Biological drugs for systemic lupus erythematosus or active lupus nephritis and rates of infectious complications. Evidence from large clinical trials

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease that frequently affects the kidneys, known as lupus nephritis (LN). Such patients are treated with antimalarials, corticosteroids or immunosuppressive drugs, and more recently, target-specific biological drugs. Although efficacy of these therapies improved SLE-related outcomes, SLE remains associated with higher rates of infections. Here, we performed a comprehensive systemic review of infectious complications in clinical trials covering drug interventions for SLE or specifically for active LN. Our search in 15 online registries yielded a total of 1477 studies of which 14 matched our prespecified criteria. These covered the biological drugs anifrolumab, belimumab, and rituximab that were tested in patients with non-renal SLE and active LN.The available safety data from the SLE trials indicated that infectious complications such as herpes zoster, upper respiratory tract infection, nasopharyngitis, bronchitis, and urinary tract infection in patients receiving placebo were quite prevalent especially in the EXPLORER (rituximab) trial. Infections occurred mostly during the first year of LN therapy. Serious adverse events and infectious complications occurred more frequently in placebo-treated patients with active LN, especially in the BLISS-LN (belimumab) and LUNAR (rituximab) trials. Anifrolumab and rituximab increased the number of clinically relevant episodes of herpes zoster compared to belimumab in patients with active LN. Anifrolumab displayed a similar trend for influenza infections, which is consistent with the specific mechanisms-of-action of anifrolumab; highlighting drug-specific effects on infectious complications. In addition, standard-of-care therapy, e.g., MMF and immunosuppressants, as well as a longer SLE duration may also affect the incidence of serious adverse events and certain infectious complications in SLE patients with active LN.Infectious complications are common in SLE but even more common in patients with active LN, especially herpes zoster is strongly associated with active LN and anifrolumab therapy (OR 2.8, 95% CI 1.18 to 6.66, p = 0.018). Immunotherapy seems to impose unspecific and specific risks for infections. The latter may imply specific precautions such as preemptive vaccination and individual risk-benefit assessments

Klinische, radiologische und biomechanische Untersuchungsergebnisse nach medialer Schlittenendoprothese Typ Oxford Phase 3

Die vorliegende Studie beschreibt 5 Jahres Ergebnisse der im Jahr 2003 mit einer medialer Schlittenendoprothese Typ Oxford Phase 3 versorgten Patienten. Neben der klinischen Untersuchung mit Erfassung des Knee Society Score (KSS) erfolgten eine umfassende radiologische Auswertung, Winkelreproduktionsmessung und Ganganalyse. Bei 100 möglichen Punkten lagen die durchschnittlichen Ergebnisse des Knee Society Score nach Insall bei 85,0 Punkten für den Knie Score und 93,8 im Function Score. Obwohl die Beweglichkeit der operierten Kniegelenke keine signifikanten Auffälligkeiten zur nicht operierten Seite aufwiesen, waren im operierten Bein postoperativ noch signifikante Defizite der Oberschenkelstreckmuskulatur vorhanden. Das kontrovers diskutierte Problem der Beeinträchtigung des Therapieerfolges durch eine retropatellare Schmerzsymptomatik kann nach den vorliegenden Untersuchungen nicht bestätigt werden. Insbesondere der Function Score wurde sowohl durch ein radiologisch objektiviertes Patellatilt aber auch eine subklinische retropatellare Schmerzsymptomatik nicht negativ beeinflusst. Die Röntgenbildauswertung ergab keine femoralen oder tibialen Lockerungszeichen. Vom Hersteller empfohlene Parameter der Implantationsgeometrie waren nur in einigen Fällen gering abweichend. Negative Auswirkungen auf den Knee Society Score ergaben sich nicht. Im Winkelreproduktionstest zeigte die propriozeptive Leistung der operierten Kniegelenke keine signifikanten Unterschiede im Vergleich zur nicht operierten Seite. Die Parameter der Ganganalyse wiesen im Vergleich zwischen operiertem und nicht operiertem Bein keine Differenzen auf. Abweichungen gegenüber einer altersadäquaten kniegesunden Kontrollgruppe bestätigten aber interindividuelle Unterschiede. Zusammenfassend zeigte die vorliegenden Arbeit, dass die endoprothetische Rekonstruktion des medialen Kompartiments mittels Oxford Phase 3 Implantat nach 5 Jahren eine erfolgreiche Therapieform der Varusgonarthrose ist. Durch Einhaltung der Implantationsvorgaben sowie entsprechende postoperative Rehabilitation zur Kräftigung der Oberschenkelmuskulatur lassen sich gute und sehr gute Therapieerfolge erzielen. Ein interindividueller Unterschied im Gangbild zwischen Endoprothesenträgern und Kniegesunden erfordert weitere prä- und postoperative Vergleichsstudien, um gesicherte Aussagen über die Ursachen der veränderten Stereotypie des Ganges treffen zu können

