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The short- and long-term variability of the surface spectral solar ultraviolet (UV) irradiance is investigated across Italy using high-quality ground-based measurements from three locations: Aosta (45.7 ∘ N, 7.4 ∘ E, 570 m a.s.l.), Rome (41.9 ∘ N, 12.5 ∘ E, 15 75 m a.s.l.), and Lampedusa (35.5 ∘ N, 12.6 ∘ E, 50 m a.s.l.). The three sites are characterized by different environmental conditions and represent almost the full latitudinal extent of the Italian territory. Data of two periods were analysed: 2006–2020 (all sites) and 1996–2020 (Rome only). The main objective of this study is to quantify the effect of the geopotential height (GPH) at 250 hPa on total ozone, and spectral irradiance at 307.5 and 324 nm. We first show that monthly anomalies in GPH, total ozone, and spectral irradiances are correlated amongst the three sites, suggesting that Italy is often affected by the same synoptical weather systems. We further find statistically significant anticorrelations between GPH and monthly anomalies in total ozone for all stations and months. Conversely, we identify positive correlations between GPH and monthly anomalies in spectral irradiance at 307.5 nm for most months. The influence of GPH on short-term variability also hold for long-term trends. For example, long-term changes in total ozone over the period 2006–2020 were associated with changes in GPH for all stations. This suggests that observed negative trends in total ozone were mainly driven by changes in lower-stratospheric ozone as upper-stratospheric ozone was increasing over this period. For several months of the year, positive trends in UV irradiance were observed, and we found that these trends were predominantly caused by changes in clouds and/or aerosols instead of total ozone. For the longer period of 1996–2020, a statistically significant annualized decrease in total ozone of ∼ 0.1 % per year was identified for Rome and could subsequently be attributed to decreasing lower-stratospheric ozone. While positive trends in spectral irradiance at 307.5 nm were observed for several months of this extended period, the negative trend in total ozone did not lead to a positive trend in the spectral irradiance at 307.5 nm in the deseasonalized data. Our study provides evidence that dynamical processes taking place in the troposphere lead to significant variability in total ozone and surface solar UV irradiance. [ABSTRACT FROM AUTHOR]

In this study the short- and long-term variability of the surface spectral solar ultraviolet (UV) irradiance are investigated over Italy using high quality ground based measurements from three sites located at quite different environmental conditions, and covering the full latitudinal extent of the Italian territory: Aosta (45.7° N, 7.4° E, 570 m a.s.l.), Rome (41.9° N, 12.5° E, 75 m a.s.l.), and Lampedusa (35.5° N, 12.6° E, 50 m a.s.l.). The variability of the irradiances at 307.5 nm, 324 nm, and of the ratio between the 307.5 nm and the 324 nm irradiances were investigated with respect to the corresponding variability in total ozone and the geopotential height at 250 hPa (GPH). The study was performed for two periods: 2006 - 2020 for all stations, and 1996 - 2020 only for Rome. A statistically significant correlation between the GPH and total ozone monthly anomalies was found for all stations and all seasons of the year. A corresponding statistically significant correlation was also found in most cases between the GPH and the 307.5 nm irradiance monthly anomalies. The correlation between GPH anomalies at different sites was statistically significant, possibly explaining the strong and significant correlation between the total ozone monthly anomalies at the three sites. A statistically significant decrease of total ozone, of ~0.1%/year was found for Rome for the period 1996 - 2020, which however did not induce increasing trends in irradiance at 307.5 nm (neither increasing trends in the ratio between the 307.5 nm and the 324 nm irradiances) at SZA = 67°. Further analyses revealed positive trends in the ratio and the 307.5 nm irradiance at smaller solar zenith angles (SZA), which can be attributed to the fact that total ozone decrease is driven by a decrease in the lower stratosphere while upper stratospheric ozone increases, and the effect of changes of upper stratospheric ozone becoming disproportionately larger for increasing SZA. It was also showed that long-term changes in total ozone follow changes in GPH, which is an additional indication that negative trends in total ozone are mainly driven by changes in lower stratospheric ozone. An anti-correlation between the GPH long-term changes and total ozone was also evident for all stations in 2006 - 2020. Positive trends in UV irradiance for this latter period which were possibly driven by changes in clouds and/or aerosols were found for Rome and Aosta. This study clearly points out the significance of dynamical processes which take place in the troposphere for the variability of total ozone and surface solar UV irradiance. [ABSTRACT FROM AUTHOR]

