S100A1 and S100B expression patterns identify differentiation status of human articular chondrocytes.

Many studies in the field of cell-based cartilage repair have focused on identifying markers associated with the differentiation status of human articular chondrocytes (HAC) that could predict their chondrogenic potency. A previous study from our group showed a correlation between the expression of S100 protein in HAC and their chondrogenic potential. The aims of the current study were to clarify which S100 proteins are associated with HAC differentiation status and to provide an S100-based assay for measuring HAC chondrogenic potential. The expression patterns of S100A1 and S100B were investigated in cartilage and in HAC cultured under conditions promoting dedifferentiation (monolayer culture) or redifferentiation (pellet culture or BMP4 treatment in monolayer culture), using characterized antibodies specifically recognizing S100A1 and S100B, by immunohistochemistry, immunocytochemistry, Western blot, and gene expression analysis. S100A1 and S100B were expressed homogeneously in all cartilage zones, and decreased during dedifferentiation. S100A1, but not S100B, was re-expressed in pellets and co-localized with collagen II. Gene expression analysis revealed concomitant modulation of S100A1, S100B, collagen type II, and aggrecan: down-regulation during monolayer culture and up-regulation upon BMP4 treatment. These results strongly support an association of S100A1, and to a lesser extent S100B, with the HAC differentiated phenotype. To facilitate their potential application, we established an S100A1/B-based flow cytometry assay for accurate assessment of HAC differentiation status. We propose S100A1 and S100B expression as a marker to develop potency assays for cartilage regeneration cell therapies, and as a redifferentiation readout in monolayer cultures aiming to investigate stimuli for chondrogenic induction.

Fluorescence lifetime imaging of the ocular fundus in mice

PURPOSE Fundus autofluorescence (AF) is characterized not only by its intensity or excitation and emission spectra but also by the lifetimes of the fluorophores. Fluorescence lifetime is influenced by the fluorophore's microenvironment and may provide information about the metabolic tissue state. We report quantitative and qualitative autofluorescence lifetime imaging of the ocular fundus in mice. METHODS A fluorescence lifetime imaging ophthalmoscope (FLIO) was used to measure fluorescence lifetimes of endogenous fluorophores in the murine retina. FLIO imaging was performed in 1-month-old C57BL/6, BALB/c, and C3A.Cg-Pde6b(+)Prph2(Rd2)/J mice. Measurements were repeated at monthly intervals over the course of 6 months. For correlation with structural changes, an optical coherence tomogram was acquired. RESULTS Fundus autofluorescence lifetime images were readily obtained in all mice. In the short spectral channel (498-560 nm), mean ± SEM AF lifetimes were 956 ± 15 picoseconds (ps) in C57BL/6; 801 ± 35 ps in BALB/c mice; and 882 ± 37 ps in C3A.Cg-Pde6b(+)Prph2(Rd2)/J mice. In the long spectral channel (560-720 nm), mean ± SEM AF lifetimes were 298 ± 14 ps in C57BL/6 mice, 241 ± 10 ps in BALB/c mice, and 288 ± 8 ps in C3A.Cg-Pde6b(+)Prph2(Rd2)/J mice. There was a general decrease in mean AF lifetimes with age. CONCLUSIONS Although fluorescence lifetime values differ among mouse strains, we found little variance within the groups. Fundus autofluorescence lifetime imaging in mice may provide additional information for understanding retinal disease processes and may facilitate monitoring of therapeutic effects in preclinical studies.

Spectral-domain optical coherence tomography findings after severe exogenous endophthalmitis

PURPOSE To report outcomes and assess structural changes in the retina in patients with severe endophthalmitis. METHODS Retrospective, nonrandomized, interventional case series at a tertiary referral centre. Spectral domain optical coherence tomography (OCT) images of both eyes were acquired at least 5 months after pars plana vitrectomy. OCT images were analyzed using retinal layer segmentation. RESULTS Nine patients (46-80 years of age) were included in this study. Average ETDRS visual acuity before treatment was 23 letters and improved to 74 letters. In our cohort we did not find a generalized reduction of retinal layers using automated layer segmentation. CONCLUSION Our findings suggest that prompt treatment of severe endophthalmitis with intravitreal antibiotics followed by pars plana vitrectomy may lead to excellent visual outcomes with minimal damage to the retinal architecture.

Investigation of retinal morphology alterations using spectral domain optical coherence tomography in a mouse model of retinal branch and central retinal vein occlusion.

Retinal vein occlusion is a leading cause of visual impairment. Experimental models of this condition based on laser photocoagulation of retinal veins have been described and extensively exploited in mammals and larger rodents such as the rat. However, few reports exist on the use of this paradigm in the mouse. The objective of this study was to investigate a model of branch and central retinal vein occlusion in the mouse and characterize in vivo longitudinal retinal morphology alterations using spectral domain optical coherence tomography. Retinal veins were experimentally occluded using laser photocoagulation after intravenous application of Rose Bengal, a photo-activator dye enhancing thrombus formation. Depending on the number of veins occluded, variable amounts of capillary dropout were seen on fluorescein angiography. Vascular endothelial growth factor levels were markedly elevated early and peaked at day one. Retinal thickness measurements with spectral domain optical coherence tomography showed significant swelling (p<0.001) compared to baseline, followed by gradual thinning plateauing two weeks after the experimental intervention (p<0.001). Histological findings at day seven correlated with spectral domain optical coherence tomography imaging. The inner layers were predominantly affected by degeneration with the outer nuclear layer and the photoreceptor outer segments largely preserved. The application of this retinal vein occlusion model in the mouse carries several advantages over its use in other larger species, such as access to a vast range of genetically modified animals. Retinal changes after experimental retinal vein occlusion in this mouse model can be non-invasively quantified by spectral domain optical coherence tomography, and may be used to monitor effects of potential therapeutic interventions.

