[Suicide stigma and suicide prevention]. / Suizidstigma und Suizidprävention.

In many societies suicide was and is an extremely controversial topic. This review article outlines the historical background of social condemnation of suicidal thoughts and actions in the western world. It summarizes current research results about the consequences of suicide stigma for affected persons and its relevance for suicide prevention. Finally, the next steps in research and prevention are discussed. Over time and in different cultures, the societal judgement of suicide has greatly varied. During antiquity, some philosophers viewed suicide negatively and by the fifth century AD suicide was widely condemned by societies across the western world. Until today suicide remains a taboo topic in Germany and other countries. Current research showed that the social condemnation of suicidal thoughts and behavior (i.e. suicide stigma) is an additional stressor among persons who experience or have experienced suicidality and their relatives. Furthermore, suicide stigma is considered to be a central barrier to seeking help for and disclosure of suicidality. Despite its relevance for suicide prevention, only a few interventions to reduce suicide stigma among members of the general public and to support affected persons in dealing with suicide stigma exist.

Familial hypercholesterolaemia in patients with ischaemic stroke or transient ischaemic attack.

BACKGROUND AND PURPOSE: Identification of patients with familial hypercholesterolaemia (FH) is a prerequisite for the appropriate management of their excess cardiovascular risk. It is currently unknown how many patients with acute ischaemic stroke or transient ischaemic attack (TIA) are affected by FH and whether systematic screening for FH is warranted in these patients. METHODS: The prevalence of a clinical diagnosis of FH was estimated in a large representative series of patients with acute ischaemic stroke or TIA (ABCD2 score ≥ 3) using the Dutch Lipid Clinic Network Algorithm (DLCNA; possible FH ≥3, probable/definite FH ≥6). RESULTS: Out of 1054 patients included in the present analysis, 14 had probable/definite FH (1.3%; 95% confidence interval 0.6-2.0) and 107 possible FH (10.2%; 8.4-12.0) corresponding to an overall prevalence of potential FH of 11.5%. Prevalences were even higher in patients with stroke/TIA manifestation before age 55 in men or 60 in women (3.1%, 0.6-5.6; and 13.1%, 8.3-17.9) and those with a prior history of cardiovascular disease (2.6%, 0.9-4.3; and 15.1%, 11.3-18.9). Of note, in two-thirds of our patients with probable/definite and possible FH, stroke or TIA was the initial clinical disease manifestation. CONCLUSIONS: The frequency of potential FH, based on clinical criteria, in patients with acute ischaemic stroke or TIA was 11.5% and that of probable/definite FH (1.3%) was similar to recently reported counts for patients with acute coronary syndrome (1.6%). FH screening using the DLCNA is feasible in clinical routine and should be considered as part of the usual diagnostic work-up.

BedMachine v3: Complete Bed Topography and Ocean Bathymetry Mapping of Greenland From Multibeam Echo Sounding Combined With Mass Conservation.

Greenland's bed topography is a primary control on ice flow, grounding line migration, calving dynamics, and subglacial drainage. Moreover, fjord bathymetry regulates the penetration of warm Atlantic water (AW) that rapidly melts and undercuts Greenland's marine-terminating glaciers. Here we present a new compilation of Greenland bed topography that assimilates seafloor bathymetry and ice thickness data through a mass conservation approach. A new 150 m horizontal resolution bed topography/bathymetric map of Greenland is constructed with seamless transitions at the ice/ocean interface, yielding major improvements over previous data sets, particularly in the marine-terminating sectors of northwest and southeast Greenland. Our map reveals that the total sea level potential of the Greenland ice sheet is 7.42 ± 0.05 m, which is 7 cm greater than previous estimates. Furthermore, it explains recent calving front response of numerous outlet glaciers and reveals new pathways by which AW can access glaciers with marine-based basins, thereby highlighting sectors of Greenland that are most vulnerable to future oceanic forcing.

Combined cell index in assessing blood donor iron stores.