In this study the short- and long-term variability of the surface spectral solar ultraviolet (UV) irradiance are investigated over Italy using high quality ground based measurements from three sites located at quite different environmental conditions, and covering the full latitudinal extent of the Italian territory: Aosta (45.7° N, 7.4° E, 570 m a.s.l.), Rome (41.9° N, 12.5° E, 75 m a.s.l.), and Lampedusa (35.5° N, 12.6° E, 50 m a.s.l.). The variability of the irradiances at 307.5 nm, 324 nm, and of the ratio between the 307.5 nm and the 324 nm irradiances were investigated with respect to the corresponding variability in total ozone and the geopotential height at 250 hPa (GPH). The study was performed for two periods: 2006 -- 2020 for all stations, and 1996 -- 2020 only for Rome. A statistically significant correlation between the GPH and total ozone monthly anomalies was found for all stations and all seasons of the year. A corresponding statistically significant correlation was also found in most cases between the GPH and the 307.5 nm irradiance monthly anomalies. The correlation between GPH anomalies at different sites was statistically significant, possibly explaining the strong and significant correlation between the total ozone monthly anomalies at the three sites. A statistically significant decrease of total ozone, of ~0.1%/year was found for Rome for the period 1996 -- 2020, which however did not induce increasing trends in irradiance at 307.5 nm (neither increasing trends in the ratio between the 307.5 nm and the 324 nm irradiances) at SZA = 67°. Further analyses revealed positive trends in the ratio and the 307.5 nm irradiance at smaller solar zenith angles (SZA), which can be attributed to the fact that total ozone decrease is driven by a decrease in the lower stratosphere while upper stratospheric ozone increases, and the effect of changes of upper stratospheric ozone becoming disproportionately larger for increasing SZA. It was also showed that long-term changes in total ozone follow changes in GPH, which is an additional indication that negative trends in total ozone are mainly driven by changes in lower stratospheric ozone. An anti- correlation between the GPH long-term changes and total ozone was also evident for all stations in 2006 -- 2020. Positive trends in UV irradiance for this latter period which were possibly driven by changes in clouds and/or aerosols were found for Rome and Aosta. This study clearly points out the significance of dynamical processes which take place in the troposphere for the variability of total ozone and surface solar UV irradiance. [ABSTRACT FROM AUTHOR]

Atmospheric fluxes of dissolved organic matter (DOM) were studied for the first time on the island of Lampedusa, a remote site in the central Mediterranean Sea (Med Sea), between 19 March 2015 and 1 April 2017. The main goals of this study were to quantify total atmospheric deposition of DOM in this area and to evaluate the impact of Saharan dust deposition on DOM dynamics in the surface waters of the Mediterranean Sea. Our data show high variability in DOM deposition rates without a clear seasonality and a dissolved organic carbon (DOC) input from the atmosphere of 120.7 mmol DOC m -2 yr -1. Over the entire time series, the average dissolved organic phosphorus (DOP) and dissolved organic nitrogen (DON) contributions to the total dissolved pools were 40 % and 26 %, respectively. The data on atmospheric elemental ratios also show that each deposition event is characterized by a specific elemental ratio, suggesting a high variability in DOM composition and the presence of multiple sources. This study indicates that the organic substances transported by Saharan dust on Lampedusa mainly come from a natural sea spray and that Saharan dust can be an important carrier of organic substances even though the load of DOC associated with dust is highly variable. Our estimates suggest that atmospheric input has a larger impact on the Med Sea than on the global ocean. Further, DOC fluxes from the atmosphere to the Med Sea can be up to 6 times larger than total river input. Longer time series combined with modeling would greatly improve our understanding of the response of DOM dynamics in the Med Sea to the change in aerosol deposition pattern due to the effect of climate change. [ABSTRACT FROM AUTHOR]

