Efficacy of a new accelerated streptokinase regime in acute myocardial infarction: a double blind randomized clinical trial.
Studies of thrombolysis in acute ST-elevation myocardial infarction (STEMI) have focused on differences in outcome between groups receiving various regimes. Expedited treatment may influence the efficacy of nonfibrin specific thrombolytic agents in restoring early patency of the infarct-related artery (IRA), which is a major determinant of survival after ST-elevation myocardial infarction (STEMI). We performed a randomized double blind clinical trial comparing an accelerated infusion (1.5 MU/20 min; group A, n = 200) with the conventional infusion (1.5 MU/60 min; group B, n = 100) of streptokinase (SK) in 300 patients with their first episode of acute STEMI. Demographics, clinical reperfusion rates, angiographic study findings, left ventricular ejection fraction (LVEF), in-hospital morbidity and mortality and one year mortality were compared between two groups. Mean age was 59 ± 12 years (79% male). There were no differences in baseline data between groups. Clinical, electrocardiographic and physiologic reperfusion indices revealed significant faster and higher reperfusion rates and better preserved LVEF at discharge in group A. Sixty-three percent of patients in either group underwent invasive coronary angiography at a mean of 5 days with comparable findings. Atrial fibrillation, malignant ventricular arrhythmias in the second day, in-hospital and late mortalities rates occurred more frequently in group B patients. In multivariate analysis, accelerated SK infusion was the only independent predictor of higher electrocardiographic reperfusion (OR = 3.2, CI: 1.93-5.3, P < 0.001). The accelerated SK infusion regimen of 1.5 MU in 20 min is safe and well tolerated with significantly faster and higher clinical reperfusion rates, more preserved LV systolic function, less atrial and ventricular sustained arrhythmias, and less in-hospital and 1 year mortality rates in acute STEMI.


Responsible decision-making for plant research and breeding innovations in the European Union.
Plant research and breeding has made substantial technical progress over the past few decades, indicating a potential for tremendous societal impact. Due to this potential, the development of policies and legislation on plant breeding and the technical progress should preferably involve all relevant stakeholders. However, we argue here that there is a substantial imbalance in the European Union (EU) regarding the influence of the various stakeholder groups on policy makers. We use evidence from three examples in order to show that the role of science is overlooked: 1) important delays in the decision process concerning the authorization of genetically modified (GM) maize events, 2) the significance attributed to non-scientific reasons in new legislation concerning the prohibition of GM events in EU member states, and 3) failure of the European Commission to deliver legal guidance to new plant breeding techniques despite sufficient scientific evidence and advisory reports. We attribute this imbalance to misinformation and misinterpretation of public perceptions and a disproportionate attention to single outlier reports, and we present ideas on how to establish a better stakeholder balance within this field.


Tadalafil for the treatment of pulmonary arterial hypertension.
Tadalafil, a long-acting phosphodiesterase-5 inhibitor (PDE-5) is the most recent oral agent to receive FDA approval for the treatment of pulmonary arterial hypertension (PAH). With several new agents emerging for the treatment of PAH, this article reviews tadalafil, the compound and its properties, clinical evidence supporting its use, and the role of tadalafil in the current treatment approach for patients with PAH. A broad PubMed literature search was performed to identify the most current data on the use of tadalafil for PAH. Tadalafil received FDA approval in 2009 following the recently published pivotal trial that demonstrated that the use of tadalafil 40 mg once daily was well tolerated, improved exercise capacity and quality of life measures and reduced time to clinical worsening in PAH patients. As the second PDE-5 inhibitor to gain approval for PAH, clinical properties such as its long half-life leading to once-daily dosing and possibly improved compliance, as well as potential cost benefit, may distinguish tadalafil from sildenafil in the widespread treatment of PAH.


Identification of ghrelin receptor blocker, D-[Lys3] GHRP-6 as a CXCR4 receptor antagonist.
[D-Lys3]-Growth Hormone Releasing Peptide-6 (DLS) is widely utilized in vivo and in vitro as a selective ghrelin receptor (GHS-R) antagonist. Unexpectedly, we identified that DLS also has the ability to block CXCL12 binding and activity through CXCR4 on T cells and peripheral blood mononuclear cells (PBMCs). Moreover, as CXCR4 has been shown to act as a major co-receptor for HIV-1 entry into CD4 positive host cells, we have also found that DLS partially blocks CXCR4-mediated HIV-1 entry and propagation in activated human PBMCs. These data demonstrate that DLS is not the specific and selective antagonist as thought for GHS-R1a and appears to have additional effects on the CXCR4 chemokine receptor. Our findings also suggest that structural analogues that mimic DLS binding properties may also have properties of blocking HIV infectivity, CXCR4 dependent cancer cell migration and attenuating chemokine-mediated immune cell trafficking in inflammatory disorders.


Cranial and endocranial diversity in extant and fossil atelids (Platyrrhini: Atelidae): A geometric morphometric study.
Platyrrhines constitute a diverse clade, with the modern Atelidae exhibiting the most variation in cranial and endocast morphology. The processes responsible for this diversification are not well understood. Here, we present a geometric morphometric study describing variation in cranial and endocranial shape of 14 species of Alouatta, Ateles, Brachyteles, and Lagothrix and two extinct taxa, Cartelles and Caipora. We examined cranial and endocranial shape variation among species using images reconstructed from CT scans and geometric morphometric techniques based on three-dimensional landmarks and semilandmarks. Principal components analyses were used to explore variation, including the Procrustes shape coordinates, summing the logarithm of the Centroid Size, the common allometric component, and residual shape components. Differences in endocranial shape are related to a relative increase or decrease in the volume of the neocortex region with respect to brainstem and cerebellum regions. The relative position of the brainstem varies from a posterior position in Alouatta to a more ventral position in Ateles. The shape of both the cranium and endocast of Caipora is within the observed variation of Brachyteles. Cartelles occupies the most differentiated position relative to the extant taxa, especially in regards to its endocranial shape. The pattern of variation in the extant species in endocranial shape is similar to the variation observed in previous cranial studies, with Alouatta as an outlier. The similarities between Caipora and Brachyteles were unexpected and intriguing given the frugivorous adaptations inferred from the fossil's dentition. Our study shows the importance of considering both extant and fossil species when studying diversification of complex traits.


Death in Children After Atractylis gummifera L. Poisoning in Morocco-Report of Three Cases and Review of Literature.
Atractylis gummifera L. is a poisonous thistle plant that grows in the Mediterranean regions especially in northern Africa like Morocco and southern Europe. It has been used frequently to treat some diseases in traditional medicine, and its ingestion is a common cause of fatal poisoning. Here, we report 3 death cases in children after accidental ingestion of the Atractylis gummifer L. We report 3 cases of death in children after accidental ingestion of the poisonous plant Atractylis gummifer L. The poisoned children were admitted to hospital in deteriorated general state with clinical symptoms, such as nausea, vomiting, epigastric, and abdominal pain, diarrhea, followed by coma. However, they died a few hours later. The postmortem investigations were performed, and the diagnosis of Atractylis gummifer L. poisoning was confirmed by toxicological examination (chromatography), the latter showed the presence of atractyloside (potassium atractylate), a toxic compound of the plant Atractylis gummifera L.Atractylis gummifer L. poisoning was discussed with review through the literature. Through the presented cases, we show that Atractylis gummifera L. poisoning remains a health problem that involves children in Morocco, where the plant grows spontaneously. Thus, teaching children to recognize dangerous plants will be helpful to prevent accidental ingestion.


[Myocardial protection: which method of cardioplegia is better?].
The remarkable advances in cardiac surgery over the last 50 years have led to the concept of "routine" open heart surgery. The introduction of novel surgical technologies, methods of anesthesiology and intensive care allowing for a reduction morbidity and mortality at perioperative period. The development of intraoperative myocardial protection has been impressive too. A tremendous body of literature has documented the physiologic basis of current cardioprotective methods and debate over the optimal technique. We tried to review current trends and future perspectives of myocardial protection in this article.


Genetic variants in RhoA and ROCK1 genes are associated with the development, progression and prognosis of prostate cancer.
The contribution of genetic variants in RhoA and ROCK1 genes towards prostate cancer risk has not been reported before. We genotyped six potentially functional genetic variants in a case-control study of 1699 subjects. Overall, we found rs2410 mutant allele and rs2269736 wild allele were risk factors for prostate cancer. Individuals carrying more than two risk alleles were exposed to hazard of prostate cancer. In addition, we demonstrated that the risk of biochemical recurrence might be linked with clinico-pathological characteristics and also genetic factors. Unfortunately, no associations were observed between all polymorphisms and clinico-pathological characteristics. Moreover, no genotype was found as significant independent prognostic predictor for biochemical recurrence survival in Multivariate Cox regression analysis after Bonferroni correction. Our study is the first to clarify the relations of genetic variants of RhoA and ROCK1 genes with development, progression and prognosis of prostate cancer. These variants may be promising novel biomarkers to facilitate clinical treatment decision-making.


[Construction and identification of eukaryotic expression vector of rat GPR17 gene].
To construct the eukaryotic expression vector of rat GPR17 (rGPR17) cDNA,and to identify its function in HEK293 cells. Total RNA was extracted from rat brain tissue; full-length GPR17 cDNA was prepared by RT-PCR, and cloned into pcDNA3.1(+) plasmid. The recombinant plasmid was converted into E.coli DH5alpha and confirmed by PCR, double enzyme digestion analysis and DNA sequencing. The recombinant plasmid pcDNA3.1(+)-rGPR17 was transiently transfected into HEK293 cells using Lipofectamin 2000. Expression of rGPR17 gene was confirmed by RT-PCR and immunofluorescence staining. The exogenous LTD(4) enhanced intracellular calcium was measured using Fluo-4. RT-PCR, double enzyme digestion analysis and sequencing showed that the rGPR17 gene was cloned into recombinant vector, and the recombinant rGPR17 was expressed after transfection in HKE293 cells. LTD(4) increased intracellular calcium release in the transfected HEK293 cells. The eukaryotic expression vector of rGPR17 cDNA has been constructed; it is functionally expressed in HEK293 cells. This work provides a basis for further research of the GPR17 receptor and its antagonists.


