The formation of mutated IgM memory B cells in rat splenic marginal zones is an antigen dependent process

Previous studies in rodents have indicated that only a minor fraction of the immunoglobulin heavy chain variable region (IGHV-Cμ) transcripts carry somatic mutations and are considered memory B cells. This is in marked contrast to humans where nearly all marginal zone B (MZ-B) cells are mutated. Here we show in rats that the proportion of mutated IgM+ MZ-B cells varies significantly between the various IGHV genes analyzed, ranging from 27% mutated IGHV5 transcripts to 65% mutated IGHV4 transcripts. The observed data on mutated sequences in clonally-related B cells with a MZ-B cell or follicular B (FO-B) cell phenotype indicates that mutated IgM+ MZ-B and FO-B cells have a common origin. To further investigate the origin of mutated IgM+ MZ-B cells we determined whether mutations occurred in rearranged IGHV-Cμ transcripts using IGHV4 and IGHV5 genes from neonatal rat MZ-B cells and FO-B cells. We were not able to detect mutations in any of the IGHV4 and IGHV5 genes expressed by MZ-B cells or FO-B cells obtained from neonatal rat spleens. Germinal centres (GCs) are absent from neonatal rat spleen in the first few weeks of their life, and no mutations were found in any of the neonatal sequences, not even in the IGHV4 gene family which accumulates the highest number of mutated sequences (66%) in the adult rat. Therefore, these data do not support the notion that MZ-B cells in rats mutate their IGHV genes as part of their developmental program, but are consistent with the notion that mutated rat MZ-B cells require GCs for their generation. Our findings support that the splenic MZ of rats harbors a significant number of memory type IgM+ MZ-B cells with mutated IGHV genes and propose that these memory MZ-B cells are probably generated as a result of an antigen driven immune response in GCs, which still remains to be proven

Presence of Germline and Full-Length IgA RNA Transcripts Among Peritoneal B-1 Cells

Next to conventional B cells (or B-2 cells), peritoneal B-1 cells have been shown to contribute significantly to the production of IgA-secreting plasma cells in the gut. Evidence for this was mainly based on studies comprising manipulated animals, including lethally X-irradiated and transgenic mice. To examine the ability of peritoneal B-1 cells from untreated mice to switch actively to IgA in vivo, we performed RT-PCR analysis on FACS-sorted peritoneal B-cell subsets from untreated BALB/c mice in order to examine the presence of germline Cα mRNA and mature Cα mRNA transcripts. Germline Cα and mature Cα transcripts were readily detectable in peritoneal B-1 cells (defined as IgMbright/IgDdull), but not, or very little, in peritoneal B-2 cells (defined as IgMdull/IgDbright). Moreover, by subdividing the B-l-cell population in CD5+ B-1a cells and CD5- B-1b cells, it was shown that in vivo expression of germline Cα and mature Cα transcripts was largely restricted to the B-1b-cell lineage. These results indicate that peritoneal B-1 cells indeed are capable to switch to IgA under normal physiological conditions and hereby further support the view that B-1 cells contribute significantly to the mucosal IgA response, albeit this function appears to be restricted to the B-1b-cell subset

Prevalence of cognitive complaints and impairment in patients with Chronic Subdural Hematoma and recovery after treatment:a systematic review

BACKGROUND: Chronic Subdural Hematoma (CSDH) is a frequently occurring neurological disease associated with older age and use of anticoagulants. Symptoms vary from headaches to coma, but also cognitive deficits can be present. However, exact prevalence and severity of cognitive deficits in CSDH are still unknown. OBJECTIVE: In this systematic review, we aim to assess cognitive status of patients with CSDH, at presentation and after treatment. METHODS: Pubmed, Embase and Psyqinfo, were searched for articles concerning cognition in CSDH. We divided cognition changes into subjective cognitive deficit (Cognitive Complaints: CC) and objective cognitive deficit (Cognitive Impairment: CI). Two reviewers independently selected studies for inclusion and subsequently extracted data. Quality assessment was done by means of the Newcastle-Ottowa Scale. Reported prevalence of CC and CI was pooled with random effects meta-analysis. RESULTS: Out of 768 identified references, 20 met inclusion criteria. Estimated prevalence of CC and CI in CSDH at presentation was 45% (95% CI: 36% to 54%). Four studies concerned a prospective evaluation of the effect of surgical treatment on cognition. These proved to be of fair to good quality after quality assessment. The estimated pre-treatment prevalence of objectified cognitive impairment was 61% (95% CI: 51% to 70%) decreasing to 18% (95% CI: 8% to 32%) post-surgery Conclusion: From this review it can be concluded that CC and CI are very common in CSDH with a tendency to improve after treatment. Therefore, we underline the importance of increased attention to cognitive status of these patients, with proper testing methods and treatment-testing intervals

Wall shear stress as measured in vivo: consequences for the design of the arterial system

