Companies that adopt multiple-pay systems risk causing rivalries between long-term employees and new hires, dividing the company into highly competitive "fiefdoms," creating equal pay and comparable ...worth problems, and generally creating discontent among employees
In the last decades, sexual abuse and violence in institutions against minors has been a repeated topic of discussion in politics and among experts in the field in Germany. The alleged abuse scandal ...in 2010 marks a central event. At that time, sexual abuse in institutions became public again starting in January 2010. This was mainly due to the confession made by the Canisius College in Berlin admitting that cases of sexual abuse had been covered up in the institution for years. Subsequently, cases also became known from other Catholic institutions. At the end of February 2010, it was reveiled that the former director had sexually abused pupils during his years of service at the Odenwaldschule Oberhambach, which was one of the flagship projects of reform pedagogy. In the course of 2010, other teachers of this school and other institutions of reform pedagogy were accused of having committed sexual assaults. These revelations about the scope and severity of past cases of child sexual abuse in German institutions set off a broad public debate. The debate led to the establishment of a politically appointed Round Table committee and an Independent Commissioner whose mandates were to reappraise the issue and develop recommendations for future policies. The Round Table Committee demanded that structural measures be implemented in institutions to protect children and adolescents from (sexual) abuse. In Germany, these measures are summarized as “Schutzkonzepte” (Safeguarding measures). The goal of these measures is to better ensure the protection of children and adolescents from sexual abuse and violence in an institution. In its final report, the Round Table Committee defined components for the safeguarding measures (see Table 1) and recommended the implementation of these measures to all institutions.
Abstract Autoimmune responses to heterogeneous nuclear ribonucleproteins (hnRNP) occur in many systemic autoimmune diseases, particularly in patients with rheumatoid arthritis (RA) and systemic lupus ...erythematosus. In RA, humoral and/or cellular autoimmunity to hnRNP-A2/B1 is the most prominent anti-nuclear reactivity, being detectable in more than 50% of patients. However, its pathogenic role has not been fully elucidated yet. Here, we report that splenocytes from rats with pristane-induced arthritis transfer disease after in vitro restimulation with hnRNP-A/B antigens. Remarkably, disease transfer can be blocked by nuclease treatment of hnRNPs and is also achieved with splenocytes stimulated with hnRNP-A/B associated DNA or RNA oligonucleotides (ON) alone. Induction of proinflammatory cytokines in splenocytes stimulated with hnRNP-A/Bs or ONs involves Toll-like receptors (TLR) 7 and 9 but not TLR3. Furthermore, although T cells are the main mediators of disease transfer they require restimulation with TLR-activated antigen-presenting cells such as macrophages in order to become arthritogenic. Thus, the autoantigenic properties of hnRNPs appear to be mediated by their associated nucleic acids binding to TLR7 and 9. Our data explain the specific selection of hnRNP-A2/B1 as autoantigen in RA and reveal the requirement of interaction between innate and adaptive immunity to initiate and drive inflammation in autoimmune arthritis.
Bovine milk αS2-casein, an intrinsically disordered protein, readily forms amyloid fibrils in vitro and is implicated in the formation of amyloid fibril deposits in mammary tissue. Its two cysteine ...residues participate in the formation of either intra- or intermolecular disulphide bonds, generating monomer and dimer species. X-ray solution scattering measurements indicated that both forms of the protein adopt large, spherical oligomers at 20 °C. Upon incubation at 37 °C, the disulphide-linked dimer showed a significantly greater propensity to form amyloid fibrils than its monomeric counterpart. Thioflavin T fluorescence, circular dichroism and infrared spectra were consistent with one or both of the dimer isomers (in a parallel or antiparallel arrangement) being predisposed toward an ordered, amyloid-like structure. Limited proteolysis experiments indicated that the region from Ala81 to Lys113 is incorporated into the fibril core, implying that this region, which is predicted by several algorithms to be amyloidogenic, initiates fibril formation of αS2-casein. The partial conservation of the cysteine motif and the frequent occurrence of disulphide-linked dimers in mammalian milks despite the associated risk of mammary amyloidosis, suggest that the dimeric conformation of αS2-casein is a functional, yet amyloidogenic, structure.
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•Bovine αS2-casein occurs in milk as either a disulphide-linked monomer or dimer.•Both αS2-casein monomer and dimer self-associate in solution to form large oligomers.•Disulphide-linked dimer has a higher propensity to form amyloid fibrils than monomer.•Predicted amyloidogenic region, A81 − K113, is protease-resistant in the fibrillar form.•Cysteines in αS2-casein are partly conserved and dimer formation is common in mammals.
