607 research outputs found

    Shear viscosity of an ordering latex suspension

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    The shear viscosity of a latex which is ordered at rest is studied as a function of the shear rate and volume fraction. At low shear rates and for moderate to high volume fractions, the flow curves show dynamic yield behavior which disappears below a volume fraction of 8%. At high shear rates, the onset to the high shear rate plateau of the viscosity can be observed. A new model for the shear viscosity for lattices at high volume fractions is described. This model is based upon theories for the shear viscosity of dilute lattices of Blachford et al. [J. Phys. Chem. 73, 1062 (1969)] and Russel [J. Fluid Mech. 85, 673 (1978)]. In terms of this model, the ordered latex is broken down under shear flow into ordered domains suspended in a disordered fluid. The larger the shear rate, the smaller the volume fraction of ordered domains. The experimental results can be described reasonably well with the model discussed here

    Shear viscosity of an ordering latex suspension

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    Functional polymorphisms of macrophage migration inhibitory factor as predictors of morbidity and mortality of pneumococcal meningitis.

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    Pneumococcal meningitis is the most frequent and critical type of bacterial meningitis. Because cytokines play an important role in the pathogenesis of bacterial meningitis, we examined whether functional polymorphisms of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) were associated with morbidity and mortality of pneumococcal meningitis. Two functional MIF promoter polymorphisms, a microsatellite (-794 CATT5-8; rs5844572) and a single-nucleotide polymorphism (-173 G/C; rs755622) were genotyped in a prospective, nationwide cohort of 405 patients with pneumococcal meningitis and in 329 controls matched for age, gender, and ethnicity. Carriages of the CATT7 and -173 C high-expression MIF alleles were associated with unfavorable outcome (P= 0.005 and 0.003) and death (P= 0.03 and 0.01). In a multivariate logistic regression model, shock [odds ratio (OR) 26.0, P= 0.02] and carriage of the CATT7 allele (OR 5.12,P= 0.04) were the main predictors of mortality. MIF levels in the cerebrospinal fluid were associated with systemic complications and death (P= 0.0002). Streptococcus pneumoniae strongly up-regulated MIF production in whole blood and transcription activity of high-expression MIF promoter Luciferase reporter constructs in THP-1 monocytes. Consistent with these findings, treatment with anti-MIF immunoglogulin G (IgG) antibodies reduced bacterial loads and improved survival in a mouse model of pneumococcal pneumonia and sepsis. The present study provides strong evidence that carriage of high-expression MIF alleles is a genetic marker of morbidity and mortality of pneumococcal meningitis and also suggests a potential role for MIF as a target of immune-modulating adjunctive therapy

    Emotional and behavioral problems in late-identified Indonesian patients with disorders of sex development

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    Objective: The aim of this study is to investigate emotional and behavioral problems among Indonesian patients with disorders of sex development (DSD) who recently came under clinical management. As diagnostic proce-dures and treatment had been delayed, patients progressively developed ambiguous bodies, difficult to conceal from outsiders. Method: We compared 118 Indonesian patients with DSD aged 6–41 years (60 children, 24 adolescents, 34 adults) and 118 healthy control subjects matched for age, gender, and residential settings. We used the Child Be-havioral Checklist (CBCL), Youth Self-Report (YSR), and Adult Self-Report (ASR) to examine differences between patient and control groups as well as differences within patients groups. Results: On the CBCL, parents of young children with DSD reported significantly more emotional and behavioral problems than parents of matched control. Parents of daughters with CAH reported that their daughters withdrew themselves from social interactions. On the ASR, adults with DSD reported significantly more internalizing problems than controls, particularly anxiety and depression. No other differences in emotional functioning were found across different diagnostic groups. Conclusions: Indonesian patients with DSD who were untreated for most of their lives suffered more emotional and behavioral problems than matched controls. Differences and similarities between our findings and observations in patients from Western countries will be discussed