OBJECTIVES: The aim of this study was to assess the appropriateness of using combined cell index (CCI) in the assessment of iron stores in blood donors. This index is calculated by the formula: red blood cell distribution width (RDW) × 104 × mean corpuscular volume (MCV)-1 × mean corpuscular haemoglobin (MCH)-1 . BACKGROUND: Ferritin measurement is a reliable method for estimating iron stores in blood donors. The sensitivity of red blood cell (RBC) parameters of complete blood count in detecting non-anaemic iron deficiency is significantly lower. Consequently, there were several attempts to increase the detection sensitivity by combining these parameters in different indices. METHODS: This study included 1084 male and 792 female whole blood donors accepted for blood donation. For six RBC parameters with the highest level of correlation relative to ferritin [Hgb, MCV, MCH, mean corpuscular haemoglobin concentration (MCHC), RDW and CCI], diagnostic efficacy in the detection of iron depletion (ferritin <12 µg L-1 ) was assessed using receiver operating characteristic (ROC) analysis. RESULTS: CCI showed the highest degree of correlation with ferritin (r = -0·373 for men and r = -0·590 for women) and the highest area under the curve (0·961 for men and 0·864 for women). Using the cut-off value of 52·6 for men and 50·6 for women, the corresponding Youden index was the highest for CCI in both genders (0·851 for men and 0·612 for women). The sensitivity and specificity of CCI in the population of male donors were higher in comparison to female donors (0·941 and 0·910 vs 0·851 and 0·761, respectively). CONCLUSIONS: Study results confirmed the satisfactory diagnostic value of CCI in detecting depleted iron stores in blood donors.

Direct formation of supermassive black holes via multi-scale gas inflows in galaxy mergers.

Observations of distant quasars indicate that supermassive black holes of billions of solar masses already existed less than a billion years after the Big Bang. Models in which the 'seeds' of such black holes form by the collapse of primordial metal-free stars cannot explain the rapid appearance of these supermassive black holes because gas accretion is not sufficiently efficient. Alternatively, these black holes may form by direct collapse of gas within isolated protogalaxies, but current models require idealized conditions, such as metal-free gas, to prevent cooling and star formation from consuming the gas reservoir. Here we report simulations showing that mergers between massive protogalaxies naturally produce the conditions for direct collapse into a supermassive black hole with no need to suppress cooling and star formation. Merger-driven gas inflows give rise to an unstable, massive nuclear gas disk of a few billion solar masses, which funnels more than 10(8) solar masses of gas to a sub-parsec-scale gas cloud in only 100,000 years. The cloud undergoes gravitational collapse, which eventually leads to the formation of a massive black hole. The black hole can subsequently grow to a billion solar masses on timescales of about 10(8) years by accreting gas from the surrounding disk.

Bulgeless dwarf galaxies and dark matter cores from supernova-driven outflows.

For almost two decades the properties of 'dwarf' galaxies have challenged the cold dark matter (CDM) model of galaxy formation. Most observed dwarf galaxies consist of a rotating stellar disk embedded in a massive dark-matter halo with a near-constant-density core. Models based on the dominance of CDM, however, invariably form galaxies with dense spheroidal stellar bulges and steep central dark-matter profiles, because low-angular-momentum baryons and dark matter sink to the centres of galaxies through accretion and repeated mergers. Processes that decrease the central density of CDM halos have been identified, but have not yet reconciled theory with observations of present-day dwarfs. This failure is potentially catastrophic for the CDM model, possibly requiring a different dark-matter particle candidate. Here we report hydrodynamical simulations (in a framework assuming the presence of CDM and a cosmological constant) in which the inhomogeneous interstellar medium is resolved. Strong outflows from supernovae remove low-angular-momentum gas, which inhibits the formation of bulges and decreases the dark-matter density to less than half of what it would otherwise be within the central kiloparsec. The analogues of dwarf galaxies-bulgeless and with shallow central dark-matter profiles-arise naturally in these simulations.

A genetic variant in the promoter of phosphate-activated glutaminase is associated with hepatic encephalopathy.