Atmospheric fluxes of dissolved organic matter (DOM) were studied for the first time at the Island of Lampedusa, a remote site in the Central Mediterranean Sea (Med Sea), close to the Sahara desert, between 19 March 2015 and 1 April 2017. The main goals of this work are: to quantify total atmospheric deposition of DOM in this area and to evaluate the impact of dust deposition on DOM dynamics in the surface waters of the Mediterranean Sea. Our data show high variability in DOM deposition rates without a clear seasonality and allow to estimate a dissolved organic carbon (DOC) input from the atmosphere of 120.7mmolDOCm-2yr-1. Over the entire time-series, the average dissolved organic phosphorous (DOP) and dissolved organic nitrogen (DON) contributions to the total dissolved pools were 40% and 26%, respectively. The data on atmospheric elemental ratios also show that each deposition event is characterized by a specific elemental ratio, suggesting a high variability in DOM composition and the presence of multiple sources. This study indicates that the organic substances transported by Saharan dust at Lampedusa site mainly have natural origin, especially from sea spray and that Saharan dust can be an important carrier of organic substances, even if the load of DOC associated with dust is highly variable. Our estimates suggest that atmospheric input has an impact to the Med Sea larger than to the global ocean and that DOC fluxes from the atmosphere to the Med Sea can be up to 6-fold larger than river input. Longer time series, combined with a modelling effort, are therefore mandatory in order to investigate the response of DOM dynamics in the Med Sea to the change in aerosol deposition pattern due to the effect of climate change. [ABSTRACT FROM AUTHOR]

Detailed measurements of radiation, atmospheric and aerosol properties were carried out in summer 2013 during the Aerosol Direct Radiative Impact on the regional climate in the MEDiterranean region (ADRIMED) campaign in the framework of the Chemistry-Aerosol Mediterranean Experiment (ChArMEx) experiment. This study focusses on the characterization of infrared (IR) optical properties and direct radiative effects of mineral dust, based on three vertical profiles of atmospheric and aerosol properties and IR broadband and narrowband radiation from airborne measurements, made in conjunction with radiosonde and ground-based observations at Lampedusa, in the central Mediterranean. Satellite IR spectra from the Infrared Atmospheric Sounder Interferometer (IASI) are also included in the analysis. The atmospheric and aerosol properties are used as input to a radiative transfer model, and various IR radiation parameters (upward and downward irradiance, nadir and zenith brightness temperature at different altitudes) are calculated and compared with observations. The model calculations are made for different sets of dust particle size distribution (PSD) and refractive index (RI), derived from observations and from the literature. The main results of the analysis are that the IR dust radiative forcing is non-negligible and strongly depends on PSD and RI. When calculations are made using the in situ measured size distribution, it is possible to identify the refractive index that produces the best match with observed IR irradiances and brightness temperatures (BTs). The most appropriate refractive indices correspond to those determined from independent measurements of mineral dust aerosols from the source regions (Tunisia, Algeria, Morocco) of dust transported over Lampedusa, suggesting that differences in the source properties should be taken into account. With the in situ size distribution and the most appropriate refractive index the estimated dust IR radiative forcing efficiency is C23.7Wm-2 at the surface, -7.9Wm-2 within the atmosphere, and +15.8Wm-2 at the top of the atmosphere. The use of column-integrated dust PSD from AERONET may also produce a good agreement with measured irradiances and BTs, but with significantly different values of the RI. This implies large differences, up to a factor of 2.5 at surface, in the estimated dust radiative forcing, and in the IR heating rate. This study shows that spectrally resolved measurements of BTs are important to better constrain the dust IR optical properties, and to obtain a reliable estimate of its radiative effects. Efforts should be directed at obtaining an improved description of the dust size distribution and its vertical distribution, as well as at including regionally resolved optical properties. [ABSTRACT FROM AUTHOR]

