HHV-8-encoded viral IL-6 collaborates with mouse IL-6 in the development of multicentric Castleman disease in mice

Human herpes virus 8 (HHV-8) or Kaposi sarcoma-associated herpes virus is the etiologic agent of Kaposi sarcoma, primary effusion lymphoma, and plasma cell-type multicentric Castleman disease (MCD). HHV-8 encodes a viral homolog of human IL-6, called viral IL-6 (vIL-6), which does not require the cellular IL-6 receptor for binding to the ubiquitously expressed gp130 receptor subunit and subsequent JAK-STAT signaling. Thus, in contrast to IL-6, vIL-6 can stimulate virtually all cells in the body. To elucidate the mechanism by which vIL-6 drives human diseases, we generated transgenic mice that constitutively express vIL-6 under control of the MHC class I promoter. The mice were found to exhibit vIL-6 serum levels comparable with those observed in HHV-8-infected patients, to contain elevated amounts of phosphorylated STAT3 in spleen and lymph nodes, where vIL-6 was produced, and to spontaneously develop key features of human plasma cell-type MCD, including splenomegaly, multifocal lymphadenopathy, hypergammaglobulinemia, and plasmacytosis. Transfer of the vIL-6 transgene onto an IL-6-deficient genetic background abrogated MCD-like phenotypes, indicating that endogenous mouse IL-6 is a crucial cofactor in the natural history of the disease. Our results in mice suggest that human IL-6 plays an important role in the pathogenesis of HHV-8-associated MCD.     

The Korean Medication Algorithm for Major Depressive Disorder (KMA-MDD): Report of the Korean Society of Depressive and Bipolar Disorders

Objective. There are many differences in biological characteristics, clinical situations, and medical insurance systems with ethnic groups or countries. The Korean Society of Depressive and Bipolar Disorders decided to develop a Korean treatment algorithm for major depressive disorder. Methods. The Korean Medication Algorithm Project for Major Depressive Disorder (KMAP-MDD) was designed with the following principles: (1) to be an ideal algorithm, (2) to be a Korean algorithm, (3) to be a medication algorithm, (4) to be an evidence-based and formal consensus algorithm. After collecting and reviewing many literature citations and reports by evidence-based rule, we constructed a survey questionnaire for formal consensus of Korean experts. By employing panels of experts to review the evidence and survey results thoroughly, we used evidence-based algorithm development as a component of a formal consensus development process. Results. We developed two algorithms for the KMA-MDD: one for major depressive disorder without psychotic feature and the other for major depressive disorder with psychotic features. Clinical guidelines for the implementation of KMA-MDD were also developed. The KMA-MDD provides specific treatment strategies for each stage. Conclusions. The KMA-MDD is the first Korean algorithm for treatment of major depressive disorder. It is based on evidence which supports the efficacy of each treatment, and it has obtained the consensus of Korean experts. We hope that the KMA-MDD will be good practical tool for clinicians who treat major depressive disorder in Korea.     

Cartilage repair of the knee with Hyalograft C:® Magnetic Resonance Imaging assessment of the glycosaminoglycan content at midterm

Purpose

The aim of this study was to assess the stability of the glycosaminoglycan (GAG) content in the long term after matrix-associated autologous chondrocyte transplantation (MACT) with Hyalograft C in the knee over a follow-up period of one year.

Methods

In this cross-sectional evaluation, 11 patients after MACT of the knee consented to delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) measurements. The mean post-operative interval before the first MR examination was 40.6 ± 22.0 months, and the second MR examination was carried out after another 12 months. The Lysholm score was assessed for clinical evaluation. Quantitative T1 measurements after intravenous negatively charged MR contrast agent administration were performed. Global post-contrast T1 of the reference cartilage and the repair tissue and a relative post-contrast T1 value were calculated.

Results

The Lysholm score improved significantly from 59.8 ± 12.9 at baseline to 86.1 ± 15.7 at the second visit (p < 0.01). The mean global T1 of the repair tissue (1st visit 581.3 ± 126.4 ms; 2nd visit 684.1 ± 169.9 ms; p = 0.104) and the mean relative T1 value showed stable results over one year (1st visit 0.81 ± 0.28; 2nd visit 0.76 ± 0.32; p = 0.4).

Conclusions

The study demonstrated stable glycosaminoglycan content of the repair tissue after MACT at midterm.     

Adaptive screening for depression — Recalibration of an item bank for the assessment of depression in persons with mental and somatic diseases and evaluation in a simulated computer-adaptive test environment

Objective

This study conducted a simulation study for computer-adaptive testing based on the Aachen Depression Item Bank (ADIB), which was developed for the assessment of depression in persons with somatic diseases. Prior to computer-adaptive test simulation, the ADIB was newly calibrated.

Methods

Recalibration was performed in a sample of 161 patients treated for a depressive syndrome, 103 patients from cardiology, and 103 patients from otorhinolaryngology (mean age 44.1, SD = 14.0; 44.7% female) and was cross-validated in a sample of 117 patients undergoing rehabilitation for cardiac diseases (mean age 58.4, SD = 10.5; 24.8% women). Unidimensionality of the itembank was checked and a Rasch analysis was performed that evaluated local dependency (LD), differential item functioning (DIF), item fit and reliability. CAT-simulation was conducted with the total sample and additional simulated data.

Results

Recalibration resulted in a strictly unidimensional item bank with 36 items, showing good Rasch model fit (item fit residuals < |2.5|) and no DIF or LD. CAT simulation revealed that 13 items on average were necessary to estimate depression in the range of − 2 and + 2 logits when terminating at SE ≤ 0.32 and 4 items if using SE ≤ 0.50. Receiver Operating Characteristics analysis showed that θ estimates based on the CAT algorithm have good criterion validity with regard to depression diagnoses (Area Under the Curve ≥ .78 for all cut-off criteria).

Conclusion

The recalibration of the ADIB succeeded and the simulation studies conducted suggest that it has good screening performance in the samples investigated and that it may reasonably add to the improvement of depression assessment.     

Acquired dysfluencies following infarction of the left mesiofrontal cortex

Abstract

The present study describes the acquired dysfluencies observed in a patient with transcortical motor aphasia (TCMA) following ischaemic infarction of the mesiofrontal cortex due to occlusion of the anterior cerebral artery. Prolongation of labial plosives and labiodental fricatives as well as hesitations concomitant with a few repetitions of syllables and sounds, respectively, were noted. The dorsolateral aspects of the frontal lobe of the dominant hemisphere have been considered the relevant site of lesion in instances of acquired stuttering concomitant with TCMA. The present case demonstrates that dysfluencies May-June be present with mesiofrontal lesions as well. The patient's stuttering was confined to production of complex sentences. Since transcortical motor aphasia is characterized by paucity of speech, consisting mostly in one- to two-word utterances, the dysfluencies of patients with this kind of disorder often might be masked. The observed stuttering-like behaviour differed in two respects from other reports on this disorder: the dysfluencies, first, were restricted to word-initial sounds and, secondly, did not occur during repetition tasks and reading aloud. Thus, acquired stuttering due to mesiofrontal lesions might represent a specific constellation of dysfluencies.