BACKGROUND: Hepatic encephalopathy (HE) is a serious complication of liver cirrhosis. Recently, a microsatellite in the promoter region of the phosphate-activated glutaminase (GLS ) gene was associated with the risk of HE. The aim of the present study was to investigate, using the critical flicker frequency (CFF) test, whether the described GLS variant increases the risk of developing HE in patients with cirrhosis. METHODS: We recruited 158 patients (66% men; mean age 59 years, range 23-86) with liver cirrhosis. Mean model for end-stage liver disease score was 13.8 (range 5-35); 48% of patients presented with Child-Pugh score B or C. The presence and severity of HE were determined by the CFF test, with frequencies ≤39 Hz denoting cases. GLS variants were genotyped by sequencing the microsatellite in the promoter region and were classified as short, long or short-long forms (depending on the length of the macrosatellite alleles). RESULTS: In total, 53% of patients had abnormal CFF results (i.e. ≤39 Hz; range for entire cohort 26-57). The GLS microsatellite distribution amongst patients was short form (20%), long form (32%) and short-long form (48%) and was consistent with Hardy-Weinberg equilibrium. CFF values differed significantly between groups (P = 0.043). Carriers of the GLS long microsatellite had a significantly higher risk of HE according to multivariate analyses (odds ratio 3.23, 95% confidence interval 1.46-7.13, P = 0.004). CONCLUSION: CFF results were significantly lower amongst carriers of the GLS long microsatellite. Our findings support the role of the GLS long microsatellite in the development of HE; this could be important for identifying susceptible patients and for the prevention of this condition.

Gene expression changes in cancellous bone of type 2 diabetics: a biomolecular basis for diabetic bone disease.

PURPOSE: Diabetes mellitus type 2 (2DM) is associated with altered bone quality. In order to analyze associated changes on a molecular level, we investigated the gene expression of key factors of osteoblast metabolism in type 2 diabetics. METHODS: Total mRNA and protein of bone samples from 2DM patients and non-diabetic patients were isolated, and subsequently, reverse transcription polymerase chain reaction (RT-PCR) or Western blot was performed. Furthermore, pro- and anti-inflammatory serum cytokine levels were determined using a cytokine array. RESULTS: Expression of runt-related transcription factor 2 (RUNX2) was increased by 53 %. Expression of the bone sialoproteins, secreted phosphoprotein 1 (SPP1; osteopontin), and integrin-binding sialoprotein (IBSP), was elevated by more than 50 %, and activating transcription factor 4 (ATF4) expression was 13 % lower in the investigated diabetes group compared to the control group. Similarly, the expression of versican (VCAN) and decorin (DCN) was upregulated twofold in the diabetic group. At the same time, 2DM patients and controls show alterations in pro- and anti-inflammatory cytokine levels in the serum. CONCLUSIONS: This study identifies considerable changes in the expression of transcription factors and extracellular matrix (ECM) components of bone in 2DM patients. Furthermore, the analysis of key differentiation factors of osteoblasts revealed significant alterations in gene expression of these factors, which may contribute to the dysregulation of energy metabolism in 2DM.

Extended haplotype association study in Crohn's disease identifies a novel, Ashkenazi Jewish-specific missense mutation in the NF-κB pathway gene, HEATR3.

The Ashkenazi Jewish population has a several-fold higher prevalence of Crohn's disease (CD) compared with non-Jewish European ancestry populations and has a unique genetic history. Haplotype association is critical to CD etiology in this population, most notably at NOD2, in which three causal, uncommon and conditionally independent NOD2 variants reside on a shared background haplotype. We present an analysis of extended haplotypes that showed significantly greater association to CD in the Ashkenazi Jewish population compared with a non-Jewish population (145 haplotypes and no haplotypes with P-value <10(-3), respectively). Two haplotype regions, one each on chromosomes 16 and 21, conferred increased disease risk within established CD loci. We performed exome sequencing of 55 Ashkenazi Jewish individuals and follow-up genotyping focused on variants in these two regions. We observed Ashkenazi Jewish-specific nominal association at R755C in TRPM2 on chromosome 21. Within the chromosome 16 region, R642S of HEATR3 and rs9922362 of BRD7 showed genome-wide significance. Expression studies of HEATR3 demonstrated a positive role in NOD2-mediated NF-κB signaling. The BRD7 signal showed conditional dependence with only the downstream rare CD-causal variants in NOD2, but not with the background haplotype; this elaborates NOD2 as a key illustration of synthetic association.

