[Establishment of a Novel Chinese Human Lung Adenocarcinoma Cell Line CPA-Yang1 which Produces Highly Bone Metastases in Immunodeficient Mice.].
Lung cancer is a common malignancy and is the major determinant of overall cancer mortality worldwidely. Approximately 70% of lung cancer patients will die from metastatic diseases. The aim of this study is to establish a Chinese lung adenocarcinoma cell line with high metastasis potency for exploring the mechanism of occurrence and development in lung cancer. The cell came from the pericardial effusion of a fifty-year old male patient with lung adenocarcinoma and the cells in primary culture were obtained successfully. Immunodeficient mice tumorigenicity was assayed. The cell growth curve was mappinged. Analysis of chromosome karyotype was tested. Tumor marker was detected by radioimmunoassay. The gene expression was measured by real-time quantitative PCR. The first passage cells were planted in immunodeficient mice subcutaneously and the tumorigenesis rate was 100% as well as later passages. Under the microscope, the cell showed larger and semi-suspension, semi-adherence. Approximately 0.8*10(6) cancerous cells were injected into left cardiac ventricle or tail vein of immunodeficient mice resulted start to appear lower limb paralysis and spine swelling deformation in the mice after inoculation two-three weeks. The bone metastasis rate was 90% in the tumor bearing mice by bone scintigraphy and pathology and only pulmonary metastasis 10% at the same time. The chromosome karyotype analysis of the cells was sub-triploid. The tumor marker CEA was detected in higher secretion by radioimmunoassay in the cell culture suspension. Quantitative real-time PCR was used to examined and compared SPC-A-1 lung adenocarcinoma, VEGF-C, IL-6, IL-8, genes were overexpressed. The novel cell line was named CPA-Yang1. Tne novel strain CPA-Yang1 is an parental cell with characteristics of bone metastasis of Chinese lung adenocarcinoma. It has stable traits, highly metastatic ability and a good experimental model for lung cancer research.


Prognosis of a large cohort of patients with hepatocellular carcinoma in a single European centre.
Only a few follow up data are available for patients with hepatocellular carcinoma (HCC) in Europe and the USA. Therefore, we analysed all HCC patients admitted to our hospital between 1988 and 1999. We documented aetiology, stage (HCC: Okuda and UICC classifications, liver cirrhosis: Child-Pugh score), and diagnostic and therapeutic measures of 281 consecutive HCC patients. Survival time was calculated as a function of staging and therapy. Cirrhosis was diagnosed in all patients. Seventy-two patients underwent liver resection, 28 liver transplantation, 31 transarterial chemoembolization and 14 percutaneous ethanol injection. One hundred and thirty-six patients received no treatment. The Okuda and the Child-Pugh classification predicted a significant decrease of median survival time, whereas the UICC classification was less powerful. HCC occurred only in patients with liver cirrhosis. Survival time correlated with therapy (or no therapy) and with the Child-Pugh Score. In European patients the Okuda classification is superior to the UICC classification and should be compared to novel classification systems.


Reduced enthalpy of metal hydride formation for Mg-Ti nanocomposites produced by spark discharge generation.
Spark discharge generation was used to synthesize Mg-Ti nanocomposites consisting primarily of a metastable body-centered-cubic (bcc) alloy of Mg and Ti. The bcc Mg-Ti alloy transformed upon hydrogenation into the face-centered-cubic fluorite Mg1-yTiyHx phase with favorable hydrogen storage properties. Both metal and metal hydride nanocomposites showed a fractal-like porous morphology, with a primary particle size of 10-20 nm. The metal content of 70 atom % (at %) Mg and 30 at % Ti, consistently determined by XRD, TEM-EDS, and ICP-OES, was distributed uniformly across the as-prepared sample. Pressure-composition isotherms for the Mg-Ti-H nanocomposites revealed large differences in the thermodynamics relative to bulk MgH2, with a much less negative enthalpy of formation of the hydride as small as -45 ± 3 kJ/molH2 as deduced from van't Hoff plots. The plateau pressures of hydrogenation were substantially higher than those for bulk MgH2 in the low temperature range from 150 to 250 °C. The reaction entropy was simultaneously reduced to values down to 84 ± 5 J/K mol H2, following a linear relationship between the enthalpy and entropy. Plausible mechanisms for the modified thermodynamics are discussed, including the effect of lattice strains, the presence of interfaces and hydrogen vacancies, and the formation of excess free volume due to local deformations. These mechanisms all rely on the finely interdispersed nanocomposite character of the samples which is maintained by grain refinement.


Bayesian Partition Models for Identifying Expression Quantitative Trait Loci.
Expression quantitative trait loci (eQTLs) are genomic locations associated with changes of expression levels of certain genes. By assaying gene expressions and genetic variations simultaneously on a genome-wide scale, scientists wish to discover genomic loci responsible for expression variations of a set of genes. The task can be viewed as a multivariate regression problem with variable selection on both responses (gene expression) and covariates (genetic variations), including also multi-way interactions among covariates. Instead of learning a predictive model of quantitative trait given combinations of genetic markers, we adopt an inverse modeling perspective to model the distribution of genetic markers conditional on gene expression traits. A particular strength of our method is its ability to detect interactive effects of genetic variations with high power even when their marginal effects are weak, addressing a key weakness of many existing eQTL mapping methods. Furthermore, we introduce a hierarchical model to capture the dependence structure among correlated genes. Through simulation studies and a real data example in yeast, we demonstrate how our Bayesian hierarchical partition model achieves a significantly improved power in detecting eQTLs compared to existing methods.


C1q/Tumor Necrosis Factor-Related Protein-3 Attenuates Brain Injury after Intracerebral Hemorrhage via AMPK-Dependent Pathway in Rat.
C1q/tumor necrosis factor (TNF)-related protein-3 (CTRP3) is a recently discovered adiponectin paralog with established metabolic regulatory properties. However, the role of CTRP3 in intracerebral hemorrhage (ICH) is still mostly unresolved. The aim of the present report was to explore the possible neuroprotective effect of CTRP3 in an ICH rat model and to elucidate the fundamental mechanisms. ICH was induced in rats by intracerebral infusion of autologous arterial blood. The effects of exogenous CTRP3 (recombinant or lentivirus CTRP3) on brain injury were explored on day 7. Treatment with CTRP3 reduced brain edema, protected against disruption of the blood-brain barrier (BBB), improved neurological functions and promoted angiogenesis. Furthermore, CTRP3 greatly intensified phosphorylation of AMP-activated protein kinase (AMPK) in addition to expression of hypoxia inducing factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF). Finally, the protective effects of CTRP3 could be blocked by either AMPK or VEGF inhibitors. Our findings give the first evidence that CTRP3 is a new proangiogenic and neuroprotective adipokine, which may exert its protective effects at least partly through an AMPK/HIF-1α/ VEGF-dependent pathway, and suggest that CTRP3 may provide a new therapeutic strategy for ICH.


The anti-infective outcomes of the distal femoral replacement coated with antibiotic cement in limb salvage surgery: A randomized clinical trial.
The aim of this study was to observe the anti-infective effect of the distal femoral tumor prosthesis coated with antibiotic cement during limb salvage treatment, and evaluate its potential prospect in clinic. In this randomized controlled trial, the en bloc resection and reconstruction were performed in 36 patients with distal femoral primary bone tumor. Patients were divided into 2 groups randomly according to the application of antibiotic bone cement coating, which included antibiotic cement coating group (16 cases) and control group (18 cases). There were 10 men and 6 women in anti-infection group, aged from 18 to 54 years (23.47 ± 3.53), and there were 12 men and 6 women in control group, aged from 19 to 56 years (24.16 ± 4.32). The tumor type, age, sex, and Enneking stage were enrolled with well-matched of the 2 groups of patients. There was no difference between bundles and routine standard care for each group. The antibiotic cement was coated on the surface of polyethylene jacket with punched holes during operation. The peri-prosthetic infection, local recurrence and distant metastasis were followed up and limb functions were evaluated by Musculoskeletal Tumor Society 93 (MSTS93) scoring system. Patients were followed up till 34.7 months (range 18∼62 months). There was no periprosthetic infection in anti-infection group. Four cases in control group showed deep infection. Infection rate had significant differences between the 2 groups (P < .05). Infection-related prosthesis mortality was 0% (0/16) in anti-infection group and 16.67% (3/18) in control group. Local recurrence and distant metastasis occurred in 7 of 34 patients with primary malignant bone tumor, wherein 2 cases of local recurrence and 1 cases of distant metastasis occurred in anti-infective group; 2 cases of local recurrence and 2 cases of distant metastasis occurred in the control group. During a latest follow-up, MSTS93 function scoring revealed a mean of 25.6 ± 4.2 in anti-infection group and 18.5 ± 3.3 in control group. The survival rate of anti-infective group is 75%, and the survival rate of control group is 61.11%. The antibiotic cement-coated technique on the surface of the polyethylene jacket of custom-made distal femoral prosthesis is simple and effective in controlling the periprosthetic infection after tumor prosthesis reconstruction.


EzCatDB: the enzyme reaction database, 2015 update.
The EzCatDB database (http://ezcatdb.cbrc.jp/EzCatDB/) has emphasized manual classification of enzyme reactions from the viewpoints of enzyme active-site structures and their catalytic mechanisms based on literature information, amino acid sequences of enzymes (UniProtKB) and the corresponding tertiary structures from the Protein Data Bank (PDB). Reaction types such as hydrolysis, transfer, addition, elimination, isomerization, hydride transfer and electron transfer have been included in the reaction classification, RLCP. This database includes information related to ligand molecules on the enzyme structures in the PDB data, classified in terms of cofactors, substrates, products and intermediates, which are also necessary to elucidate the catalytic mechanisms. Recently, the database system was updated. The 3D structures of active sites for each PDB entry can be viewed using Jmol or Rasmol software. Moreover, sequence search systems of two types were developed for the EzCatDB database: EzCat-BLAST and EzCat-FORTE. EzCat-BLAST is suitable for quick searches, adopting the BLAST algorithm, whereas EzCat-FORTE is more suitable for detecting remote homologues, adopting the algorithm for FORTE protein structure prediction software. Another system, EzMetAct, is also available to searching for major active-site structures in EzCatDB, for which PDB-formatted queries can be searched.


