplasia were noted at the end of orthodontic treatment. (1) It is possible to treat distal occlusion with Herbst appliance at the end of the growth period. (2) Root resorptions are not a contra-indication to treatment if potential benefits outweigh risks. (3) Orthodontic tooth movement appears possible and safe in patients with non-progressive fibrous dysplasia.


Enhancing host-pathogen phenotyping dynamics: early detection of tomato bacterial diseases using hyperspectral point measurement and predictive modeling.
Early diagnosis of plant diseases is needed to promote sustainable plant protection strategies. Applied predictive modeling over hyperspectral spectroscopy (HS) data can be an effective, fast, cost-effective approach for improving plant disease diagnosis. This study aimed to investigate the potential of HS point-of-measurement (POM) data for in-situ, non-destructive diagnosis of tomato bacterial speck caused by Pseudomonas syringae pv. tomato (Pst), and bacterial spot, caused by Xanthomonas euvesicatoria (Xeu), on leaves (cv. cherry). Bacterial artificial infection was performed on tomato plants at the same phenological stage. A sensing system composed by a hyperspectral spectrometer, a transmission optical fiber bundle with a slitted probe and a white light source were used for spectral data acquisition, allowing the assessment of 3478 spectral points. An applied predictive classification model was developed, consisting of a normalizing pre-processing strategy allied with a Linear Discriminant Analysis (LDA) for reducing data dimensionality and a supervised machine learning algorithm (Support Vector Machine - SVM) for the classification task. The predicted model achieved classification accuracies of 100% and 74% for Pst and Xeu test set assessments, respectively, before symptom appearance. Model predictions were coherent with host-pathogen interactions mentioned in the literature (e.g., changes in photosynthetic pigment levels, production of bacterial-specific molecules, and activation of plants' defense mechanisms). Furthermore, these results were coherent with visual phenotyping inspection and PCR results. The reported outcomes support the application of spectral point measurements acquired in-vivo for plant disease diagnosis, aiming for more precise and eco-friendly phytosanitary approaches.


Adherence with medications used to treat osteoporosis: behavioral insights.
Non-persistence (never starting or stopping medication prematurely) and non-compliance (taking medication inappropriately) with fracture prevention medication among those at high risk of fracture remain significant barriers to optimal reduction of osteoporotic fractures. Current research suggest that for patients to persist and comply with prescriptions for fracture prevention medication, they need to believe that they are at significant risk of fracture, that the prescribed medication can safely reduce their risk of fracture without exposing them to long-term harm, that equally effective non-medicinal therapies are not available, and that they can successfully execute medication use in the context of their daily task demands. Further research is needed to understand; a) the mental models of osteoporosis, fractures, and medications used to treat osteoporosis that patients employ when making decisions as to whether or not to take fracture prevention medication; and b) how patients arbitrage information from various sources (health care providers, family, friends, and other sources) to formulate their beliefs about osteoporosis and medications used to treat it.


[Palliative treatment options for esophageal and gastric cancer].
There are several different approaches available for the palliation of esophago-gastric cancer. The decision on which type of therapy is used should be made individually based on an interdisciplinary consensus.In case of inoperable esophageal carcinoma, it becomes the primary objective of the therapy to maintain oral nutrition. This can be achieved through the insertion of self expanding metal stents as a minimally invasive procedure which results in an immediate elimination of dysphagia. As alternative and/or complementary therapy, radiological techniques (external beam radiation, brachytherapy) can be applied. Other locally endoscopic techniques (laser, APC-beamer) are often used for treating local complications of esophageal and inoperable stomach carcinomas. For these carcinomas palliative chemotherapy with cisplatin has been established as a standard regimen.


Synovial lining, endothelial and inflammatory mononuclear cell proliferation in synovial membranes in psoriatic and reactive arthritis: a comparative quantitative morphometric study.
The extent of synovial cell proliferation in situ and its relationship to the destructive potential of rheumatoid arthritis (RA) is a matter of continuing debate. Notably, the situation has not been elucidated in other inflammatory arthritides [i.e. reactive (ReA) and psoriatic (PsA)], which, although they share some histopathological similarities with RA, develop different patterns of joint involvement. In order to estimate the proliferation of synovial cells in situ in PsA and ReA, and to compare this with RA and with 'non-inflammatory' joint lesions, we have utilized immunostaining of the Ki-67 antigen complemented with Ki-67/CD68 or Ki-67/leucocyte common antigen (LCA, clones 2B11 and PD7/26) double stainings to assess the extent of mononuclear inflammatory cell proliferation. Synovial samples analysed were from 33 patients: RA (n = 8), PsA (n = 13), ReA (n = 6) and six 'non-inflammatory controls' (degenerative or traumatic joint lesions). Thickening of the synovial lining (in particular in RA) and perivascular accumulations of mononuclear inflammatory cells, predominantly lymphocytes, were characteristic features in all synovitides. In contrast to the thickened avascular synovial lining in RA, in 5/13 cases with PsA, blood vessels were observed in the lining. The percentage of lining cells expressing Ki-67 antigen was higher in RA (median = 4.7, interquartile range [Q3-Q1] = 3.9, mean [95% CI] = 3.5 [1.7-5.2], P = 0.0063), PsA (median = 1.2, [Q3-Q1] = 1.9, mean [95% CI] = 1.6 [0.7-2.5], P = 0.007) and ReA (median = 1.4, [Q3-Q1] = 2.3, mean [95% CI] = 1.6 [0.1-3.1], P = 0.0235) than in controls (median = 0.1, [Q3-Q1] = 0.45, mean [95% CI] = 0.2 [0.07-0.5]). In this respect, the differences between different forms of the inflammatory arthritides were not statistically significant (P > 0.05). In RA, PsA and ReA, the percentage of labelled cells in the inflammatory mononuclear cell-rich areas was higher than in controls. The percentage of proliferating endothelial cells was also significantly higher in RA, PsA and ReA than in controls. However, in RA, endothelial expression of Ki-67 antigen was often seen in small blood vessels, whereas in PsA, Ki-67 antigen was preferably expressed in the medium to large blood vessels. Synovial lining cells of the monocyte/macrophage lineage (type A synoviocytes), but not stromal monocytes, demonstrated modest proliferation in situ. These results indicate that although proliferation of synovial lining fibroblasts is a prominent feature in RA, the extents to which this, or in situ proliferation of lymphocytes, contribute to the histopathology of PsA, ReA and RA are comparable. Vascular involvement is suggested by the proliferation of endothelial cells in RA, PsA and ReA in an overlapping manner, but, based on topological differences, such a response may represent diverse pathological features, such as angiogenesis, vascular enlargement and reparative responses to injury.


First principles reactive simulation for equation of state prediction.
The high cost of density functional theory (DFT) has hitherto limited the ab initio prediction of the equation of state (EOS). In this article, we employ a combination of large scale computing, advanced simulation techniques, and smart data science strategies to provide an unprecedented ab initio performance analysis of the high explosive pentaerythritol tetranitrate (PETN). Comparison to both experiment and thermochemical predictions reveals important quantitative limitations of DFT for EOS prediction and thus the assessment of high explosives. In particular, we find that DFT predicts the energy of PETN detonation products to be systematically too high relative to the unreacted neat crystalline material, resulting in an underprediction of the detonation velocity, pressure, and temperature at the Chapman-Jouguet state. The energetic bias can be partially accounted for by high-level electronic structure calculations of the product molecules. We also demonstrate a modeling strategy for mapping chemical composition across a wide parameter space with limited numerical data, the results of which suggest additional molecular species to consider in thermochemical modeling.


Obsessive-compulsive disorder: subclassification based on co-morbidity.
Obsessive-compulsive disorder (OCD) is probably an etiologically heterogeneous condition. Many patients manifest other psychiatric syndromes. This study investigated the relationship between OCD and co-morbid conditions to identify subtypes. Seven hundred and six individuals with OCD were assessed in the OCD Collaborative Genetics Study (OCGS). Multi-level latent class analysis was conducted based on the presence of eight co-morbid psychiatric conditions [generalized anxiety disorder (GAD), major depression, panic disorder (PD), separation anxiety disorder (SAD), tics, mania, somatization disorders (Som) and grooming disorders (GrD)]. The relationship of the derived classes to specific clinical characteristics was investigated. Two and three classes of OCD syndromes emerge from the analyses. The two-class solution describes lesser and greater co-morbidity classes and the more descriptive three-class solution is characterized by: (1) an OCD simplex class, in which major depressive disorder (MDD) is the most frequent additional disorder; (2) an OCD co-morbid tic-related class, in which tics are prominent and affective syndromes are considerably rarer; and (3) an OCD co-morbid affective-related class in which PD and affective syndromes are highly represented. The OCD co-morbid tic-related class is predominantly male and characterized by high conscientiousness. The OCD co-morbid affective-related class is predominantly female, has a young age at onset, obsessive-compulsive personality disorder (OCPD) features, high scores on the 'taboo' factor of OCD symptoms, and low conscientiousness. OCD can be classified into three classes based on co-morbidity. Membership within a class is differentially associated with other clinical characteristics. These classes, if replicated, should have important implications for research and clinical endeavors.