Detailed atmospheric and aerosol properties, and radiation measurements were carried out in summer 2013 during the Aerosol Direct Radiative Impact on the regional climate in the MEDiterranean region (ADRIMED) campaign in the framework of the Chemistry-Aerosol Mediterranean Experiment (ChArMEx) experiment. This study focusses on the characterization of infrared (IR) optical properties and direct radiative effects of mineral dust, based on three vertical profiles of atmospheric and aerosol properties and IR broadband and narrowband radiation from airborne measurements, made in conjunction with radiosonde and ground-based observations at Lampedusa, in the central Mediterranean. Satellite IR spectra from IASI are also included in the analysis. The atmospheric and aerosol properties are used as input to a radiative transfer model, and various IR radiation parameters (upward and downward irradiance, nadir and zenith brightness temperature at different altitudes) are calculated and compared with observations. The model calculations are made for different sets of dust size distribution and refractive indices, derived from observations and from the literature. The main results of the analysis are that the IR dust radiative forcing is non negligible, and strongly depends on size distribution (SD) and refractive index (RI). When calculations are made using the in situ measured size distribution, it is possible to identify the refractive index that produces the best match with observed IR irradiances and brightness temperatures (BTs). The most appropriate refractive indices correspond to those determined from independent measurements of mineral dust aerosols from the source regions (Tunisia, Algeria, Morocco) of dust transported over Lampedusa, suggesting that differences in the source properties should be taken into account. With the in situ size distribution and the most appropriate refractive index the estimated dust IR radiative forcing efficiency is +23.7 W m-2 at the surface, -7.9 W m-2 within the atmosphere, and +15.8 W m-2 at the top of the atmosphere. The use of column integrated dust SD from AERONET may also produce a good agreement with measured irradiances and BTs, but with significantly different values of the RI. This implies large differences, up to a factor of 2.5 at surface, in the estimated dust radiative forcing, and in the IR heating rate. This study shows that spectrally resolved measurements of brightness temperatures are important to better constrain the dust IR optical properties, and to obtain a reliable estimate of its radiative effects. Efforts should be directed at obtaining an improved description of the dust size distribution, its vertical distribution, and at including regionally-resolved optical properties. [ABSTRACT FROM AUTHOR]

Background: MP4-induced experimental autoimmune encephalomyelitis (EAE) is a mouse model of multiple sclerosis (MS), which enables targeted research on B cells, currently much discussed protagonists in MS pathogenesis. Here, we used this model to study the impact of the S1P1 receptor modulator FTY720 (fingolimod) on the autoreactive B cell and antibody response both in the periphery and the central nervous system (CNS).Methods: MP4-immunized mice were treated orally with FTY720 for 30 days at the peak of disease or 50 days after EAE onset. The subsequent disease course was monitored and the MP4-specific B cell/antibody response was measured by ELISPOT and ELISA. RNA sequencing was performed to determine any effects on B cell-relevant gene expression. S1P1 receptor expression by peripheral T and B cells, B cell subset distribution in the spleen and B cell infiltration into the CNS were studied by flow cytometry. The formation of B cell aggregates and of tertiary lymphoid organs (TLOs) was evaluated by histology and immunohistochemistry. Potential direct effects of FTY720 on B cell aggregation were studied in vitro.Results: FTY720 significantly attenuated clinical EAE when treatment was initiated at the peak of EAE. While there was a significant reduction in the number of T cells in the blood after FTY720 treatment, B cells were only slightly diminished. Yet, there was evidence for the modulation of B cell receptor-mediated signaling upon FTY720 treatment. In addition, we detected a significant increase in the percentage of B220+ B cells in the spleen both in acute and chronic EAE. Whereas acute treatment completely abrogated B cell aggregate formation in the CNS, the numbers of infiltrating B cells and plasma cells were comparable between vehicle- and FTY720-treated mice. In addition, there was no effect on already developed aggregates in chronic EAE. In vitro B cell aggregation assays suggested the absence of a direct effect of FTY720 on B cell aggregation. However, FTY720 impacted the evolution of B cell aggregates into TLOs.Conclusions: The data suggest differential effects of FTY720 on the B cell compartment in MP4-induced EAE. [ABSTRACT FROM AUTHOR]

We report the case of a 32-year-old male with Chlamydia trachomatis infection and admitted with chest pain, signs of myocardial damage and coronary arteries free from significant atherosclerotic disease. Cardiac magnetic resonance imaging (MRI) documented imaging patterns of myocardial involvement suggestive of acute myocarditis, and repeated cardiac MRI examinations were used to define appropriate clinical management of the patient. In particular, the decision to submit the patient to an additional antibiotic course was based on evidence of persisting myocardial edema, while no further treatments were prescribed once these imaging findings disappeared. The case emphasizes the potential value of cardiac MRI as the only non-invasive modality currently available for evaluating the temporal evolution of myocardial involvement after acute myocarditis. [ABSTRACT FROM AUTHOR]

