Identification of a B cell-dependent subpopulation of multiple sclerosis by measurements of brain-reactive B cells in the blood.

B cells are increasingly coming into play in the pathogenesis of multiple sclerosis (MS). Here, we screened peripheral blood mononuclear cells (PBMC) from patients with clinically isolated syndrome (CIS), MS, other non-inflammatory neurological, inflammatory neurological or autoimmune diseases, and healthy donors for their B cell reactivity to CNS antigen using the enzyme-linked immunospot technique (ELISPOT) after 96 h of polyclonal stimulation. Our data show that nine of 15 patients with CIS (60.0%) and 53 of 67 patients with definite MS (79.1%) displayed CNS-reactive B cells, compared to none of the control donors. The presence of CNS-reactive B cells in the blood of the majority of patients with MS or at risk to develop MS along with their absence in control subjects suggests that they might be indicative of a B cell-dependent subpopulation of the disease.

Multicenter evaluation of the Elecsys® anti-HCV II assay for the diagnosis of hepatitis C virus infection.

Routine screening of patients at risk of hepatitis C virus (HCV) infection has become a priority given recent improvements in therapeutic options and the asymptomatic nature of most chronic infections. The aim of this study was to evaluate the performance of the Elecsys® Anti-HCV II assay, a new qualitative antibody immunoassay, compared with currently available assays, and assess its suitability for routine diagnostic testing. The sensitivity of the Elecsys® Anti-HCV II, ARCHITECT® Anti-HCV, AxSYM® HCV 3.0, PRISM® HCV, Vitros® ECi Anti-HCV, Elecsys® Anti-HCV, and ADVIA Centaur® HCV assays was compared using commercially available seroconversion panels and samples from patients known to be HCV positive and infected with HCV genotypes 1-6. Specificity was investigated using samples from blood donors, unselected hospitalized patients, and patients with potential cross-reacting factors or from high-risk groups. The Elecsys® Anti-HCV II assay detected more positive bleeds than the comparator assays, was more sensitive in recognizing early HCV infection, and correctly identified all 765 samples known to be HCV positive, regardless of genotype. The overall specificity of the Elecsys(®) Anti-HCV II assay was 99.84% (n=6,850) using blood donor samples, 99.66% (n=3,922) using samples from unselected hospitalized patients, and 99.66% (n=2,397) using samples from patients with potentially cross-reacting factors or from high-risk groups. The specificity of the Elecsys® Anti-HCV II assay was superior or equal to the comparator assays. In conclusion, the Elecsys® Anti-HCV II assay is a sensitive and specific assay suitable for routine use in the reliable detection of anti-HCV antibodies.

Sex-specific differences in pain localization in female patients with endometriosis: A comparison of sexless and female human body outlines.

BACKGROUND: This study explores sex-specific differences in pain localization using pain drawings in female patients with endometriosis. Traditional human body outlines (HBOs) used for pain drawings are often viewed as male, making accurate pain assessment difficult. The study aims to compare pain localization and extent between patients presented with sexless and female HBOs. METHODS: A total of 49 female patients with endometriosis completed questionnaires and pain drawings (n = 24 and n = 26 with individually designed sexless and female HBOs, respectively). The Ruzika similarity index was used to investigate potential differences in pain drawings between sexless and female HBOs. Hypothesis testing was applied to compare the number of pixels marked in the pain extents and to investigate the suitability of the presented body outline. RESULTS: Sex of HBOs used in pain drawings had no effect on pain area, and no statistically significant differences were found in pain localization or area between female and sexless outlines. Most, but not all participants found the body outlines suitable. CONCLUSIONS: The findings suggest that differences in the resulting areas marked in the pain drawings were negligible and the preferences for sexless pain drawings were not significant, so that a sexless body outline for pain drawings could be a good choice, especially when a study does not focus on one specific sex.

Nephrotoxic Effects Caused by Occupational Exposure to Agrochemicals in a Region of Northeastern Brazil: A Cross-Sectional Study.

The objective of the present study was to evaluate the renal function of rural workers in a city of northeastern Brazil. A cross-sectional study was carried out with 208 workers in Boquim, Sergipe, Brazil. Renal function markers and butyrylcholinesterase (BChE) were evaluated and the glomerular filtration rate (GFR) was determined. The sample consisted mainly of illiterate males with a low usage of personal protective equipment and no training. Approximately 40% had some level of renal failure. Relative risk (1.59) of GFR alteration was higher in workers with more than 5 yr of exposure, mainly to organophosphates. Workers more than 60 yr of age presented a 17.06 greater risk for manifesting acute intoxication. Butyrylcholinesterase reduction was associated with reports of intoxication (relative risk of 11.36). We concluded that exposure to pesticides represented a risk factor for the development of nephrotoxic effects and alteration of renal function, which reinforced the need to implement measures to protect rural workers. Environ Toxicol Chem 2021;40:1132-1138. © 2020 SETAC.