Prevalence and characterisation of shigatoxigenic Escherichia coli isolated from beef cattle fed with prebiotics.
Ten Holstein Friesian calves were divided into two groups of five: one group was given prebiotics in their food, while the other group served as the control group. Every two weeks from birth up to 18 months, samples of feces were taken from the rectal ampulla to determine the concentration of E. coli. At each sampling session, three aliquots per sample were collected. The arithmetic mean was calculated and all values (converted into logs) were analysed with GraphPad InStat for analysis of variance, followed by the Tukey-Kramer test. A total of 69 E. coli strains were detected, 29 (42.03%) from treated animals and 40 (57.97%) from the control group. The isolates were analysed by PCR for the presence of the stx-1, stx-2, hly and eae genes and by the Kirby Bauer test for susceptibility to the most commonly used antimicrobials in cattle breeding. Hierarchical clustering of the isolates was done using Ward's method. Thirty samples were positive for the stx-1 gene, 18 for stx- 2, 12 for both stx-1 and stx-2, 8 for hly, and 10 for eae. 4.3% were resistant to sulfamides, 8.6% to tetracycline, 1.4% to gentamicin, 94.6% to cephalothin, 2.8% to chloramphenicol, 13% to ampicillin, 13% to amoxicillin/clavulanic acid, 7.2% to sulphonamides, 4.3% to ceftriaxone, 5.7% to nalidixic acid, 34.7% to ticarcillin, 88.5% to erythromycin, and 5.7% to streptomycin. The isolates from the samples taken from day 210 to day 300 were grouped into a single cluster. Bacteriological examinations showed a reduction in the concentration of E. coli in the feces of the treated animals compared to the control group. The presence of strains with shigatoxigenic Escherichia coli virulence profiles and the reduction of these in the treated animal group demonstrated that diet can play an important role in reducing E. coli prevalence in cattle.


Reduced Precision Underwrites Ego Dissolution and Therapeutic Outcomes Under Psychedelics.
Evidence suggests classic psychedelics reduce the precision of belief updating and enable access to a range of alternate hypotheses that underwrite how we make sense of the world. This process, in the higher cortices, has been postulated to explain the therapeutic efficacy of psychedelics for the treatment of internalizing disorders. We argue reduced precision also underpins change to consciousness, known as "ego dissolution," and that alterations to consciousness and attention under psychedelics have a common mechanism of reduced precision of Bayesian belief updating. Evidence, connecting the role of serotonergic receptors to large-scale connectivity changes in the cortex, suggests the precision of Bayesian belief updating may be a mechanism to modify and investigate consciousness and attention.


A Model for Urban Environment Instance Segmentation with Data Fusion.
Fine-grained urban environment instance segmentation is a fundamental and important task in the field of environment perception for autonomous vehicles. To address this goal, a model was designed with LiDAR pointcloud data and camera image data as the subject of study, and the reliability of the model was enhanced using dual fusion at the data level and feature level. By introducing the Markov Random Field algorithm, the Support Vector Machine classification results were optimized according to the spatial contextual linkage while providing the model with the prerequisite of the differentiation of similar but foreign objects, and the object classification and instance segmentation of 3D urban environments were completed by combining the Mean Shift. The dual fusion approach in this paper is a method for the deeper fusion of data from different sources, and the model, designed more accurately, describes the categories of items in the environment with a classification accuracy of 99.3%, and segments the different individuals into groups of the same kind of objects without instance labels. Moreover, our model does not have high computational resource and time cost requirements, and is a lightweight, efficient, and accurate instance segmentation model.


Regulation of the herpes simplex virus type 1 late (gamma 2) glycoprotein C gene: sequences between base pairs -34 to +29 control transient expression and responsiveness to transactivation by the products of the immediate early (alpha) 4 and 0 genes.
The glycoprotein C (gC) gene of herpes simplex virus type 1 is a true late gene, in that its expression occurs late in infection with a strict requirement for viral DNA replication. Recently, we reported on gC expression during infection with mutant viruses carrying deletions in the gC gene promoter. Analysis of RNA extracted from cells infected with individual mutants showed that the DNA sequences required for regulated expression of this late gene lie within bases -34 to +124 relative to the 5' end of the mRNA. In the present study, the deleted gC promoter sequences were fused to the bacterial chlorampheniol acetyltransferase (CAT) gene and expression was measured in short-term transfection assays after transactivation by infection with HSV or cotransfection with a second plasmid carrying the immediate early genes of HSV-1. The 63 base pair sequence located between -34 to +29 on the gC promoter was sufficient to give induction of CAT activity following infection and on cotransfection with plasmids which code for the immediate early gene products ICP4 and ICPO. This 63 base pair region contains the TATA homology and the transcriptional start site of the gC gene, and apparently contains specific promoter elements not found in a similar region of the HSV TK promoter. This was shown by removing the distal upstream region of the TK promoter, 5' to -37, and found that the TK gene was no longer activated by infection or cotransfection with an alpha 4-alpha 0 gene containing plasmid.


cDNA cloning and expression of bovine endothelin converting enzyme.
We have cloned cDNA encoding bovine endothelin converting enzyme (ECE). The predicted amino acid sequence of bovine ECE consisted of 758 amino acid residues. Northern blot analysis revealed that ECE mRNA was abundantly expressed in lung. Co-expression of the cloned cDNA of bovine ECE with human preproET-1 cDNA in CHO-K1 cells resulted in the production of mature ET-1 and this production was inhibited by phosphoramidon.


The role of the tyrosine kinase Wzc (Sll0923) and the phosphatase Wzb (Slr0328) in the production of extracellular polymeric substances (EPS) by Synechocystis PCC 6803.
Many cyanobacteria produce extracellular polymeric substances (EPS) mainly composed of heteropolysaccharides with unique characteristics that make them suitable for biotechnological applications. However, manipulation/optimization of EPS biosynthesis/characteristics is hindered by a poor understanding of the production pathways and the differences between bacterial species. In this work, genes putatively related to different pathways of cyanobacterial EPS polymerization, assembly, and export were targeted for deletion or truncation in the unicellular Synechocystis sp. PCC 6803. No evident phenotypic changes were observed for some mutants in genes occurring in multiple copies in Synechocystis genome, namely ∆wzy (∆sll0737), ∆wzx (∆sll5049), ∆kpsM (∆slr2107), and ∆kpsM∆wzy (∆slr2107∆sll0737), strongly suggesting functional redundancy. In contrast, Δwzc (Δsll0923) and Δwzb (Δslr0328) influenced both the amount and composition of the EPS, establishing that Wzc participates in the production of capsular (CPS) and released (RPS) polysaccharides, and Wzb affects RPS production. The structure of Wzb was solved (2.28 Å), revealing structural differences relative to other phosphatases involved in EPS production and suggesting a different substrate recognition mechanism. In addition, Wzc showed the ATPase and autokinase activities typical of bacterial tyrosine kinases. Most importantly, Wzb was able to dephosphorylate Wzc in vitro, suggesting that tyrosine phosphorylation/dephosphorylation plays a role in cyanobacterial EPS production.


Molecular interactions of new pregnenedione derivatives.
The in vitro inhibitory activity of five new progesterone derivatives: 17alpha-hydroxy-16beta-methylpregna-1,4,6-triene-3,20-dione 1; 16beta-methyl-17alpha-toluoyloxypregna-1,4,6-triene-3,20-dione 2; 17alpha-hydroxy-6-methylenepregn-4-ene-3,20-dione 3; 6-methylene-17alpha-toluoyloxypregn-4ene-3,20-dione 4 and 17alpha-(p-bromobenzoyloxy)-6-methylenepregn-4-ene-3,20-dione 5 was determined. These compounds were evaluated as 5alpha-reductase inhibitors as well as antagonists for the androgen receptor. Compounds 1, 2, 3, 4 and 5 showed the following inhibitory activity for the 5alpha-reductase enzyme with IC(50) values of: 1 (1.65 microM), 2 (10 microM), 3 (19 nM), 4 (100 nM) and 5 (100 nM). The results of this study also showed the effect of increasing concentrations of the novel steroids upon [(3)H]dihydrotestosterone binding to androgen receptors from male hamster prostate. The K(i) values for compounds 1, 2, 3, 4, 5 and dihydrotestosterone showed the following order of affinity for the androgen receptor: 4>5>dihydrotestosterone>2>3>1. The overall data indicated that all synthesized compounds 1, 2, 3, 4 and 5 are inhibitors of the 5alpha-reductase enzyme present in the hamster prostate. In addition compounds 1, 2, 3, 4 and 5 also presented an affinity for the androgen receptor.


Inhibition of erythroblast growth and fetal hemoglobin production by ribofuranose-substituted adenosine derivatives.
In vivo, inhibition of fetal hemoglobin (HbF) expression in humans around the time of birth causes the clinical manifestation of sickle cell and beta-thalassemia syndromes. Inhibition of HbF among cultured cells was recently described by the adenosine derivative molecule named SQ22536. Here, a primary cell culture model was utilized to further explore the inhibition of HbF by adenosine derivative molecules. SQ22536 demonstrated down-regulation of growth and HbF expression among erythroblasts cultured from fetal and adult human blood. The effects upon HbF were noted in a majority of cells, and quantitative PCR analysis demonstrated a transcriptional mechanism. Screening assays demonstrated that two additional molecules named 5'-deoxy adenosine and 2',3'-dideoxy adenosine had effects on HbF comparable to SQ22536. Other adenosine derivative molecules, adenosine receptor binding ligands, and cAMP-signaling regulators failed to inhibit HbF in matched cultures. These results suggest that structurally related ribofuranose-substituted adenosine analogues act through an unknown mechanism to inhibit HbF expression in fetal and adult human erythroblasts.