Perceptions of select registered nurses of the continuing competence program of the Saskatchewan registered nurses' association.
Nursing is a self-regulating profession, and most professional nursing jurisdictions across Canada have undertaken the creation of Continuing Competence Programs (CCPs), with the goals of promoting good nursing practice, encouraging continuous learning, contributing to the quality of nursing practice, and optimizing client outcomes. Most CCPs call for a professional portfolio to collect, synthesize, and analyze professional experiences, including documentation of peer feedback and preparation of a learning plan. In the province of Saskatchewan, Canada, there is a self-reflective tool that enables registered nurses to self-rate their achievement of a set of foundational competencies. This article explores the perceptions that select registered nurses have about the CCP in Saskatchewan and how their view of the degree of professional control (as assessed through locus of control) that they have affects their perspective about the outcomes of the program. The study was designed to assess how perceived locus of control was related to how registered nurses view the implementation of the CCP in Saskatchewan.


One DNA Methylation Regulates CHIP Gene Expression of Human Breast Cancer and Predicts Recurrence.
Carboxyl terminus of Hsc70-interacting protein (CHIP) is a ubiquitin ligase that induces ubiquitination and degradation of its target proteins including oncoproteins. We reported that its down-regulation is associated with tumor progression and metastasis of breast cancer. However, the mechanism through which CHIP gene affects cancer cells is unclear. We extracted RNA from 45 primary breast cancer samples and compared CHIP mRNA expression profiles, promoter DNA methylation status, and clinicopathological information. CHIP mRNA expression was significantly correlated with the tumor progression status. In several samples, a pinpoint CpG methylation in the CHIP gene promoter region was significantly correlated with CHIP mRNA expression. When this specific CpG was methylated in estrogen receptor (ER)-positive cases, a significant difference in 5-year recurrence was not found compared with ER-negative cases. CpG methylation contributes to the long-term prognosis of ER-positive breast cancer.


Impairment of the vasodilatation capability of the brachial artery in patients with idiopathic venous thrombosis.
Determination of the functional capability of the peripheral arteries is increasingly used as an early marker of vessel disease. The aim of this study was to evaluate flow-mediated (FMD) and glyceryl trinitrate-mediated (NMD) dilation of the brachial artery in patients with idiopathic venous thrombosis (VT). Flow-mediated brachial artery dilatation and the dilatation response to glyceryl trinitrate were measured using high-resolution ultrasound in 97 subjects (49 eligible patients of both sexes, mean age 51.5 ± 14.6 years, with idiopathic venous thrombosis, and 48 age-matched healthy controls). Compared to the control group, FMD was significantly reduced in the group of patients with idiopathic venous thrombosis -4.9% (95% CI 1.1-8.7%) vs. 12.7% (95% CI 7.8-17.6%), p<0.001. Patients also had diminished NMD of the brachial artery -12.5% (95% CI 6.6-18.4%) vs. 18.5% (95% CI 10.1-26.9%), p<0.001. In patients, significantly higher levels of circulatory markers (P-selectin, von Willebrand factor) of endothelial dysfunction were registered. Idiopathic venous thrombosis is associated with impaired flow- and GTN-mediated vasodilatory response of the brachial artery. This may suggest involvement of the functional deterioration of the vessel wall in the pathogenesis of idiopathic VT and indicate a relationship between VT and atherothrombosis.


Coexistence of multiple arterial variations in the genitourinary system.
Variations in the renal, adrenal and testicular arteries are of clinical significance as well as anatomical and embryological interest. The present case report describes the incidental finding of unilateral multiple renal arteries on the right side with bilateral variant testicular arteries, which had not been reported so far. These variations were observed during routine dissection of the abdominal region in an Iranian cadaver. The upper supplementary renal artery branched from the abdominal aorta and sent superior suprarenal artery to the adrenal gland. The lower supplementary renal artery arose from the main renal artery. Both additional arteries entered the kidney proximal to its hilum. The right testicular artery supplied the right suprarenal gland by an unusual branch. Double testicular arteries were seen on the left side with a relatively high origin from abdominal aorta. The objective of this report is to supplement the knowledge of vascular variations in the renal, suprarenal and testicular arteries that could be quite useful from a clinical point of view.


Cognitive sequelae of repeated head injury in a population of intravenous drug users.
The relationship between closed head injury and performance on neuropsychological (NP) tests was investigated in a group of intravenous drug users (IVDUs). Subjects with repeated head traumas involving loss of consciousness (LOC) performed worse than both a control group without LOC and reference group with only a single episode of LOC. There were no significant differences between the last two groups. Performance on tests of memory, attention, and motor performance was significantly worse in the group with repeated head injury. The average time since the last episode of LOC was more than 11 years. We conclude from these findings that a single episode of LOC does not result in significant cognitive impairment in this population. Two or more episodes, however, are more likely to produce chronic cognitive impairment.


Antimicrobial Resistance in Agriculture.
In this article, the current knowledge and knowledge gaps in the emergence and spread of antimicrobial resistance (AMR) in livestock and plants and importance in terms of animal and human health are discussed. Some recommendations are provided for generation of the data required in order to develop risk assessments for AMR within agriculture and for risks through the food chain to animals and humans.


Signatures of hybridization in Trypanosoma brucei.
Genetic exchange among disease-causing micro-organisms can generate progeny that combine different pathogenic traits. Though sexual reproduction has been described in trypanosomes, its impact on the epidemiology of Human African Trypanosomiasis (HAT) remains controversial. However, human infective and non-human infective strains of Trypanosoma brucei circulate in the same transmission cycles in HAT endemic areas in subsaharan Africa, providing the opportunity for mating during the developmental cycle in the tsetse fly vector. Here we investigated inheritance among progeny from a laboratory cross of T. brucei and then applied these insights to genomic analysis of field-collected isolates to identify signatures of past genetic exchange. Genomes of two parental and four hybrid progeny clones with a range of DNA contents were assembled and analysed by k-mer and single nucleotide polymorphism (SNP) frequencies to determine heterozygosity and chromosomal inheritance. Variant surface glycoprotein (VSG) genes and kinetoplast (mitochondrial) DNA maxi- and minicircles were extracted from each genome to examine how each of these components was inherited in the hybrid progeny. The same bioinformatic approaches were applied to an additional 37 genomes representing the diversity of T. brucei in subsaharan Africa and T. evansi. SNP analysis provided evidence of crossover events affecting all 11 pairs of megabase chromosomes and demonstrated that polyploid hybrids were formed post-meiotically and not by fusion of the parental diploid cells. VSGs and kinetoplast DNA minicircles were inherited biparentally, with approximately equal numbers from each parent, whereas maxicircles were inherited uniparentally. Extrapolation of these findings to field isolates allowed us to distinguish clonal descent from hybridization by comparing maxicircle genotype to VSG and minicircle repertoires. Discordance between maxicircle genotype and VSG and minicircle repertoires indicated inter-lineage hybridization. Significantly, some of the hybridization events we identified involved human infective and non-human infective trypanosomes circulating in the same geographic areas.


MALDI-TOF mass spectrometry identification of mosquitoes collected in Vietnam.
Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a tool that has revolutionised clinical microbiology and has recently been described as an innovative and effective approach to arthropod identification. In this study, mosquitoes were captured in Vietnam using four different methods (human landing catch, CDC light traps, BG-Sentinel traps, animal-baited net traps). A total of 4215 mosquitoes were captured and morphologically identified as belonging to three genera: Aedes, Anopheles and Culex. We randomly selected 1253 mosquitoes, including 662 specimens of 14 Anopheles species, 200 specimens of two Aedes species and 391 morphologically unidentified Culex specimens, for molecular and MALDI-TOF MS analysis. The DNA from 98 mosquitoes (69 Anopheles specimens, 23 Culex specimens and six Aedes sp. specimens) was subjected to molecular analysis, either to confirm our morphological identification or the MALDI-TOF MS results, as well as to identify the Culex species that were morphologically identified at the genus level and to resolve the discrepancies between the morphological identification and the MALDI-TOF MS identification. High-quality MS spectra were obtained for 1058 of the 1253 specimens (84%), including 192/200 for Aedes, 589/662 for Anopheles and 277/391 for Culex. The blind test showed that 986/997 (99%) of the specimens were correctly identified by MALDI-TOF MS, with log score values ranging from 1.708 to 2.843. Eleven specimens of Culex could not be identified based on morphological features, MALDI-TOF MS or molecular analysis. This study enabled us to identify several species of mosquitoes from Vietnam using MALDI-TOF MS, and to enrich our database of MALDI-TOF MS reference spectra.


Description of the second- and third-instar larva of South African Stenomastigus longicornis (Boheman) (Coleoptera: Staphylinidae, Scydmaeninae).
The second- and third-instar larvae of the South African species of Mastigini, Stenomastigus longicornis, are described. The serial homology of chaetotaxic structures and differences between larval instars are discussed. The larva of Stenomastigus is very similar to that of Palaeostigus, but differences in proportions of body parts, number of setae on the head, thorax and abdomen and possibly also the shape of the antennal sensory appendage can be used to distinguish them. A frontal impression surrounded by modified setae with greatly enlarged surface, presumably functioning as a glandular evaporation apparatus, and the antennomere II subdivided into three sections, are suggested as synapomorphies of Mastigini; within Mastigitae this tribe is also unique in lacking the urogomphs, which are present in larvae of Leptomastacini and Clidicini. Geniculate and slender antennae with a strongly oblique distal margin of antennomere II are a putative larval synapomorphy of Mastigitae.


Hepatocyte growth factor and its receptor signalling complex as targets in cancer therapy.
Hepatocyte growth factor (HGF) and it's receptor, cMET, have become the focus on intense scrutiny since its discovery in the late 1980s [1 2] as regards it role in cancer. HGF is now known to be a potent morphogen that can regulate tissue and organ regeneration and modulate cell morphology, it is a motogen that can stimulate cell motility and migration, and is a mitogen able to regulate cell growth and death and as an angiogenic factor [3]. HGF is can induce both angiogenesis and lymphangiogenesis [3a; 4]. That HGF and cMET have such a diversity of functions has led to intense interest in the clinical setting due to their potential in their prognostic aspect and therapeutic implications as imaging tools. This issue will focus on recent work that shows strong indications for the value of HGF and cMET in clinical settings.


SHIV-KB9 infection of rhesus monkeys does not always cause disease-contribution of host immune factors and thymic output.
Simian-human immunodeficiency virus (SHIV) infection in the macaque is a model of HIV pathogenesis. KB9, a molecular clone of SHIV 89.6P, induced rapid and profound CD4(+) T cell loss in rhesus monkeys, followed by partial recovery in some. We describe another clinical outcome after intravenous SHIV-KB9 inoculation in two of six infected rhesus macaques: lack of signs of immunodeficiency with sustained CD4(+) T cell counts, despite virus load levels similar to those of the animals with CD4(+) lymphocyte decline. To dissect the role of host factors in determining pathogenicity of this viral clone, humoral and cellular immune responses were studied. Differences in CD8(+) T cell effector responses and activation profiles and in thymic output, but not in specific antibody production, were observed in animals with different disease outcomes during acute infection. Thymic involvement may thus be a critical factor in determining disease progression.