The clinical course of EAE is reflected by the dynamics of the neuroantigen-specific T cell compartment in the blood.

Due to the limited numbers of PBMCs that can be obtained from the blood of individual mice, the key question whether central disease parameters such as onset, progression and severity correlate with the magnitude and cytokine quality of the T cell response in experimental autoimmune encephalomyelitis (EAE) has remained unanswered. Here we introduce an ELISPOT-based PBMC test system in which as little as 150 µl of murine blood are sufficient, allowing to bleed mice repeatedly while continuing to observe the clinical course of EAE. Using this technique, we demonstrate that longitudinal measurements of antigen-specific IFN-γ and IL-17 production in the blood are a highly suitable approach to predict the disease outcome in remitting-relapsing PLP:139-151- and chronic MOG:35-55-induced EAE of SJL/J and C57BL/6 mice, respectively. Our data propound cytokine monitoring as promising tool in the quest for more efficient diagnostic and prognostic options in human multiple sclerosis and other autoimmune diseases.

Evidence of risks of renal function reduction due to occupational exposure to agrochemicals: A systematic review.

Agriculture accountsfor an important economic activity worldwide and the search for the increased productivity incorporated the use of pesticides in this practice. Such compounds have significant environmental and human health effects, especially for workers exposed to them. Among the main health problems caused by pesticides are the renal alterations, which in more advanced stages comprise an important public health problem. For this reason, this systematic review aimed at gathering evidence of the risk of renal changes induced by occupational exposure to pesticides. The search was made in PubMed, Scopus, Lilacs and Scielo in December 2017, using keywords as pesticides, poisoning, kidney, renal insufficiency. After the application of inclusion criteria, 11 studies were selected. It was possible to gather evidence on the prevalence and risk (3.12-6.71) of renal injury from the occupational exposure of agricultural workers and its association with the exposure to agrichemicals, as organophosphates and herbicides.

Effect of pioglitazone treatment on behavioral symptoms in autistic children.

INTRODUCTION: Autism is complex neuro-developmental disorder which has a symptomatic diagnosis in patients characterized by disorders in language/communication, behavior, and social interactions. The exact causes for autism are largely unknown, but is has been speculated that immune and inflammatory responses, particularly those of Th2 type, may be involved. Thiazolidinediones (TZDs) are agonists of the peroxisome proliferator activated receptor gamma (PPARgamma), a nuclear hormone receptor which modulates insulin sensitivity, and have been shown to induce apoptosis in activated T-lymphocytes and exert anti-inflammatory effects in glial cells. The TZD pioglitazone (Actos) is an FDA-approved PPARgamma agonist used to treat type 2 diabetes, with a good safety profile, currently being tested in clinical trials of other neurological diseases including AD and MS. We therefore tested the safety and therapeutic potential of oral pioglitazone in a small cohort of children with diagnosed autism. CASE DESCRIPTION: The rationale and risks of taking pioglitazone were explained to the parents, consent was obtained, and treatment was initiated at either 30 or 60 mg per day p.o. A total of 25 children (average age 7.9 +/- 0.7 year old) were enrolled. Safety was assessed by measurements of metabolic profiles and blood pressure; effects on behavioral symptoms were assessed by the Aberrant Behavior Checklist (ABC), which measures hyperactivity, inappropriate speech, irritability, lethargy, and stereotypy, done at baseline and after 3-4 months of treatment. DISCUSSION AND EVALUATION: In a small cohort of autistic children, daily treatment with 30 or 60 mg p.o. pioglitazone for 3-4 months induced apparent clinical improvement without adverse events. There were no adverse effects noted and behavioral measurements revealed a significant decrease in 4 out of 5 subcategories (irritability, lethargy, stereotypy, and hyperactivity). Improved behaviors were inversely correlated with patient age, indicating stronger effects on the younger patients. CONCLUSION: Pioglitazone should be considered for further testing of therapeutic potential in autistic patients.

[Strengthening health services research: the development of the "German Network for Health Services Research" (DNVF)]. / Stärkung der Versorgungsforschung durch Vernetzung: Von der Ständigen Kongresskommission zum Deutschen Netzwerk Versorgungsforschung (DNVF).

One of the main challenges in health services research is to overcome the structural and professional boundaries restricting the opportunities for cooperation between researchers, clinicians, and practitioners in designing and conducting applied research. In our view, two steps are necessary to strengthen linkage and exchange between organizations and bodies interested in health services research. First, reconnecting the different scientific disciplines and researchers working in the field of health services research is essential. Second, it is necessary to bring both researchers and the users and funders of research together in order to ensure that the research agenda is pursuing the right questions and to foster the translation of the data generated into valuable information for practical decisions. The "German Network for Health Services Research" was launched on May 2, 2006, by 26 representatives of different national medical and public health associations. The aim of this network is to help bridge the gap between the scientific communities on the one hand and between researchers and practitioners on the other hand.