Service learning: Nursing students' civic engagement with diverse populations of children with special needs.
There is limited knowledge of nursing students' perspectives about engagement with special needs populations. The purpose of this study was to identify the advantages/benefits and disadvantages/challenges of nursing students' engagement experience with children with special mental and physical disabilities. Recommendations to enhance student engagement experiences were also provided. A descriptive, qualitative design was employed. Undergraduate nursing students (N = 28) responded to open-ended questions about their civic engagement experiences at a community-based, respite care program for children with special needs. Student accounts underwent directed content analysis, with coding, category and theme development according to the Theory of Planned Behavior. The Atlas.Ti computer program was used to manage the data. Advantages/Benefits: Filling cognitive and experiential learning gaps, rewarding connections/relationships, positive emotions, perceptions and interactions, and fun and stress relief. Disadvantage/challenges: Managing negative/uncomfortable emotions and uncertainty, witnessing and managing disruptive behaviors, negative perceptions of program operations/expectations. Students experienced cognitive, emotional, interpersonal and educational advantages and/or disadvantages while engaging with this defined population. To enhance engagement faculty can provide education and anticipatory guidance, detail responsibilities and expectations, and/or utilize simulation for student preparation. Nurses and researchers can utilize community based participatory methods to guide discussions with community-based organizations to collaboratively develop strategies to institute, evaluate and enhance student engagement during service learning experiences with children who have special needs.


BDNF downregulates β-adrenergic receptor-mediated hypotensive mechanisms in the paraventricular nucleus of the hypothalamus.
Brain-derived neurotrophic factor (BDNF) is upregulated in the paraventricular nucleus of the hypothalamus (PVN) in response to hypertensive stimuli such as stress and hyperosmolality, and BDNF acting in the PVN plays a key role in elevating sympathetic activity and blood pressure. However, downstream mechanisms mediating these effects remain unclear. We tested the hypothesis that BDNF increases blood pressure, in part by diminishing inhibitory hypotensive input from nucleus of the solitary tract (NTS) catecholaminergic neurons projecting to the PVN. Male Sprague-Dawley rats received bilateral PVN injections of viral vectors expressing either green fluorescent protein (GFP) or BDNF and bilateral NTS injections of vehicle or anti-dopamine-β-hydroxylase-conjugated saporin (DSAP), a neurotoxin that selectively lesions noradrenergic and adrenergic neurons. BDNF overexpression in the PVN without NTS lesioning significantly increased mean arterial pressure (MAP) in awake animals by 18.7 ± 1.8 mmHg. DSAP treatment also increased MAP in the GFP group, by 9.8 ± 3.2 mmHg, but failed to affect MAP in the BDNF group, indicating a BDNF-induced loss of NTS catecholaminergic hypotensive effects. In addition, in α-chloralose-urethane-anesthetized rats, hypotensive responses to PVN injections of the β-adrenergic agonist isoprenaline were significantly attenuated by BDNF overexpression, whereas PVN injections of phenylephrine had no effect on blood pressure. BDNF treatment was also found to significantly reduce β1-adrenergic receptor mRNA expression in the PVN, whereas expression of other adrenergic receptors was unaffected. In summary, increased BDNF expression in the PVN elevates blood pressure, in part by downregulating β-receptor signaling and diminishing hypotensive catecholaminergic input from the NTS to the PVN.NEW & NOTEWORTHY We have shown that BDNF, a key hypothalamic regulator of blood pressure, disrupts catecholaminergic signaling between the NTS and the PVN by reducing the responsiveness of PVN neurons to inhibitory hypotensive β-adrenergic input from the NTS. This may be occurring partly via BDNF-mediated downregulation of β1-adrenergic receptor expression in the PVN and results in an increase in blood pressure.


Development of QSARs for predicting the joint effects between cyanogenic toxicants and aldehydes.
Quantitative structure-activity relationship (QSAR) approaches are proposed in this study to predict the joint effects of mixture toxicity. The initial investigation studies the joint effects between cyanogenic toxicants and aldehydes to Photobacterium phosphoreum. Joint effects are found to result from the formation of a carbanion intermediate produced through the chemical interactions between cyanogenic toxicants and aldehydes. Further research indicates that the formation of carbanion intermediate is highly correlated with not only the charge of the carbon atom in the -CHO of aldehydes but also the charge of the carbon atom (C) in the carbochain of cyanogenic toxicants. The charge of the carbon atom in the -CHO of aldehydes is quantified by using the Hammett constant (sigma(p)), and then, sigma(p)-based QSAR models are proposed to describe the relationships between the joint effects and the chemical structures of the aldehydes. By using the charge of carbon atom (C) in the carbochain of cyanogenic toxicants, another QSAR model is proposed to describe the relationship between the joint effects and the chemical structures of cyanogenic toxicants.


Engendering development and disasters.
Over the last two decades the different impacts of disasters on women and men have been acknowledged, leading to calls to integrate gender into disaster risk reduction and response. This paper explores how evolving understandings of ways of integrating gender into development have influenced this process, critically analysing contemporary initiatives to 'engender' development that see the inclusion of women for both efficiency and equality gains. It has been argued that this has resulted in a 'feminisation of responsibility' that can reinforce rather than challenge gender relations. The construction of women affected by disasters as both an at-risk group and as a means to reduce risk suggests similar processes of feminisation. The paper argues that if disaster risk reduction initiatives are to reduce women's vulnerability, they need to focus explicitly on the root causes of this vulnerability and design programmes that specifically focus on reducing gender inequalities by challenging unequal gendered power relations.


Dipeptidyl aminopeptidase IV from porcine pancreas.
Dipeptidyl aminopeptidase IV [EC 126.96.36.199] was purified from the water extract of porcine pancreas acetone powder by a series of column chromatographies on DEAE-Sephadex and gel filtration on Sephadex G-200, and was finally subjected to gel filtration on Toyo-pearl in the presence of 1% deoxycholate. The purified enzyme was homogeneous as judged by disc gel and SDS gel electrophoreses. The enzyme was most active at pH 8.0 with Gly-Pro-beta-naphthylamide (Gly-Pro-2-NNap) as the substrate and hydrolyzed peptide bonds involving the carboxyl group of prolyl residues penultimate to unprotected termini. The enzyme was completely inactivated by diisopropyl phosphorofluoridate (DFP), but only slightly inhibited by phenylmethane sulfonylfluoride (PMSF), SH-blocking reagents and metal chelators. The isoelectric point of the enzyme was 4.8, and the molecular weight was estimated to be 230,000 by gel filtration on Sephadex G-200 and 115,000 by sodium dodecyl sulfate (SDS) gel electrophoresis, suggesting that the enzyme is composed of two identical subunits.


[Atelectasis following cesarean section. Personal experience].
Purpose of this paper is to evaluate the risk of ateletasis in patients that underwent surgery of the abdomen (cesarean section), since the reflex of cough in these patients is notably altered for the limitation of the diaphragmatic excursions, due to analgesic contracture. The inhibition of cough's reflex causes retention of secretions with consequent bronchial obstruction and atelectasis. Personal experience in 6 cases of atelectasis following cesarean section is reported.


Glutamine prevents parenteral nutrition-induced increases in intestinal permeability.
In addition to its role in absorbing nutrients, the intestinal mucosa provides an important barrier against toxins and bacteria in the bowel lumen. This study evaluated changes in rat jejunal permeability and histology after total parenteral nutrition (TPN) or TPN supplemented with glutamine. Lactulose and mannitol were used to measure jejunal permeability, and fixed stained histologic specimens were used to measure mucosal dimensions. After the insertion of central venous catheters, 18 male rats were randomly divided into three groups: CHOW, saline infusion with a standard laboratory rat diet ad libitum; TPN; and GLN, 2% L-glutamine-supplemented TPN. The TPN and GLN groups received isocaloric, isovolumic, and isonitrogenous feedings. After 7 days of infusion, a laparotomy was performed, and lactulose and mannitol were instilled into the lumen of a 25-cm ligated segment of jejunum. Urine was collected for 5 hours and assayed for lactulose, mannitol, and creatinine. The jejunum was harvested, and wet weight, villus height, mucosal thickness, and villus width were measured. Intestinal permeability to lactulose and the lactulose to mannitol ratio significantly increased after TPN compared with CHOW, and these effects were prevented with the addition of glutamine to the TPN solution. Jejunal villus height and mucosal thickness significantly decreased following TPN but were not significantly different from CHOW when glutamine was added to the TPN solution. These data suggest that TPN was associated with increased jejunal permeability and that glutamine, when added to the TPN solution, prevented this effect. In addition, glutamine reduced TPN-associated atrophy of the jejunum.