Effects of NaCl and CaCl(2) on Ion Activities in Complex Nutrient Solutions and Root Growth of Cotton.
Sodium displaces Ca(2+) from membranes (GR Cramer, A Läuchli, VS Polito Plant Physiol 1985 79: 207-211) and this can be related to the (Ca(2+))/(Na(+))(2) activity ratio in the external solution (GR Cramer, A Läuchli 1986 J Exp Bot 37: 321-330). Supplemental Ca(2+) is known to mitigate the adverse effects of salinity on plant growth. In this report we investigated the effects of NaCl (0-250 millimolar) and Ca(2+) (0.4 and 10 millimolar) on the ion activities in solution and on root growth of cotton (Gossypium hirsutum L.). Ion activities were analyzed using the computer program, GEOCHEM. Most ion activities in a 0.1 modified Hoagland solution were significantly reduced by both NaCl and supplemental Ca(2+). Ion-pair formation and precipitation were significant for some ions, especially phosphate. Root growth of 6-day-old seedlings was stimulated by low NaCl concentrations (25 millimolar). At higher NaCl concentrations, root growth was inhibited; the concentration at which this occurred depended on the Ca(2+) concentration and the growth index used. Supplemental Ca(2+) mitigated the inhibition of root growth caused by NaCl. There was a curvilinear relationship between root growth and the (Ca(2+))/(Na(+))(2) ratio in the nutrient solution. The mechanisms by which Na(+) and Ca(2+) may affect root growth are discussed.


State of the Art of Genetic Engineering in Potato: From the First Report to Its Future Potential.
Potato (Solanum tuberosum L.) is a crop of world importance that produces tubers of high nutritional quality. It is considered one of the promising crops to overcome the challenges of poverty and hunger worldwide. However, it is exposed to different biotic and abiotic stresses that can cause significant losses in production. Thus, potato is a candidate of special relevance for improvements through conventional breeding and biotechnology. Since conventional breeding is time-consuming and challenging, genetic engineering provides the opportunity to introduce/switch-off genes of interest without altering the allelic combination that characterize successful commercial cultivars or to induce targeted sequence modifications by New Breeding Techniques. There is a variety of methods for potato improvement via genetic transformation. Most of them incorporate genes of interest into the nuclear genome; nevertheless, the development of plastid transformation protocols broadened the available approaches for potato breeding. Although all methods have their advantages and disadvantages, Agrobacterium-mediated transformation is the most used approach. Alternative methods such as particle bombardment, protoplast transfection with polyethylene glycol and microinjection are also effective. Independently of the DNA delivery approach, critical steps for a successful transformation are a rapid and efficient regeneration protocol and a selection system. Several critical factors affect the transformation efficiency: vector type, insert size, Agrobacterium strain, explant type, composition of the subculture media, selective agent, among others. Moreover, transient or stable transformation, constitutive or inducible promoters, antibiotic/herbicide resistance or marker-free strategies can be considered. Although great efforts have been made to optimize all the parameters, potato transformation protocols are highly genotype-dependent. Genome editing technologies provide promising tools in genetic engineering allowing precise modification of targeted sequences. Interestingly, transient expression of genome editing components in potato protoplasts was reported to generate edited plants without the integration of any foreign DNA, which is a valuable aspect from both a scientific and a regulatory perspective. In this review, current challenges and opportunities concerning potato genetic engineering strategies developed to date are discussed. We describe their critical parameters and constrains, and the potential application of the available tools for functional analyses or biotechnological purposes. Public concerns and safety issues are also addressed.


Exogenous application of ribozymes for inhibiting gene expression.
Sequence-specific inhibition of gene expression is an attractive concept for the development of a new generation of therapeutics. Two alternatives can be envisaged for the introduction of ribozymes into cells: endogenous or exogenous delivery. In the latter, the ribozyme is prepared by chemical synthesis or transcription and delivered to the cell either unaided or with the help of liposomes. A problem with this approach is the abundance of RNases in the serum, and thus the stabilization of the ribozyme is necessary but without the impairment of catalytic efficiency. This has been achieved by several groups by 2'-modification of the pyrimidine nucleosides and the introduction of a few phosphorothioates at the termini. The selection of ribozyme-accessible sites on the target and the attachment of cholesterol and peptides to the ribozymes will be discussed. Examples of the application of these modified ribozymes in cell cultures will be presented, including the inhibition of expression of the multiple drug resistance gene, after unaided as well as liposome-aided delivery, and studies of animal models demonstrating the potential of this particular application strategy.


Role of Chondroitin Sulfation Following Spinal Cord Injury.
Traumatic spinal cord injury produces long-term neurological damage, and presents a significant public health problem with nearly 18,000 new cases per year in the U.S. The injury results in both acute and chronic changes in the spinal cord, ultimately resulting in the production of a glial scar, consisting of multiple cells including fibroblasts, macrophages, microglia, and reactive astrocytes. Within the scar, there is an accumulation of extracellular matrix (ECM) molecules-primarily tenascins and chondroitin sulfate proteoglycans (CSPGs)-which are considered to be inhibitory to axonal regeneration. In this review article, we discuss the role of CSPGs in the injury response, especially how sulfated glycosaminoglycan (GAG) chains act to inhibit plasticity and regeneration. This includes how sulfation of GAG chains influences their biological activity and interactions with potential receptors. Comprehending the role of CSPGs in the inhibitory properties of the glial scar provides critical knowledge in the much-needed production of new therapies.


A partially functional DNA helicase II mutant defective in forming stable binary complexes with ATP and DNA. A role for helicase motif III.
To address the functional significance of motif III in Escherichia coli DNA helicase II, the conserved aspartic acid at position 248 was changed to asparagine. UvrDD248N failed to form stable binary complexes with either DNA or ATP. However, UvrDD248N was capable of forming an active ternary complex when both ATP and single-stranded DNA were present. The DNA-stimulated ATPase activity of UvrDD248N was reduced relative to that of wild-type UvrD with no significant change in the apparent Km for ATP. The mutant protein also demonstrated a reduced DNA unwinding activity. The requirement for high concentrations of UvrDD248N to achieve unwinding of long duplex substrates likely reflects the reduced stability of various binary and ternary complexes that must exist in the catalytic cycle of a helicase. The data suggest that motif III may act as an interface between the ATP binding and DNA binding domains of a helicase. The uvrDD248N allele was also characterized in genetic assays. The D248N protein complemented the UV-sensitive phenotype of a uvrD deletion strain to levels nearly equivalent to wild-type helicase II. In contrast, the mutant protein only partially complemented the mutator phenotype. A correlation between the level of genetic complementation and the helicase activity of UvrDD248N is discussed.


Registered Dietitian Staffing in Dialysis: Impact on Quality Ratings in Mandate and Nonmandate States.
Texas is the only state to mandate a patient to full-time equivalent (FTE) registered dietitian (RD) ratio (<125 patients:FTE RD) in dialysis. Little research exists about the relationship between patient:FTE RD ratio and quality. Our objectives were to a) examine the effect of the mandate on patient:FTE RD ratios in Texas facilities compared to similar nonmandated facilities and b) examine the association between patient:FTE RD ratio and the patient rating of staff quality or star rating of the facility. Using data from Dialysis Facility Annual Reports, we excluded facilities with less than 125 patients and matched based on region, chain/profit status, and number of patients, pairing each Texas facility with 2 non-Texas facilities. T-tests for difference of means and chi-square tests were performed to compare facility groups characteristics and assess mandate impact. We used correlation between patient:FTE RD ratio and staff quality linearized score, and ANOVA to compare patient:FTE RD ratios between the star rating levels. The patient:FTE RD ratio was higher in non-Texas than Texas facilities (111.84 ± 40.70 vs 90.80 ± 24.02, P < .01). The Pearson correlation between patient:FTE RD ratio and linearized score rating of the dialysis center staff was essentially nonexistent (r = -0.046). We found a trend of higher patient:FTE RD ratios in facilities with lower star ratings for quality and staff but no statistical significance. The mandate effectively lowered the patient:FTE RD ratio in Texas dialysis facilities with over 125 patients, indicating that states considering such a mandate may benefit from implementing it. We found no association between patient:FTE RD staffing and quality, either objectively or via patient assessment. Further research should examine whether dialysis facilities are trending toward smaller patient sizes to circumvent staffing mandates and examine the relationship between other professions' staffing ratios and quality.


Chemogenetic Inhibition of the Amygdala Modulates Emotional Behavior Expression in Infant Rhesus Monkeys.
Manipulation of neuronal activity during the early postnatal period in monkeys has been largely limited to permanent lesion studies, which can be impacted by developmental plasticity leading to reorganization and compensation from other brain structures that can interfere with the interpretations of results. Chemogenetic tools, such as DREADDs (designer receptors exclusively activated by designer drugs), can transiently and reversibly activate or inactivate brain structures, avoiding the pitfalls of permanent lesions to better address important developmental neuroscience questions. We demonstrate that inhibitory DREADDs in the amygdala can be used to manipulate socioemotional behavior in infant monkeys. Two infant rhesus monkeys (1 male, 1 female) received AAV5-hSyn-HA-hM4Di-IRES-mCitrine injections bilaterally in the amygdala at 9 months of age. DREADD activation after systemic administration of either clozapine-N-oxide or low-dose clozapine resulted in decreased freezing and anxiety on the human intruder paradigm and changed the looking patterns on a socioemotional attention eye-tracking task, compared with vehicle administration. The DREADD-induced behaviors were reminiscent of, but not identical to, those seen after permanent amygdala lesions in infant monkeys, such that neonatal lesions produce a more extensive array of behavioral changes in response to the human intruder task that were not seen with DREADD-evoked inhibition of this region. Our results may help support the notion that the more extensive behavior changes seen after early lesions are manifested from brain reorganization that occur after permanent damage. The current study provides a proof of principle that DREADDs can be used in young infant monkeys to transiently and reversibly manipulate behavior.