Venous leg ulcer recurrences - The relationship to self-efficacy, social support and quality of life - A mixed method study.
The aim of this study was to explore the occurrence of venous leg ulcer recurrence and the relationship with self-efficacy, social support and quality of life. Furthermore, we investigated the lived experiences of those patients and their understanding of why they developed a recurrence. We used a convergent parallel mixed method design consisting of a cohort and an interpretative phenomenological study arm. Consecutive patients (N = 145) were recruited into the study. Between 2014 and 2018, three primary care centres took part in the study. Data collection methods included chart review, administered questionnaires and semi-structured interviews. The incidence of the venous leg ulcer recurrence was 33.1% within the study period. The scores for self-efficacy, social support and venous leg ulcer health-related quality of life show little variation between all measurement points and within subgroups. The qualitative findings identified two main themes: accidentally damaging the skin and avoiding venous leg ulcer recurrences. Venous leg ulcer recurrences frequently arose from accidents. Therefore, participants developed strategies to avoid additional ulcers. To optimize recurrence prevention, improvements in knowledge of people with VLUs should be considered. A mixed method, convergent, parallel design was used to explore the occurrence of venous leg ulcer recurrence and the relation of a venous leg ulcer recurrence with self-efficacy, social support and health-related quality of life. As well as the lived experiences of venous leg ulcer patients and why they developed a recurrence. The incidence of venous leg ulcer recurrences within the study period was 33.1%. Damaging the skin and avoiding a recurrence were the main identified themes.


Neuregulin induces sustained reactive oxygen species generation to mediate neuronal differentiation.
Neuregulins (NRGs), which are highly expressed in the nervous system, bind and activate two receptor tyrosine kinases, ErbB-3 and ErbB-4. Recently, we have shown that ErbB-4 receptors expressed in PC12 cells mediate NRG-induced differentiation through the MAPK signaling pathway. Here we demonstrate that NRG induces an increase in the intracellular concentration of reactive oxygen species (ROS). N-acetylcysteine, a ROS scavenger, inhibited NRG-induced activation of Ras and Erk and PC12-ErbB-4 cell differentiation. These results suggest that ROS production is involved in NRG-mediated neuronal differentiation and that ROS can regulate activation of Ras and Erk. Constitutively active Ras enhanced ROS production and dominant negative Ras inhibited NRG-induced ROS production, suggesting, a positive regulatory loop between Ras and ROS. The mitogen, EGF, induced short-term ROS production whereas NRG and NGF, which induce cell differentiation, induced prolonged ROS production. These results strongly suggest that the kinetics of ROS production may determine whether the cells will differentiate or proliferate.


Thyrotropin alpha- and beta-subunit responses to thyrotropin-releasing hormone and domperidone in normal subjects and in patients with microprolactinomas.
Microprolactinoma is a particular pathological situation characterized by the presence of increased hypothalamic dopaminergic tone reactive to tumoral hyperprolactinemia. Since dopamine (DA) is a physiological regulating factor of the secretion of thyroid-stimulating hormone (TSH), we investigated the responses of serum TSH (holo-TSH) and its subunits (alpha-subunit: alpha-sub, and TSH-beta) to thyrotropin-releasing hormone (TRH) and domperidone (DOM; an antidopaminergic drug acting outside the blood-brain barrier) in 36 euthyroid subjects (20 controls and 16 patients with microprolactinoma) in order to evaluate the possible in vivo effects of DA excess on TSH subunit secretion. No significant difference in serum TSH increase after TRH (200 micrograms i.v.) was observed between patients with microprolactinoma and controls (TSH net incremental area under the curve, nAUC: 146 +/- 9, mean +/- SE, and 143 +/- 7.7 micrograms/l/60 min, respectively), while serum alpha-sub and TSH-beta responses were markedly reduced in patients with microprolactinoma as compared to those found in normals (alpha-sub nAUC: 3.0 +/- 0.5 vs. 19.8 +/- 2.2 micrograms/l/60 min, p less than 0.001; TSH-beta nAUC: 5.0 +/- 0.8 vs. 9.5 +/- 0.9 micrograms/l/60 min, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


A comparison of organ doses between mathematical and voxel phantoms with the DS02 photon fluences.
The purpose of this study is to quantify dosimetric differences if modern sophisticated voxel phantoms were used in the dosimetry system DS02 rather than the mathematical phantoms. The mathematical models (ADAM and EVA) and voxel phantoms (REX and REGINA) developed in Germany allow a useful comparison as they are very close in body weight, body height and organ masses. In this study, organ doses are calculated with published fluence-to-absorbed-dose conversion coefficients derived from those two model sets for unidirectional plane beam irradiation geometries, with DS02 photon energy spectra at various distances from the hypocentre in Hiroshima. Results showed that organ doses from mathematical models generally agree well with those from voxel phantoms except for a few organs at lateral irradiation geometries and eye lenses at antero-posterior irradiation, even though there were significant differences between the two phantom sets and various uncertainties in dose calculations.


Rapid Profiling of the Marker Components in Artemisia annua L. and their Metabolites in Rats Using an Improved Liquid Chromatography-tandem Highresolution Mass Spectrometry-based Technology.
As parasite resistance to the main artemisinin drugs has emerged in Southern Asia, the traditional herb Artemisia annua L. (AAL) from which artemisinin (QHS) isolated was found to overcome resistance to QHS. However the component and metabolite profiles of AAL remain unclear. In this study, component profiling of marker compounds in AAL (amorphane sesquiterpene lactones and flavonoids) was performed and their subsequent metabolism was investigated in rats. For efficient component classification and structural characterization, an improved liquid chromatography- tandem high-resolution mass spectrometry (HRMS)-based analytical strategy was applied, i.e., background subtraction (BS) followed by ring-double-bond (RDB) filter in tandem with repeated BS processing. Structures of detected components/metabolites were characterized based on integrated information including their HRMSn patterns, RDB values, the established component/metabolite network, the biosynthesis pathways of AAL, and/or NMR data. A total of 38 amorphane sesquiterpene lactones and 35 flavonoids were found in AAL as prototype compounds, among which 26 components were previously undescribed. Major compounds were identified by comparing them with reference standards. Among 73 AAL prototypes administered, 38 were absorbed in the circulation as the prototype. Moreover, 20 metabolites of amorphane sesquiterpene lactones and 10 metabolites of flavonoids were detected in rats. The major metabolic pathways included oxidation, methylation, glucuronidation and sulfation. The component and metabolite network were established for marker components in AAL, which will be valuable to understand the synergistic antimalarial potency of QHS in A. annua L. The analytical strategy can also be applied to other herbal medicines.


Estimating the prevalence of disability in the community: the influence of sample design and response bias.
An estimate of the prevalence of physical disability in the community based upon a sample survey may be influenced by the sample design and the response to the method of data collection employed. In this paper we describe a postal survey of a sample of households in the London borough of Lambeth and the procedures used for calculating the influence of these factors on the estimate produced. These procedures can be used to adjust the estimate to take account of the relative chance of households falling into the sample and to correct for non-response bias.


Editorial.
Focus Issues: a Second Anniversary Note: Two years ago, in August 1997, we published 5 articles grouped under the heading "Mid-IR Laser Materials." These articles introduced Focus Issues into peer-reviewed science publishing. It seems to me that the Second Anniversary of that event merits notice and maybe a small celebration. Steven Bowman coordinated the first one, and since then we have published 25 other Focus Issues with 4-10 articles each, and other journals are beginning to try them. Focus Coordinators of future issues are certainly among the readers of this short note. I'll say more about that at the end, so read on.


Lymphocyte therapy of renal cell carcinoma.
During the past 20 years, there has been considerable interest in lymphocyte therapy as a treatment for renal cell carcinoma. There is no therapeutic role for B-lymphocyte therapy, but their products, monoclonal antibodies, now have widespread clinical applications. The major types of autologous lymphocyte therapy that have been explored in clinical trials are cytotoxic lymphokine-activated killer cells, which are natural killer cells and T-cells that have been stimulated in vitro by interleukin-2 or other similar cytokines; cytotoxic and noncytotoxic tumor infiltrating lymphocytes, which are T-cells derived from tumor tissue; other tumor antigen-stimulated T-lymphocytes derived from regional lymph nodes or peripheral blood; and noncytotoxic lymphocytes of the memory/helper phenotype. More recently, allogeneic immune therapy using nonmyeloablative hematopoietic stem cell transplant and/or donor lymphocyte therapy has also shown promise.


Isolated Rib Fractures in Elderly Falls: Not As Deadly As We Think.
Rib fractures in elderly patients have been associated with high morbidity and mortality; however, many of these patients had substantial mechanisms of injury, which may have contributed to these high rates. The purpose of this study was to determine the morbidity and mortality of elderly patients with isolated rib fractures who fell from standing. A single-institution retrospective study was conducted in a Level I trauma center using the trauma registry and a separate elderly fall from standing database. Admitted patients 65 years or older who presented with rib fractures after a fall from January 2013 to June 2017 were included. Patients with a nonthoracic Abbreviated Injury Scale score greater than 2 were excluded from the study. Of 129 patients with isolated rib fracture, 94% (n = 121) had comorbidities and 71% (n = 92) had two or more comorbidities. Almost half (41.9%; n = 54) were taking antiplatelet and anticoagulant medications, 78.3% (n = 101) were caused by a mechanical fall, and 7% (n = 9) were caused by syncope. Data showed 72.9% (n = 94) had three or more rib fractures. The mortality rate of patients was 3.9% (n = 5). Three patients had dementia at death, four had do-not-resuscitate order, and only two deaths were directly related to pulmonary status. Patients who developed pneumonia (14.7%; n = 19) and required mechanical ventilation for a median of 11 days (3.9%; n = 5) were fewer than those in in previous studies. The morbidity and mortality associated with rib fractures are significantly less than reported in the literature when additional injuries are excluded.


von Hippel-Lindau syndrome: cloning and identification of the plasma membrane Ca(++)-transporting ATPase isoform 2 gene that resides in the von Hippel-Lindau gene region.
We have isolated and analyzed full-length complementary DNA clones encoded by a 200-kilobase gene encompassing the D3S601 locus that resides in the von Hippel-Lindau (VHL) gene region. The deduced amino acid sequence shows 99% identity with the published sequence of the rat plasma membrane Ca(++)-transporting ATPase isoform 2 complementary DNA, implying that we have cloned and positioned the human plasma membrane Ca(++)-transporting ATPase isoform 2 gene within the VHL critical region. The gene is expressed in VHL target tissues and should be considered a potential candidate gene for the VHL disease.


Analysis of novel methods to determine the accuracy of the OmniPod insulin pump: a key component of the artificial pancreas system.
In this issue of Journal of Diabetes Science and Technology, Zisser and collegues describe two inexpensive methods for accurate measurement of dosage delivered by OmniPod insulin pump. The first method is based on imaging a meniscus movement in a micro-pipette and using simple image analysis; the second relies on using a digital microscope to measure the volume of a dispensed droplet while it is still attached to the cannula tip. Both methods produce accurate measurements for doses >0.2 U, and the latter method is especially appropriate for doses <0.2 U, with accuracies down to 0.9%.