In the haemophilia population, obesity has an adverse effect on health care cost, chronic complications and joint disease. Although staff of federally funded Hemophilia Treatment Centers in the United States (HTCs) anecdotally recognize these outcomes, practices to promote healthy weights have not been reported. This evaluation identifies routine practices among HTCs in body mass index (BMI) assessment, perceptions about need to address obesity and roles in offering evidence-based strategies to promote healthy weights. A telephone survey was developed to assess HTCs practices including patient BMI assessment and counselling, perceptions about the importance of healthy patient weights, and HTCs roles in weight management. Ninety of the 130 federally funded HTCs contacted elected to participate and completed the telephone survey. Of these, 67% routinely calculated BMI and 48% provided results to patients. Approximately one-third classified obesity correctly for children (30%) and adults (32%), using the Centers for Disease Control and Preventions BMI cut-offs. Most HTCs (87%) reported obesity as an issue of ‘big’ or ‘moderate’ concern and 98% indicated HTC responsibility to address this issue. Most centres (64%) address patient weight during comprehensive visits. One-third (33%) of centres include a nutritionist; of those without, 61% offer nutrition referrals when needed. Most (89%) HTCs do not have a protocol in place to address healthy weights; 53% indicated that guidelines are needed. HTCs offer services to help improve weight outcomes. Training programmes for calculating and interpreting BMI as well as identifying appropriate guidelines to apply to the HTC patient population are needed. [ABSTRACT FROM AUTHOR]

The present paper introduces a numerical study on the fire behavior of composites during exposure to a heating source at high incident power. A novel numerical model is proposed which is able to simulate the behavior of composite materials in fire environment providing the composites mass loss rate and heat release rate during heating source application. Two commercial software have been selected as platforms for the implementation of the proposed numerical model COMSOL and ANSYS. In COMSOL the model has been implemented by introducing proper field equations, while a macro, written in Ansys Parametric Design Language, has been used to allow the ANSYS FEM code to numerically simulate, by an incremental procedure, all the relevant physical phenomena related to fire. As an application, an experiment on thermal degradation over a laminated composite plate has been numerically simulated and the numerical model has been validated by comparing the COMSOL and Ansys numerical results to experimental literature data in terms of temperature profile over the panel thickness, Mass Loss Rate and Heat Release Rate. An excellent agreement has been found between the obtained numerical results and the experimental test data for both the adopted numerical platforms. However the ANSYS implementation, which showed to be the most effective in terms of accuracy of results and perspectives of applications to complex numerical models, led to the definition of a powerful tool able to assesses the fire performance of composite structures. [ABSTRACT FROM AUTHOR]

The present paper introduces a numerical study on the fire behavior of composites during exposure to a heating source at high-incident power. A three-dimensional novel numerical model is proposed, which is able to simulate the behavior of composite materials in fire environment providing the composites mass loss rate, heat release rate, and total heat released during the heating source application. The ANSYS commercial FEM software has been selected as the platform for the implementation of the proposed numerical model. The use of the ANSYS Parametric Design Language has allowed the ANSYS FEM code to numerically simulate, by a stop–restart incremental procedure, all the most relevant physical phenomena related to fire. As an application, a cone calorimeter experiment over a laminated composite plate has been numerically simulated, and the numerical model has been validated by comparing the ANSYS numerical results to experimental literature data in terms of temperature profile over the panel thickness, mass loss rate, heat release rate, and total heat released. An excellent agreement has been found between the obtained numerical results and the experimental test, confirming the validity of the proposed three-dimensional tool, taking into account the specimen edge effects, which has perspectives of application to the assessment of the fire performance of complex composite structural components. [ABSTRACT FROM PUBLISHER]

Objective To analyse life-threatening obstetric complications that occurred in public hospitals in Argentina. Design Multicentre collaborative cross-sectional study. Setting Twenty-five hospitals included in the Perinatal Network of Buenos Aires Metropolitan Area. Population Women giving birth in participating hospitals during a 1-year period. Methods All cases of severe maternal morbidity ( SMM) and maternal mortality ( MM) during pregnancy (including miscarriage and induced abortion), labour and puerperium were included. Data were collected prospectively. Main outcome measures Identification criteria, main causes and incidence of SMM; case-fatality rates, morbidity-mortality index and effective intervention's use rate. Results A total of 552 women with life-threatening conditions were identified: 518 with SMM, 34 with MM. Identification criteria for SMM were case-management (48.9%), organ dysfunction (15.2%) and mixed criteria (35.9%). Incidence of SMM was 0.8% (95% confidence interval [95% CI] 0.73-0.87%) and hospital maternal death ratio was 52.3 per 100 000 live births (95% CI 35.5-69.1). Main causes of MM were abortion complications and puerperal sepsis; main causes of SMM were postpartum haemorrhage and hypertension. Overall case-fatality rate was 6.2% (95% CI 4.4-8.6): the highest due to sepsis (14.8%) and abortion complications (13.3%). Morbidity-mortality index was 15:1 (95% CI 7.5-30.8). Use rate of known effective interventions to prevent or treat main causes of MM and SMM was 52.3% (95% CI 46.9-57.7). Conclusions This study describes the importance of life-threatening obstetric complications that took place in public hospitals with comprehensive obstetric care and the low utilisation of known effective interventions that may decrease rates of SMM and MM. It also provides arguments that justify the need to develop a surveillance system for SMM. [ABSTRACT FROM AUTHOR]