Effects of a novel 2,3-oxidosqualene cyclase inhibitor on the regulation of cholesterol biosynthesis in HepG2 cells.
Within the cholesterol biosynthesis cascade, the enzyme 2,3-oxidosqualene cyclase [EC 220.127.116.11] is of special interest due to its dual function: cyclization of 2,3-monoepoxysqualene to lanosterol and 2,3;22,23-diepoxysqualene to oxylanosterol. Further determination of the significance of this enzyme for the intracellular cholesterol homeostasis was done with BIBX 79, a new potent, specific inhibitor of this enzyme. In HepG2 cells the effects of BIBX 79 on cholesterol biosynthesis, 2,3-oxidosqualene cyclase as well as HMG-CoA reductase activities were studied. BIBX 79 is a potent inhibitor of sterol biosynthesis in HepG2 cells (IC50 4 x 10(-9) M). No other enzyme within the cholesterol biosynthesis cascade was significantly inhibited as was evidenced by a radio HPLC detection system. In contrast to simvastatin, no direct interaction with HMG-CoA reductase was observed. When incubating HepG2 cells for 16 h with the HMG-CoA reductase inhibitor simvastatin (10(-6)-10(-10) M) HMG-CoA reductase activity was increased up to 180%. BIBX 79 did also affect HMG-CoA reductase activity under these conditions: in concentrations of BIBX 79 "> or =" 10(-9) "< or =" 10(-7) M, where a partial inhibition of 2,3-oxidosqualene cyclase is observed, HMG-CoA reductase activity was decreased. However, higher concentrations of BIBX 79 that totally blocked 2,3-oxidosqualene cyclase led to an increase in HMG-CoA reductase activity. This effect of BIBX 79 on HMG-CoA reductase is thought to be mainly mediated by oxysterols that are formed by the cyclization of 2,3;22,23-diepoxysqualene. 2,3;22,23-Diepoxysqualene is preferentially cyclized by the 2,3-oxidosqualene cyclase and, consequently, only high inhibitor concentrations will also block 2,3;22,23-diepoxysqualene cyclization. Thus, by partial blockade of this enzyme, both an inhibition of lanosterol and subsequently cholesterol formation as well as a concomitant effect on HMG-CoA reductase can be achieved. Both effects complement each other and lead to an effective control of cholesterol biosynthesis. It is therefore concluded that 2,3-oxidosqualene cyclase plays a crucial role in the regulation of intracellular cholesterol homeostasis. 2,3-Oxidosqualene cyclase inhibitors offer an attractive approach for novel lipid-lowering agents.


CUEDC1 inhibits epithelial-mesenchymal transition via the TβRI/Smad signaling pathway and suppresses tumor progression in non-small cell lung cancer.
Lung cancer remains the most lethal cancer worldwide because of its high metastasis potential. Epithelial-mesenchymal transition (EMT) is known as the first step of the metastasis cascade, but the potential regulatory mechanisms of EMT have not been clearly established. In this study, we first found that low CUEDC1 expression correlated with lymph node metastasis in non-small cell lung cancer (NSCLC) patients using immunohistochemistry (IHC). CUEDC1 knockdown promoted the metastasis of NSCLC cells and EMT process and activated TβRI/Smad signaling pathway. Overexpression of CUEDC1 decreased the metastatic potential of lung cancer cells and inhibited the EMT process and inactivated TβRI/Smad signaling pathway. Immunoprecipitation (IP) assays showed that Smurf2 is a novel CUEDC1-interacting protein. Furthermore, CUEDC1 could regulate Smurf2 expression through the degradation of Smurf2. Overexpression of Smurf2 abolished CUEDC1 knockdown induced-EMT and the activation of TβRI/Smad signaling pathway, while siRNA Smurf2 reversed CUEDC1 overexpression-mediated regulation of EMT and TβRI/Smad signaling pathway. Additionally, CUEDC1 inhibited proliferation and promoted apoptosis of NSCLC cells. In vivo, CUEDC1-knockdown cells promoted metastasis and tumor growth compared with control cells. In conclusion, our findings indicate that the crucial role of CUEDC1 in NSCLC progression and provide support for its clinical investigation for therapeutic approaches.


Lesions of the cerebellopontine angle and internal auditory canal: diagnosis and differential diagnosis.
Schwannoma of the eighth cranial nerve (acoustic neuroma) is, by far, the most common cerebellopontine angle lesion. There is, however, a wide variety of differential diagnostic possibilities that must be considered when viewing images of patients with sensorineural hearing loss (SNHL), vertigo, and dizziness. This communication is intended to provide the reader with an approach to this problem. Detailed anatomy of the region is also included in this communication.


Accurate prediction of proton chemical shifts. II. Peptide analogues.
Proton chemical shifts of eight cyclic amide molecules were measured in DMSO and D2O solutions. The magnetic shieldings of the corresponding aliphatic, aromatic, and amide protons were calculated by Hartree-Fock and DFT, using the 6-311G**, 6-311++G**, and TZVP basis sets. For aliphatic protons, all of these methods reproduce the experimental values in DMSO solutions excellently after linear regression. The Hartree-Fock method tends to give slightly better agreement than DFT. The best performance is given by the HF/6-311G** method, with an rms deviation of 0.068 ppm. The deviations from experimental chemical shifts in D2O solutions are only slightly larger than those in DMSO solutions. This suggests that we can use the calculated gas phase proton chemical shifts directly to predict experimental data in various solvents, including water. For amide protons, which exchange with water and form hydrogen bonds with DMSO, only modest agreement is obtained, as expected. The present studies confirm that the GIAO approach can reach high accuracy for the relative chemical shifts of aliphatic and aromatic protons at a low cost. Such calculations may provide constraints for the conformational analysis of proteins and other macromolecules.


Morphometric and functional connectivity changes in the brain of patients with obstructive sleep apnea: A meta-analysis.
Existing evidence for brain morphometric changes and functional connectivity alterations in patients with obstructive sleep apnea is mixed. The current study aimed to meta-analyse the neuroimaging data, and thus synthesize a brain map showing locations with morphometric and functional connectivity differences between patients with obstructive sleep apnea and controls. Published studies to 2018 were retrieved and included into the analysis if they reported such between-group differences using voxel-based morphometry or resting-state functional magnetic resonance imaging, and reported the results in the form of brain coordinates based on whole-brain analysis. Twelve voxel-based morphometry and seven resting-state functional magnetic resonance imaging studies that comprised a total of 1,113 participants fulfilled the inclusion criteria. Compared with healthy controls, patients with obstructive sleep apnea had reduced resting-state connectivity in the right anterior cingulate and larger grey matter volume in the right insula. Patients with obstructive sleep apnea do have morphometric and resting-state connectivity alterations in the brain. These neural correlates may help explain the effects of obstructive sleep apnea on the emotion, cognition and quality of life of patients, and may be used in future for evaluating its treatment outcome.


Evidence that brain-derived neurotrophic factor from presynaptic nerve terminals regulates the phenotype of calbindin-containing neurons in the lateral septum.
Brain-derived neurotrophic factor (BDNF) is transported anterogradely in neurons of the CNS and can be released by activity-dependent mechanisms to regulate synaptic plasticity. However, few neural networks have been identified in which the production, transport, and effects of BDNF on postsynaptic neurons can be analyzed in detail. In this study, we have identified such a network. BDNF has been colocalized by immunocytochemistry with tyrosine hydroxylase (TH) in nerve fibers and nerve terminals within the lateral septum of rats. BDNF-containing nerve fibers terminate on a population of calbindin-containing neurons in lateral septum that contain TrkB, the high-affinity receptor for BDNF. Overexpression of BDNF in noradrenergic neurons increased levels of calbindin in septum, as well as in whole-brain lysates. Septal levels of calbindin and BDNF partially decreased after unilateral lesions of the medial forebrain bundle (MFB), induced with 6-hydroxydopamine, a treatment that abolished TH staining. These data suggest that BDNF is anterogradely transported within the MFB in catecholaminergic neurons arising from brainstem nuclei. To determine whether BDNF affects the production of calbindin in lateral septal neurons directly, we tested the effects of BDNF on cultures of septal neurons from embryonic day 16-17 rats. BDNF promoted the expression of calbindin, as well as the arborization of calbindin-containing neurons, but BDNF had no effect on cell division or survival. Together, these results suggest that BDNF, anterogradely transported in catecholaminergic neurons, regulates calbindin expression within the lateral septum.


Closed reduction and external fixation of unstable fractures of the distal radius.
The anatomical and functional outcome and complications after closed reduction and external fixation of unstable fractures of the distal radius were reviewed in 29 patients. The fractures were reduced by longitudinal traction and closed manipulation under fluoroscopic control, and the reduced position was retained by a standard half-frame Hoffmann external fixator for six to eight weeks. The mean follow-up time was four (3-7) years. The reduction failed in three patients after too early removal of the fixator (three to five weeks). For the rest of the patients the dorsal angulation, the radial length, the articular step-off, and the intra-articular gap between fragments were significantly improved. Twenty-two patients had excellent or good anatomical alignment and in seven it was fair. One patient had a superficial pin infection, six patients had transient paraesthesias, and one patient transient mild dystrophia. At follow-up one patient had some finger stiffness; this was the only persistent complication. The median Gartland and Werley functional score was 3. The functional end result was excellent or good in 22 patients, fair in four, and poor in three.


Biosynthesis of leukotriene B4 in human polymorphonuclear leukocytes: regulation by cholesterol and other lipids.
Leukotriene B4 (LTB4) is one of the most potent chemotactic compounds produced in macrophages and neutrophils. LTB4 is a product of arachidonic acid oxygenation by 5-lipoxygenase pathway. We present here the data on regulation of LT synthesis in human polymorphonuclear leukocytes by cholesterol, cholesterol sulfate and cholesterol phosphate. The addition of Pseudomonas aeruginosa lipopolysaccharides (LPS) with lipid vesicles containing phosphatidylcholine or phosphatidylcholine/cholesterol (70:30) showed that omitting cholesterol abolished the effect of LPS on LT synthesis. We show here the capacity of cholesterol sulfate, the most abundant sulfated sterol in human blood, to suppress LT production in human neutrophils and to neutralize the effect of P. aeruginosa LPS on LT synthesis. We suggest that sulfated lipids serve as specific endogenous regulators of LT synthesis in neutrophils, and anti-inflammatory therapy may be based on modification of cholesterol level and its conversion to anionic derivatives.