Dupuytren's disease in blacks.
Dupuytren's disease in blacks is believed to be rare. Our recent experience with the disease at the John Cochran Veterans Administration Hospital in St Louis is described, including 2 black patients suffering from the condition. The literature is reviewed and some aspects of pathogenesis are discussed. It is our belief that Dupuytren's disease is more common in blacks than previously reported.


Predicting Values of Neutrophil-to-Lymphocyte Ratio (NLR), High-Sensitivity C-Reactive Protein (hs-CRP), and Left Atrial Diameter (LAD) in Patients with Nonvalvular Atrial Fibrillation Recurrence After Radiofrequency Ablation.
BACKGROUND The purpose of this study was to evaluate the predictive values of lipid level, inflammatory biomarkers, and echocardiographic parameters in late NVAF (nonvalvular atrial fibrillation) recurrence after RFA (radiofrequency ablation). MATERIAL AND METHODS This retrospective single-center study enrolled 263 patients with paroxysmal or persistent NVAF who underwent initial RFA from Jan 2017 to Jan 2019. The patients were divided into a Recurrent group (n=70) and a Nonrecurrent group (n=193). Univariate and multivariate logistic regression analyses were used for evaluating the predictive factors of late NVAF recurrence. Receiver operating characteristic (ROC) curves were constructed to assess the predictive performance and the optimum cut-off level of variables. RESULTS Late NVAF recurrence occurred in 70 patients (26.6%) after initial RFA within 12-month follow-up. Patients in the Recurrent group had significant higher NLR (neutrophil-to-lymphocyte ratio), hs-CRP (high-sensitivity C-reactive protein), LVEDD (left ventricular end-diastolic dimension), LVESD (left ventricular end-systolic dimension), and LAD (left atrial diameter) than those in the Nonrecurrent group (P<0.05). In multivariate analysis, increased NLR (HR=1.438, 95% CI: 1.036-1.995, P<0.05), hs-CRP (HR=1.137, 95% CI: 1.029-1.257, P<0.05) and LAD (HR=1.089, 95% CI: 1.036-1.146, P<0.05) were independent predictors of NVAF recurrence. The area under the curve (AUC) of NLR and hs-CRP was 0.603 (95% CI 0.525-0.681) and 0.584 (95% CI 0.501-0.666), respectively. The combination of NLR, hs-CRP, and LAD revealed an AUC of 0.684 (95% CI 0.611-0.757), with cut-off values of 2.33, 2.025 ng/L, and 44.5 mm, respectively. CONCLUSIONS The combination of preoperative NLR, hs-CRP, and LAD can predict late NVAF recurrence.


[Clinical analysis of acute carpal tunnel syndrome after reduction of Colles' fracture in twenty-two patients].
To investigate the etiology, diagnosis, and treatment of acute carpal tunnel syndrome (ACTS) after reduction of Colles' fracture. Between December 2006 and June 2010, 22 patients with ACTS after reduction of Colles' fracture were treated with expectant treatment and surgical treatment. There were 9 males and 13 females with an average age of 46.2 years (range, 23-60 years). Fractures were caused by traffic accident in 9 cases, falling in 8 cases, falling from height in 2 cases, hitting in 2 cases, and crushing in 1 case. The mechanism of fracture was direct violence in 3 cases and indirect violence in 19 cases. According to Gartland & Werley classification, there were 2 cases of type I, 5 cases of type II, 14 cases of type III, and 1 case of type IV. Closed reduction was performed in 19 cases and open reduction and internal fixation (ORIF) in 3 cases. The average symptom time of ACTS after reduction of Colles' fracture was 11.6 hours (range, 1 hour 30 minutes to 48 hours) in patients undergoing closed reduction and was 24 hours in 1 patient and 2 weeks in 2 patients undergoing ORIF. Expectant treatment was performed first, the forearms were put in neutral position in closed reduction cases; if there was no relief of ACTS symptom 1 week later, the mixture of 1 mL glucocorticosteroid and 1 mL 2% lidocaine was injected into carpal tunnel once a week for 2 weeks. The mixture was injected into carpal tunnel directly once a week for 2 weeks in ORIF cases. In the patients who failed to expectant treatments, ORIF was performed. In 7 cases of type III that failed expectant treatment, ACTS symptoms were relief completely after ORIF. All the 22 patients were followed up 12 months on average (range, 8-18 months). The average time of complete disappearance of median nerve compression symptom was 11 days (range, 2-25 days). All the patients had normal finger motion, sensation, and opposition of thumb with no sensation of anaesthesia and pinprick. The results of Tinel test, Phalen test, and Reverse Phalen test were all negative. The X-ray film showed good fracture reduction and healing with an average healing time of 6 weeks (range, 3-14 weeks). According to GU Yudong's criteria for functional assessment, the results were excellent in 18 cases and good in 4 cases; the excellent and good rate was 100%. Malposition, displacement of fracture fragments, and ulnar deviation of the wrist after plaster immobilization are the most important risk factors for ACTS. Expectant treatments are recommended in patients with Colles' fracture of types I, II, and IV, but surgical treatment is the first choice for Colles' fracture of type III.


NCBI genetic resources supporting immunogenetic research.
The NCBI creates and maintains a set of integrated bibliographic, sequence, map, structure and other database resources to promote the efficient retrieval of information and the discovery of novel relationships. The connections made between elements of these resources permit researchers to start a search from a wide spectrum of entry points. These multiple dimensions of data can be roughly categorized by primary content as text or bibliographic (PubMed, PubMedCentral, OMIM, LocusLink), sequence (GenBank, Reference Sequence Project (RefSeq), dbSNP, MMDB), protein structure (MMDB) or map position (MapView). They can also becategorized by level of expert curation, which may range from validation of submissions from external groups (GenBank, PubMed, PubMedCentral,), to automatic computation (HomoloGene, UniGene), and to highly reviewed and corrected (LocusLink, MMDB, OMIM, RefSeq). Searches can be made by words (in an article title, key words, sequence annotation, database value, author) by sequence (BLAST or e-PCR against multiple sequence databases), or by map coordinates. By computing or curating bi-directional links between related objects, NCBI can represent content on the genetics, molecular biology, and clinical considerations of interest to immunogeneticists. There is also an emerging resource developed by the NCBI in collaboration with the IHWG devoted to the presentation of MHC data (dbMHC). How dbMHC will augment existing resources at the NCBI is described.


Comparative health systems: international collaborative education using the internet.
Between January and June 1998, postgraduate and undergraduate students from seven centres participated in a discussion of suicide from a public health perspective, using a listserver on the Internet. Most contributions were in English but a few were in Spanish with subsequent translation. Eighteen out of 32 students responding to evaluation, found the module worthwhile and their learning objectives were met. After making a few modifications to procedures resulting from the evaluation, further rounds of discussion were started in October 1998. International discussion groups using listservers on the Internet provide a new and apparently effective method of education.


Human natural killer (NK) cells present staphylococcal enterotoxin B (SEB) to T lymphocytes.
Superantigen-mediated T cell activation requires the participation of antigen-presenting cells (APC). Once superantigen has bound class II MHC molecules on the surface of APC, it then can interact with the T cell receptor to induce T cell activation. Superantigen-mediated T lymphocyte activation, along with its consequent cytokine production is thought to be the basis for the pathophysiology of conditions such as toxic shock syndrome, Kawasaki's disease and possibly rheumatoid arthritis. We examined the role of CD56+ NK lymphocytes in the interaction between superantigens and T lymphocytes. First, we found that a subpopulation of CD56+ cells freshly isolated from human peripheral blood expressed class II MHC molecules. The amount of HLA-DR expression varied between individuals, ranging from 9.3% to 37.7%. CD56+ (NK) cells were purified from the peripheral blood by cell sorting and were tested for their ability to support SEB-mediated T cell activation as assessed by surface expression of IL-2 receptor alpha-chain (CD25) on CD3+ lymphocytes. We observed that when enriched T cells were incubated with SEB in the presence of NK cells, there was a significant up-regulation of CD25 expression of the T cells. When HLA-DR+ cells were removed from sorted CD56+ populations, the remaining HLA-DR- NK cells were unable to support SEB-mediated T cell activation. Also, SEB up-regulated the expression of HLA-DR on CD56+ cells in peripheral blood mononuclear cell (PBMC) populations after 24 h of incubation, implying that the ability of NK cells to function as superantigen-presenting cells is up-regulated by superantigens themselves. Together, these data demonstrate for the first time that human CD56+ HLA-DR+ NK cells can function as superantigen-presenting cells, and imply that NK cells may be involved in the activation of non-specific T cell reactivity during early host defences against superantigen-elaborating microorganisms in vivo. Furthermore, the physical linkage of NK cells and T cells by the interaction of superantigen with HLA class II molecules and T cell receptors, respectively, may lead to NK cell activation and augmented lytic potential, helping to clear the body of superantigen-elaborating microorganisms.


Using a mentorship model to localise the Practical Approach to Care Kit (PACK): from South Africa to Brazil.
Brazil's Sistema Único de Saúde, or Unified Health System policy, has delivered major improvements in health coverage and outcomes, but challenges remain, including the rise of non-communicable diseases (NCDs) and variations in quality of care across the country. Some of these challenges may be met through the adaptation and implementation of a South African primary care strategy, the Practical Approach to Care Kit (PACK). Developed by the University of Cape Town's Knowledge Translation Unit (KTU), PACK is intended for in-country adaptation by employing a mentorship model. Using this approach, the PACK Adult guide and training materials were localised for use in Florianópolis, Santa Catarina, Brazil, as part of an initiative to reform primary care, expand care for NCDs and make services more accessible and equitable. The value of the collaboration between the KTU and Florianópolis municipality is the transfer of skills and avoidance of duplication of effort involved in de-novo guide development, while ensuring that materials are locally acceptable and applicable. The collaboration has informed the development of the KTU's PACK mentorship package and led to a relationship between the groups of developers, ensuring ongoing learning and research, with the potential of assisting the further scale-up of PACK in Brazil.