EPA guidance on the early detection of clinical high risk states of psychoses

The aim of this guidance paper of the European Psychiatric Association is to provide evidence-based recommendations on the early detection of a clinical high risk (CHR) for psychosis in patients with mental problems. To this aim, we conducted a meta-analysis of studies reporting on conversion rates to psychosis in non-overlapping samples meeting any at least any one of the main CHR criteria: ultra-high risk (UHR) and/or basic symptoms criteria. Further, effects of potential moderators (different UHR criteria definitions, single UHR criteria and age) on conversion rates were examined. Conversion rates in the identified 42 samples with altogether more than 4000 CHR patients who had mainly been identified by UHR criteria and/or the basic symptom criterion ‘cognitive disturbances’ (COGDIS) showed considerable heterogeneity. While UHR criteria and COGDIS were related to similar conversion rates until 2-year follow-up, conversion rates of COGDIS were significantly higher thereafter. Differences in onset and frequency requirements of symptomatic UHR criteria or in their different consideration of functional decline, substance use and co-morbidity did not seem to impact on conversion rates. The ‘genetic risk and functional decline’ UHR criterion was rarely met and only showed an insignificant pooled sample effect. However, age significantly affected UHR conversion rates with lower rates in children and adolescents. Although more research into potential sources of heterogeneity in conversion rates is needed to facilitate improvement of CHR criteria, six evidence-based recommendations for an early detection of psychosis were developed as a basis for the EPA guidance on early intervention in CHR states.

Factors influencing the accuracy of fetal weight estimation with a focus on preterm birth at the limit of viability: a systematic literature review

BACKGROUND Fetal weight estimation (FWE) is an important factor for clinical management decisions, especially in imminent preterm birth at the limit of viability between 23(0/7) and 26(0/7) weeks of gestation. It is crucial to detect and eliminate factors that have a negative impact on the accuracy of FWE. DATA SOURCES In this systematic literature review, we investigated 14 factors that may influence the accuracy of FWE, in particular in preterm neonates born at the limit of viability. RESULTS We found that gestational age, maternal body mass index, amniotic fluid index and ruptured membranes, presentation of the fetus, location of the placenta and the presence of multiple fetuses do not seem to have an impact on FWE accuracy. The influence of the examiner's grade of experience and that of fetal gender were discussed controversially. Fetal weight, time interval between estimation and delivery and the use of different formulas seem to have an evident effect on FWE accuracy. No results were obtained on the impact of active labor. DISCUSSION This review reveals that only few studies investigated factors possibly influencing the accuracy of FWE in preterm neonates at the limit of viability. Further research in this specific age group on potential confounding factors is needed.

Fluorescence lifetime imaging in retinal artery occlusion.

PURPOSE Fluorescence lifetime imaging ophthalmoscopy is a technique to measure decay times of endogenous retinal fluorophores. The purpose of this study was to investigate fluorescence lifetimes in eyes with central and branch retinal artery occlusion. METHODS Twenty-four patients with central or branch retinal artery occlusion were included in this study. The contralateral unaffected fellow eye was used as control. Measurements were performed using a fluorescence lifetime imaging ophthalmoscope based on a HRA Spectralis system. Fluorescence excitation wavelength was 473 nm, and mean lifetimes were measured in a short (498-560 nm) and in a long (560-720 nm) spectral channel. Fluorescence lifetimes in the area of retinal artery occlusion were measured and compared to corresponding areas in contralateral unaffected eyes. Additionally, findings were correlated to optical coherence tomography measurements. RESULTS Retinal lifetime images of 24 patients with retinal artery occlusion were analyzed. Mean retinal fluorescence lifetimes were prolonged by 50% in the short and 20% in the long spectral channel in ischemic retinal areas up to 3 days after retinal artery occlusion compared to the contralateral unaffected eyes. In the postacute disease stage there was no difference between the lifetimes of affected areas and unaffected fellow eyes. CONCLUSIONS Retinal artery occlusion leads to significantly longer fluorescence lifetimes of the retina in the acute phase and may serve as a useful indicator for acute ischemic retinal damage.

Age matters in the prevalence and clinical significance of ultra-high-risk for psychosis symptoms and criteria in the general population: Findings from the BEAR and BEARS-kid studies

Early detection of psychosis is an important topic in psychiatry. Yet, there is limited information on the prevalence and clinical significance of high-risk symptoms in children and adolescents as compared to adults. We examined ultra-high-risk (UHR) symptoms and criteria in a sample of individuals aged 8-40 years from the general population of Canton Bern, Switzerland, enrolled from June 2011 to May 2014. The current presence of attenuated psychotic symptoms (APS) and brief intermittent psychotic symptoms (BLIPS) and the fulfillment of onset/worsening and frequency requirements for these symptoms in UHR criteria were assessed using the Structured Interview for Psychosis Risk Syndromes. Additionally, perceptive and non-perceptive APS were differentiated. Psychosocial functioning and current non-psychotic DSM-IV axis I disorders were also surveyed. Well-trained psychologists performed assessments. Altogether, 9.9% of subjects reported APS and none BLIPS, and 1.3% met all the UHR requirements for APS. APS were related to more current axis I disorders and impaired psychosocial functioning, indicating some clinical significance. A strong age effect was detected around age 16: compared to older individuals, 8-15-year olds reported more perceptive APS, that is, unusual perceptual experiences and attenuated hallucinations. Perceptive APS were generally less related to functional impairment, regardless of age. Conversely, non-perceptive APS were related to low functioning, although this relationship was weaker in those below age 16. Future studies should address the differential effects of perceptive and non-perceptive APS, and their interaction with age, also in terms of conversion to psychosis.