► Agricultural N run-off can be reduced efficiently by flooding low-lying fields with drainage water. ► Even if the pool of iron-bound P is high the low-lying fields do not release significant ...amounts of P. ► Seasonal P accumulation in vegetation is high compared to P through-flow.
Re-established riparian wetlands used to mitigate nitrogen (N) loss from agricultural soils to surface water may lose phosphorus (P) from the top soils that often have received fertilizers. This could lead to eutrophication of lakes and estuaries. For a 2-year period we established mass balances of N and P in two restored riparian wetlands of ∼0.6ha situated on mineral soil. Monitoring began 5 years after restoration. Both wetlands received drainage water from upland agricultural fields rich in nitrate (1.5–12.3mgNL−1) and low in total P (TP) (0.016–0.04mgPL−1). Water balances were reasonably accounted for (15% imbalance at most). Water passed the wetlands as sheet flow without exchange with groundwater because of clay horizons in sub-soils, and sheet pilings along the stream banks allowed continuous measurements of inflow and outflow. The Egeskov riparian wetland (wetland:upland ratio 0.13) removed 121 and 28kgNha−1yr−1 (43 and 75% of the load) and retained 0.08kgPha−1 (6% of the load) in year one and had a net release of 0.15kgPha−1 (25% of the load) in year two. The Stor Å riparian wetland (wetland:upland ratio 0.02) removed 229 and 158kgNha−1yr−1 (32 and 26%). Net releases of P were 0.33 and 0.90kgPha−1yr−1 (22 and 127%). Nitrogen removal rates are on par with published rates for similar wetlands, while the P release rates appear surprisingly low. Phosphate outlet concentrations resembled the equilibrium concentrations (EPC0) where no phosphate exchange occurred between top soils and drainage water, suggesting that P release or retention was controlled by phosphate adsorption. This value was 0.015mgPL−1 for Egeskov and 0.047mgPL−1 for Stor Å. The high phosphate affinity was probably governed by high ratios between oxidized iron and iron-bound P. The top soils (10cm) contained 87 and 201kgPha−1 as iron-bound P and herbaceous vegetation accumulated 10.7 and 16.5kgPha−1yr−1. These figures are 55–136 and 8–11 times higher than the annual P-load to the wetlands, and we suggest that annual harvest of vegetation could maintain or even improve the P retention capacity of these wetlands.
Cardiovascular disease (CVD) is increased among people with HIV (PWH), but little is known regarding the prevalence and extent of coronary artery disease (CAD) and associated biological factors in ...PWH with low to moderate traditional CVD risk.
To determine unique factors associated with CVD in PWH and to assess CAD by coronary computed tomography angiography (CTA) and critical pathways of arterial inflammation and immune activation.
This cohort study among male and female PWH, aged 40 to 75 years, without known CVD, receiving stable antiretroviral therapy, and with low to moderate atherosclerotic cardiovascular disease (ASCVD) risk according to the 2013 American College of Cardiology/American Heart Association pooled cohort equation, was part of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE), a large, ongoing primary prevention trial of statin therapy among PWH conducted at 31 US sites. Participants were enrolled from May 2015 to February 2018. Data analysis was conducted from May to December 2020.
HIV disease.
The primary outcome was the prevalence and composition of CAD assessed by coronary CTA and, secondarily, the association of CAD with traditional risk indices and circulating biomarkers, including insulin, monocyte chemoattractant protein 1 (MCP-1), interleukin (IL) 6, soluble CD14 (sCD14), sCD163, lipoprotein-associated phospholipase A2 (LpPLA2), oxidized low-density lipoprotein (oxLDL), and high-sensitivity C-reactive protein (hsCRP).
The sample included 755 participants, with a mean (SD) age of 51 (6) years, 124 (16%) female participants, 267 (35%) Black or African American participants, 182 (24%) Latinx participants, a low median (interquartile range) ASCVD risk (4.5% 2.6%-6.8%), and well-controlled viremia. Overall, plaque was seen in 368 participants (49%), including among 52 of 175 participants (30%) with atherosclerotic CVD (ASCVD) risk of less than 2.5%. Luminal obstruction of at least 50% was rare (25 3%), but vulnerable plaque and high Leaman score (ie, >5) were more frequently observed (172 of 755 23% and 118 of 743 16%, respectively). Overall, 251 of 718 participants (35%) demonstrated coronary artery calcium score scores greater than 0. IL-6, LpPLA2, oxLDL, and MCP-1 levels were higher in those with plaque compared with those without (eg, median IQR IL-6 level, 1.71 1.05-3.04 pg/mL vs 1.45 0.96-2.60 pg/mL; P = .008). LpPLA2 and IL-6 levels were associated with plaque in adjusted modeling, independent of traditional risk indices and HIV parameters (eg, IL-6: adjusted odds ratio, 1.07; 95% CI, 1.02-1.12; P = .01).