Revealing Prognosis-Related Pathways at the Individual Level by a Comprehensive Analysis of Different Cancer Transcription Data.
Identifying perturbed pathways at an individual level is important to discover the causes of cancer and develop individualized custom therapeutic strategies. Though prognostic gene lists have had success in prognosis prediction, using single genes that are related to the relevant system or specific network cannot fully reveal the process of tumorigenesis. We hypothesize that in individual samples, the disruption of transcription homeostasis can influence the occurrence, development, and metastasis of tumors and has implications for patient survival outcomes. Here, we introduced the individual-level pathway score, which can measure the correlation perturbation of the pathways in a single sample well. We applied this method to the expression data of 16 different cancer types from The Cancer Genome Atlas (TCGA) database. Our results indicate that different cancer types as well as their tumor-adjacent tissues can be clearly distinguished by the individual-level pathway score. Additionally, we found that there was strong heterogeneity among different cancer types and the percentage of perturbed pathways as well as the perturbation proportions of tumor samples in each pathway were significantly different. Finally, the prognosis-related pathways of different cancer types were obtained by survival analysis. We demonstrated that the individual-level pathway score (iPS) is capable of classifying cancer types and identifying some key prognosis-related pathways.


Effects of fominoben-HCl on rat liver.
The effect of Fominoben-HCl (Noleptan) was studied in male rats given 200 mg/kg/day over one, two or four weeks. In all three experiments a slight enlargement of the liver was observed. After one-week treatment, activity of microsomal mixed-function oxidase was stimulated without an increase in cytochrome P-450 content. After 2 or 4 weeks of treatment the activity of microsomal mixed-function oxidase expressed as the activity per microsomal protein remained unchanged. The fominoben-HCl-caused biochemical changes and the slight increase in organ weight of the liver were completely reversible within 2 weeks after cessation of treatment.


Role of constitutively activated protein tyrosine kinases in malignant myeloproliferative disorders: an update.
Modern molecular technology helped identify more than 10 protein tyrosine kinases related to myeloid malignancies, which allowed the development of small molecule inhibitors targeting deregulated protein tyrosine kinase activity. Protein tyrosine kinase deregulation can occur as a consequence of fusion gene formation because of chromosomal translocations, or as distinct gain-of-function point mutations. Although the tyrosine kinase inhibitor imatinib mesylate (Gleevec) targeting the ABL protein tyrosine kinase has revolutionized current chronic myeloid leukemia therapy, it became rapidly evident that overcoming the multiple cellular resistance mechanisms will be very challenging. To develop efficient therapeutic alternatives, one must understand the complex signal transduction mechanisms involved in transformation by deregulated protein tyrosine kinases. This article reviews the most recently identified molecular mechanisms involved in cell transformation by the BCR/ABL protein tyrosine kinase fusion and presents new members of the increasing family of deregulated protein tyrosine kinases involved in myeloproliferative disorders. In addition, the article discusses new, promising small molecule protein tyrosine kinase inhibitors and the molecular mechanism that may lead to resistance to these drugs. Finally, the article highlights putative alternative strategies that could be used to block signal transduction pathways of deregulated protein tyrosine kinase activity.


The role of angiotensin II receptors in vascular regulation.
Plasma-membrane receptors for angiotensin II (AII) have been identified in many AII-responsive tissues involved in the control of blood pressure via direct or indirect actions on vascular contractility. The specific, high-affinity receptors for AII in adrenal zona glomerulosa, vascular smooth muscle, kidney, brain, and anterior pituitary gland exhibit generally similar binding properties. However, the AII receptors in adrenal zona glomerulosa and vascular smooth muscle undergo reciprocal regulatory changes during alterations in sodium intake. These appear to be mediated by changes in circulating AII and are accompanied by parallel changes in sensitivity to AII. The AII receptors in the anterior pituitary gland are located in lactotrophs and corticotrophs and mediate the stimulatory actions of AII upon prolactin and ACTH secretion, acting in conjunction with other hypothalamic regulators. The anterior pituitary receptors are not affected by changes in sodium balance or AII infusion, in contrast to adrenal and vascular AII receptors, but exhibit similar ligand-binding properties to the sites present in other tissues. In the brain, AII receptors are present in several discrete regions and are particularly concentrated in the circumventricular organs. During dehydration, AII receptors are increased in the subfornical organ, but show no significant changes in the other circumventricular organs. The increase in subfornical-organ receptors is analogous to the up-regulation of AII sites in the adrenal cortex during sodium deficiency and may have a potentiating action upon the dipsogenic role of AII during dehydration. Mapping of AII receptors of the brain by topical autoradiography has revealed a highly characteristic pattern of distribution in brain regions concerned with drinking, adrenergic control, blood-pressure regulation, and hypothalamic control of pituitary-hormone secretion. In the rat kidney, AII receptors have been localized in the cortex and medulla by topical autoradiography with 125I-[Sar1]AII. The renal cortical receptors appear to be localized in glomeruli, whereas the AII receptors in the renal medulla are distributed diffusely in medullary tissue and also as localized radiating stripes which correspond to the vasa rectae bundles. The location of the renal receptors for AII in cortical and medullary sites emphasizes the multiplicity of actions of the octapeptide upon the individual compartments of the kidney.


What role for human rhinoviruses in the lower respiratory tract?
Human rhinoviruses (HRV) usually cause upper airway infections. However, viral replication in the tracheobronchial tree has been disclosed, although its clinical role is poorly known. We evaluated the prevalence of HRV in 159 bronchoalveolar lavages from 88 patients and describe a lung transplant recipient with a high HRV load in association with acute rejection. HRV was detected in 22/88 patients (25.0%): 7/18 lung transplant recipients, 11/41 immunocompetent, and 4/29 immunocompromised (p = n.s.). No lung disease was significantly associated with HRV positivity. It should be recommended to include HRV in the virological diagnostic work-up of lower respiratory specimens to elucidate their role.


Pregnancy and nursing.
The IBD patient should be optimistic about a potential pregnancy. Inactive IBD is not associated with decreased fertility. Inactive IBD does not affect the course of pregnancy; however, IBD has been associated with increased preterm deliveries. Active IBD during pregnancy is associated with increased stillbirths and spontaneous abortions but not with increased congenital abnormalities. Pregnancy does not cause exacerbation of previously quiescent IBD. If the disease is active at conception, it remains active or worsens in approximately two thirds of patients. Corticosteroids, sulfasalazine, and 5-ASA drugs are safe and should be used to maintain or induce remission. Antimetabolites may possibly be proved safe in the future during pregnancy but cannot yet be recommended. Both enteral nutrition and total parenteral nutrition can and should be used safely and effectively during pregnancy. Radiographs are to be used in diagnosis if an emergent condition, such as perforation or toxic megacolon, is suspected. The chance of an offspring developing IBD is about 9% but rises to 34% if both parents have IBD.


Prognostic Implications of Pyroptosis-Related Gene Signatures in Lung Squamous Cell Carcinoma.
Background: Lung squamous cell carcinoma (LUSC) has been a highly malignant tumor with very poor prognosis. It is confirmed that pyroptosis refers to the deaths of cells in a programmed and inflammatory manner. Nevertheless, the correlation between expression of genes related with pyroptosis and their prognosis remains uncertain in LUSC. Methods: Utilization of The Cancer Genome Atlas (TCGA) cohort has been done for evaluating the prognostics of pyroptosis-related genes for survival and constructing a signature with multiple genes. The least absolute shrinkage and selection operator (LASSO) Cox regression was performed for establishing such pyroptosis-related gene signature. Results: Eventually, identification of 28 genes in relation to pyroptosis was made in LUSC and healthy lung tissues. Upon the basis of these differentially-expressed genes (DEGs), the patients of LUSC can be divided into two subtypes. Nine gene signatures were established using LASSO. The surviving rate for low-risk group was apparently greater in contrast with the high-risk group (p < .001). According to our finding, risk score worked as an independent predictive factor of OS among LUSC sufferers in combination with clinical characteristics. In line with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, the enrichment of immunity-related genes and decreasing immunity status among the high-risk group. Conclusion: Genes in relation with pyroptosis played an essential role in tumor immunity, which is capable of predicting the prognosis for LUSCs.


Update: Cold weather injuries, active and reserve components, U.S. Armed Forces, July 2012-June 2017.
From July 2016 through June 2017, a total of 387 members of the active (n=328) and reserve (n=59) components had at least one medical encounter with a primary diagnosis of cold injury. Among active component service members, the total number of cold injuries in the 2016-2017 cold season was the lowest since 1999 and the overall incidence rate was lower than in any of the previous four cold seasons. Frostbite was the most common type of cold injury. During the five cold seasons in the surveillance period (2012-2017), rates tended to be higher among service members who were in the youngest age groups, female, non-Hispanic black, or in the Army. The numbers of cold injuries associated with overseas deployments have fallen precipitously in the past three cold seasons and included just 10 cases in the most recent year.


To treat or not to treat - Successful hepatitis C virus eradication in a patient with advanced hepatocellular carcinoma and complete response to sorafenib.
Background and aims Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Infection with the hepatitis C virus (HCV) is one of the most frequent underlying diseases leading to HCC development. Sorafenib is the standard of care for HCC patients not amenable to local treatment, resection, or liver transplantation. Although overall survival can be increased, objective response rates in patients treated with sorafenib are low. In HCC patients who underwent resection or ablation, HCV eradication with interferon-based regimens reduces the risk of recurrence. However, it is not known and under strong debate if patients with HCC should be treated with interferon-free regimens. Furthermore, it is not known if patients with advanced HCC at the time of diagnosis should be treated with antiviral therapy. Methods A patient with histologically confirmed advanced-stage HCC due to HCV-related cirrhosis was treated with sorafenib according to current guideline recommendations. Furthermore, he received subsequent treatment with direct antiviral agents (DAAs). Results The patient achieved a complete response after sorafenib treatment was initiated. Sorafenib treatment was terminated 1 year after complete response. As no recurrence of HCC was evident after treatment cessation, antiviral treatment was initiated with paritaprevir/ritonavir, ombitasvir, dasabuvir, and dose-reduced ribavirin because of chronic kidney disease. The patient achieved a sustained viral response. Conclusions Complete response to sorafenib treatment is scarce. Antiviral treatment should be considered in such patients as well as in patients with HCC who underwent resection or ablation.


Immunoglobulin A and liver diseases.
Immunoglobulin A (IgA) is a major immunoglobulin isotype in the gut and plays a role in maintenance of gut homeostasis. Secretory IgA (SIgA) has multiple functions in the gut, such as to regulate microbiota composition, to protect intestinal epithelium from pathogenic microorganisms, and to help for immune-system development. The liver is the front-line organ that receives gut-derived products through the portal vein, implying that the liver could be severely affected by a disrupted intestinal homeostasis. Indeed, some liver diseases like alcoholic liver disease are associated with an altered composition of gut microbiota and increased blood endotoxin levels. Therefore, deficiency of SIgA function appears as a significant factor for the pathogenesis of liver diseases associated with altered gut microbiome. In this review, we describe SIgA functions on the gut microbiome and discuss the role of IgA for liver diseases, especially alcoholic liver disease and non-alcoholic fatty liver disease/non-alcoholic steatohepatitis.