Endoplasmic Reticulum Stress Activation during Total Knee Arthroplasty.
Total knee arthroplasty (TKA) is the most common remediation for knee pain from osteoarthritis (OA) and is performed 650,000 annually in the U.S. A tourniquet is commonly used during TKA which causes ischemia and reperfusion (I/R) to the lower limb but the effects of I/R on muscle are not fully understood. Previous reports suggest upregulation of cell-stress and catabolism and downregulation of markers of cap-dependent translation during and after TKA. I/R has also been shown to cause endoplasmic reticulum (ER) stress and induce the unfolded protein response (UPR). We hypothesized that the UPR would be activated in response to ER stress during TKA. We obtained muscle biopsies from the vastus lateralis at baseline, before TKA; at maximal ischemia, prior to tourniquet deflation; and during reperfusion in the operating room. Phosphorylation of 4E-BP1 and AKT decreased during ischemia (-28%, p < .05; -20%, p < .05 respectively) along with an increase in eIF2α phosphorylation (64%, p < .05) suggesting decreased translation initiation. Cleaved ATF6 protein increased in ischemia (39%, p = .056) but returned to baseline during reperfusion. CASP3 activation increased during reperfusion compared to baseline (23%, p < .05). XBP1 splicing assays revealed an increase in spliced transcript during ischemia (31%, p < .05) which diminished during reperfusion. These results suggest that in response to I/R during TKA all three branches of the ER stress response are activated.


Low-dose aspirin prevents pregnancy-induced hypertension and pre-eclampsia in angiotensin-sensitive primigravidae.
The possibility of preventing pregnancy-induced hypertension (PIH) and pre-eclampsia in primigravidae by suppressing production of thromboxane A2 with low-dose aspirin was investigated in a randomised, placebo-controlled, double-blind trial. 46 normotensive women at 28 weeks' gestation, judged to be at risk of PIH or pre-eclampsia because of an increased blood-pressure response to intravenously infused angiotensin II, were studied. 23 women received 60 mg aspirin daily, and the same number received matching placebo until delivery. In the placebo group PIH, pre-eclampsia, and eclampsia developed in 4, 7, and 1 cases, respectively, whereas only 2 women in the aspirin group had mild PIH. There were no adverse effects of treatment in mothers or infants. Low-dose aspirin may restore prostacyclin/thromboxane imbalance, previously suggested as an important aetiological factor in PIH and pre-eclampsia.


Status of mature and old-growth forests in the Pacific Northwest.
Nearly 10 million ha of federal lands in the Pacific Northwest have been managed under the Northwest Forest Plan since 1994. The plan reduced logging levels by 80%; only recently, however have inventories on status and condition of mature and old-growth forests become available. Our objectives were to (1) determine the areal extent of old (> 150 years) and mature (50-150 years) conifer forests based on 2000 Landsat 7 ETM+ imagery, (2) examine levels of protection, (3) determine the degree of additional protection afforded to old and mature conifer forests if late-successional reserves (LSRs) and inventoried roadless areas (IRAs) were fully protected, and (4) review management options to achieve greater protection of older forests. The historical extent of old-growth forest in the Pacific Northwest was roughly two-thirds (16,672,976 ha) of the total land area. Since the time of European settlement, approximately 72% of the original old-growth conifer forest has been lost, largely through logging and other developments. Of the remaining old growth, the Central and Southern Cascades and Klamath-Siskiyou account for nearly half Mature conifer area (4,758,596 ha) nearly equaled the amount of old conifer More than 78% of the old growth and 50% of mature forest were located on public lands. Approximately one-quarter (1,201,622 ha) of the old-growth conifer (or 7% of the historical old-growth area) was classified as GAP status 1 (strictly protected) or GAP status 2 (moderately protected). The total area of LSRs was slightly more than 3 million ha, approximately 36% (1,073,299 ha) of which contained old-growth conifer forest. Combined old and mature conifer within LSRs was approximately 59% of the total LSR area. The total amount of IRA for the Pacific Northwest was approximately 1,563,370 ha; of this, 526,912 ha (34%) was old growth. The combined area of old-growth conifer forest accounted for by protected areas (GAP 1 and 2), LSRs, and IRAs was 2,401,780 ha, which accounts for 66% of the old-growth conifer forests on public land, 51% of the old conifer in the region, and 14% of the amount that occurred historically. Outside these land designations, an additional 1,240,271 ha of old growth are on other public land and another 1,023,392 ha are on private lands throughout the Pacific Northwest. Our results indicate the need to periodically monitor status and condition of older forests and strengthen protections of old growth in the region.


Relationship between Eysenck's measure of psychoticism and scores on the environmental deprivation scale with convicted felons.
23 parolees and 8 probationers were administered the Environmental Deprivation Scale interview and the Eysenck Personality Questionnaire-Revised. Scores on each scale, different in method and design, have been correlated with anti-social behavior. The scores on both measures were compared and a significant correlation of .51 found between the scores on the Environmental Deprivation Scale and the Psychoticism scale on Eysenck's questionnaire. Also, a negative correlation of .34 was found between scores on the Environmental Deprivation Scale and the Extraversion scale on Eysenck's questionnaire, but none for either scale and time spent in prison. A stronger assessment of clients for guiding intervention seems needed. Limitations include lack of control for education, age, and ethnicity.


Identification of reentry circuit sites during catheter mapping and radiofrequency ablation of ventricular tachycardia late after myocardial infarction.
Ventricular tachycardia reentry circuits in chronic infarct scars can contain slow conduction zones, which are difficult to distinguish from bystander areas adjacent to the circuit during catheter mapping. This study developed criteria for identifying reentry circuit sites using computer simulations. These criteria then were tested during catheter mapping in humans to predict sites at which radiofrequency current application terminated ventricular tachycardia. In computer simulations, effects of single stimuli and stimulus trains at sites in and adjacent to reentry circuits were analyzed. Entrainment with concealed fusion, defined as ventricular tachycardia entrainment with no change in QRS morphology, could occur during stimulation in reentry circuit common pathways and adjacent bystander sites. Pacing at reentry circuit common pathway sites, the stimulus to QRS (S-QRS) interval equals the electrogram to QRS interval (EG-QRS) during tachycardia. The postpacing interval from the last stimulus to the following electrogram equals the tachycardia cycle length. Pacing at bystander sites the S-QRS exceeds the EG-QRS interval when the conduction time from the bystander site to the circuit is short but may be less than or equal to the EG-QRS interval when the conduction time to the circuit is long. The postpacing interval, however, always exceeds the tachycardia cycle length. When conduction in the circuit slows during pacing, the S-QRS and postpacing intervals increase and the slowest stimulus train most closely reflects conduction times during tachycardia. Endocardial catheter mapping and radiofrequency ablation were performed during 31 monomorphic ventricular tachycardias in 15 patients with drug refractory ventricular tachycardia late after myocardial infarction. During ventricular tachycardia, trains of electrical stimuli or scanning single stimuli were evaluated before application of radiofrequency current at the same site. Radiofrequency current terminated ventricular tachycardia at 24 of 241 sites (10%) in 12 of 15 patients (80%). Ventricular tachycardia termination occurred more frequently at sites with entrainment with concealed fusion (odds ratio, 3.4; 95% confidence interval [CI], 1.4 to 8.3), a postpacing interval approximating the ventricular tachycardia cycle length (odds ratio, 4.6; 95% CI, 1.6 to 12.9) and an S-QRS interval during entrainment of more than 60 milliseconds and less than 70% of the ventricular tachycardia cycle length (odds ratio, 4.9; 95% CI, 1.4 to 17.1). Ventricular tachycardia termination was also predicted by the presence of isolated diastolic potentials or continuous electrical activity (odds ratio, 5.2; 95% CI, 1.8 to 15.5), but these electrograms were infrequent (8% of all sites). Combinations of entrainment with concealed fusion, postpacing interval, S-QRS intervals, and isolated diastolic potentials or continuous electrical activity predicted a more than 35% incidence of ventricular tachycardia termination during radiofrequency current application versus a 4% incidence when none suggested that the site was in the reentry circuit. Analysis of the postpacing interval and S-QRS interval suggested that 25% of the sites with entrainment with concealed fusion were in bystander areas not within the reentry circuit. At restudy 5 to 7 days later, 6 patients had no monomorphic ventricular tachycardia inducible, and inducible ventricular tachycardias were modified in 4 patients. None of these 10 patients have suffered arrhythmia recurrences during a follow-up of 316 +/- 199 days, although 4 continue to receive previously ineffective medications. Regions giving rise to reentry after myocardial infarction are complex and can include bystander areas, slow conduction zones, and isthmuses for impulse propagation at which radiofrequency current lesions can interrupt reentry.


Inter- and intra-observer reliability of calculating cumulative lumbar spine loads.
The aim of this study was to quantify the precision of manual video digitization of three typical industrial tasks, as evaluated by the comparison of four cumulative kinetic parameters at the L4/L5 intervertebral joint: compression, joint shear, reaction shear and moment. Ten observers were recruited (five male and five female), with an undergraduate background in human anatomy. On each of three test days, each observer digitized five repeats of each of three typical industrial lifting tasks of 5 to 6 s in duration. A rigid link segment model that incorporated a single muscle equivalent model was used to calculate the cumulative loading based on the digitized coordinates. Inter-observer reliability was assessed using a mixed model ANOVA, and no significant differences were found to result from observer, gender, day or trial. Intraclass correlation coefficients (ICC) were calculated within each task to quantify intra-observer reliability. Overall, the ICCs were excellent (>0.75), with the exception of moderate values for reaction shear for Tasks 2 and 3. Compression and moment demonstrated the highest reliability of the four parameters studied, which is beneficial from an ergonomic standpoint, as compression is the most commonly used parameter for job assessments. This study demonstrated manual video digitization to be a reliable tool for the quantification of cumulative spinal loading, both within a given observer, and across days, trials and observers.


[Mechanisms underlying chronic fatigue, a symptom too often overlooked II- From deregulated immunity to neuroinflammation and its consequences].
Hypothalamus stimulation by inflammatory and / or stress signals can trigger activation of the HPA (hypothalamic-pituitary-adrenal) axis, which includes the hypothalamus, pituitary and adrenal gland. Acute activation of the HPA axis is fundamental for the fight or flight response. It allows a maximal energy mobilization available for an effort, whilst erasing fatigue. On the contrary, the chronic activation of this axis decreases muscle efficiency and leads to chronic fatigue. In this second part of our review will be discussed several strategic points that need to be considered for attempting to understand and treat together inflammation and chronic fatigue.