Early gas stripping as the origin of the darkest galaxies in the Universe.

The known galaxies most dominated by dark matter (Draco, Ursa Minor and Andromeda IX) are satellites of the Milky Way and the Andromeda galaxies. They are members of a class of faint galaxies, devoid of gas, known as dwarf spheroidals, and have by far the highest ratio of dark to luminous matter. None of the models proposed to unravel their origin can simultaneously explain their exceptional dark matter content and their proximity to a much larger galaxy. Here we report simulations showing that the progenitors of these galaxies were probably gas-dominated dwarf galaxies that became satellites of a larger galaxy earlier than the other dwarf spheroidals. We find that a combination of tidal shocks and ram pressure swept away the entire gas content of such progenitors about ten billion years ago because heating by the cosmic ultraviolet background kept the gas loosely bound: a tiny stellar component embedded in a relatively massive dark halo survived until today. All luminous galaxies should be surrounded by a few extremely dark-matter-dominated dwarf spheroidal satellites, and these should have the shortest orbital periods among dwarf spheroidals because they were accreted early.

Fronto-parietal alpha ERD and visuo-spatial attention in pregnant women.

Many pregnant women report impairments in their attentional capacities. However, comparative studies between pregnant and non-pregnant women using standardised attention paradigms are rare and inconsistent. During attention tasks alpha activity is known to suppress irrelevant sensory inputs and previous studies show that a large event-related desynchronisation (ERD) in the alpha range prior to target-onset predicts enhanced attentional processing. We quantified the relationship between performance (accuracy, response time) in a standardised visuo-spatial attention task and alpha ERD (∼6-12 Hz) as well as saliva estradiol level in fifteen pregnant women (M = 26.6, SD = 3.0 years) compared to fifteen non-pregnant, naturally cycling women (M = 23.1, SD = 4.3 years). Compared to non-pregnant women, alpha frequency was increased in pregnant women. Furthermore, pregnant women showed a greater magnitude of the alpha ERD prior to target-onset and a moderate increase in accuracy compared to non-pregnant women. In addition, accuracy correlated negatively with estradiol in pregnant women as well as with frontal alpha ERD in all women. These correlational findings indicate that pregnancy-related enhancement in alpha desynchronisation in a fronto-parietal network might modulate accuracy during a visuo-spatial attention task.

Effect of 5 weeks of oral acetazolamide on patients with pulmonary vascular disease: A randomized, double-blind, cross-over trial.

BACKGROUND: The carbonic anhydrase inhibitor acetazolamide stimulates ventilation through metabolic acidosis mediated by renal bicarbonate excretion. In animal models, acetazolamide attenuates acute hypoxia-induced pulmonary hypertension (PH), but its efficacy in treating patients with PH due to pulmonary vascular disease (PVD) is unknown. METHODS: 28 PVD patients (15 pulmonary arterial hypertension, 13 distal chronic thromboembolic PH), 13 women, mean±SD age 61.6±15.0 years stable on PVD medications, were randomised in a double-blind crossover protocol to 5 weeks acetazolamide (250mg b.i.d) or placebo separated by a ≥2 week washout period. Primary endpoint was the change in 6-minute walk distance (6MWD) at 5 weeks. Additional endpoints included safety, tolerability, WHO functional class, quality of life, arterial blood gases, and hemodynamics (by echocardiography). RESULTS: Acetazolamide had no effect on 6MWD compared to placebo (treatment effect: mean change [95%CI] -18 [-40 to 4]m, p=0.102) but increased arterial blood oxygenation through hyperventilation induced by metabolic acidosis. Other measures including pulmonary hemodynamics were unchanged. No severe adverse effects occurred, side effects that occurred significantly more frequently with acetazolamide vs. placebo were change in taste (22/0%), paraesthesia (37/4%) and mild dyspnea (26/4%). CONCLUSIONS: In patients with PVD, acetazolamide did not change 6MWD compared to placebo despite improved blood oxygenation. Some patients reported a tolerable increase in dyspnoea during acetazolamide treatment, related to hyperventilation, induced by the mild drug-induced metabolic acidosis. Our findings do not support the use of acetazolamide to improve exercise in patients with PVD at this dosing. GOV IDENTIFIER: NCT02755298.

