The utility of cancer whole genome and transcriptome sequencing (cWGTS) in oncology is increasingly recognized. However, implementation of cWGTS is challenged by the need to deliver results within ...clinically relevant timeframes, concerns about assay sensitivity, reporting and prioritization of findings. In a prospective research study we develop a workflow that reports comprehensive cWGTS results in 9 days. Comparison of cWGTS to diagnostic panel assays demonstrates the potential of cWGTS to capture all clinically reported mutations with comparable sensitivity in a single workflow. Benchmarking identifies a minimum of 80× as optimal depth for clinical WGS sequencing. Integration of germline, somatic DNA and RNA-seq data enable data-driven variant prioritization and reporting, with oncogenic findings reported in 54% more patients than standard of care. These results establish key technical considerations for the implementation of cWGTS as an integrated test in clinical oncology.
Introduction
GnRh agonists are drugs used in various gynecological pathologies, among which is endometriosis. They act by stimulating GnRh receptors in the pituitary gland. This sustained and ...continuous stimulation of GnRh, will initially generate an increase in the release of luteinizing hormones and follicle-stimulating hormones, subsequently losing sensitivity to the receptors, internalizing them, and thus suppressing the release of these hormones, which would entail an ovarian suppression, thereby inhibiting the release of estrogens and progesterone. Psychiatric adverse effects have been described. Gonzalez-Rodriguez et al (Front Psychiatry 2020; 11:479), described this association with changes in mood, and the presence of a series of cases where the link between GnRh agonist and the possibility of presenting psychotic symptoms is observed. Wieck (Curr Top Behav Neurosci 2011;8:173-87), Frokjaer (J Neurosci Res 2020;98(7):1283-1292), Brzezinski-Sinai et al (Front Psychiatry 2020;11:693) reported that this association could be related with the relationship of the hypothalamic-pituitary-gonadal axis, hormonal fluctuation and its relationship with the dopaminergic regulation, a genetic component that would increase the predisposition to trigger psychiatric pathology in patients with greater sensitivity to hormonal fluctuations, and the loss of neuroprotection generated by the decrease of estrogens in the central nervous system. All of this in the context of multiple environmental and genetic factors that participate together in the appearance of the disease.
Objectives
To describe the importance of detecting the risk factors that can precipitate a psychotic episode, including the use of certain drugs, such as GnRh agonists.
Methods
We describe a case of a 45 year old patient with endometriosis with multiple organ involvement who went to the emergency room due to behavioral changes in the context of a brief psychotic disorder with “ad-integrum” recovery.
Results
A retrospective analysis of the case is conducted, observing an association between the introduction of GnRh agonists and the presentation of a first psychotic episode.
Conclusions
The importance of this case lies in the limited evidence of this association in the literature, and the implication of these drugs in the triggering of psychiatric pathology, being an aspect to be considered by psychiatrists in their patient’s follow-up.
Disclosure of Interest
None Declared
► Relative stiffness versus relative density measurements for reticulated mesh and stochastic open cellular copper were shown to follow the Gibson–Ashby foam model. ► Microstructures for the mesh ...struts and foam ligaments illustrated a propensity of copper oxide precipitates which provided structural hardness and strength. ► These components, fabricated by electron beam melting, exhibit interesting prospects for specialized, complex heat-transfer devices.
Cu reticulated mesh and stochastic open cellular foams were fabricated by additive manufacturing using electron beam melting. Fabricated densities ranged from 0.73
g/cm
3 to 6.67
g/cm
3. The precursor Cu powder contained Cu
2O precipitates and the fabricated components contained arrays of Cu
2O precipitates and interconnected dislocation microstructures having average spacings of ∼2
μm, which provide hardness values ∼75% above commercial Cu products. Plots of stiffness (Young's modulus) versus density and relative stiffness versus relative density were in very close agreement with the Gibson–Ashby model for open cellular foams. These open cellular structure components exhibit considerable potential for novel, complex, multi-functional electrical and thermal management systems, especially complex, monolithic heat exchange devices.