Identification of an orally active, nonpeptidyl oxytocin antagonist.
L-366,509, a member of a novel class of nonpeptidyl compounds, has been characterized as an orally active oxytocin (OT) antagonist. L-366,509 exhibits a moderate binding affinity (K(i) values, 370-780 nM) for the rat, rhesus and human uterine OT receptor. L-366,509 also binds to vasopressin receptor subtypes (arginine vasopressin-V1 and V2) with measurable affinity in rat (K(i) values, 25-30 microM) and primate (K(i) values, 2-6 microM) tissues. In rat uterine slices, L-366,509 inhibits (IC50 = 1.6 microM) the stimulation of phosphatidylinositol turnover induced by OT but not bradykinin. In the rat isolated uterus, L-366,509 is a competitive and reversible OT antagonist (pA2 = 7.32). In vivo, L-366,509 given i.v. (10 mg/kg) or intraduodenally (10-50 mg/kg) to rats causes a marked and long-lasting inhibition of OT-stimulated uterine activity. OT antagonist activity in a pregnant rhesus macaque (approximately day 135 gestation) is also observed with L-366,509 after i.v. or p.o. dosing. L-366,509 represents a prototype for a new chemical class of OT antagonists with significant p.o. bioavailability.


Biopsychosocial pathways in dementia inequalities: Introduction to the Michigan Cognitive Aging Project.
Racial/ethnic inequalities in dementia risk are a major public health and health justice concern. Group differences that persist despite adjustment for socioeconomic and vascular indicators suggest that known dementia risk factors exhibit differential impact across race/ethnicity and/or there are unrecognized dementia risk factors that are racially patterned. This article provides targeted examples of both of these possibilities. First, depressive symptoms and white matter hyperintensities represent two known dementia risk factors that more strongly relate to negative cognitive outcomes among Black older adults than Whites, pointing to the need to consider contextual factors. Second, racial discrimination and external perceived control predict worse brain and cognitive aging above and beyond known risk factors. These psychosocial factors warrant explicit consideration in dementia cohort studies. Several challenges appear to be particularly relevant to the study of dementia inequalities, including selective survival and recruitment. These challenges complicate not only cross-study comparisons, but also within-study causal inferences. This article provides recommendations for addressing these challenges in order to accelerate high-quality research on dementia inequalities. Stemming from these recommendations, the article introduces the design and methods of the Michigan Cognitive Aging Project, a new, racially-balanced cohort study of Black and White adults transitioning to late life. In sum, careful research with community partners is needed to more fully explore the factors and contexts that create and sustain racial/ethnic disparities, as well as those that buffer against them. The ultimate goal of this research is to facilitate the dismantling of structural barriers to health justice for diverse older people. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Alpha-macroglobulin-like plasma inactivator for Vibrio vulnificus metalloprotease.
The metalloprotease produced by Vibrio vulnificus (VVP) is known to be quickly inactivated by plasma proteins which belong to the class of alpha-macroglobulins in vitro at a molar ratio of 1:1. But the in vivo potential of the inactivators has not been studied. Macroalbumin (MA), a member of alpha-macroglobulins in guinea pig plasma, was found to inactivate VVP by means of physical entrapment in vitro. In vivo actions of VVP, permeability-enhancing and hemorrhagic actions, were greatly augmented by simultaneous injection of the antibody against MA, which had no effect on in vitro proteolytic action toward azocasein. The interstitial-tissue space in the normal guinea pig skin contains a negligible amount of MA. However, sufficient MA was present in the extravascular fluid collected after the intradermal injection of VVP. Besides, in the extravascular fluid, VVP formed a complex with MA and no inactivator other than MA was found. These results indicate that plasma MA leaked from the vascular system owing to the permeability-enhancing and hemorrhagic actions of VVP, resulting in inactivation of VVP in situ.


The early response to a novel coronavirus in the Middle East.
The detection of a novel coronavirus in patients from the Arabian Peninsula in late 2012 raised serious concerns of a possible international outbreak. Ministries of health of the three affected countries invited missions from the World Health Organization to participate in a review of data and capacity to detect and respond to further cases. Recommendations were made for investigations to answer critical questions about human-to-human transmission and the geographic extent of the virus. Additional recommendations were made to improve surveillance capacity by acquiring the capacity to test for the virus and enhance syndromic surveillance. Available evidence continues to suggest an unknown animal reservoir for the virus with sporadic zoonotic transmission the primary epidemiological pattern of transmission. Human-to-human transmission, while it can occur, does not appear to be sustained in the community.


Evaluation of automatic antimicrobial susceptibility testing with the MS-2 system.
We present the results of sensitivity of 191 Gram-negative bacteria towards the following antibiotics: aminoglycosides (amikacin, gentamicin, tobramycin, netilmicin), cephalosporines (moxalactam, cefotaxime, ceftazidime) and piperacilline obtained by agar diffusion method (Kirby-Bauer) versus automatic system MS 2 Abbott. Essential accord expressed in percentage is for amikacin 96%, for gentamicin 93%, for moxalactam 91%, for tobramycin 95%, for cefotaxime 92%, for piperacilline 89%, for netilmicin 90%, for ceftazidime 92. Full accord gives more discrepant results especially for cephalosporins. For aminoglycosides no significative differences were observed between the two methods. For cephalosporins the incidence of discordance was a little more high. A better sensitivity was obtained by Kirby-Bauer method versus automatic system, which can be considered a therapeutical tool as it furnishes rapidly (4 hours) MIC values, useful to establish antibiotic doses.


['You and I Smoke-free': Implementation and Provision of Brief Smoking Counseling Program in Pregnancy Counseling Centers].
Results of brief smoking counseling program implemented in pregnancy counseling centers are presented. Counseling was provided in 28 of 39 pregnancy counseling centers. A total of 693 out of 719 pregnant women invited to participate in the program during the study period of 6 months agreed to participate. Among the participants, 30.5% were smokers. Proactive approaches can reach a high proportion of the target population.


Fabrication of nanoporous arrays from photosensitive organic-inorganic hybrid materials by using an UV soft nanoimprint technique.
A honeycomb-like regular nanoporous pattern built in the photosensitive organic-inorganic hybrid film was fabricated by an UV soft nanoimprint technique. Polydimethylsiloxane (PDMS) soft mold was firstly replicated from an anodic aluminum oxide (AAO) template obtained by using a two-step anodization method. Scanning electron microscopy images show that the AAO template has a regular honeycomb-like nanoporous structure, while the PDMS soft mold has a relief structure of nanopillar arrays. Photosensitive TiO2-contained organic-inorganic hybrid films, which were prepared by combining a low temperature sol-gel process with a spin-coating technique, were used as the imprinted layer. Thus, a honeycomb-like regular nanoporous pattern built in the hybrid film can be easily obtained by imprinting the PDMS soft mold into the photosensitive hybrid film under an UV-irradiation. The as-fabricated organic-inorganic regular nonporous arrays have potential applications in two-dimensional photonic crystal.


Morphogenesis of maize embryos requires ZmPRPL35-1 encoding a plastid ribosomal protein.
In emb (embryo specific) mutants of maize (Zea mays), the two fertilization products have opposite fates: Although the endosperm develops normally, the embryo shows more or less severe aberrations in its development, resulting in nonviable seed. We show here that in mutant emb8516, the development of mutant embryos deviates as soon as the transition stage from that of wild-type siblings. The basic events of pattern formation take place because mutant embryos display an apical-basal polarity and differentiate a protoderm. However, morphogenesis is strongly aberrant. Young mutant embryos are characterized by protuberances at their suspensor-like extremity, leading eventually to structures of irregular shape and variable size. The lack of a scutellum or coleoptile attest to the virtual absence of morphogenesis at the embryo proper-like extremity. Molecular cloning of the mutation was achieved based on cosegregation between the mutant phenotype and the insertion of a MuDR element. The Mu insertion is located in gene ZmPRPL35-1, likely coding for protein L35 of the large subunit of plastid ribosomes. The isolation of a second allele g2422 and the complementation of mutant emb8516 with a genomic clone of ZmPRPL35-1 confirm that a lesion in ZmPRPL35-1 causes the emb phenotype. ZmPRPL35-1 is a low-copy gene present at two loci on chromosome arms 6L and 9L. The gene is constitutively expressed in all major tissues of wild-type maize plants. Lack of expression in emb/emb endosperm shows that endosperm development does not require a functional copy of ZmPRPL35-1 and suggests a link between plastids and embryo-specific signaling events.


Transcription elongation regulator 1 (TCERG1) regulates competent RNA polymerase II-mediated elongation of HIV-1 transcription and facilitates efficient viral replication.
Control of RNA polymerase II (RNAPII) release from pausing has been proposed as a checkpoint mechanism to ensure optimal RNAPII activity, especially in large, highly regulated genes. HIV-1 gene expression is highly regulated at the level of elongation, which includes transcriptional pausing that is mediated by both viral and cellular factors. Here, we present evidence for a specific role of the elongation-related factor TCERG1 in regulating the extent of HIV-1 elongation and viral replication in vivo. We show that TCERG1 depletion diminishes the basal and viral Tat-activated transcription from the HIV-1 LTR. In support of a role for an elongation mechanism in the transcriptional control of HIV-1, we found that TCERG1 modifies the levels of pre-mRNAs generated at distal regions of HIV-1. Most importantly, TCERG1 directly affects the elongation rate of RNAPII transcription in vivo. Furthermore, our data demonstrate that TCERG1 regulates HIV-1 transcription by increasing the rate of RNAPII elongation through the phosphorylation of serine 2 within the carboxyl-terminal domain (CTD) of RNAPII and suggest a mechanism for the involvement of TCERG1 in relieving pausing. Finally, we show that TCERG1 is required for HIV-1 replication. Our study reveals that TCERG1 regulates HIV-1 transcriptional elongation by increasing the elongation rate of RNAPII and phosphorylation of Ser 2 within the CTD. Based on our data, we propose a general mechanism for TCERG1 acting on genes that are regulated at the level of elongation by increasing the rate of RNAPII transcription through the phosphorylation of Ser2. In the case of HIV-1, our evidence provides the basis for further investigation of TCERG1 as a potential therapeutic target for the inhibition of HIV-1 replication.


