Immune reconstitution inflammatory syndrome (IRIS) after HAART may become manifest in form of aseptic severe leucoencephalopathy. All HIV-1-positive patients in this case series had widespread ...laboratory tests and follow-up MRI in order to investigate the course and the underlying pathophysiology of IRIS-associated leucoencephalopathy. All patients were treated with corticosteroids, in spite of additional immunosuppression. Three patients were successfully treated with corticosteroids and survived up to now, one died. A neuropathological examination was performed showing massive aseptic intraparenchymal and perivascular invasion of cytotoxic CD8 cells. It is assumed that IRIS-associated leucoencephalopathy is based on other preconditions in Africans and Caucasians.
Defolliculated is a novel spontaneous mouse mutation that maps to chromosome 11 close to the type I keratin locus. Histology shows abnormal differentiation of the sebaceous gland, with the sebocytes ...producing little or no sebum and undergoing abnormal cornification. The hair follicles fail to regress during catagen leading to abnormally long follicles. In contrast the hair shafts are shorter than normal, suggesting altered differentiation or proliferation of matrix cells during anagen. The shafts emerge from the follicle with cornified material still attached. The dermis contains increased numbers of immune cells, including T cells (CD4-positive), macrophages, and mast cells, at all time points examined. Complete elimination of all pelage and tail follicles occurs after two to three hair cycles, apparently by necrosis. Defolliculated may be a useful model for determining further functions of the sebaceous gland, and for understanding the regulation of catagen and hair follicle immunology.
Abstract The deletion of ORF11 severely impaired VZV infection of human skin xenografts. Here, we investigate the characteristics and functions of the ORF11 gene product. ORF11 is expressed as a 118 ...kDa polypeptide in VZV-infected cells; the protein is present in the nucleus and cytoplasm and is incorporated into VZ virions. Although ORF11 had little effect in transactivating VZV gene promoters in transfection assays, deleting ORF11 from the virus was associated with reduced expression of immediate early proteins IE4, IE62 and IE63, and the major glycoprotein, gE. ORF11 was identified as an RNA binding protein and its RNA binding domain was defined. However, disrupting the ORF11 RNA binding domain did not affect skin infection, indicating that RNA binding capacity, conserved among the alphahepesviruses homologues, is not essential while the contribution of ORF11 to the expression of the IE proteins and gE may be required for VZV pathogenesis in skin in vivo.
We have previously described linkage/association between reelin gene polymorphisms and autistic disorder. APOE also participates in the Reelin signaling pathway, by competitively antagonizing Reelin ...binding to APOE receptor 2 and to very-low-density lipoprotein receptors. The APOE2 protein variant displays the lowest receptor binding affinity compared with APOE3 and APOE4. In this study, we assess linkage/association between primary autism and APOE alleles in 223 complete trios, from 119 simplex Italian families and 44 simplex and 29 multiplex Caucasian-American families. Statistically significant disequilibrium favors the transmission of epsilon2 alleles to autistic offspring, over epsilon3 and epsilon4 (allele-wise transmission/disequilibrium test TDT, chi2 = 6.16, 2 degrees of freedom d.f., P<0.05; genotype-wise TDT, chi2 = 10.68, 3 d.f., P<0.05). A novel epsilon3r allele was also discovered in an autistic child and his mother. Autistic patients do not differ significantly from unaffected siblings (allele-wise TDT comparing autistic patients versus unaffected sibs, chi2 = 1.83, 2 d.f., P<0.40, not significant). The major limitation of this study consists of our small sample size of trios including one unaffected sibling, currently not possessing the statistical power necessary to conclusively discriminate a specific association of epsilon2 with autism, from a distorted segregation pattern characterized by enhanced epsilon2 transmission rates both to affected and unaffected offspring. Our findings are thus compatible with either (a) pathogenetic contributions by epsilon2 alleles to autism spectrum vulnerability, requiring additional environmental and/or genetic factors to yield an autistic syndrome, and/or (b) a protective effect of epsilon2 alleles against the enhanced risk of miscarriage and infertility previously described among parents of autistic children.
Operative Strategien bei Typ-A-Dissektion Pichlmaier, M.; Reichelt, A.; Günther, S. ...
Zeitschrift für Herz-, Thorax- und Gefässchirurgie,
06/2015, Letnik:
29, Številka:
3
Journal Article
Zusammenfassung
Die akute Typ-A-Dissektion bedarf nach Ansicht der Autoren der sofortigen operativen Behandlung in einem herzchirurgisch versierten Zentrum. Primäres Ziel stellt das Überleben des ...Patienten dar. Hierauf basierend sollten prä- und intraoperative Entscheidungen in Bezug auf die Komplexität des Eingriffs getroffen werden. Dennoch erlauben bessere technische Möglichkeiten und zunehmende Expertise in der Behandlung auch komplexer Aortenerkrankungen heute bereits aggressivere Strategien mit Hinblick auf die Optimierung der Langzeitprognose. Ob in Zukunft der komplette Aortenbogenersatz mit Hybridprothese die Therapie der Wahl darstellen wird, bleibt zu beweisen. Gleiches gilt für aufwendige rekonstruktive Verfahren an der Aortenwurzel. Da Reeingriffe an der Aortenwurzel komplikationsträchtiger sind als am Aortenbogen, sollte aber der Aortenwurzel grundsätzlich der Vorzug gegenüber der Aorta descendens im Entscheidungsprozess um das haltbarere Verfahren gegeben werden. Umgekehrt könnte in Zukunft auch eine endovaskuläre Versorgung bei ausgesuchten Patienten im fortgeschrittenen Alter einen Stellenwert erlangen.