A single-arm, open-label study of alemtuzumab in treatment-refractory patients with multiple sclerosis.

BACKGROUND: Alemtuzumab (CD52-specific humanized monoclonal antibody) was found to be an effective therapy for treatment-naive patients with relapsing-remitting multiple sclerosis. OBJECTIVE: Evaluate alemtuzumab's effects in patients with treatment-refractory relapsing-remitting multiple sclerosis. METHODS: Forty-five relapsing-remitting multiple sclerosis patients who experienced ≥2 relapses during 2 years prior to the study entry whilst receiving interferon therapy were administered 24 mg i.v. alemtuzumab/day for 5 days at baseline and 3 days 12 months later. Patients received premedication with 1 g i.v. methylprednisolone on days 1-3 at both times. RESULTS: After 2-year follow-up, the annualized relapse rate was reduced by 94% compared to pre-treatment levels, from 1.6 (2 years prior to treatment) to 0.17 for the 2 years following (P<0.0001). Moreover, 86% of patients showed stable or improved scores on the Expanded Disability Status Scale, and only 1 experienced an increase in disability lasting ≥6 months. The majority (70-88%) showed stable or improved leg, arm and cognitive function as measured by the Multiple Sclerosis Functional Composite. Serious adverse events observed in single patients were transient neutropenia and pneumonia, pulmonary emboli and deep vein thrombosis. Five patients developed clinical thyroid disorders but no opportunistic infections or cases of immune thrombocytopenic purpura were observed. CONCLUSIONS: Alemtuzumab effectively reduced relapse rates and improved clinical scores in patients with active relapsing-remitting multiple sclerosis not controlled by interferon therapy.

Lidocaine/tetracaine patch (Rapydan) for topical anaesthesia before arterial access: a double-blind, randomized trial.

BACKGROUND: Arterial catheterization is painful and is associated with patient stress and anxiety. Analgesia is usually provided by subcutaneous injection of local anaesthetic. An alternative is topical anaesthesia, such as Rapydan which is a novel topical anaesthetic patch containing 70 mg each of lidocaine and tetracaine. We therefore tested the hypothesis that Rapydan patch analgesia is non-inferior to subcutaneous local anaesthetic. METHODS: Ninety patients undergoing elective major cardiac surgery were included in this prospective, double-blind clinical trial. Patients were randomly assigned to receive either a lidocaine/tetracaine patch, followed by subcutaneous injection 0.5 ml of normal saline solution, or placebo patch with subsequent subcutaneous injection of 0.5 ml of lidocaine 1%. Pain during arterial catheterization using 100-mm-long visual analogue scale (VAS) was the primary outcome. Other outcomes were pain during anaesthetic/saline injection and plasma tetracaine concentrations. RESULTS: VAS pain scores during arterial puncture were comparable in both groups and Rapydan was non-inferior to subcutaneous lidocaine. Pain scores at the time of subcutaneous injection were significantly lower (better) in patients assigned to the lidocaine/tetracaine patch than to lidocaine (P=0.001). Plasma tetracaine concentrations never exceeded the detection limit of 25 ng ml(-1) at any time in any patient. CONCLUSIONS: Both the lidocaine/tetracaine patch and subcutaneous injection of lidocaine provided comparable pain control during arterial catheter insertion. Subcutaneous lidocaine caused discomfort during injection, whereas the lidocaine/tetracaine patch required placement 20 min before the procedure. Given adequate time, the patch provided better overall analgesia by obviating the need for subcutaneous infiltration.

