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Objective: The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the "Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder" scale currently used in the Consortium on Lithium Genetics (ConLiGen) study.
Materials and Methods: Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (\(\kappa\))] and reliability [intra-class correlation coefficient (ICC)] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling.
Results: Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (\(\kappa\) = 0.66 and \(\kappa\) = 0.54, respectively), without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (\(ICC_1 = 0.71\) and \(ICC_2 = 0.75\), respectively). Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders).
Conclusions: We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study.
Folliculin Controls the Intracellular Survival and Trans-Epithelial Passage of Neisseria gonorrhoeae
(2020)
Neisseria gonorrhoeae, a Gram-negative obligate human pathogenic bacterium, infects human epithelial cells and causes sexually transmitted diseases. Emerging multi-antibiotic resistant gonococci and increasing numbers of infections complicate the treatment of infected patients. Here, we used an shRNA library screen and next-generation sequencing to identify factors involved in epithelial cell infection. Folliculin (FLCN), a 64 kDa protein with a tumor repressor function was identified as a novel host factor important for N. gonorrhoeae survival after uptake. We further determined that FLCN did not affect N. gonorrhoeae adherence and invasion but was essential for its survival in the cells by modulating autophagy. In addition, FLCN was also required to maintain cell to cell contacts in the epithelial layer. In an infection model with polarized cells, FLCN inhibited the polarized localization of E-cadherin and the transcytosis of gonococci across polarized epithelial cells. In conclusion, we demonstrate here the connection between FLCN and bacterial infection and in particular the role of FLCN in the intracellular survival and transcytosis of gonococci across polarized epithelial cell layers.
In this casuistry, two accidents from Germany and Switzerland are presented that happened during the shot of recoilless anti-tankweapons. In both cases, the injuries led to the death of two soldiers: A 22-year-old soldier in Germany was struck by the countermass of a so-called Davis gun which had been fired by a comrade during a firing exercise; he died from his severe injuries,especially in the abdominal part of the body. As a peculiarity of the wound morphology, it was found to be a thick-layered,metallic, gray material in the wound cavity, which corresponded to the material of the counter mass that was ejected opposite tothe shooting direction. The other case took place in Switzerland, where a 24-year-old soldier was seriously injured during anexercise with portable anti-tank rockets. At the time the shot was fired, he stood behind the launcher and was hit by the propulsionjet of the rocket motor. He died as well from his severe injuries, which were located at the chest done by the gas jet and by the veryhigh pressure. In both cases, two different causes of death were present: massive blunt violence in the first case versus a jet of hotgases of very high speed and temperature in the second case.
In forensic science determination of the origin and sex of skeletal remains is an important task for identification purposes. In this study we investigated the krotaphion-sphenion distance (K‑S distance) in the pterion region of German, Euro-American, African-American and Rwandan skulls of modern individuals from the nineteenth to the twenty-first century to look for statistically significant differences in sex and ancestry. We found a statistically significant sex-specific difference in the K‑S distance, which was greater in male skulls than in female skulls for both sides of the skull. Our study also showed that there is a statistically significant difference in the K‑S distance between the four populations studied. Landmarks and morphometric parameters measured in our investigations, which were not used for the present examination were provided to the software program Fordisc for its reference data to enhance the range of its usability for identification of unknown skulls or partial skulls of European individuals.