Longitudinal Effects of the Family Support Program Chancenreich on Parental Involvement and the Language Skills of Preschool Children

When they enter primary school children already vary significantly in their language skills, depending at least in part on their family’s social background. In particular, the home learning environment plays a significant role in children’s development. For that reason, early intervention programs have been developed to obviate learning difficulties and to promote health, children’s development, and educational equality. The family support program Chancenreich aims to encourage the interaction and relationship between parents and children through two different course formats. The present study examines the longitudinal effects of attending the Chancenreich program and different course formats on (a) parents attending further educational services for children after completing the program, (b) children’s vocabulary and level of grammar development at the age of 5 and (c) the children’s vocabulary development between the ages of 3 and 5. Furthermore, we examine the relationship between family characteristics and the attendance rates of different course formats of the Chancenreich program at the first and second point of measurement. The study follows a longitudinal design with two points of measurements (T1: Mage = 41 months, T2: Mage = 68 months), and a sample size of 121 parents and their children at T2 in the intervention group and 41 parents and their children in the comparison group. Findings indicate that attendance of the Chancenreich program’s courses is related to child and family characteristics and to later patterns of course participation after completing the program. Further, both children’s level of vocabulary skills (PPVT) at the age of 5 and their development between the ages of 3 and 5 benefit from the parental participation in parenting skills training at the age of 3. Implications and future research on the effectiveness of family support programs are discussed

Environmental behavior and ecotoxicity of engineered nanoparticles to algae, plants, and fungi

Developments in nanotechnology are leading to a rapid proliferation of new materials that are likely to become a source of engineered nanoparticles (ENPs) to the environment, where their possible ecotoxicological impacts remain unknown. The surface properties of ENPs are of essential importance for their aggregation behavior, and thus for their mobility in aquatic and terrestrial systems and for their interactions with algae, plants and, fungi. Interactions of ENPs with natural organic matter have to be considered as well, as those will alter the ENPs aggregation behavior in surface waters or in soils. Cells of plants, algae, and fungi possess cell walls that constitute a primary site for interaction and a barrier for the entrance of ENPs. Mechanisms allowing ENPs to pass through cell walls and membranes are as yet poorly understood. Inside cells, ENPs might directly provoke alterations of membranes and other cell structures and molecules, as well as protective mechanisms. Indirect effects of ENPs depend on their chemical and physical properties and may include physical restraints (clogging effects), solubilization of toxic ENP compounds, or production of reactive oxygen species. Many questions regarding the bioavailability of ENPs, their uptake by algae, plants, and fungi and the toxicity mechanisms remain to be elucidate

Role of Cystathionine Gamma-Lyase in Immediate Renal Impairment and Inflammatory Response in Acute Ischemic Kidney Injury