The brain antigen-specific B cell response correlates with glatiramer acetate responsiveness in relapsing-remitting multiple sclerosis patients.

B cells have only recently begun to attract attention in the immunopathology of multiple sclerosis (MS). Suitable markers for the prediction of treatment success with immunomodulatory drugs are still missing. Here we evaluated the B cell response to brain antigens in n = 34 relapsing-remitting MS (RRMS) patients treated with glatiramer acetate (GA) using the enzyme-linked immunospot technique (ELISPOT). Our data demonstrate that patients can be subdivided into responders that show brain-specific B cell reactivity in the blood and patients without this reactivity. Only in patients that classified as B cell responders, there was a significant positive correlation between treatment duration and the time since last relapse in our study. This correlation was GA-specific because it was absent in a control group that consisted of interferon-ß (IFN-ß)-treated RRMS patients (n = 23). These data suggest that GA has an effect on brain-reactive B cells in a subset of patients and that only this subset benefits from treatment. The detection of brain-reactive B cells is likely to be a suitable tool to identify drug responders.

Periodontal disease as a risk factor for ischemic stroke.

BACKGROUND AND PURPOSE: Chronic infectious diseases may increase the risk of stroke. We investigated whether periodontal disease, including periodontitis and gingivitis, is a risk factor for cerebral ischemia. METHODS: We performed a case-control study with 303 patients examined within 7 days after acute ischemic stroke or transient ischemic attack, 300 population controls, and 168 hospital controls with nonvascular and noninflammatory neurological diseases. All subjects received a complete clinical and radiographic dental examination. The individual mean clinical attachment loss measured at 4 sites per tooth served as the main indicator for periodontitis. RESULTS: Patients had higher clinical attachment loss than population (P<0.001) and hospital (P=0.010) controls. After adjustment for age, sex, number of teeth, vascular risk factors and diseases, childhood and adult socioeconomic conditions, and lifestyle factors, the risk of cerebral ischemia increased with more severe periodontitis. Subjects with severe periodontitis (mean clinical attachment loss >6 mm) had a 4.3-times-higher (95% confidence interval, 1.85 to 10.2) risk of cerebral ischemia than subjects with mild or without periodontitis (

Enrichment of hyperforin from St. John's wort (Hypericum perforatum) by pilot-scale supercritical carbon dioxide extraction.

St. John's Wort (Hypericum perforatum L.) was extracted with supercritical carbon dioxide using a pilot batch extraction plant. The effects of pressure, temperature, flow rate and extraction time were examined with respect to extraction yield and hyperforin content. Supercritical carbon dioxide showed a high selectivity for phloroglucinols. Extracts were analyzed using an isocratic HPLC method with a mixture of hyperforin/adhyperforin as an external standard. Within the studied range of extraction pressure (90-150 bar) and extraction time (1-5 h), extraction at 90 bar for 3 h and 120 bar for 1 h provided higher hyperforin content (up to 35%) in the resulting extracts. An increase in extraction temperature showed a negative effect, leading to increased degradation of hyperforin into orthoforin. When the total mass of carbon dioxide passing the extraction vessel was kept constant, changes in mass flow rate did not affect the extraction result.

Unmet needs of patients feeling severely affected by multiple sclerosis in Germany: a qualitative study.

BACKGROUND: The needs of patients feeling severely affected by multiple sclerosis (MS) have rarely been investigated. However this is essential information to know before care can be improved, including adding palliative care (PC) services where helpful. Since it remains unclear at what point specialized palliative care should begin for this patient group, this study focuses on needs in general. OBJECTIVE: The objective was to explore the subjectively unmet needs of patients feeling severely affected by MS. METHODS: The study used a qualitative cross-sectional approach for needs assessment. Fifteen patients self-reporting feeling severely affected by MS were recruited and interviewed using a combination of purposive and convenience sampling (five were accompanied by a caregiver relative). Interviews were recorded and transcribed verbatim, followed by qualitative content analysis. RESULTS: Unmet needs were identified in the main categories "support of family and friends," "health care services," "managing everyday life," and "maintaining biographical continuity." Patients expressed the desire for more support from their families and to be viewed as distinct individuals. They see a substantial deficit in the physician-patient relationship and in the coordination of services. A decrease in expressed unmet needs was found for patients more severely affected and less socially integrated. CONCLUSIONS: To address the unmet needs of severely affected MS patients, health care services need to be improved and linked with existing PC services. Special attention is required to form supporting professional-patient relationships. Multiprofessional services should be accessible for patients, while integrating relatives. All services should have an individual approach to provide needs-tailored support.

