Corneal Cross-Linking in a 4-Year-Old Child With Keratoconus and Down Syndrome

PURPOSE To describe the clinical outcome of corneal cross-linking (CXL) in a young child with keratoconus. METHODS This is a case report of a young girl with keratoconus with ophthalmologic findings and 3-year follow-up. Follow-up visits included visual acuity measurement, retinoscopy, corneal tomography, and topography. RESULTS A girl with Down syndrome was diagnosed with bilateral keratoconus and relative amblyopia at the age of 4 years. The best-corrected near visual acuity was 20/100 binocularly. Corneal tomography showed the following parameters: OD K(max) 47.2 diopters (D), thinnest location 442 μm; OS K(max) 49.6 D, thinnest location 432 μm. Three months later, the keratoconus in the left eye progressed (K(max) 50.2 D, thinnest location 424 μm), and CXL was performed. One year later, CXL was necessary also in the right eye because of progression. The girl was most recently reexamined at the age of 7 years. The corrected near visual acuity was 20/80 in both eyes. The corneal curvature slightly flattened, and the corneal thickness stabilized (OD K(max) 46.8 D, thinnest location 389 μm; OS K(max) 49.4 D, thinnest location 360 μm). CONCLUSIONS Onset of keratoconus can occur in early childhood, especially in patients with Down syndrome. In this case, CXL was performed at 4 and 5 years of age without complications and stopped further keratoconus progression.

Entwicklung und Validierung einer Skala der Bereitschaft zu verzeihen (SBV)

Verzeihen dient der Bewältigung von Kränkungen und zwischenmenschlichen Konflikten. Es werden Definitionen und Operationalisierungen aus dem englischen Sprachraum vorgestellt. Die Entwicklung eines deutschsprachigen szenarienbasierten Instruments zur Erhebung der Bereitschaft zu verzeihen wird beschrieben. Es wird eine Differenzierung des Konstruktes in zwei Komponenten vorgeschlagen: (a) die Bereitschaft, anderen Menschen zu verzeihen, wenn diese ihre Tat bedauern, (b) die Bereitschaft, anderen Menschen zu verzeihen, wenn diese ihre Tat nicht bedauern. Die Messeigenschaften der neu entwickelten Skala wurden in fünf Studien an insgesamt 1824 Probanden untersucht. Die Ergebnisse zeigen, dass das Instrument gute psychometrische Eigenschaften besitzt. Die theoretische Differenzierung des Konstrukts wird empirisch bestätigt. Hinweise auf die Konstruktvalidität der Skala ergeben sich aus Zusammenhängen mit theoretisch einschlägigen Referenzkonstrukten: der habituellen Ärgerneigung, der Wahrnehmung und Klarheit über eigene und fremde Gefühle, positiver und negativer Affektivität, den fünf Persönlichkeitsfaktoren und sozialer Erwünschtheit. Für die Konstruktvalidität der Skala sprechen ferner konvergente Korrelationen mit anderen Maßen der Bereitschaft zu verzeihen.

The Psychological Outcome of Religious Coping with Stressful Life Events in a Swiss Sample of Church Attendees

Background: Recent research suggested thatreligious coping, based on dispositional religiousness and spirituality (R/S), is an important modulating factor in the process of dealing with adversity. In contrast to the United States, the effect of R/S on psychological adjustment to stress is a widely unexplored area in Europe. Methods: We examined a Swiss sample of 328 church attendees in the aftermath of stressful life events to explore associations of positive or negative religious coping with the psychological outcome. Applying a cross-sectional design, we used Huber’s Centrality Scale to specify religiousness and Pargament’s measure of religious coping (RCOPE) for the assessment of positive and negative religious coping. Depressive symptoms and anxiety as outcome variables were examined by the Brief Symptom Inventory. The Stress-Related Growth Scale and the Marburg questionnaire for the assessment of well-being were used to assess positive outcome aspects. We conducted Mann-Whitney tests for group comparisons and cumulative logit analysis for the assessmentof associations of religious coping with our outcome variables. Results: Both forms of religious coping were positively associated with stress-related growth (p < 0.01). However, negative religious coping additionally reduced well-being (p = 0.05, β = 0.52, 95% CI = 0.27–0.99) and increased anxiety (p = 0.02, β = 1.94, 95% CI = 1.10–3.39) and depressive symptoms (p = 0.01, β = 2.27, 95% CI = 1.27–4.06). Conclusions: The effects of religious coping on the psychological adjustment to stressful life events seem relevant. These findings should be confirmed in prospective studies.