Osteoporosis in adult males is an under-recognized problem. Patients with haemophilia have several predisposing factors for developing decreased bone mineral density (BMD) including prolonged periods of immobility, reduced weight bearing and co-morbidities associated with bone loss. To establish prevalence and risk factors associated with decreased BMD in patients with haemophilia. Adults with moderate or severe haemophilia A or B underwent dual-energy X-ray absorptiometry (DXA). BMD was correlated to laboratory values, joint mobility measurements and physical activity questionnaires. Thirty patients completed evaluations. The median age was 41.5 years (range 18–61). Median lowest T-score by DXA was −1.7 (range: −5.8 to +0.6), with the femoral neck being the site of the lowest T-scores. Based on World Health Organization criteria, 70% of patients had decreased BMD. Twenty-seven per cent of the participants ( n = 8) had osteoporosis and 43% ( n = 13) had osteopenia. Variables associated with increased bone loss included lower serum 25-hydroxyvitamin D levels ( P = 0.03), lower body mass index ( P = 0.047), lower activity scores ( P = 0.02), decreased joint range of motion ( P = 0.046), HIV ( P = 0.03), HCV ( P = 0.02), history of inhibitor ( P = 0.01) and age ( P = 0.03). Adults with haemophilia are at increased risk for developing osteoporosis. A history of HCV and HIV infections, decreased joint range-of-motion, decreased activity levels, history of an inhibitor and low body weight predict bone loss and suggest a population to target for screening. A high prevalence of vitamin D insufficiency was observed. Future studies should investigate interventions, including vitamin D supplementation, to prevent bone loss and fractures for this at-risk population. [ABSTRACT FROM AUTHOR]

The interaction of the β-amyloid peptide (Aβ) with neuronal membranes could play a key role in the pathogenesis of Alzheimer’s disease. Recent studies have focused on the interactions of Aβ oligomers to explain the neuronal toxicity accompanying Alzheimer’s disease. In our study, we have investigated the role of lipid interactions with soluble Aβ(28–35) (wild-type) and its mutants A30G and A30I in their aggregation and conformational preferences. CD and Trp fluorescence spectroscopic studies indicated that, immediately on dissolution, these peptides adopted a random coil structure. Upon addition of negatively charged 1,2-dipalmitoyl- syn-glycero-3-phospho- rac-(glycerol) sodium salt (PG) lipid, the wild-type and A30I mutant underwent reorganization into a predominant β-sheet structure. However, no conformational changes were observed in the A30G mutant on interaction with PG. In contrast, the presence of zwitterionic 1,2-dipalmitoyl- syn-glycero-3-phosphatidylcholine (PC) lipid had no effect on the conformation of these three peptides. These observations were also confirmed with atomic force microscopy and the thioflavin-T assay. In the presence of PG vesicles, both the wild-type and A30I mutant formed fibrillar structures within 2 days of incubation in NaCl/Pi, but not in their absence. Again, no oligomerization was observed with PC vesicles. The Trp studies also revealed that both ends of the three peptides are not buried deep in the vesicle membrane. Furthermore, fluorescence spectroscopy using the environment-sensitive probe 1,6-diphenyl-1,3,5-hexatriene showed an increase in the membrane fluidity upon exposure of the vesicles to the peptides. The latter effect may result from the lipid head group interactions with the peptides. Fluorescence resonance energy transfer experiments revealed that these peptides undergo a random coil-to-sheet conversion in solution on aging and that this process is accelerated by negatively charged lipid vesicles. These results indicate that aggregation depends on hydrophobicity and propensity to form β-sheets of the amyloid peptide, and thus offer new insights into the mechanism of amyloid neurodegenerative disease. [ABSTRACT FROM AUTHOR]