Selenium Vacancies and Synergistic Effect of Near- and Far-Field-Enabled Ultrasensitive Surface-Enhanced Raman-Scattering-Active Substrates for Malaria Detection.
Defect engineering with the active control of defect states brings remarkable enhancement on surface-enhanced Raman scattering (SERS) by magnifying semiconductor-molecule interaction. Such light-trapping architectures can increase the light path length, which promotes photon-analytes interactions and further improves the SERS sensitivity. However, by far the reported semiconductor SERS-active substrates based on these strategies are often nonuniform and commonly in the form of isolated laminates or random clusters, which limit their reliability and stability for practical applications. Herein, we develop self-grown single-crystalline "V-shape" SnSe2-x (SnSe1.5, SnSe1.75, SnSe2) nanoflake arrays (SnSe2-x NFAs) with controlled selenium vacancies over large-area (10 cm × 10 cm) for ultrahigh-sensitivity SERS. First-principles density functional theory (DFT) is used to calculate the band gap and the electronic density of states (DOS). Based on the Herzberg-Teller theory regarding the vibronic coupling, the results of theoretical calculation reveal that the downshift of band edge and high DOS of SnSe1.75 can effectively enhance the vibronic coupling within the SnSe1.75-R6G system, which in turn enhances the photoinduced charge transfer resonance and contributes to the SERS activity with a remarkable enhancement factor of 1.68 × 107. Furthermore, we propose and demonstrate ultrasensitive (10-15 M for R6G), uniform, and reliable SERS substrates by forming SnSe1.75 NFAs/Au heterostructures via a facile Au evaporation process. We attribute the superior performance of our SnSe1.75 NFAs/Au heterostructures to the following reasons: (1) selenium vacancies and (2) synergistic effect of the near and far fields. In addition, we successfully build a detection platform to achieve rapid (∼15 min for the whole process), antibody-free, in situ, and reliable early malaria detection (100% detection rate for 10 samples with 160 points) in whole blood, and molecular hemozoin (<100/mL) can be detected. Our approach not only provides an efficient technique to obtain large-area, uniform, and reliable SERS-active substrates but also offers a substantial impact on addressing practical issues in many application scenarios such as the detection of insect-borne infectious diseases.


Detection and Verification of QTL for Salinity Tolerance at Germination and Seedling Stages Using Wild Barley Introgression Lines.
Salinity is one of the major environmental factors that negatively affect crop development, particularly at the early growth stage of a plant and consequently the final yield. Therefore, a set of 50 wild barley (Hordeum vulgare ssp. spontaneum, Hsp) introgression lines (ILs) was used to detect QTL alleles improving germination and seedling growth under control, 75 mM, and 150 mM NaCl conditions. Large variation was observed for germination and seedling growth related traits that were highly heritable under salinity stress. In addition, highly significant differences were obtained for five salinity tolerance indices and between treatments as well. A total of 90 and 35 significant QTL were identified for ten investigated traits and for tolerance indices, respectively. The Hsp introgression alleles are involved in improving salinity tolerance at forty (43.9%) out of 90 QTL including introgression lines S42IL-109 (2H), S42IL-116 (4H), S42IL-132 (6H), S42IL-133 (7H), S42IL-148 (6H), and S42IL-176 (5H). Interestingly, seven exotic QTL alleles were successfully validated in the wild barley ILs including S42IL-127 (5H), 139 (7H), 125 (5H), 117 (4H), 118 (4H), 121 (4H), and 137 (7H). We conclude that the barley introgression lines contain numerous germination and seedling growth-improving novel QTL alleles, which are effective under salinity conditions.


Structure and stability of recombinant bovine odorant-binding protein: III. Peculiarities of the wild type bOBP unfolding in crowded milieu.
Contrary to the majority of the members of the lipocalin family, which are stable monomers with the specific OBP fold (a β-barrel consisting of a 8-stranded anti-parallel β-sheet followed by a short α-helical segment, a ninth β-strand, and a disordered C-terminal tail) and a conserved disulfide bond, bovine odorant-binding protein (bOBP) does not have such a disulfide bond and forms a domain-swapped dimer that involves crossing the α-helical region from each monomer over the β-barrel of the other monomer. Furthermore, although natural bOBP isolated from bovine tissues exists as a stable domain-swapped dimer, recombinant bOBP has decreased dimerization potential and therefore exists as a mixture of monomeric and dimeric variants. In this article, we investigated the effect model crowding agents of similar chemical nature but different molecular mass on conformational stability of the recombinant bOBP. These experiments were conducted in order to shed light on the potential influence of model crowded environment on the unfolding-refolding equilibrium. To this end, we looked at the influence of PEG-600, PEG-4000, and PEG-12000 in concentrations of 80, 150, and 300 mg/mL on the equilibrium unfolding and refolding transitions induced in the recombinant bOBP by guanidine hydrochloride. We are showing here that the effect of crowding agents on the structure and conformational stability of the recombinant bOBP depends on the size of the crowder, with the smaller crowding agents being more effective in the stabilization of the bOBP native dimeric state against the guanidine hydrochloride denaturing action. This effect of the crowding agents is concentration dependent, with the high concentrations of the agents being more effective.


Efficacy of virtual reality techniques in cardiopulmonary resuscitation training: protocol for a meta-analysis of randomised controlled trials and trial sequential analysis.
Cardiopulmonary resuscitation (CPR) is the most critical procedure in the rescue of patients with sudden cardiac death (SCD). The success rate of CPR remains far below expectations, which made CPR education identified as the top priority for SCD. CPR training using the virtual reality (VR) technique is a feasible training method, with a wider population and lower cost, but its efficacy remains controversial. Thus, we will perform a protocol for a systematic review and meta-analysis to identify the efficacy of the VR technique on CPR quality. We will search PubMed, Web of Science, Cochrane Library, Ovid Medline, Embase, China National Knowledge Infrastructure, Chinese BioMedical Literature, Wanfang and VIP databases from inception to November 2021, to identify randomised controlled trials and the first period in randomised cross-over trials assessing the efficacy of VR techniques versus non-VR techniques for adult participants accepting adult CPR training. No language restrictions will be considered. Data synthesis will be performed using RevMan V.5.4 and Stata/MP V.16.0. Outcome measures will be present as relative risk with 95% CIs for dichotomous data and mean difference with 95% CIs for continuous data. The primary outcome will be the CPR quality defined as chest compression rate and depth. Secondary outcomes will be the overall performance of CPR. Heterogeneity will be assessed by the χ2 test and I2 statistic. Data will be synthesised by either fixed-effects or random-effects models according to the I2 value. Trial sequential analysis and modified Jadad Scale will be used to control the risks of random errors and evaluate the evidence quality. Egger's regression test and funnel plots will be used to assess the publication bias. Ethical approval was not required for this systematic review protocol. The findings will be disseminated through peer-reviewed publications. CRD42021281059.


Catalytic Synthesis of Luminescent Pyrimidines via Acceptor-less Dehydrogenative Coupling.
A simple catalytic synthesis of luminescent pyrimidines from benzamidines and alcohols is reported. These one-pot, acceptor-less dehydrogenative coupling reactions are catalyzed by a ruthenium hydrido chloride complex (1), supported by a chelating P^N ligand (L1) bearing a benzannulated phenanthridine donor arm. The pyrimidines thus produced are emissive in solution, with photoluminescence quantum yields reaching 72%. Details of the catalytic synthesis and characterization of the pyrimidines in both solution and the solid state are reported, along with computational modeling of the emissive excited states of representative examples.


[Laparoscopic radical hysterectomy and pelvic lymphadenectomy: analysis of 14 cases].
To evaluate the feasibility and safety of surgical removal of the tumors through laparoscopy in patients with early-stage uterine cancer. A retrospective analysis of the clinical data of 10 cervical cancer and 4 endometrial cancer cases, in which laparoscopic radical hysterectomy and pelvic lymphadenectomy were performed following the same surgical procedures as in laparotomy. The mean operating time was 302 min, and mean estimated blood loss was 760 ml, with the mean postoperative gastrointestinal recovery time of 30 h and average number of removed lymph nodes of 22. Laparoscopic surgery has equivalent curative effect to laparotomy, and laparoscopic radical hysterectomy and pelvic lymphadenectomy in the patients with early-stage uterine cancer is both feasible and efficient.


Effect of edentulism on spirometric tests.
The impact of denture wear in edentulous subjects while performing routine spirometric measurements has never been systematically investigated. We compared the values of FVC, FEV(1), PEFR, FEF(50%), FIV(1), and FIF(50%) recorded with and without dentures in three groups of edentulous subjects: 36 asymptomatic subjects with normal spirometry (N), 22 patients with chronic obstructive pulmonary disease (COPD), and 18 with interstitial lung disease (ILD). In 14 subjects retropharyngeal space with and without dentures was assessed by cephalometry. Subjects with N and ILD had significantly lower airflow rates without dentures, whereas subjects with COPD had no significant difference in spirometric values recorded with or without dentures. The retropharyngeal space was significantly decreased by removing dentures (from 1.52 +/- 0.07 to 1.16 +/- 0.09 cm, SEM, p < 0.0001). These findings indicate that in edentulous subjects with a normal or restrictive pattern, the recording of flow-volume curves with or without dentures produces small but significant differences. Although such differences do not appear to have clinical significance, the fact that when dentures are used some respiratory flows are higher would favor the use of dentures in edentulous subjects during spirometric evaluation.


Characterization of Berry Pomace Powders as Dietary Fiber-Rich Food Ingredients with Functional Properties.
This study aimed to evaluate and compare the dried pomace powder of cranberries, lingonberries, sea buckthorns, and black currants as potential food ingredients with functional properties. The composition and several physicochemical and adsorption properties associated with their functionality were investigated. Tested berry pomace powders were rich in dietary soluble fiber (4.92-12.74 g/100 g DM) and insoluble fiber (40.95-65.36 g/100 g DM). The highest level of total phenolics was observed in the black currant pomace (11.09 GAE/g DM), whereas the sea buckthorn pomace revealed the highest protein concentration (21.09 g/100 g DM). All the berry pomace powders that were tested exhibited good water-holding capacity (2.78-4.24 g/g) and swelling capacity (4.99-9.98 mL/g), and poor oil-binding capacity (1.09-1.57 g/g). The strongest hypoglycemic properties were observed for the lingonberry and black currant pomace powders. The berry pomace powders presented effective in vitro hypolipidemic properties. The cholesterol-binding capacities ranged from 21.11 to 23.13 mg/g. The black currant and cranberry pomace powders demonstrated higher sodium-cholate-binding capacity than those of the lingonberry and sea buckthorn pomace powders. This study shows promising results that the powders of tested berry pomace could be used for further application in foods.