The role of metabotropic glutamate receptor 5 in the pathogenesis of mood disorders and addiction: combining preclinical evidence with human Positron Emission Tomography (PET) studies.

In the present review, we deliver an overview of the involvement of metabotropic glutamate receptor 5 (mGluR5) activity and density in pathological anxiety, mood disorders and addiction. Specifically, we will describe mGluR5 studies in humans that employed Positron Emission Tomography (PET) and combined the findings with preclinical animal research. This combined view of different methodological approaches-from basic neurobiological approaches to human studies-might give a more comprehensive and clinically relevant view of mGluR5 function in mental health than the view on preclinical data alone. We will also review the current research data on mGluR5 along the Research Domain Criteria (RDoC). Firstly, we found evidence of abnormal glutamate activity related to the positive and negative valence systems, which would suggest that antagonistic mGluR5 intervention has prominent anti-addictive, anti-depressive and anxiolytic effects. Secondly, there is evidence that mGluR5 plays an important role in systems for social functioning and the response to social stress. Finally, mGluR5's important role in sleep homeostasis suggests that this glutamate receptor may play an important role in RDoC's arousal and modulatory systems domain. Glutamate was previously mostly investigated in non-human studies, however initial human clinical PET research now also supports the hypothesis that, by mediating brain excitability, neuroplasticity and social cognition, abnormal metabotropic glutamate activity might predispose individuals to a broad range of psychiatric problems.

T-cell reprogramming through targeted CD4-coreceptor and T-cell receptor expression on maturing thymocytes by latent Circoviridae family member porcine circovirus type 2 cell infections in the thymus

Although porcine circovirus type 2 (PCV2)-associated diseases have been evaluated for known immune evasion strategies, the pathogenicity of these viruses remained concealed for decades. Surprisingly, the same viruses that cause panzootics in livestock are widespread in young, unaffected animals. Recently, evidence has emerged that circovirus-like viruses are also linked to complex diseases in humans, including children. We detected PCV2 genome-carrying cells in fetal pig thymi. To elucidate virus pathogenicity, we developed a new pig infection model by in vivo transfection of recombinant PCV2 and the immunosuppressant cofactor cyclosporine A. Using flow cytometry, immunofluorescence and fluorescence in situ hybridization, we found evidence that PCV2 dictates positive and negative selection of maturing T cells in the thymus. We show for the first time that PCV2-infected cells reside at the corticomedullary junction of the thymus. In diseased animals, we found polyclonal deletion of single positive cells (SPs) that may result from a loss of major histocompatibility complex class-II expression at the corticomedullary junction. The percentage of PCV2 antigen-presenting cells correlated with the degree of viremia and, in turn, the severity of the defect in thymocyte maturation. Moreover, the reversed T-cell receptor/CD4-coreceptor expression dichotomy on thymocytes at the CD4(+)CD8(interm) and CD4SP cell stage is viremia-dependent, resulting in a specific hypo-responsiveness of T-helper cells. We compare our results with the only other better-studied member of Circoviridae, chicken anemia virus. Our data show that PCV2 infection leads to thymocyte selection dysregulation, adding a valuable dimension to our understanding of virus pathogenicity.

Azacyclic FTY720 Analogues That Limit Nutrient Transporter Expression but Lack S1P Receptor Activity and Negative Chronotropic Effects Offer a Novel and Effective Strategy to Kill Cancer Cells in Vivo

FTY720 sequesters lymphocytes in secondary lymphoid organs through effects on sphingosine-1-phosphate (S1P) receptors. However, at higher doses than are required for immunosuppression, FTY720 also functions as an anticancer agent in multiple animal models. Our published work indicates that the anticancer effects of FTY720 do not depend on actions at S1P receptors but instead stem from FTY720s ability to restrict access to extracellular nutrients by down-regulating nutrient transporter proteins. This result was significant because S1P receptor activation is responsible for FTY720s dose-limiting toxicity, bradycardia, that prevents its use in cancer patients. Here, we describe diastereomeric and enantiomeric 3- and 4-C-aryl 2-hydroxymethyl pyrrolidines that are more active than the previously known analogues. Of importance is that these compounds fail to activate S1P1 or S1P3 receptors in vivo but retain inhibitory effects on nutrient transporter proteins and anticancer activity in solid tumor xenograft models. Our studies reaffirm that the anticancer activity of FTY720 does not depend upon S1P receptor activation and uphold the promise of using S1P receptor-inactive azacyclic FTY720 analogues in human cancer patients.