Based upon theory, wall shear stress (WSS), an important determinant of endothelial function and gene expression, has been assumed to be constant along the arterial tree and the same in a particular artery across species. In vivo measurements of WSS, however, have shown that these assumptions are far from valid. In this survey we will discuss the assessment of WSS in the arterial system in vivo and present the results obtained in large arteries and arterioles. In vivo WSS can be estimated from wall shear rate, as derived from non-invasively recorded velocity profiles, and whole blood viscosity in large arteries and plasma viscosity in arterioles, avoiding theoretical assumptions. In large arteries velocity profiles can be recorded by means of a specially designed ultrasound system and in arterioles via optical techniques using fluorescent flow velocity tracers. It is shown that in humans mean WSS is substantially higher in the carotid artery (1.1–1.3 Pa) than in the brachial (0.4–0.5 Pa) and femoral (0.3–0.5 Pa) arteries. Also in animals mean WSS varies substantially along the arterial tree. Mean WSS in arterioles varies between about 1.0 and 5.0 Pa in the various studies and is dependent on the site of measurement in these vessels. Across species mean WSS in a particular artery decreases linearly with body mass, e.g., in the infra-renal aorta from 8.8 Pa in mice to 0.5 Pa in humans. The observation that mean WSS is far from constant along the arterial tree implies that Murray’s cube law on flow-diameter relations cannot be applied to the whole arterial system. Because blood flow velocity is not constant along the arterial tree either, a square law also does not hold. The exponent in the power law likely varies along the arterial system, probably from 2 in large arteries near the heart to 3 in arterioles. The in vivo findings also imply that in in vitro studies no average shear stress value can be taken to study effects on endothelial cells derived from different vascular areas or from the same artery in different species. The cells have to be studied under the shear stress conditions they are exposed to in real life

Magnetic resonance imaging, computed tomography, and 68Ga-DOTATOC positron emission tomography for imaging skull base meningiomas with infracranial extension treated with stereotactic radiotherapy - a case series

<p>Abstract</p> <p>Introduction</p> <p>Magnetic resonance imaging (MRI) and computed tomography (CT) with ⁶⁸Ga-DOTATOC positron emission tomography (⁶⁸Ga-DOTATOC-PET) were compared retrospectively for their ability to delineate infracranial extension of skull base (SB) meningiomas treated with fractionated stereotactic radiotherapy.</p> <p>Methods</p> <p>Fifty patients with 56 meningiomas of the SB underwent MRI, CT, and ⁶⁸Ga-DOTATOC PET/CT prior to fractionated stereotactic radiotherapy. The study group consisted of 16 patients who had infracranial meningioma extension, visible on MRI ± CT (MRI/CT) <it>or </it>PET, and were evaluated further. The respective findings were reviewed independently, analyzed with respect to correlations, and compared with each other.</p> <p>Results</p> <p>Within the study group, SB transgression was associated with bony changes visible by CT in 14 patients (81%). Tumorous changes of the foramen ovale and rotundum were evident in 13 and 8 cases, respectively, which were accompanied by skeletal muscular invasion in 8 lesions. We analysed six designated anatomical sites of the SB in each of the 16 patients. Of the 96 sites, 42 had infiltration that was delineable by MRI/CT and PET in 35 cases and by PET only in 7 cases. The mean infracranial volume that was delineable in PET was 10.1 ± 10.6 cm³, which was somewhat larger than the volume detectable in MRI/CT (8.4 ± 7.9 cm³).</p> <p>Conclusions</p> <p>⁶⁸Ga-DOTATOC-PET allows detection and assessment of the extent of infracranial meningioma invasion. This method seems to be useful for planning fractionated stereotactic radiation when used in addition to conventional imaging modalities that are often inconclusive in the SB region.</p

An Early Study on the Mechanisms that Allow Tissue-Engineered Vascular Grafts to Resist Intimal Hyperplasia

Intimal hyperplasia is one of the prominent failure mechanisms for arteriovenous fistulas and arteriovenous access grafts. Human tissue-engineered vascular grafts (TEVGs) were implanted as arteriovenous grafts in a novel baboon model. Ultrasound was used to monitor flow rates and vascular diameters throughout the study. Intimal hyperplasia in the outflow vein of TEVGs was assessed at the anastomosis and at juxta-anastomotic regions via histological analysis, and was compared to intimal hyperplasia with polytetrafluoroethylene (PTFE) grafts in the baboon model and in literature reports from other animal models. Less venous intimal hyperplasia was observed in histological sections with arteriovenous TEVGs than with arteriovenous PTFE grafts. TEVGs were associated with a mild, noninflammatory intimal hyperplasia. The extent of intimal tissue that formed with TEVG placement correlated with the rate of blood flow through tissue engineered vascular grafts at 2 weeks postimplant. Outflow vein dilatation was observed with increased flow rate. Both mid-graft flow rates and outflow vein diameters reached a plateau by week 4, which suggested that venous remodeling and intimal hyperplasia largely occurred within the first 4 weeks of implant in the baboon model. Given their compliant and noninflammatory nature, TEVGs appear resistant to triggers for venous intimal hyperplasia that are common for PTFE arteriovenous grafts, including (1) abundant proinflammatory macrophage populations that are associated with PTFE grafts and (2) compliance mismatch between PTFE grafts and the outflow vein. Our findings suggest that arteriovenous TEVGs develop only a mild form of venous intimal hyperplasia, which results from the typical hemodynamic changes that are associated with arteriovenous settings