Mycoleptones A-C and polyketides from the endophyte Mycoleptodiscus indicus.
Three new azaphilones with an unusual methylene bridge, named mycoleptones A, B, and C (2, 4, and 5), were isolated from cultures of Mycoleptodiscus indicus, a fungus associated with the South American medicinal plant Borreria verticillata. Additionally, four known polyketides, austdiol (1), eugenitin (3), 6-methoxyeugenin (6), and 9-hydroxyeugenin (7), were also isolated. The structural characterization of compounds was carried out by nuclear magnetic resonance spectroscopy, high-resolution mass spectrometry, electronic circular dichroism spectroscopy, time-dependent density functional theory calculations, and X-ray crystallography. Compounds 1-9 were weakly active when tested in antileishmanial and cytotoxicity assays.


Ten-year trends of dietary intake in a middle-aged French population: relationship with educational level.
To compare dietary intakes at a 10 y interval of a population aged 35-64 living in France. Trends in nutrient intake and food consumption were examined with a special emphasis on the relationships between educational level and dietary behaviour. Two independent surveys conducted in 1985-1987 (S1) and 1995-1997 (S2) in the framework of the WHO MONICA project. Dietary intake was assessed with a 3-day record method and a food frequency questionnaire. The samples analysed included 416 men and 446 women for S1, 393 men and 409 women for S2. A significant improvement of the quality of fat intake was observed between S1 and S2, independently of educational level, with an increase of the age adjusted P/S ratio from 0.42 to 0.50 in men (P=10(-4)) and from 0.41 to 0.50 in women (P=10(-4)), whereas the daily cholesterol intake dropped from 552.0 to 466.9 mg and from 447.2 to 384.6 mg in men and women, respectively (P=10(-4)). These variations were associated with a decrease in the consumption of high-fat foods and an increase in that of low-fat products (poultry, low-fat dairy foods, fish) in all educational classes. By contrast, the consumption of fruit and vegetables, which was highly associated with educational level, varied little over time. Our results indicate slight improvement in fat quality, independently of educational level, while fruit and vegetable intake, which appeared more dependent on educational level, was only poorly modified over the 10 y interval.


Helicobacter pylori CagA induces AGS cell elongation through a cell retraction defect that is independent of Cdc42, Rac1, and Arp2/3.
Helicobacter pylori, which infects over one-half the world's population, is a significant risk factor in a spectrum of gastric diseases, including peptic ulcers and gastric cancer. Strains of H. pylori that deliver the effector molecule CagA into host cells via a type IV secretion system are associated with more severe disease outcomes. In a tissue culture model of infection, CagA delivery results in a dramatic cellular elongation referred to as the "hummingbird" phenotype, which is characterized by long, thin cellular extensions. These actin-based cytoskeletal rearrangements are reminiscent of structures that are regulated by Rho GTPases and the Arp2/3 complex. We tested whether these signaling pathways were important in the H. pylori-induced cell elongation phenotype. Contrary to our expectations, we found that these molecules are dispensable for cell elongation. Instead, time-lapse video microscopy revealed that cells infected by cagA(+) H. pylori become elongated because they fail to release their back ends during cell locomotion. Consistent with a model in which CagA causes cell elongation by inhibiting the disassembly of adhesive cell contacts at migrating cells' lagging ends, immunohistochemical analysis revealed that focal adhesion complexes persist at the distal tips of elongated cell projections. Thus, our data implicate a set of signaling molecules in the hummingbird phenotype that are different than the molecules previously suspected.


Cost comparison of state hospital and community-based care for seriously mentally ill adults.
In 1989, Philadelphia began a bold experiment involving the total shutdown of a 500-bed state hospital. This study examines the service utilization and cost of treating individuals with serious mental illness in a community-based care system in which the state hospital was replaced with 60 extended acute care beds in general hospitals and 583 residential beds. A pre-post study design was used to determine the utilization and cost differences before and after the state hospital closed for individuals with a diagnosis of schizophrenia who required extended psychiatric hospitalization following an acute care crisis episode in a general hospital. The number and cost of days spent in general and in extended hospital and residential treatment were compared on an episode and an annual basis. The results of this analysis showed that after the state hospital closed, the direct treatment cost of an episode of care increased from $68,446 to $78,929, and the average annual cost of care per patient increased from $48,631 to $66,794 because of an increase in acute care hospitalization. This study suggests that an "admission" cohort of seriously mentally ill patients requires an optimal mix of acute care, extended care, and residential beds, as well as ambulatory services, in order for cost-efficient care to be delivered during a crisis period. Determining the appropriate allocation and supply of beds in different settings is essential if community mental health systems are to manage the care of individuals with serious mental illness outside of institutional settings.


"You just have to make the pain go away"--children's experiences of pain management.
This paper reports a study of the descriptions young children use and their expectations for pain management interventions experienced during hospitalization. The alleviation of children's pain has been investigated through the eyes of health care providers and parents, but the children's own perspective has largely been ignored. To date, there is a growing tendency to listen to the children when making final decisions on treatment in child health care. The evidence shows that children should be regarded as experts on their pain to maximize the options for pain management and to provide high-quality care. Forty-four children who were inpatients in four pediatric units in a university hospital participated in the study. The data were collected by means of a qualitative interview with the children until theoretic saturation was reached. The data analysis was based on inductive content analysis. The findings indicate that the children used multiple strategies while trying to deal with their pains during hospitalization and expected professional competence from health care professionals. Moreover, the children valued the care and attention provided by significant others. When managing pain in hospitalized children with a wide diversity of sources, the complexity of pain as a physiologic, psychologic, social, and cultural phenomenon must not be overlooked.


Metoprine, a histamine N-methyltransferase inhibitor, attenuates methamphetamine-induced hyperlocomotion via activation of histaminergic neurotransmission in mice.
Metoprine increases the content of histamine in brain by inhibiting histamine N-methyltransferase (HMT), a centrally acting histamine degrading enzyme. We present data demonstrating that pretreatment with metoprine attenuates the hyperlocomotive effects of METH in mice using a multi-configuration behavior apparatus designed to monitor four behavioral outcomes [horizontal locomotion, appetitive behavior (food access), and food and water intake]. Metoprine pretreatment itself induced hyperlocomotion in mice challenged with saline during the large part of light phase. The trend was also observed during the following dark phase. This is the first report that metoprine has a long-lasting locomotor stimulating property. Similarly, in a tail suspension test, a single injection of metoprine significantly reduced total time of immobility in mice, consistent with the idea that metoprine possesses motor stimulating properties. Metoprine pretreatment did not affect other aspects of behavior. Metoprine did not affect the appetitive and drinking behavior while exerted an effect on stereotypy. No stereotyped behavior was observed in mice pretreated with vehicle followed by METH, while stereotyped sniffing was observed in mice pretreated with metoprine followed by METH. The metoprine pretreatment attenuated METH-induced hyperlocomotion during the first 2 h of light phase, suggesting that metoprine-induced locomotor stimulating property might be different from that of METH. The hypothalamic content of histamine (but not its brain metabolite) was increased after metoprine or METH administration. Both METH and metoprine reduced dopamine and histamine turnover in the striatum and the nucleus accumbens and the hypothalamus, respectively, and there is a significant metoprine pretreatment x METH challenge interaction in the histamine turnover. It is likely that metoprine may attenuate METH-induced hyperlocomotion via activation of histaminergic neurotransmission. Metoprine also might induce a long-lasting locomotor stimulating effect via a putative mechanism different from that whereby METH induces the locomotor stimulating effect.


Multiplexed detection of SARS-CoV-2 genomic and subgenomic RNA using in situ hybridization.
The widespread Coronavirus Disease 2019 (COVID-19) is caused by infection with the novel coronavirus SARS-CoV-2. Currently, we have a limited toolset available for visualizing SARS-CoV-2 in cells and tissues, particularly in tissues from patients who died from COVID-19. Generally, single-molecule RNA FISH techniques have shown mixed results in formalin fixed paraffin embedded tissues such as those preserved from human autopsies. Here, we present a platform for preparing autopsy tissue for visualizing SARS-CoV-2 RNA using RNA FISH with amplification by hybridization chain reaction (HCR). We developed probe sets that target different regions of SARS-CoV-2 (including ORF1a and N) as well as probe sets that specifically target SARS-CoV-2 subgenomic mRNAs. We validated these probe sets in cell culture and tissues (lung, lymph node, and placenta) from infected patients. Using this technology, we observe distinct subcellular localization patterns of the ORF1a and N regions, with the ORF1a concentrated around the nucleus and the N showing a diffuse distribution across the cytoplasm. In human lung tissue, we performed multiplexed RNA FISH HCR for SARS-CoV-2 and cell-type specific marker genes. We found viral RNA in cells containing the alveolar type 2 (AT2) cell marker gene (SFTPC) and the alveolar macrophage marker gene (MARCO), but did not identify viral RNA in cells containing the alveolar type 1 (AT1) cell marker gene (AGER). Moreover, we observed distinct subcellular localization patterns of viral RNA in AT2 cells and alveolar macrophages, consistent with phagocytosis of infected cells. In sum, we demonstrate the use of RNA FISH HCR for visualizing different RNA species from SARS-CoV-2 in cell lines and FFPE autopsy specimens. Furthermore, we multiplex this assay with probes for cellular genes to determine what cell-types are infected within the lung. We anticipate that this platform could be broadly useful for studying SARS-CoV-2 pathology in tissues as well as extended for other applications including investigating the viral life cycle, viral diagnostics, and drug screening.


