Persistent cortisol non-suppression after clinical recovery predicts symptomatic relapse in unipolar depression

We assessed the length and the quality of remission of 13 unipolar endogenous depressed patients, DST non-suppressors before treatment, in a 2-year prospective study. During this period, we recorded stressful life events. Persistent dexamethasone non-suppression, after treatment and complete clinical recovery, correlated highly with early clinical relapse. All six non-normalizers but only one normalizer were rehospitalized within the following 2 years for a major depressive relapse. Persistent DST non-suppression was unrelated to any impact of drug discontinuation, the occurence of stresful life events or the length of illness-free intervals in the patient's prior course of illness. Persistent DST non-suppression appears to have significant prognostic value.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27703/1/0000089.pd

An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. RESULTS: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. CONCLUSIONS: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups

Self-interested exchange fiction & the indigenous psychology of loob as an explanation to altruistic donation behavior: An economic approach

Holmes, Miller and Lerner (2001) have conducted a field experiment with the use of two field studies, which verified the hypothesis that people are more willing to help a charitable organization when the donation is considered as an economic transaction rather than a charitable act or appeal. The participants of study 1, though the offered product is of little interest or appeal to them, still donated more money to the charity with the use of product in exchange for their donation. The participants were also responsive to the level of need upon being offered a product in exchange for their donation, thus cohering to the idea of the exchange provided psychological cover explaining their act of compassion. While in study 2, the existence of a more bargain price increased the willingness of the participants to purchase a product, but within the idea of a high need of the victim from a charitable organization. The proponents used an induced, controlled and modified experimental design patterned after the study of Holmes, Miller and Lerner (2001). With the goal of verifying the existence of exchange fiction in the Philippines, the proponents utilized three treatments namely the donation condition which tested the respondents\u27 propensity to donate a sum of money under one of the two conditions: direct donation or exchange condition, the location condition which classified the respondents according to their locations (rural, urban, foreign) with the intention of determining the location group where exchange fiction is prevalent, the need manipulation which aims to show the responsiveness of the respondents to the victim\u27s need. As the field experiment was conducted by the proponents, it was found out that Filipino DLSU-M students are more of a homo sociologicus than homo economicus. The same idea could also be said to the foreign DLSU-M students. This just means that the foreign students have assimilated and adopted almost the same Filipino culture within their present environment

Ti-Doped Sapphire (Al(2)O(3)) Single Crystals Grown by the Kyropoulos Technique and Optical Characterizations.

International audienceTransparent high optical quality and large Ti-sapphire (Ti(3+)-doped Al(2)O(3)) single crystals have been grown by the Kyropoulos technique (KT) for optical amplification. The present work shows that by the utilization of KT growth technology and the optimization of the growth conditions it is possible to grow Ti-doped Al(2)O(3), 100 mm in diameter and 5 kg in weight. We have demonstrated that large Ti(0.25 atom %)-doped Al(2)O(3) crystals show high chemical homogeneities and good optical properties and amplify the energy without any special annealing. Ti-doped sapphire crystals are for high power laser applications and particularly for the shortest pulses ever produced from a laser oscillator

Tumor necrosis factor α- and interleukin-1β-dependent induction of CCL3 expression by nucleus pulposus cells promotes macrophage migration through CCR1

OBJECTIVE: To investigate tumor necrosis factor α (TNFα) and interleukin-1β (IL-1β) regulation of CCL3 expression in nucleus pulposus (NP) cells and in macrophage migration. METHODS: Quantitative reverse transcription-polymerase chain reaction and immunohistochemistry were used to measure CCL3 expression in NP cells. Transfections were used to determine the role of NF-κB, CCAAT/enhancer binding protein (C/EBPβ), and MAPK on cytokine-mediated CCL3 promoter activity. The effect of NP-conditioned medium on macrophage migration was measured using a Transwell system. RESULTS: An increase in CCL3 expression and promoter activity was observed in NP cells after TNFα or IL-1β treatment. Treatment of cells with NF-κB and MAPK inhibitors abolished the effect of the cytokines on CCL3 expression. The inductive effect of p65 and C/EBPβ on the CCL3 promoter was confirmed through gain-of-function and loss-of-function studies. Notably, cotransfection with p50 completely blocked cytokine- and p65-dependent induction. In contrast, c-Rel and RelB had little effect on promoter activity. Lentiviral transduction with short hairpin RNA for p65 (shp65) and shIKKβ significantly decreased the TNFα-dependent increase in CCL3 expression. Analysis of degenerated human NP tissue samples showed that CCL3, but not CCL4, expression correlated positively with the grade of tissue degeneration. Importantly, treatment of macrophages with conditioned medium of NP cells treated with TNFα or IL-1β promoted their migration. Pretreatment of macrophages with an antagonist of CCR1, the primary receptor for CCL3 and CCL4, blocked cytokine-mediated migration. CONCLUSION: Our findings indicate that TNFα and IL-1β modulate the expression of CCL3 in NP cells by controlling the activation of MAPK, NF-κB, and C/EBPβ signaling. The CCL3-CCR1 axis may play an important role in promoting macrophage infiltration in degenerated, herniated discs.</p

Understanding allergic multimorbidity within the non-eosinophilic interactome

Background: The mechanisms explaining multimorbidity between asthma, dermatitis and rhinitis (allergic multimorbidity) are not well known. We investigated these mechanisms and their specificity in distinct cell types by means of an interactome-based analysis of expression data. Methods: Genes associated to the diseases were identified using data mining approaches, and their multimorbidity mechanisms in distinct cell types were characterized by means of an in silico analysis of the topology of the human interactome. Results: We characterized specific pathomechanisms for multimorbidities between asthma, dermatitis and rhinitis for distinct emergent non-eosinophilic cell types. We observed differential roles for cytokine signaling, TLR-mediated signaling and metabolic pathways for multimorbidities across distinct cell types. Furthermore, we also identified individual genes potentially associated to multimorbidity mechanisms. Conclusions: Our results support the existence of differentiated multimorbidity mechanisms between asthma, dermatitis and rhinitis at cell type level, as well as mechanisms common to distinct cell types. These results will help understanding the biology underlying allergic multimorbidity, assisting in the design of new clinical studies.This work was supported by Mechanisms of the Development of ALLergy (MeDALL), a collaborative project done within the EU under the Health Cooperation Work Programme of the Seventh Framework programme (grant agreement number 261357). EM is supported by grants from the European Research Council (n° 757919) and the Swedish Research Council. NL is a recipient of a postdoctoral fellowship from the French National Research Agency in the framework of the "Investissements d’avenir" program (ANR-15-IDEX-02). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 6AM Data Mining provided support in the form of a salary for DA, but did not have any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section