[Detections of refractive risk factors for amblyopia with Plusoptix Autorefractor A09]. / Erkennung refraktiver Amblyopierisikofaktoren mittels Plusoptix Autorefractor A09.

BACKGROUND: Amblyopia is the most frequent cause for decreased vision in childhood. Important risk factors for amblyopia (ARF) are refractive errors. The aim of this study was to examine the reliability of the Plusoptix Autorefractor A09 (POA09) to detect refractive ARF. METHOD: This prospective non-blinded, one-armed study was conducted between February 2012 and September 2015. Children aged 6 months to 12 years were screened in kindergarten and schools for refractive errors. Thresholds for screening failure were hyperopia ≥ 3.5 diopters (D), myopia ≥ 3.0 D, anisometropia ≥ 1.5 D and astigmatism ≥ 1.5 D (axis 90° or 180°â€¯± 10°) or ≥ 1.0 D (≥ 10° axis deviation of 90° or 180°). Children who failed screening were advised to see an ophthalmologist for a comprehensive eye examination. After the visit, parents were asked for the results of the examination. A reference group of children who did not fail screening also received a comprehensive eye examination. Based on the number of children who failed screening, we calculated the proportion of correctly detected refractive errors. Based on the children of the reference group we calculated the proportion of correctly excluded refractive errors and the false negative rate. RESULTS: In this study 3170 children were screened, 715 children (22.3%) failed screening. For 460 of these (64.3%) follow-up was available and for 132 children information on refractive errors in cycloplegia was available. Most frequent refractive errors at screening were astigmatism (90.9%) and anisometropia (11.4%). Most frequent refractive errors in cycloplegia were astigmatism (56.8%) and hyperopia (18.9%). The proportion of correctly detected refractive errors in the screening was highest for astigmatism (60%) and anisometropia (53.3%), followed by hyperopia (33.3%) and myopia (25%). CONCLUSION: The reliability of POA09 to detect refractive ARF in children without cycloplegia was limited, highlighting the importance of a systematic amblyopia screening. A screening in cycloplegia can increase the proportion of correctly detected refractive ARF and should be studied.

Interrupting CD28 costimulation before antigen rechallenge affects CD8(+) T-cell expansion and effector functions during secondary response in mice.

The role of CD28-mediated costimulation in secondary CD8(+) T-cell responses remains controversial. Here, we have used two tools - blocking mouse anti-mouse CD28-specific antibodies and inducible CD28-deleting mice - to obtain definitive answers in mice infected with ovalbumin-secreting Listeria monocytogenes. We report that both blockade and global deletion of CD28 reveal its requirement for full clonal expansion and effector functions such as degranulation and IFN-γ production during the secondary immune response. In contrast, cell-intrinsic deletion of CD28 in transferred TCR-transgenic CD8(+) T cells before primary infection leads to impaired clonal expansion but an increase in cells able to express effector functions in both primary and secondary responses. We suggest that the proliferation-impaired CD8(+) T cells respond to CD28-dependent help from their environment by enhanced functional differentiation. Finally, we report that cell-intrinsic deletion of CD28 after the peak of the primary response does not affect the establishment, maintenance, or recall of long-term memory. Thus, if given sufficient time, the progeny of primed CD8(+) T cells adapt to the absence of this costimulator.

CD28 and IL-4: two heavyweights controlling the balance between immunity and inflammation.

The costimulatory receptor CD28 and IL-4Ralpha containing cytokine receptors play key roles in controlling the size and quality of pathogen-specific immune responses. Thus, CD28-mediated costimulation is needed for effective primary T-cell expansion and for the generation and activation of regulatory T-cells (Treg cells), which protect from immunopathology. Similarly, IL-4Ralpha signals are required for alternative activation of macrophages, which counteract inflammation by type 1 responses. Furthermore,immune modulation by CD28 and IL-4 is interconnected through the promotion of IL-4 producing T-helper 2 cells by CD28 signals. Using conditionally IL-4Ralpha and CD28 deleting mice, as well as monoclonal antibodies, which block or stimulate CD28, or mAb that deplete Treg cells, we have studied the roles of CD28 and IL-4Ralpha in experimental mouse models of virus (influenza), intracellular bacteria (L. monocytogenes, M. tuberculosis), and parasite infections (T. congolense, L. major). We observed that in some, but not all settings, Treg cells and type 2 immune deviation, including activation of alternative macrophages can be manipulated to protect the host either from infection or from immunopathology with an overall beneficial outcome. Furthermore, we provide direct evidence that secondary CD8 T-cell responses to i.c. bacteria are dependent on CD28-mediated costimulation.

Polypyrimidine tract binding protein induces human papillomavirus type 16 late gene expression by interfering with splicing inhibitory elements at the major late 5' splice site, SD3632.

We have initiated a screen for cellular factors that can induce human papillomavirus type 16 (HPV-16) late gene expression in human cancer cells. We report that the overexpression of polypyrimidine tract binding protein (PTB), also known as heterologous nuclear ribonucleoprotein I (hnRNP I), induces HPV-16 late gene expression in cells transfected with subgenomic HPV-16 plasmids or with full-length HPV-16 genomes and in persistently HPV-16-infected cells. In contrast, other hnRNPs such as hnRNP B1/A2, hnRNP F, and hnRNP Q do not induce HPV-16 late gene expression. PTB activates SD3632, the only 5' splice site on the HPV-16 genome that is used exclusively by late mRNAs. PTB interferes with splicing inhibitory sequences located immediately upstream and downstream of SD3632, thereby activating late gene expression. One AU-rich PTB-responsive element was mapped to a 198-nucleotide sequence located downstream of SD3632. The deletion of this element induced HPV-16 late gene expression in the absence of PTB. Our results suggest that the overexpression of PTB interferes with cellular factors that interact with the inhibitory sequences. One may speculate that an increase in PTB levels or a reduction in the concentration of a PTB antagonist is required for the activation of HPV-16 late gene expression during the viral life cycle.