In this study of a large primary prevention cohort of individuals with well-controlled HIV and low to moderate ASCVD risk, CAD, including noncalcified, nonobstructive, and vulnerable plaque, was highly prevalent. Participants with plaque demonstrated higher levels of immune activation and arterial inflammation, independent of traditional ASCVD risk and HIV parameters.
CD8+ T lymphocytes play a major role in antiviral immune defense. Their significance for acute hepatitis C is unclear. Our aim was to correlate the CD8+ T cell response with the outcome of infection. ...Eighteen patients with acute hepatitis C and 19 normal donors were studied. Hepatitis C virus (HCV)—specific CD8+ T cells were identified in the enzyme-linked immunospot assay by their interferon-γ (IFN-γ) production after specific stimulation. The highest numbers of IFN-γ—producing HCV-specific CD8+ T cells were found in patients with acute hepatitis C and a self-limited course of disease during the first 6 months after onset of disease, but these numbers dropped thereafter to undetectable levels. The differences in responsiveness between patients with self-limited disease versus patients with a chronic course were statistically significant (P < .001). Our data show that the number of IFN—γ-producing HCV-specific CD8+ T cells during the first 6 months after onset of disease is associated with eradication of the HCV infection.
Groundwater flow and nutrient transport were studied in a riparian meadow during a three-year period. The meadow is situated along a first order stream in the River Gjern catchment area, Jutland, ...Denmark. Field data included measurements of hydraulic head, hydraulic conductivity and soil characteristics. Groundwater sampled from piezometers was analysed for nitrate, ammonium and phosphate. Nitrogen and phosphorus contents in above-ground plant biomass were also measured. For the interpretation of our data we developed a one-dimensional hydraulic-transport model for the lateral groundwater flow, transport of nitrate, and nitrate removal in the meadow. The model is based on Darcy’s equation, and input data are horizontal and vertical distances, hydraulic heads, hydraulic conductivities, and nitrate concentrations. We also developed a scheme for evaluating uncertainties of the modeling results.
Annual removal of nitrate in the saturated zone of the riparian meadow was 326, 340, and
119
kg
NO
3
-
-N
ha
-
1
y
-
1
(59–68% of groundwater input) through the three-year period. The largest nitrate removal took place outside the growing seasons. Net loss of ammonium from the saturated zone was 0.4, 6.7, and
10.3
kg
NH
4
+
-N
ha
-
1
y
-
1
. In two of the years this was counter-balanced by atmospheric nitrogen deposition. Phosphate was not retained during the first two years but lost at rates of 0.88 and 0.36
kg
P
ha
−1
y
−1. In year 3 phosphate retention was 0.47
kg
P
ha
−1
y
−1.
These data show how a riparian ecotone along a first order stream can reduces nitrogen pollution from agricultural areas. Also, the pronounced year to year variations in our nutrient budgets show that shorter studies, for example based on one year of observations, should be interpreted cautiously as representing a general picture of nutrient pathways.
Rodents and dogs conditioned with total-lymphoid irradiation (TLI), with or without antithymocyte globulin (ATG), have been shown to develop mixed chimerism and immune tolerance without ...graft-versus-host disease (GVHD) after the infusion of major histocompatability complex (MHC)-mismatched donor bone marrow cells given alone or in combination with an organ allograft.
Four human leukocyte antigen (HLA)-mismatched recipients of living donor kidney transplants were conditioned with TLI and ATG posttransplantation and infused with cyropreserved donor granulocyte colony-stimulating factor (G-CSF) "mobilized" hematopoietic progenitor (CD34+) cells (3-5x10(6) cells/kg) thereafter. Maintenance prednisone and cyclosporine dosages were tapered, and recipients were monitored for chimerism, GVHD, graft function, T-cell subsets in the blood, and antidonor reactivity in the mixed leukocyte reaction (MLR).
Three of the four patients achieved multilineage macrochimerism, with up to 16% of donor-type cells among blood mononuclear cells without evidence of GVHD. Prolonged depletion of CD4+ T cells was observed in all four patients. Rejection episodes were not observed in the three macrochimeric recipients, and immunosuppressive drugs were withdrawn in the first patient by 12 months. Prednisone was withdrawn from a second patient at 9 months, and cyclosporine was tapered thereafter.
Multilineage macrochimerism can be achieved without GVHD in HLA-mismatched recipients of combined kidney and hematopoietic progenitor transplants. Conditioning of the host with posttransplant TLI and ATG was nonmyeloablative and was not associated with severe infections. Recipients continue to be studied for the development of immune tolerance.
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