Efficacy, Acceptability, and Tolerability of Antipsychotics in Treatment-Resistant Schizophrenia: A Network Meta-analysis.

Importance In treatment-resistant schizophrenia, clozapine is considered the standard treatment. However, clozapine use has restrictions owing to its many adverse effects. Moreover, an increasing number of randomized clinical trials (RCTs) of other antipsychotics have been published. Objective To integrate all the randomized evidence from the available antipsychotics used for treatment-resistant schizophrenia by performing a network meta-analysis. Data Sources MEDLINE, EMBASE, Biosis, PsycINFO, PubMed, Cochrane Central Register of Controlled Trials, World Health Organization International Trial Registry, and clinicaltrials.gov were searched up to June 30, 2014. Study Selection At least 2 independent reviewers selected published and unpublished single- and double-blind RCTs in treatment-resistant schizophrenia (any study-defined criterion) that compared any antipsychotic (at any dose and in any form of administration) with another antipsychotic or placebo. Data Extraction and Synthesis At least 2 independent reviewers extracted all data into standard forms and assessed the quality of all included trials with the Cochrane Collaboration's risk-of-bias tool. Data were pooled using a random-effects model in a Bayesian setting. Main Outcomes and Measures The primary outcome was efficacy as measured by overall change in symptoms of schizophrenia. Secondary outcomes included change in positive and negative symptoms of schizophrenia, categorical response to treatment, dropouts for any reason and for inefficacy of treatment, and important adverse events. Results Forty blinded RCTs with 5172 unique participants (71.5% men; mean [SD] age, 38.8 [3.7] years) were included in the analysis. Few significant differences were found in all outcomes. In the primary outcome (reported as standardized mean difference; 95% credible interval), olanzapine was more effective than quetiapine (-0.29; -0.56 to -0.02), haloperidol (-0. 29; -0.44 to -0.13), and sertindole (-0.46; -0.80 to -0.06); clozapine was more effective than haloperidol (-0.22; -0.38 to -0.07) and sertindole (-0.40; -0.74 to -0.04); and risperidone was more effective than sertindole (-0.32; -0.63 to -0.01). A pattern of superiority for olanzapine, clozapine, and risperidone was seen in other efficacy outcomes, but results were not consistent and effect sizes were usually small. In addition, relatively few RCTs were available for antipsychotics other than clozapine, haloperidol, olanzapine, and risperidone. The most surprising finding was that clozapine was not significantly better than most other drugs. Conclusions and Relevance Insufficient evidence exists on which antipsychotic is more efficacious for patients with treatment-resistant schizophrenia, and blinded RCTs-in contrast to unblinded, randomized effectiveness studies-provide little evidence of the superiority of clozapine compared with other second-generation antipsychotics. Future clozapine studies with high doses and patients with extremely treatment-refractory schizophrenia might be most promising to change the current evidence.

Ultra-low-dose dual-source CT coronary angiography with high pitch: diagnostic yield of a volumetric planning scan and effects on dose reduction and imaging strategy

OBJECTIVE To evaluate the role of an ultra-low-dose dual-source CT coronary angiography (CTCA) scan with high pitch for delimiting the range of the subsequent standard CTCA scan. METHODS 30 patients with an indication for CTCA were prospectively examined using a two-scan dual-source CTCA protocol (2.0 × 64.0 × 0.6 mm; pitch, 3.4; rotation time of 280 ms; 100 kV): Scan 1 was acquired with one-fifth of the tube current suggested by the automatic exposure control software [CareDose 4D™ (Siemens Healthcare, Erlangen, Germany) using 100 kV and 370 mAs as a reference] with the scan length from the tracheal bifurcation to the diaphragmatic border. Scan 2 was acquired with standard tube current extending with reduced scan length based on Scan 1. Nine central coronary artery segments were analysed qualitatively on both scans. RESULTS Scan 2 (105.1 ± 10.1 mm) was significantly shorter than Scan 1 (127.0 ± 8.7 mm). Image quality scores were significantly better for Scan 2. However, in 5 of 6 (83%) patients with stenotic coronary artery disease, a stenosis was already detected in Scan 1 and in 13 of 24 (54%) patients with non-stenotic coronary arteries, a stenosis was already excluded by Scan 1. Using Scan 2 as reference, the positive- and negative-predictive value of Scan 1 was 83% (5 of 6 patients) and 100% (13 of 13 patients), respectively. CONCLUSION An ultra-low-dose CTCA planning scan enables a reliable scan length reduction of the following standard CTCA scan and allows for correct diagnosis in a substantial proportion of patients. ADVANCES IN KNOWLEDGE Further dose reductions are possible owing to a change in the individual patient's imaging strategy as a prior ultra-low-dose CTCA scan may already rule out the presence of a stenosis or may lead to a direct transferal to an invasive catheter procedure.