    Exome Array Analysis of Susceptibility to Pneumococcal Meningitis

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    Host genetic variability may contribute to susceptibility of bacterial meningitis, but which genes contribute to the susceptibility to this complex disease remains undefined. We performed a genetic association study in 469 community-acquired pneumococcal meningitis cases and 2072 population-based controls from the Utrecht Health Project in order to find genetic variants associated with pneumococcal meningitis susceptibility. A HumanExome BeadChip was used to genotype 102,097 SNPs in the collected DNA samples. Associations were tested with the Fisher exact test. None of the genetic variants tested reached Bonferroni corrected significance (p-value <5 × 10−7). Our strongest signals associated with susceptibility to pneumococcal meningitis were rs139064549 on chromosome 1 in the COL11A1 gene (p = 1.51 × 10−6; G allele OR 3.21 [95% CI 2.05–5.02]) and rs9309464 in the EXOC6B gene on chromosome 2 (p = 6.01 × 10−5; G allele OR 0.66 [95% CI 0.54–0.81]). The sequence kernel association test (SKAT) tests for associations between multiple variants in a gene region and pneumococcal meningitis susceptibility yielded one significant associated gene namely COL11A1 (p = 1.03 × 10−7). Replication studies are needed to validate these results. If replicated, the functionality of these genetic variations should be further studied to identify by which means they influence the pathophysiology of pneumococcal meningitis

    CD4 T cells remain the major source of HIV-1 during end stage disease.

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    OBJECTIVE: To assess the source of HIV-1 production in lymphoid tissue biopsies from HIV-infected patients, with no prior anti-retroviral protease inhibitor treatment, with a CD4 cell count > 150 x 10(6)/l (group I) or < 50 x 10(6)/l (group II), co-infected with Mycobacterium tuberculosis or Mycobacterium avium complex. DESIGN AND METHODS: Lymphoid tissue biopsies from 11 HIV-1-infected patients, taken for diagnostic purposes, were studied by HIV-1 RNA in situ hybridization and immunohistochemistry. RESULTS: Patients of group I showed well organized granulomas, in contrast with patients of group II, in which granuloma formation was absent. HIV-1 RNA-positive cells in group I patients were found mainly around the granulomas, whereas in group II HIV-1-producing cells were confined to areas with remaining intact lymphoid tissue. Despite the abundant presence of macrophages, the productively infected HIV-1-positive cells in both groups were almost exclusively CD4 T cells. CONCLUSION: In contrast with previously published data, CD4 T cells appear to remain the major source of HIV-1 production in end-stage disease

    Naturally Occurring Lipid A Mutants in Neisseria meningitidis from Patients with Invasive Meningococcal Disease Are Associated with Reduced Coagulopathy

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    Neisseria meningitidis is a major cause of bacterial meningitis and sepsis worldwide. Lipopolysaccharide (LPS), a major component of the Gram-negative bacterial outer membrane, is sensed by mammalian cells through Toll-like receptor 4 (TLR4), resulting in activation of proinflammatory cytokine pathways. TLR4 recognizes the lipid A moiety of the LPS molecule, and the chemical composition of the lipid A determines how well it is recognized by TLR4. N. meningitidis has been reported to produce lipid A with six acyl chains, the optimal number for TLR4 recognition. Indeed, meningococcal sepsis is generally seen as the prototypical endotoxin-mediated disease. In the present study, we screened meningococcal disease isolates from 464 patients for their ability to induce cytokine production in vitro. We found that around 9% of them were dramatically less potent than wild-type strains. Analysis of the lipid A of several of the low-activity strains by mass spectrometry revealed they were penta-acylated, suggesting a mutation in the lpxL1 or lpxL2 genes required for addition of secondary acyl chains. Sequencing of these genes showed that all the low activity strains had mutations that inactivated the lpxL1 gene. In order to see whether lpxL1 mutants might give a different clinical picture, we investigated the clinical correlate of these mutations in a prospective nationwide observational cohort study of adults with meningococcal meningitis. Patients infected with an lpxL1 mutant presented significantly less frequently with rash and had higher thrombocyte counts, consistent with reduced cytokine induction and less activation of tissue-factor mediated coagulopathy. In conclusion, here we report for the first time that a surprisingly large fraction of meningococcal clinical isolates have LPS with underacylated lipid A due to mutations in the lpxL1 gene. The resulting low-activity LPS may have an important role in virulence by aiding the bacteria to evade the innate immune system. Our results provide the first example of a specific mutation in N. meningitidis that can be correlated with the clinical course of meningococcal disease

    The course of the radial nerve in the distal humerus: A novel, anatomy based, radiographic assessment