Summary:We sought to assess if leaving in place a previously inserted noncolonized or infected implantable catheter (IC) is associated with an increase in morbidity in patients undergoing autologous peripheral stem cell transplantation (APSCT). Medical records from all patients between March 1997 and January 2002 undergoing APSCT with an IC in place were reviewed. Case group (IC in place) was compared with a control group (no IC) from 6 days prior to 60 days after APSCT. In all, 43 cases were matched with 43 controls by underlying disease, age and sex. In both groups, duration of neutropenia and use of antimicrobial prophylaxis were comparable. Underlying malignancies were lymphoma (22/24), multiple myeloma (14/12), leukemia (3/3), and others (7/7) in case and control groups. Cases and controls had comparable rates of risk for fever, bloodstream infection, use of vancomycin and amphotericin B, and death, as well as comparable lengths of stay and readmissions. ICs were used in 20 of 43 patients. Using the IC did not significantly increase the risk of fever, bloodstream infection, length of stay, and/or readmissions after APSCT but was associated with increased use of antibacterial and antifungal agents. Leaving in place a previously inserted, noncolonized or infected IC did not increase morbidity in patients undergoing APSCT.Bone Marrow Transplantation (2005) 36, 131–134. doi:10.1038/sj.bmt.1705018 Published online 23 May 2005 [ABSTRACT FROM AUTHOR]

Summary. Chronic proliferative synovitis secondary to haemathroses is a major complication in patients with severe haemophilia. Current management strategies include prophylactic infusions of the missing coagulation factor, corticosteroids, synoviorthesis and/or synovectomy with variable degrees of benefit. In addition, patients with coagulation factor inhibitors are not amenable to the invasive therapeutic modalities. The gross and microscopic findings of the synovitis in haemophilic arthritis are remarkably similar to those seen in patients with rheumatoid arthritis, although the pathophysiology of these two conditions are quite different. Haemophilic arthropathy, in the later stages, resembles degenerative rather than inflammatory joint disease. Oral d-penicillamine, a drug effective in the proliferative synovitis of rheumatoid arthritis, was evaluated in 16 patients. Ten patients had an unequivocal response, while three had a reduction in palpable synovium and three had no response. Thus 81% of the patients had a beneficial response. Minor reversible drug side-effects occurred in two patients (proteinuria in one and a rash in the second). The results of this study suggest that d-penicillamine is an effective and safe drug for the treatment of haemophilic chronic synovitis. [ABSTRACT FROM AUTHOR]

Oxidative stress and mitochondrial dysfunction have long been considered to play a role in Friedreich's ataxia, a neurodegenerative disease due to a GAA expansion in a gene coding for a mitochondrial protein (frataxin), implicated in the regulation of iron metabolism. Since glutathione is an important antioxidant whose role has been recently proposed in the pathogenesis of some neurodegenerative diseases, we investigated glutathione metabolism in the blood of 14 patients with Friedreich's ataxia by measuring total, free and protein-bound glutathione concentrations. Blood samples were obtained from 14 unrelated patients with Friedreich's ataxia (nine males, five females) and 20 age-matched healthy controls (10 males, 10 females). Total and free glutathione concentrations were determined by reverse-phase liquid chromatography with fluorescence detection; the glutathionyl-haemoglobin separation from healthy and pathological subjects was obtained by electrospray ionization–mass spectrometry. We consistently found a reduction of free glutathione levels (0·55 ± 0·06 nmol mg-1 haemoglobin, vs. 8·4 ± 1·79 nmol mg-1 haemoglobin, P < 0·001) in the blood of patients with Friedreich's ataxia, a total glutathione concentration comparable to the controls (15 ± 2·6 nmol mg-1 haemoglobin, vs. 15·4 ± 1·4 nmol mg-1 haemoglobin), and a significant increase of glutathione bound to haemoglobin (15 ± 1·5 vs. 8 ± 1·8%, P < 0·05) in erythrocytes. Our findings give evidence of an impairment in vivo of glutathione homeostasis in Friedreich's ataxia, suggesting a relevant role of free radical cytotoxicity in the pathophysiology of the disease; this study may also prove useful in the search for an oxidative stress marker in neurodegeneration. [ABSTRACT FROM AUTHOR]

Discusses the case of a woman with noramidopyrine-induced acute pulmonary permeability edema. Mechanical ventilation with positive end-expiratory pressure; Anteroposterior chest radiograph; Hemodynamic pattern.