Many people with dementia reside in care facilities. Little is known about how key parameters impact upon their quality of life (QOL). All 209 people with dementia in six facilities received a ...standardized assessment (Neuropsychiatric Inventory NPI, Barthel Scale, psychotropic drugs). One hundred twelve residents were assessed using Dementia Care Mapping, an observational method for QOL indices. Lower performance on activities of daily living (reduced well-being WB r = +0.39, p < .0001; social withdrawal SW r = +0.42, p < .0001; engagement in activities EA r = +0.31, p = .001) and taking psychotropics (WB 2.5 vs. 3.2, t = .2.3, p = .02; SW 11.4% vs. 2.7%, t = 3.0, p = .004; EA 56.5% vs. 71.9%; t = 3.5, p = .001) were associated with reduced QOL, but symptoms from the NPI were not. More focused prescribing of psychotropics and better staff training are essential.
The globally cultivated Brassica species possess diverse aliphatic glucosinolates, which are important for plant defense and animal nutrition. The committed step in the side chain elongation of ...methionine-derived aliphatic glucosinolates is catalyzed by methylthioalkylmalate synthase, which likely evolved from the isopropylmalate synthases of leucine biosynthesis. However, the molecular basis for the evolution of methylthioalkylmalate synthase and its generation of natural product diversity in Brassica is poorly understood. Here, we show that Brassica genomes encode multiple methylthioalkylmalate synthases that have differences in expression profiles and 2-oxo substrate preferences, which account for the diversity of aliphatic glucosinolates across Brassica accessions. Analysis of the 2.1 Å resolution x-ray crystal structure of Brassica juncea methylthioalkylmalate synthase identified key active site residues responsible for controlling the specificity for different 2-oxo substrates and the determinants of side chain length in aliphatic glucosinolates. Overall, these results provide the evolutionary and biochemical foundation for the diversification of glucosinolate profiles across globally cultivated Brassica species, which could be used with ongoing breeding strategies toward the manipulation of beneficial glucosinolate compounds for animal health and plant protection.
Einleitung:
Die LVRS ist eine wichtige Therapieoption in der Behandlung des terminalen Lungenemphysems. Um das Outcome der Patienten zu verbessern, wurde ein symptomorientierter AT-Algorithmus ...entwickelt. Hier wird das atmungstherapeutische Outcome nach LVRS vor und nach Einführung des Algorithmus verglichen.
Methoden:
Zwischen 05/2012 und 03/2016 wurden n = 96 Patienten mit VATS-LVRS in diese Studie eingeschlossen. Die Daten wurden prospektiv dokumentiert. Alle Patienten erhielten prä- und postoperativ eine Blutgasanalyse (BGA) und einen 6-Minuten-Gehtest (6-MWT), sowie eine Befragung zum Dyspnoeempfinden. Die Ergebnisse wurden in zwei Gruppen (vor (G1) und nach (G2) Einführung des Algorithmus) verglichen.
Ergebnisse:
In G1 wurden n = 15 Patienten (2012 bis 2013, 5 weiblich, Durchschnittsalter 65 ± 10J.) eingeschlossen. Seit 03/2014 wurden in Gruppe 2 n = 81 Patienten aufgenommen (2014 bis 2016, 27 weiblich, Durchschnittsalter 59 ± 18J.). Die Patienten in G2 wiesen respiratorisch und körperlich einen schlechteren präoperativen Zustand auf als die Patienten in G1. Postoperativ zeigte sich in G1 eine signifikante Verbesserung der 6MWT-Strecke (p = 0,03) und der Oxygenierung (p = 0,0005). In G2 konnte ebenfalls eine signifikante Verbesserung der 6MWT-Strecke (p = 0,03) und der Oxygenierung (p = 0,02) beobachtet werden. Das Dyspnoeempfinden verbesserte sich in G2 in höherem Maße.
Schlussfolgerung:
Die Einführung des AT-Algorithmus führt bei Patienten nach VATS-LVRS zur signifikanten Verbesserung der Oxygenierung, der Belastungsfähigkeit und des Dyspnoeempfindens im Vergleich zum prä-OP Status. Insbesondere Patienten mit stark reduziertem respiratorischen und körperlichen Zustand scheinen von systematischer Atmungstherapie zu profitieren. Weitere Analysen sind erforderlich um den langfristigen Benefit des Algorithmus zu beurteilen.
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