[Heparin-induced thrombocytopenia type II with early aortocoronary bypass occlusion and stent thrombosis after PTCA of the RCA--treatment with lepirudin (Refludan) and abciximab (Reo pro) during recanalization of the RCA].
Heparin-induced thrombocytopenia type II (HIT type II) is the most serious complication of heparin treatment apart from bleeding, which is the most common side effect. Eleven days after coronary bypass grafting, a 71 year old patient showed a posterolateral myocardial infarction and a thrombocytopenia of 80,000/microliter. This was considered a postoperative thrombocytopenia. Coronary angiography revealed closed venous bypass grafts. The right coronary artery (RCA) was revascularized by percutaneous transluminal coronary angioplasty (PTCA) and stent placement. During both coronary angiography and PTCA, heparin was administered to the patient. The platelet number did not change. Four days later the patient showed an inferior myocardial infarction and an AV-block III degrees and a syncope. The following coronary angiography revealed RCA stent occlusion. HIT type II was presumed and recanalization was carried out using Lepirudin (Refludan) as the anticoagulant. After placing the guide wire, thrombi could be seen in the proximal RCA. Abciximab (Reo pro), a monoclonal antibody against the glycoprotein IIb/IIIa receptor was additionally administered. Coronary angiography on the next day revealed only a small remaining thrombus. The AV-block disappeared immediately after revascularization. The diagnosis of HIT type II was confirmed through heparin-induced-platelet-activation-test (Hipa-test) and immunoassay (PF 4/heparin-ELISA). This case report illustrates the complicated diagnosis of HIT type II and the successful simultaneous use of Lepirudin (Refludan) and Abciximab (Reo pro). The number of platelets should be checked daily during heparin treatment. In the case of a thrombocytopenia, the treatment should be stopped immediately, and Hipa-test and PF 4/heparin-ELISA should be carried out.


Hypertrophy of the extra-articular tendon of the long head of biceps correlates with the location and size of a rotator cuff tear.
The aim of this study was to assess hypertrophy of the extra-articular tendon of the long head of biceps (LHB) in patients with a rotator cuff tear. The study involved 638 shoulders in 334 patients (175 men, 159 women, mean age 62.6 years; 25 to 81) with unilateral symptomatic rotator cuff tears. The cross-sectional area (CSA) of the LHB tendon in the bicipital groove was measured pre-operatively in both shoulders using ultrasound. There were 154 asymptomatic rotator cuff tears in the contralateral shoulder. Comparisons were made between those with a symptomatic tear, an asymptomatic tear and those with no rotator cuff tear. In the affected shoulders, the CSAs were compared in relation to the location and size of the rotator cuff tear. The mean CSA was 21.0 mm2 (4 to 71) in those with a symptomatic rotator cuff tear, 19.9 mm2 (4 to 75) in those with an asymptomatic rotator cuff tear and 14.1 mm2 (5 to 43) in those with no rotator cuff tear. The mean CSA in patients with both symptomatic and asymptomatic rotator cuff tears was significantly larger than in those with no rotator cuff tear (p < 0.001). In the affected shoulders, there were significant differences between patients with more than a medium sized posterosuperior cuff tear and those with an antero-superior cuff tear. Regardless of the symptoms, there was significant hypertrophy of the extra-articular LHB tendon in patients with a rotator cuff tear. The values were significantly related to the size of the tear. Cite this article: Bone Joint J 2017;99-B:806-11.


Exploring the Legionella pneumophila positivity rate in hotel water samples from Antalya, Turkey.
The genus Legionella is a fastidious Gram-negative bacteria widely distributed in natural waters and man made water supply systems. Legionella pneumophila is the aetiological agent of approximately 90% of reported Legionellosis cases, and serogroup 1 is the most frequent cause of infections. Legionnaires' disease is often associated with travel and continues to be a public health concern at present. The correct water management quality practices and rapid methods for analyzing Legionella species in environmental water is a key point for the prevention of Legionnaires' disease outbreaks. This study aimed to evaluate the positivity rates and serotyping of Legionella species from water samples in the region of Antalya, Turkey, which is an important tourism center. During January-December 2010, a total of 1403 samples of water that were collected from various hotels (n = 56) located in Antalya were investigated for Legionella pneumophila. All samples were screened for L. pneumophila by culture method according to "ISO 11731-2" criteria. The culture positive Legionella strains were serologically identified by latex agglutination test. A total of 142 Legionella pneumophila isolates were recovered from 21 (37.5%) of 56 hotels. The total frequency of L. pneumophila isolation from water samples was found as 10.1%. Serological typing of 142 Legionella isolates by latex agglutination test revealed that strains belonging to L. pneumophila serogroups 2-14 predominated in the examined samples (85%), while strains of L. pneumophila serogroup 1 were less numerous (15%). According to our knowledge, our study with the greatest number of water samples from Turkey demonstrates that L. pneumophila serogroups 2-14 is the most common isolate. Rapid isolation of L. pneumophila from environmental water samples is essential for the investigation of travel related outbreaks and the possible resources. Further studies are needed to have epidemiological data and to determine the types of L. pneumophila isolates from Turkey.


Current Innovations in Peripheral Nerve Stimulation.
Peripheral nerve stimulation has been used in the treatment of several chronic pain conditions including pain due to peripheral nerve dysfunctions, complex regional pain syndrome, and cranial neuralgias. It has been shown to be effective for chronic, intractable pain that is refractory to conventional therapies such as physical therapy, medications, transcutaneous electrical stimulations, and nerve blocks. Recently, a new generation of peripheral nerve stimulation devices has been developed; these allow external pulse generators to transmit impulses wirelessly to the implanted electrode, and their implantation is significantly less invasive. In this review, we discuss the history, pathophysiology, indications, implantation process, and outcomes of employing peripheral nerve stimulation to treat chronic pain conditions.


Triggering of Thumb by a Ganglion Cyst of the Flexor Tendon Sheath at A1 Pulley: A Case Report.
Ganglions of the wrist and hand are commonly seen but the most common sites are in the dorsum of the wrist followed by the volar side in the distal forearm at the wrist crease. The Ganglion cysts arising from the flexor tendon sheath are rare and only a few are reported in the literature. We report a rare case of a ganglion cyst of the flexor tendon sheath at A1 pulley of thumb in a 35-year-old male who came with the complaint of chronic triggering of the left thumb. The histopathological examination confirmed the ganglion which was removed from the A1 pulley area. A1 pulley ganglion causing trigger thumb is uncommon entity. Although, traditional treatment for this is conservative or aspiration. High recurrence is observed. When it comes to preservation of fine movements such as thumb, aggressive approach involving exploration and excision of cyst gives good functional outcome and reduces chance of recurrence.


Imaging of DNA and Protein-DNA Complexes with Atomic Force Microscopy.
This article reviews atomic force microscopy (AFM) studies of DNA structure and dynamics and protein-DNA complexes, including recent advances in the visualization of protein-DNA complexes with the use of cutting-edge, high-speed AFM. Special emphasis is given to direct nanoscale visualization of dynamics of protein-DNA complexes. In the area of DNA structure and dynamics, structural studies of local non-B conformations of DNA and the interplay of local and global DNA conformations are reviewed. The application of time-lapse AFM nanoscale imaging of DNA dynamics is illustrated by studies of Holliday junction branch migration. Structure and dynamics of protein-DNA interactions include problems related to site-specific DNA recombination, DNA replication, and DNA mismatch repair. Studies involving the structure and dynamics of chromatin are also described.


Potential role of sorafenib in the treatment of acute myeloid leukemia.
The identification of aberrant cellular pathways and dysfunctional molecules important in neoplastic transformation has begun to provide us with a number of targets for drug development. It is likely that many of these agents will be incorporated into our existing treatment strategies that include cytotoxic agents. Sorafenib, a multi-kinase inhibitor has been approved in the United States for the treatment of renal cell carcinoma as well as hepatocellular cancer. Its potential role in hematological malignancies, particularly acute myeloid leukemia (AML) is under evaluation. Here we describe the biological pathways in AML that are the potential targets of sorafenib action and discuss the early clinical data with the agent in solid tumors and AML.


MicroRNA-145 downregulation associates with advanced tumor progression and poor prognosis in patients suffering osteosarcoma.
Microribonucleic acid (miRNA)-145 (miR-145) has been identified as a tumor suppressor in several types of human cancers. Especially, miR-145 expression has been found to be significantly decreased in osteosarcoma tissues, and enforced expression of this miRNA could inhibit invasion and angiopoiesis of osteosarcoma cells. However, its clinical significance in osteosarcoma is still unclear. Therefore, the aim of this study was to analyze the association of miR-145 expression with clinicopathologic features and prognosis in patients suffering osteosarcoma. miR-145 expression was detected by quantitative real-time reverse transcriptase polymerase chain reaction analysis using 166 pairs of osteosarcoma and noncancerous bone tissues. Then, the associations of miR-145 expression with clinicopathological factors or survival of patients suffering osteosarcoma were determined. The expression levels of miR-145 in osteosarcoma tissues were significantly lower than those in corresponding noncancerous bone tissues (P < 0.0001). In addition, miR-145 downregulation more frequently occurred in osteosarcoma specimens with advanced clinical stage (P = 0.003) and positive distant metastasis (P = 0.008). Moreover, the univariate analysis demonstrated that osteosarcoma patients with low miR-145 expression had poorer overall (P = 0.003) and disease-free survival (P < 0.001). Furthermore, the multivariate analysis identified low miR-145 expression as an independent prognostic factor for both overall (P = 0.01) and disease-free survival (P = 0.008). For the first time, the current data offer convincing evidence that the down-regulation of miR-145 may be associated with tumor aggressiveness and tumor metastasis of osteosarcoma, and that this miRNA may be an independent prognostic marker for osteosarcoma patients.