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    Iatrogenic nerve injury during fracture surgery of the upper arm is a well-known complication. Prevention of this type of injuries would be of great value. The literature describes several methods to reduce this type of injury, but no perfect solution is at hand. In this study we introduce a new radiographic evaluation of the course and variation of the radial nerve in the distal part of the humerus in relation to bony landmarks as observed on a plain (trauma) radiographs. Aim of this new approach is to reduce the chance of iatrogenic nerve injury by defining of a danger zone in the distal upper arm regarding the radial nerve and hence give an advise for future implant fabrication. Methods and findings: Measurements were done on both arms of ten specially embalmed specimens. Arms were dissected and radiopaque wires attached to the radial nerve in the distal part of the upper arm. Digital radiographs were obtained to determine the course of the radial nerve in the distal 20 cm of the humerus in relation to bony landmarks; medial epicondyle and capitellum-trochlea projection (CCT). Analysis was done with ImageJ and Microsoft Excel software. We also compared humeral nail specifications from different companies with the course of the radial nerve to predict possible radial nerve damage. Results: The distance from the medial epicondyle to point where the radial nerve bends from posterior to lateral was 142 mm on AP radiographs and 152 mm measured on the lateral radiographs. The average distance from the medial epicondyle to point where the radial nerve bends from lateral to anterior on AP radiographs was 66 mm. On the lateral radiographs where the nerve moves away from the anterior cortex 83 mm to the center of capitellum and trochlea (CCT). The distance from the bifurcation of the radial nerve into the posterior interosseous nerve (PIN) and superficial radial nerve was 21 mm on AP radiographs and 42 mm on the lateral radiographs (CCT). Conclusions: The course of the radial nerve in the distal part of the upper arm has great variety. Lateral fixation is relatively safe in a zone between the center of capitellum-trochlea and 48 mm proximal to this point. The danger zone in lateral fixation is in-between 48–122 mm proximal from CCT. In anteroposterior direction; distal fixation is dangerous between 21–101 mm measured from the medial epicondyle. The more distal, the more medial the nerve courses making it more valuable to iatrogenic damage. The IMN we compared with our data all show potential risk in case of (blind) distal locking, especially from lateral to medial direction

    Determinants of Symptomatic Intracranial Hemorrhage After Endovascular Stroke Treatment:A Retrospective Cohort Study

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    Background: Symptomatic intracranial hemorrhage (sICH) is a serious complication after endovascular treatment for ischemic stroke. We aimed to identify determinants of its occurrence and location. Methods: We retrospectively analyzed data from the Dutch MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) and MR CLEAN registry. We included adult patients with a large vessel occlusion in the anterior circulation who underwent endovascular treatment within 6.5 hours of stroke onset. We used univariable and multivariable logistic regression analyses to identify determinants of overall sICH occurrence, sICH within infarcted brain tissue, and sICH outside infarcted brain tissue. Results: SICH occurred in 203 (6%) of 3313 included patients and was located within infarcted brain tissue in 50 (25%), outside infarcted brain tissue in 23 (11%), and both within and outside infarcted brain tissue in 116 (57%) patients. In 14 patients (7%), data on location were missing. Prior antiplatelet use, baseline systolic blood pressure, baseline plasma glucose levels, post-endovascular treatment modified treatment in cerebral ischemia score, and duration of procedure were associated with all outcome parameters. In addition, determinants of sICH within infarcted brain tissue included history of myocardial infarction (adjusted odds ratio, 1.65 [95% CI, 1.06-2.56]) and poor collateral score (adjusted odds ratio, 1.42 [95% CI, 1.02-1.95]), whereas determinants of sICH outside infarcted brain tissue included level of occlusion on computed tomography angiography (internal carotid artery or internal carotid artery terminus compared with M1: adjusted odds ratio, 1.79 [95% CI, 1.16-2.78]). Conclusions: Several factors, some potentially modifiable, are associated with sICH occurrence. Further studies should investigate whether modification of baseline systolic blood pressure or plasma glucose level could reduce the risk of sICH. In addition, determinants differ per location of sICH, supporting the hypothesis of varying underlying mechanisms. Registration: URL: https://www.isrctn.com/; Unique identifier: ISRCTN10888758
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