Epigenomic technologies: an interview with Jörg Tost.
Jörg Tost received his PhD in genetics from the University of Saarbrücken (Germany) in 2004 for devising novel methods for the analysis of haplotypes and DNA methylation patterns. After a postdoctoral stay in the technology development department of the Centre National de Génotypage (Evry, France), he led the Epigenetics groups from 2006 to 2012, before becoming the Director of Laboratory for Epigenetics and Environment at the Centre National de Recherche en Génomique Humaine (CNRGH). The laboratory is involved in the development and application of technologies to analyze DNA methylation, miRNAs and other epigenetic modifications quantitatively at high resolution at target loci and genome-wide using state-of-the-art sequencing technologies as well as the development of bioinformatic tools for the processing of such data. The laboratory mainly focuses on the analysis of epigenetic changes in neurodegenerative, autoimmune and inflammatory diseases as well as the alteration of the epigenetic profiles in function of environmental exposure. A second research axis investigates novel technologies for the analysis of mutations of clinical relevance present at very low proportions in the analyzed samples and their impact on treatment management. Tost has an H-index of 50 and is the author or co-author of more than 195 publications.


[A long-term survival case of advanced gastric cancer undergoing radical gastrectomy by second-look operation after successful chemotherapy (CDDP, MMC, 5-FU)].
A 55-year-old woman with gastric cancer underwent laparotomy and was found to have an unresectable tumor characterized by S3 (invasion of the pancreas), N3, P0 and H0. She was then treated by combined administration of cisplatinum, mitomycin C and 5-fluorouracil. A remarkable response (CR) was confirmed by upper gastrointestinal roentgenography and endoscopy. Upon reoperation about 8 weeks after chemotherapy, a successful radical total gastrectomy with R2 (partially R3) lymphnode dissection was performed. Histological examination of the specimens, including the stomach and lymphnodes, revealed no cancer cells in any region (pCR). She had been given UFT and PSK for 4 years 4 months after reoperation. She has lived for 5 years 2 months after reoperation without any signs of recurrence or metastases.


In-house trauma surgeons do not decrease mortality in a level I trauma center.
The value of an in-house trauma surgeon is debated. Previous studies focus on comparing in-house and on-call surgeons at different institutions or different periods in time. The purpose of this study was to simultaneously evaluate in-house and on-call trauma surgeons in a single Level I trauma center and to determine the impact of in-house trauma surgeons on the mortality of severely injured patients. All records were reviewed for patients classified as major resuscitations from July 1997 through November 1999. Multiple logistic regression was performed to determine predictors of mortality on the basis of trauma surgeon status (in-house vs. on-call) and response time, while controlling for Injury Severity Score (ISS) and Revised Trauma Score. Of the 4,278 admissions, 537 were trauma codes. Mean ISS was 20.16 +/- 11.59. There was no difference between groups admitted by in-house surgeons versus on-call surgeons with respect to ISS or Revised Trauma Score. Mortality for the group was 24.8% (133 of 537); no statistical difference existed between observed and expected mortality by TRISS. The average response time was 3.96 minutes for the in-house group and 14.70 minutes for the on-call group (p < 0.001). Neither the call status nor the response time of the trauma surgeon significantly decreased emergency department or hospital mortality. There was a trend for improved outcome in those patients cared for by an in-house surgeon who were upgraded to a code, transferred into the institution, admitted during the night, or neurologically impaired. This trend did not reach statistical significance. When the trauma surgeon was rapidly available (< 15 minutes), there was no difference in emergency department or hospital mortality between in-house and on-call trauma surgeons. Selected subgroups of severely injured patients may benefit from an in-house trauma surgeon. If trauma surgeons are not readily available in an institution, an in-house call policy may be necessary for the prompt resuscitation of critically ill patients.


The spectrum of presentation and management of Fournier's gangrene--an experience of 73 cases.
To study the spectrum of presentation and outcome of different treatment modalities in Fournier's gangrene. It's a prospective analysis of 73 diagnosed patients of Fournier's gangrene admitted and treated in surgical department of a public sector university from June 2000 to June 2008. All patients were admitted through casualty with varying proportions of necrotizing infection of the perineal and genital fascia, with gangrene of the overlying skin. After resuscitation and preliminary investigations, including culture of the necrotic tissue, the patients were treated either conservatively by broad spectrum antibiotics, cardiopulmonary support, nutritional and fluid support or surgically by repeated aggressive wound debridement under anaesthesia. The behaviour of the disease, different modalities of treatment offered, response and outcome of the management were all collected on a proforma for statistical analysis on SPSS version 12. Seventy three patients with a mean age of 57.32 +/- 13.87 years and range of 33-86 years presented with varying degrees of Fournier's gangrene. Of the total population, 67 (91.78%) were males and 6 (8.213%) were females. Fifty nine (80.82%) patients had one or the other co-morbidity with maximum number (n = 44, 60.2%) having diabetes mellitus. State of diabetes control was found to be an important prognostic factor. A source of infection was identified in skin, ano-rectal and perineal regions in 42 (57.53%) patients. Thirteen (17.80%) patients died despite aggressive conservative or surgical treatment. Fournier's gangrene continues to be a lethal disease despite overall improvement in the antibiotic spectrum and surgical techniques. Diabetes remains the most important prognostic factor in the outcome of disease.


[Uncertain prognosis of European family evolution].
The author discusses past and future changes in the family in Europe. "During the years 1965-1985 demographic characteristics of...Western Europe indicate decline of fertility, nuptiality, growth of the number of divorces as well as growth of illegitimate deliveries....Family sociologists consider the present changes as [a] phenomenon of transformation of the Western-European family." (SUMMARY IN ENG AND RUS)


[Negative image of the self and of the other; the two-pronged approach in affect phobia therapy].
A negative self-image is a well-known symptom in many psychiatric disorders. Many treatments, such as cognitive behavioral therapy (CBT) and psychodynamic therapy (PD), are therefore used. CBT focuses on the self-image, while PD works with the self-image and the image of the other. A fictitious case shows how affect phobia therapy (AFT), a representative of PD, examines this dual focus. When comparing the dual AFT approach with the single CBT treatment, it appears that both approaches improve self-image, the image of the other and interpersonal functioning.


A phase I study of weekly topotecan and Paclitaxel in previously treated epithelial ovarian carcinoma patients.
We have previously reported on the feasibility of weekly topotecan as single-agent therapy in previously treated patients with ovarian cancer. The objective of this study was to assess the maximum tolerated dose (MTD) of weekly bolus intravenous (IV) topotecan combined with weekly paclitaxel in a comparable patient population. Previously treated ovarian cancer patients with measurable disease and/or elevated cancer antigen 125 (CA-125) received (as second-line or third-line therapy) weekly 30-min bolus IV topotecan starting at 2 mg/m(2) combined with weekly paclitaxel starting at a dose of 60 mg/m(2). In this intrapatient dose-escalation study, topotecan and paclitaxel were escalated in parallel until the MTD was reached, defined as the first dose level at which >or= 2 of 6 patients experienced dose-limiting toxicity. Twenty-one of 26 patients were evaluable for toxicity and received a total of 306 weeks of therapy (median, 13 weeks; range, 5 to 33 weeks). No significant dose-limiting toxicity was observed up to a weekly bolus IV topotecan dose of 3 mg/m(2) and a concurrent paclitaxel dose of 80 mg/m(2). The MTD was topotecan 3.5 mg/m(2) plus 90 mg/m(2) paclitaxel. The dose-limiting toxicities included anemia and fatigue, with 10 of 21 patients receiving epoetin alfa for grade 3 or 4 anemia; only 1 patient required a blood transfusion. Two patients had a treatment delay of at least 1 week and only 1 patient required a dose reduction to maintain the weekly schedule. Based on the results of this study, the recommended initial dose for this novel regimen is topotecan 3 mg/m(2) and paclitaxel 80 mg/m(2). Further investigation of the efficacy of weekly topotecan plus paclitaxel in less heavily pretreated patients is warranted.


Effect of amendments on the extractability, retention and plant uptake of metals on a sewage-irrigated soil.
Laboratory and greenhouse experiments were conducted to evaluate the effects of farmyard manure (FYM), CaCO(3) and single superphosphate (SSP) on retention and availability of Zn, Cu and Ni in sewage-irrigated soil. We also assessed the suitability of 0.05M EDTA for predicting the effectiveness of these amendments in reducing the phytoavailability of metals. Results indicated that EDTA could successfully predict the phytoavailability of Zn and Ni in amended soil, whereas it failed in case of Cu. By and large, application of CaCO(3), either alone or in combination with FYM had a positive effect on the retention of Zn, Cu and Ni in soil. Application of CaCO(3) alone or in combination with FYM was equally effective in reducing the Zn content in lettuce, whereas sole application of CaCO(3) significantly reduced Ni content. However, only SSP was found to be effective in reducing the Cu content in lettuce.


Risperidone-related reversal of primary enuresis: an unusual case report.
Occasional reports have documented treatment-emergent enuresis with medication regimens that include risperidone. In contrast to these reports, we present a 12-year-old girl with mild mental retardation and primary nocturnal enuresis who received risperidone (0.5 mg/day) for the isolated symptom of inappropriate smiling. Surprisingly, in addition to reduction in inappropriate smiling, risperidone also substantially decreased the frequency of enuresis. These benefits with risperidone were confirmed in an on-off-on treatment sequence. To our knowledge, this is the first case in literature of primary enuresis responding to low-dose risperidone. Low-dose risperidone may merit study in children with enuresis. Clinical implications and possible mechanisms are discussed.


Core Decompression and Autologous Bone Marrow Concentrate for Treatment of Femoral Head Osteonecrosis: A Randomized Prospective Study.
The aim of this study was to investigate the safety of injection of bone marrow aspirate concentrate during core decompression and to study its clinical (visual analogue scale; Harris-Hip-score) and radiological outcomes (magnetic resonance imaging). In this prospective and randomized clinical trial we evaluated 24 consecutive patients with non-traumatic femoral head necrosis (FHN) during a period of two years after intervention. In vitro analysis of mesenchymal stem cells was performed by evaluating the fibroblast colony forming units (CFU-Fs). Postoperatively, significant decrease in pain associated with a functional benefit lasting was observed. However, there was no difference in the clinical outcome between the two study groups. Over the period of two years there was no significant difference between the head survival rate between both groups. In contrast to that, we could not perceive any significant change in the volume of FHN in both treatment groups related to the longitudinal course after treating. The number of CFU showed a significant increase after centrifugation. This trial could not detect a benefit from the additional injection of bone marrow concentrate with regard to bone regeneration and clinical outcome in the short term.


