Impaired increase of retinal capillary blood flow to flicker light exposure in arterial hypertension

We hypothesized that the increase of retinal capillary blood flow (RCF) to flicker light exposure is impaired in subjects with arterial hypertension. In 146 nondiabetic untreated male subjects with (n=50) or without (n=96) arterial hypertension, RCF was measured before and after flicker light exposure noninvasively and in vivo using scanning laser Doppler flowmetry. In addition, in a subgroup of 28 subjects, the change of RCF to flicker light exposure was again assessed during parallel infusion of nitric oxide synthase inhibitor N-monomethyl-l-arginine (L-NMMA). The increase of RCF to flicker light exposure was lower in patients with untreated hypertension compared with normotensive subjects when expressed in absolute terms (7.69±54 versus 27.2±44 AU; P adjusted=0.013) or percent changes (2.95±14 versus 8.33±12%; P adjusted=0.023). Systolic (β=-0.216; P=0.023) but not diastolic blood pressure (β=-0.117; P=0.243) or mean arterial pressure (β=-0.178; P=0.073) was negatively related to the percent change of RCF to flicker light exposure, independently of other cardiovascular risk factors. In the subgroup of 28 subjects, the increase of RCF to flicker light exposure was similar at baseline and during parallel infusion of L-NMMA when expressed in absolute terms (20.0±51 versus 22.6±56 AU; P=0.731) or percent changes (7.12±16 versus 8.29±18%; P=0.607). The increase of RCF to flicker light exposure is impaired in arterial hypertension. In the subgroup of the total study cohort, nitric oxide was not a major determinant of the increase of RCF to flicker light exposure.     

Toll-like receptor 2-mediated innate immune response in human nonparenchymal liver cells toward adeno-associated viral vectors

Adeno-associated viral vectors (rAAV) are frequently used in gene therapy trials. Although rAAV vectors are of low immunogenicity, humoral as well as T cell responses may be induced. While the former limits vector reapplication, the expansion of cytotoxic T cells correlates with liver inflammation and loss of transduced hepatocytes. Because adaptive immune responses are a consequence of recognition by the innate immune system, we aimed to characterize cell autonomous immune responses elicited by rAAV in primary human hepatocytes and nonparenchymal liver cells. Surprisingly, Kupffer cells, but also liver sinusoidal endothelial cells, mounted responses to rAAV, whereas neither rAAV2 nor rAAV8 were recognized by hepatocytes. Viral capsids were sensed at the cell surface as pathogen-associated molecular patterns by Toll-like receptor 2. In contrast to the Toll-like receptor 9-mediated recognition observed in plasmacytoid dendritic cells, immune recognition of rAAV in primary human liver cells did not induce a type I interferon response, but up-regulated inflammatory cytokines through activation of nuclear factor κB. CONCLUSION: Using primary human liver cells, we identified a novel mechanism of rAAV recognition in the liver, demonstrating that alternative means of sensing rAAV particles have evolved. Minimizing this recognition will be key to improving rAAV-mediated gene transfer and reducing side effects in clinical trials due to immune responses against rAAV.     

Anti‐LFA‐1 or rapamycin overcome costimulation blockade‐resistant rejection in sensitized bone marrow recipients

While costimulation blockade‐based mixed chimerism protocols work well for inducing tolerance in rodents, translation to preclinical large animal/nonhuman primate models has been less successful. One recognized cause for these difficulties is the high frequency of alloreactive memory T cells (Tmem) found in the (pre)clinical setting as opposed to laboratory mice. In the present study, we therefore developed a murine bone marrow transplantation (BMT) model employing recipients harboring polyclonal donor‐reactive Tmem without concomitant humoral sensitization. This model was then used to identify strategies to overcome this additional immune barrier. We found that B6 recipients that were enriched with 3 × 10⁷ T cells isolated from B6 mice that had been previously grafted with Balb/c skin, rejected Balb/c BM despite costimulation blockade with anti‐CD40L and CTLA4Ig (while recipients not enriched developed chimerism). Adjunctive short‐term treatment of sensitized BMT recipients with rapamycin or anti‐LFA‐1 mAb was demonstrated to be effective in controlling Tmem in this model, leading to long‐term mixed chimerism and donor‐specific tolerance. Thus, rapamycin and anti‐LFA‐1 mAb are effective in overcoming the potent barrier that donor‐reactive Tmem pose to the induction of mixed chimerism and tolerance despite costimulation blockade.     

Species of the Colletotrichum gloeosporioides complex associated with anthracnose diseases of Proteaceae

Anthracnose disease of Proteaceae has in the past chiefly been attributed to infections by C. acutatum, C. boninense and C. gloeosporioides. In the present study, a multi-locus phylogenetic analysis (ACT, CAL, CHS-1, GAPDH, GS, ITS, TUB2) revealed that strains of the C. gloeosporioides complex associated with Proteaceae belong to at least six species. These include C. alienum, C. aotearoa, C. kahawae (subsp. ciggaro), C. siamense, and two new taxa, C. proteae and C. grevilleae. The most economically important pathogen of Proteaceae seems to be C. alienum, and not C. gloeosporioides as previously reported. All taxa associated with Proteaceae are morphologically described on different media in culture, except strains of C. siamense, which proved to be sterile. Furthermore, C. populi is synonymised with C. aenigma.     

Impact of a prior medical degree on students' dental school performance in Innsbruck, Austria

The purpose of this study was to identify the performance differences between two groups of Austrian dental students (one with a prior medical degree and one without a medical degree) during their dental school training and final dental licensure examination. A specific aim was to determine if having a medical degree is a predictive factor for dental students' scores on the Austrian Dental Admission Test (Austrian DAT), performance in the dental clinic, and scores on final exam. The study consisted of a retrospective analysis of 122 students (thirty-nine with a medical degree and eighty-three without a medical degree) who were enrolled in the Dental Clinic at Innsbruck Medical University, Innsbruck, Austria, between 2001 and 2006. Three performance categories were considered: Austrian DAT results, clinical performance after the first clinical year in dental school, and performance on the final dental licensure examination. Information on students' age, gender, and previous medical degree was collected from official records. Analyses with student's t-test and Pearson's chi-square test revealed that the students with a medical degree had significantly higher Austrian DAT total test scores, grade point averages after the first clinical year, and scores on the final exam. Additionally, those students had significantly better performance on the final exam in prosthodontics and oral and maxillofacial surgery. The linear regression analysis showed that a medical degree had an independent effect on average scores on the final exam, age, and Austrian DAT test scores, while gender showed no statistically significant effect. Overall, the study found that dental students with a prior medical degree had significantly higher Austrian DAT total test scores and performed significantly better in the first clinical year and on the final exam than those without a prior medical degree.     

Working with patients’ strengths: A microprocess approach

Abstract

Previous research has supported the immediate activation of patients’ strengths (resource activation) as an important change mechanism in psychotherapy. Two different studies of integrative cognitive–behavioral therapy (CBT) treatments demonstrated that fostered strengths-oriented CBT treatments were more effective than the control conditions. Within these two studies, the authors tested the effect of specific resource-activating strategies at the beginning of therapy (Sessions 2, 5, and 8) using a pairwise matched control group design. The in-session processes were measured by video observer ratings (N=96 sessions). Results indicate that in the strengths-fostering treatments therapists and patients focus more strongly on patient competencies and personal goals in comparison to the control groups. These in-session processes have a direct impact on session outcome (particularly self-esteem, mastery, and clarification experiences). Results are discussed in regard to actively implementing resource-activating behavior as superordinate principles of change and their relevance for therapy outcome.