High-dimensional profiling reveals Tc17 cell enrichment in active Crohn's disease and identifies a potentially targetable signature.

The immune-pathology in Crohn's disease is linked to dysregulated CD4+ T cell responses biased towards pathogenic TH17 cells. However, the role of CD8+ T cells able to produce IL-17 (Tc17 cells) remains unclear. Here we characterize the peripheral blood and intestinal tissue of Crohn's disease patients (n = 61) with flow and mass cytometry and reveal a strong increase of Tc17 cells in active disease, mainly due to induction of conventional T cells. Mass cytometry shows that Tc17 cells express a distinct immune signature (CD6high, CD39, CD69, PD-1, CD27low) which was validated in an independent patient cohort. This signature stratifies patients into groups with distinct flare-free survival associated with differential CD6 expression. Targeting of CD6 in vitro reduces IL-17, IFN-γ and TNF production. These results identify a distinct Tc17 cell population in Crohn's disease with proinflammatory features linked to disease activity. The Tc17 signature informs clinical outcomes and may guide personalized treatment decisions.

TEMPus VoLA: The timed Epstein multi-pressure vessel at low accelerations.

The field of planetary system formation relies extensively on our understanding of the aerodynamic interaction between gas and dust in protoplanetary disks. Of particular importance are the mechanisms triggering fluid instabilities and clumping of dust particles into aggregates, and their subsequent inclusion into planetesimals. We introduce the timed Epstein multi-pressure vessel at low accelerations, which is an experimental apparatus for the study of particle dynamics and rarefied gas under micro-gravity conditions. This facility contains three experiments dedicated to studying aerodynamic processes: (i) the development of pressure gradients due to collective particle-gas interaction, (ii) the drag coefficients of dust aggregates with variable particle-gas velocity, and (iii) the effect of dust on the profile of a shear flow and resultant onset of turbulence. The approach is innovative with respect to previous experiments because we access an untouched parameter space in terms of dust particle packing fraction, and Knudsen, Stokes, and Reynolds numbers. The mechanisms investigated are also relevant for our understanding of the emission of dust from active surfaces, such as cometary nuclei, and new experimental data will help interpreting previous datasets (Rosetta) and prepare future spacecraft observations (Comet Interceptor). We report on the performance of the experiments, which has been tested over the course of multiple flight campaigns. The project is now ready to benefit from additional flight campaigns, to cover a wide parameter space. The outcome will be a comprehensive framework to test models and numerical recipes for studying collective dust particle aerodynamics under space-like conditions.

Visuomotor performance at high altitude in COPD patients. Randomized placebo-controlled trial of acetazolamide.

Introduction: We evaluated whether exposure to high altitude impairs visuomotor learning in lowlanders with chronic obstructive pulmonary disease (COPD) and whether this can be prevented by acetazolamide treatment. Methods: 45 patients with COPD, living <800 m, FEV1 ≥40 to <80%predicted, were randomized to acetazolamide (375 mg/d) or placebo, administered 24h before and during a 2-day stay in a clinic at 3100 m. Visuomotor performance was evaluated with a validated, computer-assisted test (Motor-Task-Manager) at 760 m above sea level (baseline, before starting the study drug), within 4h after arrival at 3100 m and in the morning after one night at 3100 m. Main outcome was the directional error (DE) of cursor movements controlled by the participant via mouse on a computer screen during a target tracking task. Effects of high altitude and acetazolamide on DE during an adaptation phase, immediate recall and post-sleep recall were evaluated by regression analyses. www.ClinicalTrials.gov NCT03165890. Results: In 22 patients receiving placebo, DE at 3100 m increased during adaptation by mean 2.5°, 95%CI 2.2° to 2.7° (p < 0.001), during immediate recall by 5.3°, 4.6° to 6.1° (p < 0.001), and post-sleep recall by 5.8°, 5.0 to 6.7° (p < 0.001), vs. corresponding values at 760 m. In 23 participants receiving acetazolamide, corresponding DE were reduced by -0.3° (-0.6° to 0.1°, p = 0.120), -2.7° (-3.7° to -1.6°, p < 0.001) and -3.1° (-4.3° to -2.0°, p < 0.001), compared to placebo at 3100 m. Conclusion: Lowlanders with COPD travelling to 3100 m experienced altitude-induced impairments in immediate and post-sleep recall of a visuomotor task. Preventive acetazolamide treatment mitigated these undesirable effects.