COSIMA calibration for the detection and characterization of the cometary solid organic matter

On the orbiter of the Rosetta spacecraft, the Cometary Secondary Ion Mass Analyser (COSIMA) will provide new in situ insights about the chemical composition of cometary grains all along 67P/Churyumov–Gerasimenko (67P/CG) journey until the end of December 2015 nominally. The aim of this paper is to present the pre-calibration which has already been performed as well as the different methods which have been developed in order to facilitate the interpretation of the COSIMA mass spectra and more especially of their organic content. The first step was to establish a mass spectra library in positive and negative ion mode of targeted molecules and to determine the specific features of each compound and chemical family analyzed. As the exact nature of the refractory cometary organic matter is nowadays unknown, this library is obviously not exhaustive. Therefore this library has also been the starting point for the research of indicators, which enable to highlight the presence of compounds containing specific atom or structure. These indicators correspond to the intensity ratio of specific peaks in the mass spectrum. They have allowed us to identify sample containing nitrogen atom, aliphatic chains or those containing polyaromatic hydrocarbons. From these indicators, a preliminary calibration line, from which the N/C ratio could be derived, has also been established. The research of specific mass difference could also be helpful to identify peaks related to quasi-molecular ions in an unknown mass spectrum. The Bayesian Positive Source Separation (BPSS) technique will also be very helpful for data analysis. This work is the starting point for the analysis of the cometary refractory organic matter. Nevertheless, calibration work will continue in order to reach the best possible interpretation of the COSIMA observations.

Pulmonary hypoplasia and anasarca syndrome in Cika cattle

BACKGROUND: Hydrops foetalis is defined as excessive fluid accumulation within the foetal extravascular compartments and body cavities. It has been described in human and veterinary medicine, but despite several descriptive studies its aetiology is still not fully clarified. Pulmonary hypoplasia and anasarca (PHA) syndrome is a rare congenital abnormality in cattle that is characterised by hydrops foetalis including extreme subcutaneous oedema (anasarca) and undeveloped or poorly formed lungs (pulmonary hypoplasia). Until now, sporadic cases of PHA were reported in cattle breeds like Australian Dexter, Belted Galloway, Maine-Anjou, and Shorthorn. This report describes the first known cases of PHA syndrome in Slovenian Cika cattle. CASE PRESENTATION: A 13-year-old cow aborted a male calf in the seventh month of pregnancy, while a male calf was delivered by caesarean section on the due date from a 14-year-old cow. The pedigree analysis showed that the calves were sired by the same bull, the dams were paternal half-sisters and the second calf was the product of a dam-son mating. Gross lesions were similar in both cases and characterized by severe anasarca, hydrothorax, hydropericardium, ascites, hypoplastic lungs, absence of lymph nodes, and an enlarged heart. The first calf was also athymic. Histopathology of the second affected calf confirmed severe oedema of the subcutis and interstitium of the organs, and pulmonary hypoplasia. The lymph vessels in the subcutis and other organs were severely dilated. Histopathology of the second calf revealed also lack of bronchus associated lymphoid tissue and adrenal gland hypoplasia. CONCLUSIONS: The findings were consistent with known forms of the bovine PHA syndrome. This is the first report of the PHA syndrome occurring in the local endangered breed of Cika cattle. Observed inbreeding practice supports that this lethal defect most likely follows an autosomal recessive mode of inheritance. In the light of the disease phenotype it is assumed that a mutation causing an impaired development of lymph vessels is responsible for the hydrops foetalis associated malformations in bovine PHA.