[The role of preoperative percutaneous isolated hepatic perfusion and hepatectomy in multidisciplinary treatment].
We report a case of multiple bilobar hepatocellular carcinoma( HCC) that was successfully treated with a multidisciplinary treatment including preoperative percutaneous isolated hepatic perfusion and hepatectomy. The patient was a 61- year-old man who was detected as having HCC mainly in segment 4 and 8 of the liver and multiple bilobar intrahepatic metastasis during follow-up evaluation for chronic hepatitis B. Curative resection was difficult because the patient had insufficient liver function and because of the location of the tumor. Hence, we performed preoperative percutaneous isolated hepatic perfusion (PIHP) to control the multiple HCC. Seven weeks after the PIHP, the tumor size had reduced, and therefore we performed an extended left hepatic lobectomy. In addition to these treatment modalities, we performed transcatheter arterial chemoembolization (TACE) 3 times owing to recurrent HCC in the right liver lobe. Considering that HCC in segment 8 can be treated with TACE, we performed partial hepatectomy. As of the last follow-up visit, the patient was alive without disease recurrence. Thus, preoperative PIHP may improve the resectability rate in patients with multiple bilobar HCC for which curative resection is difficult to perform.


Positive intraoperative cultures and canine total hip replacement: risk factors, periprosthetic infection, and surgical success.
The results of closing intraoperative cultures from 27 canine total hip replacements (THR) were reviewed. The relationship between these culture results and presurgical and surgical factors, and the short- and long-term success of THR were assessed. Eleven out of 27 cases had a positive culture, but none of these 11 cases were diagnosed with periprosthetic infection at follow-up examination. The duration of the clinical signs of hip disease prior to THR was significantly greater for those cases with a positive culture (P=0.034). The incidence of positive cultures was not related to surgical success.


Peripheral blood dendritic cells and GM-CSF as an adjuvant for hepatitis B vaccination in hemodialysis patients.
Dysfunctional antigen presentation may underlie the impaired antibody response to hepatitis B vaccination in hemodialysis patients. Dendritic cells are considered to be the most important antigen presenting cells, but their presence and function in hemodialysis patients is unclear. Granulocyte-monocyte-colony stimulating factor (GM-CSF) has been given successfully to hemodialysis patients to increase the proportion of responders to hepatitis B vaccination. Although GM-CSF acts on both monocytes and dendritic cells, the mechanisms underlying its adjuvant quality are largely unknown. In this study we analyzed monocytes and dendritic cells in the peripheral blood of hemodialysis patient that had responded to a standard hepatitis B vaccination procedure (responders), patients who had not responded (nonresponders), and healthy controls. The nonresponders were given two additional booster vaccines, both preceded by administration of GM-CSF the day before. After two booster vaccinations with GM-CSF, six out of seven patients developed a protective antibody response to hepatitis B. The memory T-cell response to tetanus toxoid was significantly lower in nonresponders compared to controls. The monocytes of dialysis patients and healthy controls showed a similar expression of relevant cell surface molecules. However, the numbers of circulating dendritic cells were on average 50% reduced compared to healthy controls, with a further reduction after GM-CSF administration. This was accompanied by a decrease of T-cell proliferation in antigen presentation assays. Monocytes showed increased major histocompatibility complex (MHC) class II, CD54, and CD40 expression, while their antigen-presenting capacity remained unchanged. GM-CSF is an effective adjuvant for hepatitis B vaccination in primary nonresponding hemodialysis patients, but paradoxically decreases the antigen presenting capacity of peripheral blood mononuclear cells and the number of circulating dendritic cells.


PARASITE-MEDIATED SELECTION AGAINST INBRED SOAY SHEEP IN A FREE-LIVING ISLAND POPULATON.
Parasites are thought to provide a selective force capable of promoting genetic variation in natural populations. One rarely considered pathway for this action is via parasite-mediated selection against inbreeding. If parasites impose a fitness cost on their host and the offspring of close relatives have greater susceptibility to parasites due to the increased homozygosity that results from inbreeding, then parasite-mediated mortality may select against inbred individuals. This hypothesis has not yet been tested within a natural vertebrate population. Here we show that relatively inbred Soay sheep (Ovis aries), as assessed by microsatellite heterozygosity, are more susceptible to parasitism by gastrointestinal nematodes, with interactions indicating greatest susceptibility among adult sheep at high population density. During periods of high overwinter mortality on the island of Hirta, St. Kilda, Scotland, highly parasitised individuals were less likely to survive. More inbred individuals were also less likely to survive, which is due to their increased susceptibility to parasitism, because survival was random with respect to inbreeding among sheep that were experimentally cleared of their gastrointestinal parasite burden by anthelminthic treatment. As a consequence of this selection, average microsatellite heterozygosity increases with age in St. Kildan Soay sheep. We suggest that parasite-mediated selection acts to maintain genetic variation in this small island population by removing less heterozygous individuals.


In vitro and in vivo effects of hydrolysates from conglycinin on intestinal microbial community of mice after Escherichia coli infection.
To detect the effect of pepsin-hydrolysate conglycinin (PTC) on the growth of Escherichia coli O(138)in vitro, and investigate the effect of PTC on intestinal microbial community of mice after E. coli infection. Serial dilution method was used to detect the antibacterial activity of PTC in 96-well cell-cultivated plates. Fifty-five KM mice were randomly assigned to five groups: normal, feeding-E. coli control, HCl-full hydrolysis of conglycinin, conglycinin and PTC. Orally administrated with hydrolysates from conglycinin for 21 days, each mouse was fed with 2 x 10(8) CFU ml(-1) of E. coli O(138) on the 22nd day. The mice activities were monitored and polymerase chain reaction-denaturing gradient gel electrophoresis was used to analyse the microbial community in mice faeces. The results showed that PTC could inhibit growth of E. coli O(138) at nitrogen concentrations of more than 520 mg l(-1). There was high similarity of intestinal microbial community in mice between PTC and normal groups. PTC inhibits growth of E. coli O(138), keeps mice healthy following oral administration of E. coli infection and maintains a balanced active microbial community in their gastrointestinal tract. This study demonstrated the antibacterial activity of PTC against E. coli and its ability to maintain healthy intestinal microbial community in mice even after they were infected with E. coli. This observation is significant in the application of PTC to prevent gastrointestinal diseases caused by E. coli and unbalanced intestinal microflora.


Genetic mapping of microsatellite markers around the arcelin bruchid resistance locus in common bean.
The deployment in common beans (Phaseolus vulgaris L.) of arcelin-based bruchid resistance could help reduce post-harvest storage losses to the Mexican bean weevil [(Zabrotes subfasciatus (Boheman)]. Arcelin is a member of the arcelin-phytohemagglutinin-alpha-amylase inhibitor (APA) family of seed proteins, which has been extensively studied but not widely used in bean breeding programs. The purpose of this study was to evaluate microsatellite markers for genetic analysis of arcelin-based bruchid resistance and to determine the orientation of markers and the rate of recombination around the APA locus. A total of 10 previously developed microsatellites and 22 newly developed markers based on a sequenced BAC from the APA locus were screened for polymorphism and of these 15 were mapped with an F(2) population of 157 individuals resulting from a susceptible x resistant cross of SEQ1006 x RAZ106 that segregated for both the arcelin 1 allele and resistance to the bruchid, Z. subfasciatus. Microsatellites derived from APA gene sequences were linked within 0.8 cM of each other and were placed relative to the rest of the b04 linkage group. In a comparison of genetic to physical distance on the BAC sequence, recombination was found to be moderate with a ratio of 125 kb/cM, but repressed within the APA locus itself. Several markers were predicted to be very effective for genetic studies or marker-assisted selection, based on their significant associations with bruchid resistance and on low adult insect emergence and positions flanking the arcelin and phytohemagglutinin genes.


Determination of reactive oxygen species in nasal polyps.
A strong relationship between tissue damage and reactive oxygen species (ROS) has been established by previous studies. The aim of the current study was to evaluate the presence of ROS in nasal polyps (NP) by measuring luminol and lucigenin amplified chemiluminescence (CL). Three groups of specimens were studied. Group 1 composed of NPs of 15 patients, and group 2 constituted of healthy appearing nonpolypoid nasal mucosa of the same patients. Group 3 specimens (control group) were obtained from 15 patients who underwent septoplasty and/or inferior turbinectomy operations, and detected to be free of rhinosinusitis. None of the patients had a history of allergy, asthma, or aspirin sensitivity, and all patients showed negative results to a skin prick test. The ROS levels were measured directly with luminol and lucigenin amplified CL. CL measurements revealed significant differences between ROS constituents of NP (group 1) and control (group 3) tissue samples. CL measurements of healthy appearing nonpolypoid nasal mucosa (group 2) of the NP patients revealed values that were scattered between the values of the other two groups. Although insignificant, ROS levels of the nonpolypoid nasal mucosa (group 2) were found to be higher than normal controls (group 3). In this study, ROS levels of NP tissue samples were directly measured. In our study, by measuring high ROS levels in NP samples, a strong relationship between tissue damage in NPs and ROS has been demonstrated, and the contribution of ROS in the pathophysiology of nasal polyposis has been emphasized.