Hydrogen sulfide (H2S) is known to act protectively during renal ischemia/reperfusion injury (IRI). However, the role of the endogenous H2S in acute kidney injury (AKI) is largely unclear. Here, we analyzed the role of cystathionine gamma-lyase (CTH) in acute renal IRI using CTH-deficient (Cth−/−) mice whose renal H2S levels were approximately 50% of control (wild- type) mice. Although levels of serum creatinine and renal expression of AKI marker proteins were equivalent between Cth−/− and control mice, histological analysis revealed that IRI caused less renal tubular damage in Cth−/− mice. Flow cytometric analysis revealed that renal population of infiltrated granulocytes/macrophages was equivalent in these mice. However, renal expression levels of certain inflammatory cytokines/adhesion molecules believed to play a role in IRI were found to be lower after IRI only in Cth−/− mice. Our results indicate that the systemic CTH loss does not deteriorate but rather ameliorates the immediate AKI outcome probably due to reduced inflammatory responses in the kidney. The renal expression of CTH and other H2S-producing enzymes was markedly suppressed after IRI, which could be an integrated adaptive response for renal cell protection

Delivery of E. coli Nissle to the mouse gut by mucoadhesive microcontainers does not improve its competitive ability against strains linked to ulcerative colitis

For patients with ulcerative colitis (UC), administration of the probiotic E. coli Nissle (EcN) holds promise for alleviation of disease symptoms. The mechanisms are unclear, but it has been hypothesised that a capacity of the probiotic to outcompete potentially detrimental UC-associated E. coli strains plays an important role. However, this could previously not be confirmed in a mouse model of competition between EcN and two UC-associated strains, as reported by Petersen et al. 2011. In the present study, we re-evaluated the idea, hypothesising that delivery of EcN by a micro device dosing system (microcontainers), designed for delivery into the intestinal mucus, could support colonisation and confer a competition advantage compared to classical oral dosing. Six groups of mice were pre-colonised with one of two UC-associated E. coli strains followed by oral delivery of EcN, either in capsules containing microcontainers with freeze-dried EcN powder, capsules containing freeze-dried EcN powder, or as a fresh sucrose suspension. Co-colonisation between the probiotic and the disease-associated strains was observed regardless of dosing method, and no competition advantages linked to microcontainer delivery were identified within this setup. Other approaches are thus needed if the competitive capacity of EcN in the gut should be improved.For patients with ulcerative colitis (UC), administration of the probiotic E. coli Nissle (EcN) holds promise for alleviation of disease symptoms. The mechanisms are unclear, but it has been hypothesised that a capacity of the probiotic to outcompete potentially detrimental UC-associated E. coli strains plays an important role. However, this could previously not be confirmed in a mouse model of competition between EcN and two UC-associated strains, as reported by Petersen et al. 2011. In the present study, we re-evaluated the idea, hypothesising that delivery of EcN by a micro device dosing system (microcontainers), designed for delivery into the intestinal mucus, could support colonisation and confer a competition advantage compared to classical oral dosing. Six groups of mice were pre-colonised with one of two UC-associated E. coli strains followed by oral delivery of EcN, either in capsules containing microcontainers with freeze-dried EcN powder, capsules containing freeze-dried EcN powder, or as a fresh sucrose suspension. Co-colonisation between the probiotic and the disease-associated strains was observed regardless of dosing method, and no competition advantages linked to microcontainer delivery were identified within this setup. Other approaches are thus needed if the competitive capacity of EcN in the gut should be improved.</p

Observation of Photoion Backward Emission in Photoionization of He and N2

We experimentally investigate the effects of the linear photon momentum on the momentum distributions of photoions and photoelectrons generated in one-photon ionization in an energy range of 300 eV $\leq~E_\gamma~\leq$ 40 keV. Our results show that for each ionization event the photon momentum is imparted onto the photoion, which is essentially the system's center of mass. Nevertheless, the mean value of the ion momentum distribution along the light propagation direction is backward-directed by $-3/5$ times the photon momentum. These results experimentally confirm a 90 year old prediction.Comment: 5 pages, 3 figure