Background: In a subgroup of patients suffering from progressive multiple sclerosis (MS), which is an inflammation-mediated neurodegenerative disease of the central nervous system (CNS), B cell aggregates were discovered within the meninges. Occurrence of these structures was associated with a more severe disease course and cortical histopathology. We have developed the B cell-dependent MP4-induced experimental autoimmune encephalomyelitis (EAE) as a mouse model to mimic this trait of the human disease. The aim of this study was to determine a potential role of lymphoid tissue inducer (LTi) and TH17 cells in the process of B cell aggregate formation in the MP4 model.Methods: We performed flow cytometry of cerebellar and splenic tissue of MP4-immunized mice in the acute and chronic stage of the disease to analyze the presence of CD3-CD5-CD4+RORγt+ LTi and CD3+CD5+CD4+RORγt+ TH17 cells. Myelin oligodendrocyte glycoprotein (MOG):35-55-induced EAE was used as B cell-independent control model. We further determined the gene expression profile of B cell aggregates using laser capture microdissection, followed by RNA sequencing.Results: While we were able to detect LTi cells in the embryonic spleen and adult intestine, which served as positive controls, there was no evidence for the existence of such a population in acute or chronic EAE in neither of the two models. Yet, we detected CD3-CD5-CD4-RORγt+ innate lymphoid cells (ILCs) and TH17 cells in the CNS, the latter especially in the chronic stage of MP4-induced EAE. Moreover, we observed a unique gene signature in CNS B cell aggregates compared to draining lymph nodes of MP4-immunized mice and to cerebellum as well as draining lymph nodes of mice with MOG:35-55-induced EAE.Conclusion: The absence of LTi cells in the cerebellum suggests that other cells might take over the function as an initiator of lymphoid tissue formation in the CNS. Overall, the development of ectopic lymphoid organs is a complex process based on an interplay between several molecules and signals. Here, we propose some potential candidates, which might be involved in the formation of B cell aggregates in the CNS of MP4-immunized mice. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) for which several new treatment options were recently introduced. Among them is the monoclonal anti-CD52 antibody alemtuzumab that depletes mainly B cells and T cells in the immune periphery. Considering the ongoing controversy about the involvement of B cells and in particular the formation of B cell aggregates in the brains of progressive MS patients, an in-depth understanding of the effects of anti-CD52 antibody treatment on the B cell compartment in the CNS itself is desirable.Methods: We used myelin basic protein (MBP)-proteolipid protein (PLP)-induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6 (B6) mice as B cell-dependent model of MS. Mice were treated intraperitoneally either at the peak of EAE or at 60 days after onset with 200 μg murine anti-CD52 vs. IgG2a isotype control antibody for five consecutive days. Disease was subsequently monitored for 10 days. The antigen-specific B cell/antibody response was measured by ELISPOT and ELISA. Effects on CNS infiltration and B cell aggregation were determined by immunohistochemistry. Neurodegeneration was evaluated by Luxol Fast Blue, SMI-32, and Olig2/APC staining as well as by electron microscopy and phosphorylated heavy neurofilament serum ELISA.Results: Treatment with anti-CD52 antibody attenuated EAE only when administered at the peak of disease. While there was no effect on the production of MP4-specific IgG, the treatment almost completely depleted CNS infiltrates and B cell aggregates even when given as late as 60 days after onset. On the ultrastructural level, we observed significantly less axonal damage in the spinal cord and cerebellum in chronic EAE after anti-CD52 treatment.Conclusion: Anti-CD52 treatment abrogated B cell infiltration and disrupted existing B cell aggregates in the CNS. [ABSTRACT FROM AUTHOR]

The authors discuss the glial potassium channel, KIR4.1 antibodies, as biomarkers in multiple sclerosis. They argue that a clarification of the pathogenicity of KIR4.1 antibodies is necessary. The posibility of a serum immunoglobulin G (IgG) reactivity against KIR4.1 presenting an epiphenomenon and the presence of an additional target for autoreactive B cells beyond the central nervous system (CNS) is also explored.

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-β)-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. [ABSTRACT FROM AUTHOR]