Rolled-up magnetic sensor: nanomembrane architecture for in-flow detection of magnetic objects.

Detection and analysis of magnetic nanoobjects is a crucial task in modern diagnostic and therapeutic techniques applied to medicine and biology. Accomplishment of this task calls for the development and implementation of electronic elements directly in fluidic channels, which still remains an open and nontrivial issue. Here, we present a novel concept based on rolled-up nanotechnology for fabrication of multifunctional devices, which can be straightforwardly integrated into existing fluidic architectures. We apply strain engineering to roll-up a functional nanomembrane consisting of a magnetic sensor element based on [Py/Cu](30) multilayers, revealing giant magnetoresistance (GMR). The comparison of the sensor's characteristics before and after the roll-up process is found to be similar, allowing for a reliable and predictable method to fabricate high-quality ultracompact GMR devices. The performance of the rolled-up magnetic sensor was optimized to achieve high sensitivity to weak magnetic fields. We demonstrate that the rolled-up tube itself can be efficiently used as a fluidic channel, while the integrated magnetic sensor provides an important functionality to detect and respond to a magnetic field. The performance of the rolled-up magnetic sensor for the in-flow detection of ferromagnetic CrO(2) nanoparticles embedded in a biocompatible polymeric hydrogel shell is highlighted.

Effects of pioglitazone on diffusion tensor imaging indices in multiple sclerosis patients.

Pioglitazone is an FDA-approved peroxisome proliferator activated receptor gamma (PPARgamma) agonist. We tested the hypothesis that treatment with pioglitazone reduces new lesion development in patients with RRMS. Twenty-two patients were treated with pioglitazone or placebo and monitored by diffusion tensor imaging (DTI) at baseline and after 12 months. A negative correlation was found between the 1-year change in relative anisotropy (RA) and fluid attenuated inversion recovery (FLAIR) lesion burden in the pioglitazone group. Regions of interest (ROIs) having high ADC and low RA values at baseline had a significantly higher chance to develop into lesions in the placebo group than similar ROIs in the pioglitazone group. These findings suggest that baseline DTI parameters can provide a prognostic surrogate marker for lesions, and that pioglitazone can reduce conversion of normal appearing white matter to lesions.

A pilot test of pioglitazone as an add-on in patients with relapsing remitting multiple sclerosis.

The peroxisome proliferator-activated receptor gamma agonist pioglitazone is FDA-approved for treatment of type-2 diabetes due to insulin sensitizing effects. However pioglitazone has anti-inflammatory and neuroprotective effects, reduces glial and T-cell activation, and reduces signs in an animal model of multiple sclerosis (MS). We tested the effects of daily treatment with pioglitazone in a small cohort of relapsing remitting MS patients. RRMS patients taking IFNbeta-1alpha and having an EDSS score <6.5 were randomized to treatment with pioglitazone (30 mg daily, p.o.) or placebo and monitored clinically and by MRI for 1 year. Primary outcomes were safety and tolerability, secondary outcomes included changes in neurological outcome, lesion burden, and gray matter volume. After 1 year 11 patients in the pioglitazone arm and 10 in the placebo arm completed the trial. Pioglitazone was well tolerated with a similar incidence of non-serious adverse events in placebo and treatment groups. After 1 year there were no significant differences in clinical symptoms as assessed by EDSS; however MRI showed a significant reduction in gray matter atrophy, and a trend for reduced lesion burden in the treatment group. These results show that pioglitazone was well tolerated in RRMS patients with indications of beneficial effects, warranting further trials to establish clinical efficacy.

The association of gingivitis and periodontitis with ischemic stroke.

OBJECTIVES: The aim of this study was to assess the associations of different periodontal parameters with cerebral ischemia. METHODS: In a case-control study, 303 consecutive patients with ischemic stroke or transient ischemic attack, and 300 representative population controls received a complete clinical and radiographic dental examination. Patients were examined on average 3 days after ischemia. The individual mean clinical attachment loss measured at four sites per tooth was used as indicator variable for periodontitis. RESULTS: Patients had higher clinical attachment loss than population (p<0.001). After adjustment for age, gender, number of teeth, vascular risk factors and diseases, childhood and adult socioeconomic conditions and lifestyle factors, a mean clinical attachment loss >6 mm had a 7.4 times (95% confidence interval 1.55-15.3) a gingival index >1.2 a 18.3 times (5.84-57.26) and a radiographic bone loss a 3.6 times (1.58-8.28) higher risk of cerebral ischemia than subjects without periodontitis or gingivitis, respectively. CONCLUSION: Periodontitis is an independent risk factor for cerebral ischemia and acute exacerbation of inflammatory processes in the periodontium might be a trigger for the event of cerebral ischemia.