Liposomal leakage induced by virus-derived peptides, viral proteins, and entire virions: rapid analysis by chip electrophoresis.
Permeabilization of model lipid membranes by virus-derived peptides, viral proteins, and entire virions of human rhinovirus was assessed by quantifying the release of a fluorescent dye from liposomes via a novel chip electrophoretic assay. Liposomal leakage readily occurred upon incubation with the pH-sensitive synthetic fusogenic peptide GALA and, less efficiently, with a 24mer peptide (P1-N) derived from the N-terminus of the capsid protein VP1 of human rhinovirus 2 (HRV2) at acidic pH. Negative stain transmission electron microscopy showed that liposomes incubated with the rhinovirus-derived peptide remained largely intact. At similar concentrations, the GALA peptide caused gross morphological changes of the liposomes. On a molar basis, the leakage-inducing efficiency of the P1 peptide was by about 2 orders of magnitude inferior to that of recombinant VP1 (from HRV89) and entire HRV2. This underscores the role in membrane destabilization of VP1 domains remote from the N-terminus and the arrangement of the peptide in the context of the icosahedral virion. Our method is rapid, requires tiny amounts of sample, and allows for the parallel determination of released and retained liposomal cargo.


Nursing ethics into the next millennium: a context-sensitive approach for nursing ethics.
The aim of this article is to argue for the need for a context-sensitive approach to the understanding of ethical issues in nursing practice as we face the next millennium. This approach means that the idea of universalism must be questioned because ethics is an interpersonal activity, set in a specific context. This view is based on issues that arise in international collaborative research as well as in research focused on ethical problems in nursing practice. Moral values are indigenous to a particular culture and influence beliefs about health and illness as well as what priorities are to be made in providing health care. Nursing practice must include thoughtful reflection on the meaning of moral concepts and principles in terms of culture. Theoretical developments in nursing ethics must be based on empirical research focusing on contextual aspects of health care.


Left Ventricular Longitudinal Contractility Predicts Acute-on-Chronic Liver Failure Development and Mortality After Transjugular Intrahepatic Portosystemic Shunt.
Acute deterioration of liver cirrhosis (e.g., infections, acute-on-chronic liver failure [ACLF]) requires an increase in cardiac contractility. The insufficiency to respond to these situations could be deleterious. Left ventricular global longitudinal strain (LV-GLS) has been shown to reflect left cardiac contractility in cirrhosis better than other parameters and might bear prognostic value. Therefore, this retrospective study investigated the role of LV-GLS in the outcome after transjugular intrahepatic portosystemic shunt (TIPS) and the development of ACLF. We included 114 patients (48 female patients) from the Noninvasive Evaluation Program for TIPS and Their Follow-Up Network (NEPTUN) cohort. This number provided sufficient quality and structured follow-up with the possibility of calculating major scores (Child, Model for End-Stage Liver Disease [MELD], Chronic Liver Failure Consortium acute decompensation [CLIF-C AD] scores) and recording of the events (development of decompensation episode and ACLF). We analyzed the association of LV-GLS with overall mortality and development of ACLF in patients with TIPS. LV-GLS was independently associated with overall mortality (hazard ratio [HR], 1.123; 95% confidence interval [CI],1.010-1.250) together with aspartate aminotransferase (HR, 1.009; 95% CI, 1.004-1.014) and CLIF-C AD score (HR, 1.080; 95% CI, 1.018-1.137). Area under the receiver operating characteristic curve (AUROC) analysis for LV-GLS for overall survival showed higher area under the curve (AUC) than MELD and CLIF-C AD scores (AUC, 0.688 versus 0.646 and 0.573, respectively). The best AUROC-determined LV-GLS cutoff was -16.6% to identify patients with a significantly worse outcome after TIPS at 3 months, 6 months, and overall. LV-GLS was independently associated with development of ACLF (HR, 1.613; 95% CI, 1.025-2.540) together with a MELD score above 15 (HR, 2.222; 95% CI, 1.400-3.528). Conclusion: LV-GLS is useful for identifying patients at risk of developing ACLF and a worse outcome after TIPS. Although validation is required, this tool might help to stratify risk in patients receiving TIPS.


Ultrasound-Assisted Catheter-Directed Thrombolysis: A Novel and Promising Endovascular Therapeutic Modality for Intermediate-Risk Pulmonary Embolism.
Intermediate-risk pulmonary embolism (PE), also known as submassive PE, occurs in a substantial group of patients and carries a significant mortality risk. With adequate risk stratification, catheter-directed techniques could be used as a therapeutic approach in the intermediate-risk PE. Ultrasound-assisted catheter-directed thrombolysis (UCDT) represents a novel endovascular technique with good clinical and safety outcomes. Ultrasound-assisted catheter-directed thrombolysis can achieve reduction in the thrombus burden and improvement of pulmonary hemodynamics and right ventricular (RV) dysfunction and/or dilatation, without major procedure-related complications, major bleeding, or hemorrhagic strokes. This narrative review will focus on the major studies involving the efficacy and safety of UCDT in the intermediate-risk PE population. Prospective, randomized clinical trials with long-term follow-up and a large sample size are needed for further evaluation of mortality benefit and to further define which subgroup of patients may benefit from this novel endovascular technique.


Attenuated fibroblast sheath around the basement membrane zone in the trachea.
In the connective tissue underlying the epithelium of the airways, there are thin attenuated cells that appear to be fibroblasts. These cells are close to the basal lamina and delineate an area equivalent to the basement membrane zone (BMZ). Using the mean data from transversely and longitudinally sectioned attenuated fibroblasts, we estimate that the diameter of the attenuated fibroblast is approximately 28.0 microns and its thickness 0.55 microns. Serial sections indicate there are pores of various sizes in the attenuated fibroblast. Also, the presence of cell segments less than 5 microns in length suggests there are processes from the edge of the cell which would give it a stellate appearance. These large flat cells form a sheath covering 66 to 70% of the BMZ at an average distance of 1.9 microns from the basal lamina. In addition, they make contact with the basal lamina approximately 7,000 times per mm2 of basal lamina. The majority of the contacts with the basal lamina are beneath basal cells. Cells of the attenuated fibroblast sheath are probably associated with lung morphogenesis, wound healing, and development of the BMZ. Their existence as a sheath demonstrates an anatomical unit associated with fibroblast-epithelial cell interactions in airway epithelium.


Evolvable Acoustic Field Generated by a Transducer with 3D-Printed Fresnel Lens.
Evolvable acoustic fields are considered an effective method for solving technical problems related to fields such as biological imaging, particle manipulation, drug therapy and intervention. However, because of technical difficulties and the limited technology available for realizing flexible adjustments of sound fields, few studies have reported on this aspect in recent years. Herein, we propose a novel solution, using a Fresnel lens-focused ultrasonic transducer for generating excited-signal-dependent acoustic pressure patterns. Finite element analysis (FEA) is used to predict the performance of a transducer with a Fresnel lens. The Fresnel lens is printed using 3D additive manufacturing. Normalized intensity maps of the acoustic pressure fields are characterized from the Fresnel lens-focused transducer under various numbers of excited-signal cycles. The results demonstrate that under different cycle excitations, a temporal evolution acoustic intensity can be generated and regulated by an ultrasound transducer with a 3D Fresnel lens. This acoustical pattern control method is not only simple to realize but also has considerable application prospects.


[Treatment of non small cell lung cancer].
According to the recent data lung cancer in Czech republic is the most common malignancy in men (incidence 93/100 000) and is the leading cause of cancer death in men (mortality 90/100 000). In women is the incidence of lung cancer 30/100 000. Non-small-cell lung cancer (NSCLC) accounts for 70% to 75% of all lung cancers, while small-cell lung cancer (SCLC) accounts for 25% to 30% of cases. These two types of lung cance have a different biological characteristics which leads to a different approach in the treatment of NSCLC and SCLC. The treatment of NSCLC is based on clinical stage of disease and different treatment modalities alone or in combination are used: surgery, radiotherapy, chemotherapy and recently a novel treatment strategy--targeted therapy with biologic agents.


An inside job: subversion of the host secretory pathway by intestinal pathogens.
The cellular secretory pathway, composed of the endoplasmic reticulum, Golgi apparatus, and cellular vesicles, mediates the intracellular trafficking of proteins and lipids. Gastrointestinal pathogens frequently affect the functions of enterocytes, the differentiated cells involved in secretion and absorption of extracellular molecules. Microbial pathogenesis can be enhanced by altering the trafficking of key molecules such as brush border enzymes, soluble immune mediators such as cytokines and chemokines, and MHC Class I molecules, all of which rely on the secretory pathway for their appropriate cellular localization. This review focuses on our current understanding of the distinct mechanisms employed by enteric pathogens to antagonize the secretory pathway. Many pathogens encode individual or multiple proteins to antagonize the secretory pathway, including disrupting the trafficking of vesicles between the endoplasmic reticulum, Golgi, and plasma membrane. This antagonism allows for increased pathogenesis and can assist, directly or indirectly, in microbial replication. Virtually all arms of the secretory pathway are targeted by intestinal pathogens, supporting the pathogenic significance of shutting this pathway down. This review summarizes the mechanisms utilized by gut pathogens to disrupt the cellular secretory pathway and addresses potential therapeutic targets to combat these highly prevalent and burdensome microbes.


The role of interferons in the resistance to murine cytomegalovirus.
The protective effect of IFN alpha/beta or IFN-gamma against MCMV infection in mouse embryo fibroblasts (MEF) of genetically resistant and susceptible strains have been examined. For this purpose, MEF derived from Balb/c, C3H, DBA2, C57BL6 mouse strains were used. Cells were pretreated for 24 hrs with either IFN alpha/beta or IFN-gamma and subsequently infected with MCMV at different M.O.I. No difference in susceptibility to MCMV was observed between untreated Balb/c, C3H, C57 and DBA2-MEF when infected at a M.O.I. of 5 whereas at a M.O.I. of 1 or 0.5 untreated DBA2-MEF displayed the highest susceptibility to viral infection. Pretreatment of MEF with IFN alpha/beta showed that the degree of protection to MCMV was dependent on the M.O.I. used. At a M.O.I. of 5, IFN alpha/beta did not inhibit viral replication in any MEF tested, whereas at a M.O.I. of 1 or 0.5 was protective in C3H-MEF and to a lesser extent in Balb/c-MEF. No protection was observed in DBA2 and C57-MEF. Different results were observed when MEF were pretreated with IFN-gamma. C57-MEF were protected when infected at a M.O.I. of 5 or 1; no protection was observed at a M.O.I. of 0.5. Balb/c-MEF were protected only at a M.O.I. of 1. No protection was observed in C3H and DBA2-MEF.