Study of Virtual Reality Immersive Technology Enhanced Mathematics Geometry Learning.
Mathematics is an important foundation for the development of science education. In the past, when instructors taught mathematical concepts of geometry shapes, they usually used traditional textbooks and aids to conduct teaching activities, which resulted in students not being able to understand the principles completely. Nowadays, it has become a trend to integrate emerging technologies into mathematics courses and to use digital instructional aids. Emerging technologies can effectively enhance students' sensory experience while strengthening their impressions and understandings of subject concepts. In this paper, we apply virtual reality immersive technologies to develop a "virtual reality immersive learning mathematics geometry system," which is used to teach mathematical geometry concepts. Teachers use the system to develop three basic mathematical geometry learning materials: "Triangular pyramid volume = 1/3 prism volume," "Cone volume calculation," and "Triangle center of gravity derivation." In the experimental activity, the teacher uses virtual reality teaching aids to guide students to learn mathematical geometry concepts in a fun way so that they can achieve the effectiveness of immersive learning. This study explores the impact of using the virtual reality immersive learning mathematics geometry system on students' technology acceptance, learning motivations, and learning performance. The experimental result showed that using the virtual reality immersive learning mathematics geometry system can improve the learning motivation and learning performance of students. The findings indicated that the experimental group had better learning outcomes after completing the learning tasks of three geometric units. The experimental group used the virtual reality immersive learning mathematics geometry system which can lead to better learning outcomes. According to the ARCS questionnaire, students in the experimental group were confident to understand new subjects. At the same time, the mode of completing the game can effectively give students a sense of accomplishment. The use of emerging technologies in the classroom can be an attractive learning mode for students.


10th Anniversary of the International Society for Medical Laser Applications.
This short report is about the International Society for Medical Laser Applications (ISLA). A short list of the most frequently used methods within the research areas of the ISLA is included along with a description of how the great potential of these new laser methods led to numerous improvements in patient treatment. The ISLA attaches great importance to being an opinion leader in the context of evidence-based laser medicine. Many further developments are planned that will enrich the range of methods.


Pandemic (H1N1) 2009 cases, Buenos Aires, Argentina.
To determine clinical and virologic characteristics of pandemic (H1N1) 2009 in Buenos Aires, Argentina, we conducted real-time reverse transcription-PCR on samples from patients with influenza-like illness, June 11-30, 2009. Of 513 patients tested, 54% were positive for influenza virus subtype H1N1. Infection rate was lowest for patients >or=60 years of age.


Regulation of ribosomal RNA accumulation by auxin in artichoke tissue.
Artichoke (Helianthus tuberosus L.) tuber tissue cultured in the presence of the auxin 2,4-dichlorophenoxyacetic acid accumulates ribosomal RNA at a rate of 0.135 micrograms per hour per explant whereas there is little accumulation in nontreated tissue. The addition of auxin enhanced the transcription of the 2.5 x 10(6) precursor 3.5-fold and increased the rate of processing 1.8-fold. The major effect of auxin, however, was a vast increase in the rate of processing of the 1.39 x 10(6) precursor to the 1.3 x 10(6) mature ribosomal RNA. The incorporation of label into the 0.7 x 10(6) mature ribosomal RNA of treated tissue was in 10-fold excess over the control after a 30-minute pulse and remained so throughout the remainder of the labeling period. This level, however, was not reached for the complementary 1.3 mature RNA until 3 hours of continuous labeling, decreasing from a initial value of 40-fold excess. A complication in the processing of ribosomal RNA is the apparent increase in the stability of the 0.7 x 10(6) mature RNA with auxin treatment.


Heterogeneity of human eosinophils. II. Variability of respiratory burst activity related to cell density.
Recent work has suggested that there may be heterogeneity amongst human eosinophils. In order to study this further, blood and tissue eosinophils were separated by density gradient centrifugation in discontinuous gradients of metrizamide. Blood eosinophils were obtained from 16 patients with blood eosinophil counts above 1 X 10(9)/l. Resident eosinophils were isolated from alveolar fluid in three of these patients and from pleural effusion in two others. A large proportion of the eosinophils in these patients were of light buoyant density (hypodense) and a high percentage of these showed morphological evidence of hypogranulation. Hypodense eosinophils had a reduced capacity to reduce nitroblue tetrazolium or develop chemiluminescence after stimulation with phorbol myristate acetate. It was concluded that there is structural and metabolic heterogeneity amongst blood and tissue eosinophils in patients with a variety of eosinophilic disorders.


[The mode of evaluation of functional condition of kidneys under autoimmune diseases.]
The kidneys are one of main homeostatic organs participating in regulation of concentration of osmotic active substances, ionic composition and acid-base balance, in maintenance of volume of fluid of internal medium of organism fulfilling excretory function. The analysis of urine is largely applied in laboratory practice for detecting different pathological conditions. The actual study was organized to develop simple, accessible and economic mode of evaluation of functional condition of kidneys in patients with somatic diseases, detection of their early dysfunction and timely implementation of adjustment. The study was carried out on sampling of 78 patients: 58 persons with inflammatory diseases of intestine (ulcerous colitis, Crohn's disease) and 20 healthy persons (volunteers). The proposed technique is based on detection of total pool of metabolites in day urine of patients. The spectrophotometer is applied to detect main groups of metabolites of urine within range of wavelength 210-300 nm. The excess amount of pathologic components, toxically effecting and affecting homeostasis of internal medium of organism, is detected under establishment of total optical density. Its value is ≥30 standard unit and also sum of optical density within range 210-230 and 270-290 nm, equal 10 and 7 standard units correspondingly testify presence of glomerular and tubular apparatus of kidneys.


Flat detectors and new aspects of radiation safety.
Flat detectors are the heart of high-performance imaging systems that provide new capabilities as well as new hazards. The superior image quality enables operators to work with heavier patients and steeper projections. Under these conditions, exposure control computers automatically increase the production of x-rays to compensate for absorption by body tissues. Image quality is preserved, and operators may not be aware of the very high skin doses delivered during prolonged procedures. Although it is assumed that flat detector systems are safe, the potential for radiation overexposure and skin injury is real. This article examines the unique radiation hazards of flat detector fluoroscopy and suggests practical steps that clinicians can take to protect themselves and their patients from radiation injury.


[Experimental study on histological changes of articular cartilage of femoral head under nonweight-bearing conditions].
Histological changes of articular cartilage of the femoral head in the nonweight-bearing conditions were investigated using 10-week-old Wistar rats whose hind limbs had been unilaterally transected. At 2 weeks after limb transection, decreased DNA synthesis in chondrocytes and depletion of glycosaminoglycan in the cartilage matrix in the intermediate zone of the articular cartilage were observed. After 8 weeks, articular cartilage thickness decreased significantly, and at 16 weeks the number of chondrocytes diminished in comparison with those of a weight-bearing femoral head. At 20 weeks, chondrocyte death and reduced width of articular cartilage became evident. No osteoarthritic changes, however, were observed under nonweight-bearing conditions. These findings suggest that weight-bearing is very important in maintaining of both the structure and metabolism of the articular cartilage.


Assembly of zwitterionic phospholipid/conjugated polyelectrolyte complexes: structure and photophysical properties.
We report on the formation of complexes between zwitterionic phospholipid vesicles and an anionic fluorescent conjugated polyelectrolyte and the effect of mono- and divalent cations on the photophysical properties of these complexes. Our goal is to gain an understanding of the interplay of morphology and exciton transport in these complexes, information that is critical to designing efficient lipid/conjugated polymer-based sensors. Our studies further underscore the potential application of lipid/conjugated polymer complexes in light-harvesting devices. Our work focuses on the negatively charged conjugated polyelectrolyte poly[5-methoxy-2-(3-sulfopropoxy)-1,4-phenylenevinylene] (MPS-PPV) and its interaction with the zwitterionic lipid dioleoylphosphatidylcholine (DOPC). We utilize monovalent and divalent cations as a tool to control and explore the interaction of MPS-PPV with lipids. We show that Ca(2+) ions promote the complexation of zwitterionic lipids and MPS-PPV in comparison to Na(+) ions. The addition of increasing amounts of zwitterionic phospholipids in the form of vesicles gradually disrupts MPS-PPV aggregates albeit vesicle structure is preserved in Na(+) buffer. Lipid complexation and the resulting MPS-PPV aggregate disruption produces an intensity enhancement and blue shifting of the MPS-PPV emission peak. In the absence of Ca(2+), the intensity enhancement and blue shift reach a plateau at larger than a 10:1 lipid/MPS-PPV monomer mole ratio. In the presence of Ca(2+), a plateau is reached at equimolar concentrations of MPS-PPV and lipid. Vesicle particle coalescence and agglomerate formation are observed herein. Lipid complexation and concomitant MPS-PPV shielding is shown to diminish the quenching of MPS-PPV emission by water-soluble quencher methyl viologen. FRET experiments conducted with membrane-intercalating acceptor dye DiD further underscore the large lipid/polymer interaction mediated by Ca(2+). We observe efficient light harvesting and MPS-PPV-amplified emission quenching in Ca(2+) buffer and to a lesser extent in Na(+) buffer. Our results highlight how the interplay of a zwitterionic lipid, cations, and buffer, in combination with the conjugated polyelectrolyte MPS-PPV, provides rich diversity in architecture and photophysical properties.


Combination therapy of specific aeroallergens immunotherapy and omalizumab, in children with severe asthma.
In most cases, severe asthma in children has an allergic etiology, but allergen-specific immunotherapy (AIT) is contraindicated. This study aimed at analyzing the safety and efficacy of AIT in patients with severe asthma treated with omalizumab (OM). A descriptive real-life study was carried out by reviewing medical records. Effectiveness was measured by the degree of control (CAN questionnaire), number of hospitalizations per year, number of exacerbations per year, and maintenance treatment and lung function (FEV1). Some adverse reactions occurred (AAI-EAACI-WAO guidelines). The retrospective study included 29 patients up to 18 years of age with severe asthma with OM plus AIT treatment. AIT treatment was started in a cluster schedule when patients treated with OM achieved disease control. Before starting AIT, patients were treated with OM for 1 year for achieving asthmatic control. AIT to mites (51%), Alternaria (37.9%), or pollens (10.3%) was administered. After one year with OM plus AIT,statistically significant differences in CAN scores and FEV1 measures were observed (P < 0.001). No patients under treatment with OM plus AIT required hospital admission. During the clustering schedule, only 3/64 doses showed systemic adverse reactions. During the AIT maintenance treatment, 348 doses were administered, with no significant adverse reactions. In this population-based study in children with severe asthma, the combined treatment with OM plus AIT was safe and effective. This strategy allows these pediatric patients to be safely treated with AIT.