Adverse effects of extra-articular corticosteroid injections: a systematic review

<p>Abstract</p> <p>Background</p> <p>To estimate the occurrence and type of adverse effects after application of an extra-articular (soft tissue) corticosteroid injection.</p> <p>Methods</p> <p>A systematic review of the literature was made based on a PubMed and Embase search covering the period 1956 to January 2010. Case reports were included, as were prospective and retrospective studies that reported adverse events of corticosteroid injection. All clinical trials which used extra-articular corticosteroid injections were examined. We divided the reported adverse events into major (defined as those needing intervention or not disappearing) and minor ones (transient, not requiring intervention).</p> <p>Results</p> <p>The search yielded 87 relevant studies:44 case reports, 37 prospective studies and 6 retrospective studies. The major adverse events included osteomyelitis and protothecosis; one fatal necrotizing fasciitis; cellulitis and ecchymosis; tendon ruptures; atrophy of the plantar fat was described after injecting a neuroma; and local skin effects appeared as atrophy, hypopigmentation or as skin defect. The minor adverse events effects ranged from skin rash to flushing and disturbed menstrual pattern. Increased pain or steroid flare after injection was reported in 19 studies. After extra-articular injection, the incidence of major adverse events ranged from 0-5.8% and that of minor adverse events from 0-81%. It was not feasible to pool the risk for adverse effects due to heterogeneity of study populations and difference in interventions and variance in reporting.</p> <p>Conclusion</p> <p>In this literature review it was difficult to accurately quantify the incidence of adverse effects after extra-articular corticosteroid injection. The reported adverse events were relatively mild, although one fatal reaction was reported.</p

Quality Measures for the Diagnosis and Non-Operative Management of Carpal Tunnel Syndrome in Occupational Settings

Introduction: Providing higher quality medical care to workers with occupationally associated carpal tunnel syndrome (CTS) may reduce disability, facilitate return to work, and lower the associated costs. Although many workers’ compensation systems have adopted treatment guidelines to reduce the overuse of unnecessary care, limited attention has been paid to ensuring that the care workers do receive is high quality. Further, guidelines are not designed to enable objective assessments of quality of care. This study sought to develop quality measures for the diagnostic evaluation and non-operative management of CTS, including managing occupational activities and functional limitations. Methods: Using a variation of the well-established RAND/UCLA Appropriateness Method, we developed draft quality measures using guidelines and literature reviews. Next, in a two-round modified-Delphi process, a multidisciplinary panel of 11 U.S. experts in CTS rated the measures on validity and feasibility. Results: Of 40 draft measures, experts rated 31 (78%) valid and feasible. Nine measures pertained to diagnostic evaluation, such as assessing symptoms, signs, and risk factors. Eleven pertain to non-operative treatments, such as the use of splints, steroid injections, and medications. Eleven others address assessing the association between symptoms and work, managing occupational activities, and accommodating functional limitations. Conclusions: These measures will complement existing treatment guidelines by enabling providers, payers, policymakers, and researchers to assess quality of care for CTS in an objective, structured manner. Given the characteristics of previous measures developed with these methods, greater adherence to these measures will probably lead to improved patient outcomes at a population level

Quantitative Evaluation of Artifact Removal in Real Magnetoencephalogram Signals with Blind Source Separation

The magnetoencephalogram (MEG) is contaminated with undesired signals, which are called artifacts. Some of the most important ones are the cardiac and the ocular artifacts (CA and OA, respectively), and the power line noise (PLN). Blind source separation (BSS) has been used to reduce the influence of the artifacts in the data. There is a plethora of BSS-based artifact removal approaches, but few comparative analyses. In this study, MEG background activity from 26 subjects was processed with five widespread BSS (AMUSE, SOBI, JADE, extended Infomax, and FastICA) and one constrained BSS (cBSS) techniques. Then, the ability of several combinations of BSS algorithm, epoch length, and artifact detection metric to automatically reduce the CA, OA, and PLN were quantified with objective criteria. The results pinpointed to cBSS as a very suitable approach to remove the CA. Additionally, a combination of AMUSE or SOBI and artifact detection metrics based on entropy or power criteria decreased the OA. Finally, the PLN was reduced by means of a spectral metric. These findings confirm the utility of BSS to help in the artifact removal for MEG background activity