Effects of O(2) Tension and Temperature during Light Uptake of CO(2) on the Dark Release of CO(2) by Excised C(3) and C(4) Leaves.
A study was conducted on a C(4) (Panicum maximum) and a C(3) (Panicum bisulcatum) species to determine the nature of the dark release of (14)CO(2) with respect to its responses to changes in temperature and O(2) tension during light CO(2) uptake of (14)CO(2).The total one minute uptake of (14)CO(2) increased with increased temperatures up to 30 degrees C for both species at all O(2) tensions.The total release of (14)CO(2) during the first four minutes of dark by the C(4) species was 5 to 10 times greater than the C(3) species; however, there was no consistent pattern in the C(4) species as a function of temperature or O(2) tension. In contrast, the dark release by the C(3) species was similar to that of light uptake as a function of temperature or O(2) tension. The percentage of the one-minute (14)CO(2) fixation that was released as (14)CO(2) during the first four minutes of dark increased with O(2) tension for the three highest temperatures (20, 30, and 38 degrees C) and remained, though reduced, after a 10-minute dark chase in (12)CO(2) for the C(3) species.IT WAS CONCLUDED THAT: (a) the source of the dark CO(2) release in C(3) species is different from that of C(4) species; (b) the dark CO(2) release in C(3) species likely is derived from intermediates of photorespiration and is similar to the postillumination burst of CO(2); and (c) the source(s) of the dark CO(2) release in C(4) species is not photorespiration.


Interference by phosphatases in the spectrophotometric assay for phosphoenolpyruvate carboxylase.
The aim of this work was to discover the extent of interference by phosphoenolpyruvate (PEP) phosphatase in spectrophotometric assays of PEP carboxylase (EC 18.104.22.168) in crude extracts of plant organs. The presence of PEP phosphatase and lactate dehydrogenase (EC 188.8.131.52) in extracts leads to PEP-dependent NADH oxidation that is independent of PEP carboxylase activity, and hence to overestimation of PEP carboxylase activity. In extracts of three organs of pea (Pisum sativum L.: leaves, developing embryos, and Rhizobium nodules), two organs of wheat (Triticum aestivum L.: developing grain and endosperm), and leaves of Moricandia arvensis (L.) D.C., lactate dehydrogenase activity was at most only 16% of that of PEP carboxylase at the pH optimum for PEP carboxylase activity. Endogenous PEP phosphatase and lactate dehydrogenase are thus unlikely to interfere seriously with the assay for PEP carboxylase at its optimum pH. Addition of lactate dehydrogenase to PEP carboxylase assays- a proposed means of correcting for nonenzymic decarboxylation of oxaloacetate to pyruvate-resulted in increases in PEP-dependent NADH oxidation from zero (Rhizobium nodules) to 131% (wheat grains). There was no obvious relationship between the magnitude of this increase and conditions in the assay that might promote oxaloacetate decarboxylation. However, the magnitude of the increase was highly positively correlated with the activity of PEP phosphatase in the extract. Addition of lactate dehydrogenase to PEP carboxylase assays can thus result in very large overestimations of PEP carboxylase activity, and should only be used as a means of correction for oxaloacetate decarboxylation for extracts with negligible PEP phosphatase activity.


Onyx® in the management of cranial arteriovenous malformations.
The ethylene vinyl alcohol copolymer, Onyx® (ev3, Inc., MN, USA), is an embolic agent used in the management of arteriovenous malformations (AVMs) and was approved by the US FDA in 2005. Use of Onyx has resulted in higher curative rates compared with previous embolic agents such as N-butyl-2-cyanoacrylate. Onyx has several advantages over previous embolic agents. For instance, Onyx is a copolymer and does not adhere to catheters but solidifies slowly owing to the diffusion of its solvent dimethyl sulfoxide. This review focuses on different results obtained from the experience of different neurointerventionalists with an emphasis on the aim to cure. The studies presented are compared in terms of curative rates, morbidity and mortality. Ideas are presented for future treatment options for AVM rupture using nanotargeted therapy with the guide of specific markers highly expressed on the surface of cells or tissues of interest. Such nanotargeted therapy might transform AVM treatment with new embolic agents.


Value-added chemicals from biomass-derived furans: radical functionalisations of 5-chloromethylfurfural (CMF) by metal-free ATRA reactions.
Biomass-derived 5-chloromethylfurfural (CMF), a congener of the well-known carbohydrate-based platform chemical 5-hydroxymethylfurfural (HMF), can efficiently be functionalised by radical transformations of its benzylic chloromethyl group. We report here the first examples of these radical reactions by way of metal-free, triethylborane/oxygen-induced atom transfer radical addition (ATRA) reactions between CMF and styrenes, which proceed with high yield and selectivity. The key intermediate, the 2-formyl-5-furfuryl radical derived from CMF, and its radical addition reactions were studied with regard to its electronic structure, i.e. spin density distribution and frontier molecular orbitals based on the NBO ansatz and activation barriers of the addition step using DFT and post-HF methods.


On cultural similarities in attitudes toward eating of women students in Pennsylvania and South Korea.
This study compared attitudes toward eating among 226 women undergraduates at universities in Pennsylvania and South Korea. Analysis indicated that both groups (ns = 111 and 115, respectively) had similar percentages (21% and 18%, respectively) of respondents with scores suggesting symptomatology of eating disorders. Mean differences between groups on the Eating Attitudes Test-26 were not significant. Implications for research are discussed.


Up-regulation of GAP-43 and growth of axons in rat spinal cord after compression injury.
The growth-associated protein-43 (GAP-43) is an axonal phosphoprotein which is expressed at high levels during development and is reinduced by regeneration in the PNS. Consequently it is believed to be a key molecule in the regulation of axonal growth. However, injury to the CNS does not result in significant regeneration and this has been suggested to correlate with a failure of central neurons to up-regulate GAP-43 after axotomy. We have examined a model of spinal cord injury which is unique in two respects; first dural integrity is maintained by compression of the cord with smooth forceps (thus excluding connective tissue elements) and, secondly, considerable axonal growth has been reported through the resulting lesion. Our previous studies have shown that GAP-43 is extensively distributed in the rat spinal cord (see accompanying paper), but here we have used anti-GAP-43 antiserum at a dilution which did not yield any immunostaining in normal cord. However, supranormal levels of GAP-43 were detected in cell bodies and axons around the lesion within four days of compression injury. Double immunostaining with the RT97 monoclonal antibody indicated that a small subpopulation of neurons local to the site of compression were axotomized and expressed GAP-43 and phosphorylated neurofilament epitopes in their cell bodies. Although damage to long axon tracts was extensive, there was no evidence of regeneration in white matter. On the other hand cavities which formed in grey matter provided an environment for axonal elongation. Immunolabelling with markers for astrocytes and endothelial cells was used to evaluate the interaction of elongating axons with endogenous CNS cell types. Sprouting axons, identified by the presence of elevated levels of GAP-43, did not appear to grow in contact with astrocytes but preliminary evidence suggested that newly formed capillaries provided an appropriate substrate.


Multiple L1 progenitors in prosimian primates: phylogenetic evidence from ORF1 sequences.
One of the uncertainties regarding the evolution of L1 elements is whether there are numerous progenitor genes. We present phylogenetic evidence from ORF1 sequences of slow loris (Nycticebus coucang) and galago (Galago crassicaudatus) that there were at least two distinct progenitors, active at the same time, in the ancestor of this family of prosimian primates. A maximum parsimony analysis that included representative L1s from human, rabbit, and rodents, along with the prosimian sequences, revealed that one of the galago L1s (Gc11) grouped very strongly with the slow loris sequences. The remaining galago elements formed their own unique and strongly supported clade. An analysis of replacement and silent site changes for each link of the most parsimonious tree indicated that during the descent of the Gc11 sequence approximately two times more synonymous than nonsynonymous substitutions had occurred, implying that the Gc11 founder was functional for some time after the split of galago and slow loris. Strong purifying selection was also evident on the galago branch of the tree. These data indicate that there were two distinct and contemporaneous L1 progenitors in the lorisoid ancestor, evolving under purifying selection, that were retained as functional L1s in the galago lineage (and presumably also in the slow loris). The prosimian ORF1 sequences could be further subdivided into subfamilies. ORF1 sequences from both the galago and slow loris have a premature termination codon near the 3' end, not shared by the other mammalian sequences, that shortens the open reading frame by 288 bp. An analysis of synonymous and nonsynonymous substitutions for the 5' and 3' portions, that included intra- and inter-subfamily comparisons, as well as comparisons among the other mammalian sequences, suggested that this premature stop codon is a prosimian acquisition that has rendered the 3' portion of ORF1 in these primates noncoding.


Overlap between eQTL and QTL associated with production traits and fertility in dairy cattle.
Identifying causative mutations or genes through which quantitative trait loci (QTL) act has proven very difficult. Using information such as gene expression may help to identify genes and mutations underlying QTL. Our objective was to identify regions associated both with production traits or fertility and with gene expression, in dairy cattle. We used three different approaches to discover QTL that are also expression QTL (eQTL): 1) estimate the correlation between local genomic estimated breeding values (GEBV) and gene expression, 2) investigate whether the 300 intervals explaining most genetic variance for a trait contain more eQTL than 300 randomly selected intervals, and 3) a colocalisation analysis. Phenotypes and genotypes up to sequence level of 35,775 dairy bulls and cows were used for QTL mapping, and gene expression and genotypes of 131 cows were used to identify eQTL. With all three approaches, we identified some overlap between eQTL and QTL, though the majority of QTL in our dataset did not seem to be eQTL. The most significant associations between QTL and eQTL were found for intervals on chromosome 18, where local GEBV for all traits showed a strong association with the expression of the FUK and DDX19B. Intervals whose local GEBV for a trait correlated highly significantly with the expression of a nearby gene explained only a very small part of the genetic variance for that trait. It is likely that part of these correlations were due to linkage disequilibrium (LD) in the interval. While the 300 intervals explaining most genetic variance explained most of the GEBV variance, they contained only slightly more eQTL than 300 randomly selected intervals that explained a minimal portion of the GEBV variance. Furthermore, some variants showed a high colocalisation probability, but this was only the case for few variants. Several reasons may have contributed to the low level of overlap between QTL and eQTL detected in our study, including a lack of power in the eQTL study and long-range LD making it difficult to separate QTL and eQTL. Furthermore, it may be that eQTL explain only a small fraction of QTL.