Diagnosis and treatment of primary immunodeficiency disease in patients with gastrointestinal symptoms.

An estimated 250,000 individuals in the Unites States have been diagnosed with a primary immunodeficiency disease (PIDD). Early diagnosis and treatment of PIDD are critical to minimizing morbidity and improving quality of life. Patients with certain subtypes of PIDD may present with gastrointestinal complaints such as chronic or acute diarrhea, malabsorption, gastrointestinal pain, and inflammatory bowel diseases. Therefore, gastroenterologists are well positioned to help identify patients with PIDD. The hallmarks of PIDD include recurrent or persistent infections, infections due to microorganisms that rarely cause significant disease in immunocompetent people, unusually severe or life-threatening infections, and either low or persistently high white blood cell counts. An assessment for PIDD involves detailed patient and family histories, a physical examination, and diagnostic screening tests. Immunoglobulin replacement therapy is the cornerstone of treatment for most subtypes of PIDD.

Survival patterns of Streptococcus suis serotypes 1 and 14 in porcine blood indicate cross-reactive bactericidal antibodies in naturally infected pigs.

Streptococcus suis serotype (cps) 1 and cps14 have been detected in association with severe diseases such as meningitis and polyarthritis in pigs. Though these two cps are very similar, only cps14 is an important zoonotic agent in Asia and only cps1 is described to be associated with diseases in suckling piglets rather than weaning piglets. The main objective of this study was to assess restriction of survival of cps14 and cps1 in porcine blood by IgG and IgM putatively cross-reacting with these two cps. Furthermore, we differentiate recent European cps1/14 strains by agglutination, cpsK sequencing, MLST and virulence-associated gene profiling. Our data confirmed cps1 of clonal complex 1 as an important pathotype causing polyarthritis in suckling piglets in Europe. The experimental design included also bactericidal assays with blood samples drawn at different ages of piglets naturally infected with different S. suis cps types including cps1 but not cps14. We report survival of a cps1 and a cps14 strain (both of sequence type 1) in blood of suckling piglets with high levels of maternal IgG binding to the bacterial surface. In contrast, killing of cps1 and cps14 was recorded in older piglets due to an increase of IgM as demonstrated by specific cleavage of IgM. Heterologous absorption of antibodies with cps1 or cps14 is sufficient to significantly increase the survival of the other cps. In conclusion, IgM elicited by natural S. suis infection is crucial for killing of S. suis cps1 and cps14 in older weaning piglets and has most likely the potential to cross-react between cps1 and cps14.

Terminal maturation of resting B cells by proliferation-independent B cells differentiation factors.

Using response to four different BCDF preparations as a model of B cell maturation, we have shown that induction of B cell proliferation abrogates terminal maturation of these cells. In fact, response to some BCDFs can occur in the presence of inhibitors of DNA replication, suggesting that there are proliferation-independent as well as proliferation-dependent BCDFs. These findings cannot be explained by changes in the kinetics of the BCDF response, nor can they be reversed by repletion of media or changing cell densities. Proliferation-independent BCDFs appear to exert their effects on dense, resting 4F2- B cells rather than more activated B cells. This is in contrast to B cell differentiation signals of IL-2 alone or SAC and IL-2 in concert. These data suggest that the current models of B cell activation and maturation may require some reorganization, relegating the proliferative phase of B cell maturation to a lesser role. In addition, evidence is provided for the fact that the resting B cell may have the full complement of receptors for BCDF as well as BCGF and BCPF and may help account for the inherent nonspecificity of the immune response.