Manchester response reveals the spirit of our NHS staff.
As they always do in the nation's hour of need, nurses came to the rescue last week by responding so impressively to the terrorist attack in Manchester. Staff at eight hospitals were directly involved in caring for victims, while many more played their part by providing care and emotional support to the wider community of north-west England and beyond.


Severe hypernatremia during postoperative care in patients with craniopharyngioma.
We aimed to describe and predict the risk of severe hypernatremia after surgical resection of craniopharyngioma and to identify the association of water intake, urine output, and sodium level change in the patients. The outcome was postoperative severe hypernatremia. We identified risk factors associated with hypernatremia using multivariable regression. We trained machine learning models to predict the outcome. We compared serum sodium change, intravenous input, oral input, total input, urine output, and net fluid balance according to different nurse shifts. Among 234 included patients, 125 developed severe hypernatremia after surgery. The peak incidence occurred during day 0 and day 6 after surgery. The risk was increased in patients with gross total resection (odds ratio (OR) 2.41, P < 0.001), high Puget classification (OR 4.44, P = 0.026), preoperative adrenal insufficiency (OR 2.01, P = 0.040), and preoperative hypernatremia (OR 5.55, P < 0.001). The random forest algorithm had the highest area under the receiver operating characteristic curve (0.770, 95% CI, 0.727-0.813) in predicting the outcome and was validated in the prospective validation cohort. Overnight shifts were associated with the highest serum sodium increase (P = 0.010), less intravenous input (P < 0.001), and less desmopressin use (P < 0.001). The overall incidence of severe hypernatremia after surgical resection of craniopharyngioma was significant, especially in patients with gross total resection, hypothalamus distortion, preoperative adrenal insufficiency, and preoperative severe hypernatremia. Less intravenous input and less desmopressin use were associated with serum sodium increases, especially during overnight shifts.


Up, Down, and All Around: Diagnosis and Treatment of Novel STAT3 Variant.
The number of identified monogenic causes of childhood-onset autoimmunity due to nodal and extranodal lymphoproliferation has increased. These pathogenic genetic variants provide the potential for pathway-specific treatment. Novel variants also require pathway-specific verification. In this report, we describe a 14-year-old patient with a novel variant in STAT3. We report clinical and laboratory findings that support STAT3 p.G419R as a novel pathogenic STAT3 gain-of-function variant.


Treatment of Sagittal Fracture of the Zygomatic Arch Root Assisted by Surgical Navigation Technology.
Sagittal fracture at the temporal root of the zygomatic arch often occurs as a part of zygomaticomaxillary fractures. The authors described the application of computer-assisted navigation in the lag screw insertion for the fixation of sagittal fracture at the temporal root of zygomatic arch. Using the presurgical planning of the computer-assisted navigation system, the trajectory of lag screw insertion was designed, and the insertion depth was calculated. In the presurgical planning, the trajectory of screw insertion was placed with an anterior inclination of 10° to 15° (mean: 12.24°), and the screw insertion depth was 9.0 to 12.0 mm (mean: 10.65 mm). In the operation, the screw insertion in the fixation of the sagittal fracture was performed under the guidance of navigation system according to the presurgical planning. The postoperative CT scan showed exact reduction and fixation of the sagittal fracture in all cases. Computer-assisted navigation is a useful tool for the lag screw insertion in the precise fixation of sagittal fracture at the temporal root of the zygomatic arch in complex zygomaticomaxillary fractures.


Postcollision multifragmentation in fullerene-surface impact: Microscopic insights via molecular dynamics simulations.
Postcollision multifragmentation which we have recently observed experimentally in C60 (-)-surface impact is the phenomenon of a delayed multiparticle breakup of a highly collisionally vibrationally excited large molecule/cluster (the precursor species) into several polyatomic fragments, after leaving the surface. In this paper, we show that the molecular dynamics simulations of near-grazing C60 collisions with a gold surface at 300 eV impact energy (very similar to the experimental conditions) successfully reproduce the experimentally observed characteristics of the postcollision multifragmentation process. The calculated mass resolved kinetic energy distributions and the time dependent yield curves of the Cn fragments revealed a precursor mediated, velocity correlated, delayed fragmentation event along the outgoing trajectory, far away from the surface. Most of the large fragments (n ≥ 5) are formed within a time window of 2-20 ps after leaving the surface, corresponding to the vertical distances of 3-30 nm from the surface. Analysis of delay times and actual time duration for multifragmentation reveal that a large part can be described as simultaneous postcollision (delayed) multifragmentation events. The delayed nature of the event seems to be due to an early sequence of structural transformations of the precursor.


Citizen participation and the health policies of Unasur.
This paper examines how the Union of South American Nations (Unasur) concerned itself with ensuring democracy and participation in the construction of health policies. It aims to explain the meaning of health democracy, and its importance for making the right to health effective. The concern is that the decision on these politics of the bloc should be in harmony with the interests of their citizens, so as to identify ethical activity of the States in international relations. An analysis was made of the documents of constitution, and resolutions on health policy, of this bloc, and statements were found with objectives and principles about democracy and citizen participation; but no institutionalization of mechanisms that might make participative democracy in health operational was found.


Upflow column reactor design for dechlorination of chlorinated pulping wastes by Penicillium camemberti.
A Penicillium camemberti strain isolated in our laboratory has been studied for its ability to degrade chlorinated pulping wastes, presumably containing a variety of chlorinated polyphenols. In batch tests, the highest removals (76% AOX, 61% color and 65% TOC) were obtained with 0.2 g/l feed acetate concentration. The tendency of the fungus to dechlorinate bleachery effluents better under non-shaking conditions and to attach onto surfaces suggested the use of immobilized cells rather than freely suspended ones in further exploitation of the process. An upflow glass wool packed column reactor established with this fungus could be operated for nearly two years in the laboratory. At best around 70% AOX could be removed from chlorinated pulping wastes in 7.3 h of contact with no aeration and with a minimal amount of carbon supplement (0.2 g/l). Finally, an asymptotic mathematical formula for determining Michaelis-Menten kinetic rates has been derived. The kinetic rates K(m) (the Michaelis constant or saturation constant for the substrate) and V(m) (the product of maximum rate for the enzymatic reaction and biomass concentration) were then calculated as 126.386 mg/l and 2.83017 mg/lh, respectively.


Nonstructural Protein NSs Hampers Cellular Antiviral Response through LSm14A during Severe Fever with Thrombocytopenia Syndrome Virus Infection.
The nonstructural protein (NSs) of severe fever with thrombocytopenia syndrome virus (SFTSV) plays multiple functions in the virus life cycle. Proteomic screening for host proteins interacting with NSs identified the cellular protein LSm14A. LSm14A, a member of the LSm family involved in RNA processing in the processing bodies, binds to viral RNA or synthetic homolog and mediates IFN regulatory factor 3 activation and IFN-β induction. NSs interacted with and colocalized with LSm14A, and this interaction effectively inhibited downstream phosphorylation and dimerization of IFN regulatory factor 3, resulting in the suppression of antiviral signaling and IFN induction in several cell types of human origin. Knockdown of NSs resulted in the suppression of SFTSV replication in host cells. Viral RNA bound to LSm14A-NSs protein complex during the interaction. A newly discovered LRRD motif of NSs functioned to interact with LSm14A. Altogether, our data demonstrated a mechanism used by SFTSV to inhibit host innate immune response.


A screen-printed, amperometric biosensor array incorporated into a novel automated system for the simultaneous determination of organophosphate pesticides.
Organophosphate pesticides present serious risks to human and environmental health. A rapid reliable, economical and portable analytical system will be of great benefit in the detection and prevention of contamination. A biosensor array based on six acetylcholinesterase enzymes for use in a novel automated instrument incorporating a neural network program is described. Electrochemical analysis was carried out using chronoamperometry and the measurement was taken 10s after applying a potential of 0 V vs. Ag/AgCl. The total analysis time for the complete assay was less than 6 min. The array was used to produce calibration data with six organophosphate pesticides (OPs) in the concentration range of 10(-5) M to 10(-9) M to train a neural network. The output of the neural network was subsequently evaluated using different sample matrices. There were no detrimental matrix effects observed from water, phosphate buffer, food or vegetable extracts. Furthermore, the sensor system was not detrimentally affected by the contents of water samples taken from each stage of the water treatment process. The biosensor system successfully identified and quantified all samples where an OP was present in water, food and vegetable extracts containing different OPs. There were no false positives or false negatives observed during the evaluation of the analytical system. The biosensor arrays and automated instrument were evaluated in situ in field experiments where the instrument was successfully applied to the analysis of a range of environmental samples. It is envisaged that the analytical system could provide a rapid detection system for the early warning of contamination in water and food.