A novel pathogenicity gene is required in the rice blast fungus to suppress the basal defenses of the host.
For successful colonization and further reproduction in host plants, pathogens need to overcome the innate defenses of the plant. We demonstrate that a novel pathogenicity gene, DES1, in Magnaporthe oryzae regulates counter-defenses against host basal resistance. The DES1 gene was identified by screening for pathogenicity-defective mutants in a T-DNA insertional mutant library. Bioinformatic analysis revealed that this gene encodes a serine-rich protein that has unknown biochemical properties, and its homologs are strictly conserved in filamentous Ascomycetes. Targeted gene deletion of DES1 had no apparent effect on developmental morphogenesis, including vegetative growth, conidial germination, appressorium formation, and appressorium-mediated penetration. Conidial size of the mutant became smaller than that of the wild type, but the mutant displayed no defects on cell wall integrity. The Deltades1 mutant was hypersensitive to exogenous oxidative stress and the activity and transcription level of extracellular enzymes including peroxidases and laccases were severely decreased in the mutant. In addition, ferrous ion leakage was observed in the Deltades1 mutant. In the interaction with a susceptible rice cultivar, rice cells inoculated with the Deltades1 mutant exhibited strong defense responses accompanied by brown granules in primary infected cells, the accumulation of reactive oxygen species (ROS), the generation of autofluorescent materials, and PR gene induction in neighboring tissues. The Deltades1 mutant displayed a significant reduction in infectious hyphal extension, which caused a decrease in pathogenicity. Notably, the suppression of ROS generation by treatment with diphenyleneiodonium (DPI), an inhibitor of NADPH oxidases, resulted in a significant reduction in the defense responses in plant tissues challenged with the Deltades1 mutant. Furthermore, the Deltades1 mutant recovered its normal infectious growth in DPI-treated plant tissues. These results suggest that DES1 functions as a novel pathogenicity gene that regulates the activity of fungal proteins, compromising ROS-mediated plant defense.


Developmental expression, pattern of distribution, and effect on cell aggregation implicate a neuron-glial junctional domain protein in neuronal migration.
We developed a panel of monoclonal antibodies to cerebellar astroglial cells and selected for study those that revealed microdomain structures on the cell surface of neocortical and cerebellar astrocytes. One antibody, 15D7-AD7, recognized the approximately 72 kDa polypeptide doublet that was identified previously by the polyclonal antibody D4 as a component of the microdomain structure formed between migrating neurons and radial glial cell processes (Cameron and Rakic [1994] J. Neurosci. 14:3139-3155). Immunofluorescent localization studies reveal a spatial and temporal pattern of 15D7 immunoreactivity in multiple brain regions that correlates well with time periods when neuronal cell migration is a prominent morphogenetic event. In areas where the process of migration is underway, 15D7 immunoreactivity is detected simultaneously in both radial glial cells and cells that have the positional and morphologic features characteristic of migrating neurons. Subsequent to the completion of migration, immunoreactivity is detected in the transitional forms of radial glial cells and mature astrocytes, but not in neurons. Cell aggregation analyses reveal that 15D7 antibodies perturb the rate of aggregation for astrocyte-astrocyte, neuron-neuron, and mixed cell-cell combinations. Taken together, the present studies suggest that the polypeptides recognized by the 15D7 antibodies likely participate in an adhesive process, principally within the ventricular and subventricular zones, that is essential at the onset of the cell migration process.


Do patients understand how PHRs work?
As Personal Health Records (PHRs) gain momentum, designers need to ensure that users understand the functions and benefits of PHRs. This study examines patients' readiness to use PHRs. Results show that although most participants envision themselves using the system, five areas of concern about the use of PHRs remain. The gap between current and ideal understanding highlights the need for formalized methods to help patients understand what PHRs are and how to use them.


[Determination of nutrient elements in transgenic insect-resistant cotton tissues by three different spectroscopical methods].
In order to find out the effects of exogenous genes, such as Bt and Bt coupled with CpTI, on nutrition metabolism in transgenic plants, totally eleven types of nutrient elements in transgenic Bt (Z30) and Bt-CpTI (CCRI41 and SGK321) cotton were determined using methods of flame atomic absorption spectroscopy, flame atomic emission spectroscopy and spectrophotometry at flowering stage and boll-opening stage. The results showed that the chemical composition of plant nutrition in transgenic insect-resistant cotton differed in comparison with non-transgenic cotton counterparts related to varieties, tissues and stages. The content of total N in transgenic cotton changed most significantly. Especially, it increased by 21% for transgenic Bt cotton Z30 compared to non-transgenic cotton Z16. These changes in total N content were probably caused by both transgenes expression in transgenic cotton and other processes not studied in this experiment. The content of Mg, Na and Cu in transgenic cotton varied significantly only in some certain varieties or tissues. It was unobvious how the incorporation of transgenes impacted on the content of organic C, total P, total S, K, Ca, Fe and Zn in transgenic cotton. The authors speculated that there were no significant changes in utilization and accumulation of these nutrient elements between transgenic insect-resistant cotton and their non-transgenic cotton counterparts (Z16, CCRI23 and SY321, respectively).


Investigation of the association between the test day milk fat-protein ratio and clinical mastitis using a Poisson regression approach for analysis of time-to-event data.
The objective of the present study was to investigate the association between the milk fat-protein ratio and the incidence rate of clinical mastitis including repeated cases of clinical mastitis to determine the usefulness of this association to monitor metabolic disorders as risk factors for udder health. Herd records from 10 dairy herds of Holstein cows in Saxony, Germany, from September 2005-2011 (36,827 lactations of 17,657 cows) were used for statistical analysis. A mixed Poisson regression model with the weekly incidence rate of clinical mastitis as outcome variable was fitted. The model included repeated events of the outcome, time-varying covariates and multilevel clustering. Because the recording of clinical mastitis might have been imperfect, a probabilistic bias analysis was conducted to assess the impact of the misclassification of clinical mastitis on the conventional results. The lactational incidence of clinical mastitis was 38.2%. In 36.2% and 34.9% of the lactations, there was at least one dairy herd test day with a fat-protein ratio of <1.0 or >1.5, respectively. Misclassification of clinical mastitis was assumed to have resulted in bias towards the null. A clinical mastitis case increased the incidence rate of following cases of the same cow. Fat-protein ratios of <1.0 and >1.5 were associated with higher incidence rates of clinical mastitis depending on week in milk. The effect of a fat-protein ratio >1.5 on the incidence rate of clinical mastitis increased considerably over the course of lactation, whereas the effect of a fat-protein ratio <1.0 decreased. Fat-protein ratios <1.0 or >1.5 on the precedent test days of all cows irrespective of their time in milk seemed to be better predictors for clinical mastitis than the first test day results per lactation.


Development and experience-dependent modulation of the defensive behaviors of mice to visual threats.
Rodents demonstrate defensive behaviors such as fleeing or freezing upon recognizing a looming shadow above them. Although individuals' experiences in their habitat can modulate the defensive behavior phenotype, the effects of systematically manipulating the individual's visual experience on vision-guided defensive behaviors have not been studied. We aimed to describe the developmental process of defensive behaviors in response to visual threats and the effects of visual deprivation. We found that the probability of escape response occurrence increased 3 weeks postnatally, and then stabilized. When visual experience was perturbed by dark rearing from postnatal day (P) 21 for a week, the developmental increase in escape probability was clearly suppressed, while the freezing probability increased. Intriguingly, exposure to the looming stimuli at P28 reversed the suppression of escape response development at P35. These results clearly indicate that the development of defensive behaviors in response to looming stimuli is affected by an individual's sensory experience.


Bioactivity of essential oils from leaves and bark of Laurelia sempervirens and Drimys winteri against Acyrthosiphon pisum.
The pea aphid, Acyrthosiphon pisum (Harris), is a cosmopolitan pest that attacks a wide range of legume crops and vectors important plant virus diseases. In this project, essential oils from the leaf (L) and bark (B) of Laurelia sempervirens (Ruiz & Pavón) Tul. (L) and Drimys winteri JR Forster & G Forster (D) were extracted, and their deterrent and insecticidal activities were tested under laboratory conditions. By use of GC-MS, safrole was found as the main constituent in LL and LB oils, while the main constituents were more diverse in DL and DB oils. In the deterrent bioassays with A. pisum under choice conditions, the four oils were active, with LL being the most active, followed by LB, DB and DL. The respective deterrence indices were 1.0, 0.89, 0.87 and 0.46 when aphids were exposed for 24 h to 4 µL mL(-1) . Although there was no aphid mortality when oils were sprayed on faba bean leaves before aphid infestation, there was 58 and 42% mortality when settled aphids were directly sprayed with 4.0 µL mL(-1) of LL and LB respectively; DB and DL oils caused ≤18% mortality. In a third series, the essential oils of LL and LB caused 100% mortality when applied at a dose of 64 µL L(-1) air by fumigation to faba bean plants infested with A. pisum; at the same dose, DB and DL oils caused 68 and 63% mortality respectively. When fumigation was limited to 2 h, the respective LC(50) values for LL and LB oils were 10.6-14.3 µL L(-1) air and 9.8-13.2 µL L(-1) air. Because of their high deterrent and insecticidal activities, the essential oils from leaf and bark of L. sempervirens may be explored as potential natural aphicides.


Community management of anti-malarials in Africa and iatrogenic risk.
Distribution of anti-malarials at the community level is one of the interventions recommended to reduce mortality from febrile illnesses. Inappropriate treatment of fever with anti-malarials may result in missed diagnosis and delays in appropriate treatments including consideration of other illnesses than malaria. We report the case of an 8-year-old black girl receiving prophylaxis with sulfadoxine-pyrimethamine from the caretaker of the community during her holidays in Ivory Coast. A persistent fever suspected to be due to malaria was treated inappropriately with atovaquone-proguanil and then with sulfadoxine-pyrimethamine again. Cumulative toxicity of anti-malarials leads to irreversible hepatic damages requiring hepatic transplantation. Community caretakers must be aware of the potential side effects and the contraindications of anti-malarials. Early identification of drug-induced toxicity and immediate discontinuation of the drug are the more effective tools to limit the progression of tissue damage.