[A Cognitive Behavioural-Based Intervention in Reducing Test Anxiety in High School Students: A Pilot Cluster Randomized Controlled Trial].
School-age test anxiety is an important risk factor for school performance. Notwithstanding, few studies seek to identify which strategies are effective in improving test anxiety. The aim of this study was to assess whether a cognitive-behavioural intervention for high school students could significantly reduce test anxiety. Two-arm, cluster-randomized controlled, unblinded, parallel, trial. Participants were 10th grade students from Alves Martins High School in Viseu, Portugal. Students were randomized at class level to receive a cognitive-behavioural-based intervention combined with mindfulness, psychoeducation, and relaxation techniques, or to a control group with no intervention. Participants' anxiety levels were measured using the Test Anxiety Questionnaire. The analysis of the effect of the intervention was carried out on an intention-to-treat basis at the class level, using multilevel mixed effects models and Bayesian modelling. The intervention had a significant effect in reducing test anxiety (d = 0.81, 95% CI 0.45;1.17, Bayes factor = 31.3). Male gender was an independent risk factor for smaller reductions in anxiety levels. The intervention was more effective in reducing the worry component of test anxiety (d = 0.76, 95% CI 0.41;1.11, Bayes factor = 19.9) than the emotionality component (d = 0.63, 95% CI 0.31;0.95, Bayes factor = 6.6). A cognitive-behavioural intervention specifically designed to reduce test anxiety, using a combination of mindfulness, psychoeducation and relaxation techniques, was effective in reducing test anxiety levels. Retrospectively registered on clinicaltrials.gov (NCT05481099) in 08/01/2022.


Restrictive spirometry pattern is associated with low physical activity levels. A population based international study.
Restrictive spirometry pattern is an under-recognised disorder with a poor morbidity and mortality prognosis. We compared physical activity levels between adults with a restrictive spirometry pattern and with normal spirometry. Restrictive spirometry pattern was defined as a having post-bronchodilator FEV1/FVC ≥ Lower Limit of Normal and a FVC<80% predicted in two population-based studies (ECRHS-III and SAPALDIA3). Physical activity was measured using the International Physical Activity Questionnaire. The odds of having low physical activity (<1st study-specific tertile) was evaluated using adjusted logistic regression models. Subjects with a restrictive spirometry pattern (n = 280/4721 in ECRHS, n = 143/3570 in SAPALDIA) reported lower levels of physical activity than those with normal spirometry (median of 1770 vs 2253 MET·min/week in ECRHS, and 3519 vs 3945 MET·min/week in SAPALDIA). Subjects with a restrictive spirometry pattern were more likely to report low physical activity (meta-analysis odds ratio: 1.41 [95%CI 1.07-1.86]) than those with a normal spirometry. Obesity, respiratory symptoms, co-morbidities and previous physical activity levels did not fully explain this finding. Adults with a restrictive spirometry pattern were more likely to report low levels of physical activity than those with normal spirometry. These results highlight the need to identify and act on this understudied but prevalent condition.


Implantation of the right and left internal mammary arteries with epicardiectomy and free omental graft: a preliminary experimental report.
In animal experiments the right internal mammary artery was implanted into the outflow tract of the right ventricle during performance of left mammary artery implantation with epicardiectomy and free omental graft. The effect of double mammary artery implantation operation was tested by triple coronary artery ameroid constriction in 24 animals. In 20 animals studied both implanted arteries remained open and had commenced to bud and branch at the time of examination. The double implant operation is still an experimental procedure.


Comparison of musculoskeletal ultrasound practices of a rheumatologist and a radiologist.
There is considerable debate regarding the role of the rheumatologist ultrasonographer and how this development will impact on musculoskeletal ultrasound (MSUS) performed by radiologists. We compared the MSUS practices of a rheumatologist and a radiologist working within the same National Health Service Trust. A retrospective review of MSUS reports of consecutive scans performed by a consultant rheumatologist with a special interest in MSUS and a consultant musculoskeletal radiologist. Reports were analysed for referring specialties, indications for MSUS, joint regions scanned, MSUS findings, frequency with which patients were referred for injection and how often injection was performed. A total of 170 patients were referred to the rheumatologist for MSUS of 282 joint regions (91% referred by rheumatologists). Of those, 84 (49%) patients had MSUS examination of more than one joint region, with up to five regions scanned per sitting. One hundred patients were referred to the radiologist for MSUS of 111 joint regions (49% referred by orthopaedic surgeons). The most frequently requested primary indication for MSUS performed by the rheumatologist was detection of synovitis [74 (44%) patients] while MSUS performed by the radiologist was most frequently for assessment for major structural changes [44 (44%) patients]. The rheumatologist performed MSUS-guided injection in 59 of 170 (35%) patients scanned and the radiologist in 13 of 100 (13%). MSUS performed by the rheumatologist was predominantly requested by rheumatologists to aid diagnosis of synovial and tendon inflammation and to guide injections, while MSUS performed by the radiologist was predominantly requested by orthopaedic surgeons to aid diagnosis of structural pathology. Curriculums in MSUS designed for rheumatologists may need to place appropriate emphasis on the identification of synovial and tendon inflammation, and injection guidance.


Congenital tuberculosis: a rare manifestation of a common infection.
The epidemiology of tuberculosis has changed dramatically over the past 5 years with significant shifts in at-risk populations, resulting in increased disease among young adults and children, especially among those from developing countries. Congenital tuberculosis is rare, and the clinical presentation of tuberculosis during pregnancy and infancy is often non-specific, making recognition difficult. Advances have been made with diagnostic tools, in public health practices, and with treatment recommendations. Controversy and debate continue regarding the safety and use of isoniazid for latent tuberculosis infection during pregnancy. New vaccine development may be promising for the future, but much work is needed to understand the complicated immune response to tuberculosis.


[Liver abscess in a dog. A case report].
The presented case report describes diagnostic and therapy of a liver abscess in a male Golden Retriever dog. The dog was adversely affected by fever, apathy, and vomitus. Diagnostic imaging including radiography, sonography and computed tomography, revealed an abscess-forming lesion of 10 × 5 cm in the left middle liver lobe with detectable multiple gas accumulation within the lesion. The surgical therapy included lobectomy with adjacent omentopexy. Four days after the operation the dog was discharged in a good general condition and with physiological body temperature. Detecting multiple gas accumulation in circular, inhomogeneous lesions by sonography allowed confirmation of the diagnosis. Surgical removal of the affected liver lobe led to recovery of the patient. In human medicine, less invasive methods are preferred, e.g. percutaneous drainage and alcoholization of the lesion. Exclusive medicamentous therapy yields the worst outcome in humans.


[Lipid metabolism abnormalities and atherosclerosis in patients on maintenance hemodialysis].
Cardiovascular disease is the leading cause of death in maintenance hemodialyzed patients with end-stage chronic renal failure. Lipid abnormalities have been identified as significant risk factors for the development of premature atherosclerosis in such patients. These abnormalities include significant elevations of serum triglycerides and triglyceride-rich lipoproteins (VLDL, IDL, remnant particles), Ip(a), decrease in LDL and HDL, accompanied by changes in apolipoprotein content. The article reviews quantitative and qualitative changes in lipoprotein composition and their possible pathogenesis. The role of such changes in atherogenesis is also discussed.


Granulocytopenia associated with thymoma in a domestic shorthaired cat.
A 5-year-old, spayed female cat was referred because of a mass in the cranial mediastinum noted on thoracic radiographs. A thymoma was diagnosed following ultrasound and biopsy of the mass. Treatment was initiated with coarse-fraction radiation therapy using external-beam therapy (four fractions of 5 Gy). The mass responded, but granulocytopenia developed. Bone marrow examination showed a myeloid to erythroid ratio of approximately 1:1, with a left shift within the myeloid line. These findings, as well as the lack of toxic changes within the peripheral blood neutrophils, suggested immune-mediated destruction of peripheral granulocytes. Immune suppression with prednisone and cyclosporine was instituted. After 7 weeks, the neutrophil count returned to normal. The tumor was removed, and cyclosporine was reduced and eventually discontinued 3 weeks postsurgery.


Proposal for a New TNM Stage based on the 7th and 8th American Joint Committee on Cancer pTNM Staging Classification for Gastric Cancer.
Background: The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for gastric cancer incorporated several new changes. We aimed to assess the comparative prognostic values of the 7th and 8th AJCC pTNM staging systems in patients with gastric cancer (GC), and accordingly, to put forward a refined staging classification. Methods: The SEER database was queried to identify GC patients between 2004 and 2009. GC patients from Sun Yat-sen University Cancer Center (SYSUCC) were used as external validation data. The Kaplan-Meier method and Cox proportional hazards regression models were used to analyze cause-specific survival (CSS). The prognostic performance of different staging schemes was assessed using the concordance index (c-index), Akaike's information criterion (AIC), and likelihood ratio χ2 test. Results: In the SEER cohort, stage migration occurred in 8.74% of patients. Survival analysis showed that it was better to treat T4bN0M0 + T4aN2M0 as stage IIIB and T4bN3bM0 as stage IV. Based on this, we established a new staging system which exhibited a superior c-index (0.7501) to the 7th and 8th AJCC staging systems (0.7498 and 0.7500, respectively). The new staging system also outperformed the 7th and 8th AJCC staging systems in terms of AIC and the likelihood ratio χ2 test. The predictive superiority of the new staging system remained valid in the SYSUCC database. Conclusions: We demonstrated that some stage modifications in the 8th AJCC pathologic staging were unnecessary. Therefore we established a new staging system, which was superior to the 7th and 8th staging systems.