Total knee replacement implants consisting of a Co–29Cr–6Mo alloy femoral component and a Ti–6Al–4V tibial component are the basis for the additive manufacturing of novel solid, mesh, and foam ...monoliths using electron beam melting (EBM). Ti–6Al–4V solid prototype microstructures were primarily
α
-phase acicular platelets while the mesh and foam structures were characterized by
α
′
-martensite with some residual
α
. The Co–29Cr–6Mo containing 0.22% C formed columnar (directional) Cr
23C
6 carbides spaced ∼2 μm in the build direction, while HIP-annealed Co–Cr alloy exhibited an intrinsic stacking fault microstructure. A log–log plot of relative stiffness versus relative density for Ti–6Al–4V and Co–29Cr–6Mo open-cellular mesh and foams resulted in a fitted line with a nearly ideal slope,
n
=
2.1
. A stress shielding design graph constructed from these data permitted mesh and foam implant prototypes to be fabricated for compatible bone stiffness.
RegulonDB (http://regulondb.ccg.unam.mx/) is the primary reference database of the best-known regulatory network of any free-living organism, that of Escherichia coli K-12. The major conceptual ...change since 3 years ago is an expanded biological context so that transcriptional regulation is now part of a unit that initiates with the signal and continues with the signal transduction to the core of regulation, modifying expression of the affected target genes responsible for the response. We call these genetic sensory response units, or Gensor Units. We have initiated their high-level curation, with graphic maps and superreactions with links to other databases. Additional connectivity uses expandable submaps. RegulonDB has summaries for every transcription factor (TF) and TF-binding sites with internal symmetry. Several DNA-binding motifs and their sizes have been redefined and relocated. In addition to data from the literature, we have incorporated our own information on transcription start sites (TSSs) and transcriptional units (TUs), obtained by using high-throughput whole-genome sequencing technologies. A new portable drawing tool for genomic features is also now available, as well as new ways to download the data, including web services, files for several relational database manager systems and text files including BioPAX format.
Abstract Objectives The aim of this study was to compare the evolution of the first kidney in relation to the second kidney transplanted from the same donor, focusing on the impact that a longer cold ...ischemia time may have as an independent variable. Material and Methods The study included 44 pairs of kidneys transplanted from the same donor between February 2008 and October 2010, divided into Groups 1 and 2 according to the graft placement order. The variables analyzed were age, sex, comorbidities, number of transfusions, length of hospital stay, maximum peak PRA, immunologic incompatibility, ischemia time, delayed graft function (DGF), presence of rejection, creatinine clearance at first week, at 3 months and at 1 year, and vascular and tract complications in each group. Results The mean cold ischemia time was 15.6 hours in Group 1 and 20.1 hours in Group 2 ( P < .001). The average recipient age was 52.79 years in Group 1 and 54.52 years in Group 2, with an equal sex ratio in the two groups; an average of 2.06 PRC were transfused prior to transplantation in Group 1 and 0.93 PRC in Group 2; the average length of stay was similar in the two groups. Major DR incompatibility was only found in Group 2 ( P < .03). Creatinine clearance at first week, DGF and acute rejection showed worse results in Group 2, but these differences were not significant. Vascular complications were present in 4.5% and 2.3% of Groups 1 and 2, respectively, and tract complications were 6.8% and 11.4%. Conclusions A greater tendency to DGF, early rejection and tract complications were found in the group with longer ischemia time, although the difference was not statistically significant. Larger series will be necessary to confirm our results.
Clinical trials in heart failure have focused on the improvement in symptoms or decreases in the risk of death and other cardiovascular events. Little is known about the effect of drugs on the risk ...of clinical deterioration in surviving patients.
We compared the angiotensin-neprilysin inhibitor LCZ696 (400 mg daily) with the angiotensin-converting enzyme inhibitor enalapril (20 mg daily) in 8399 patients with heart failure and reduced ejection fraction in a double-blind trial. The analyses focused on prespecified measures of nonfatal clinical deterioration. In comparison with the enalapril group, fewer LCZ696-treated patients required intensification of medical treatment for heart failure (520 versus 604; hazard ratio, 0.84; 95% confidence interval, 0.74-0.94; P=0.003) or an emergency department visit for worsening heart failure (hazard ratio, 0.66; 95% confidence interval, 0.52-0.85; P=0.001). The patients in the LCZ696 group had 23% fewer hospitalizations for worsening heart failure (851 versus 1079; P<0.001) and were less likely to require intensive care (768 versus 879; 18% rate reduction, P=0.005), to receive intravenous positive inotropic agents (31% risk reduction, P<0.001), and to have implantation of a heart failure device or cardiac transplantation (22% risk reduction, P=0.07). The reduction in heart failure hospitalization with LCZ696 was evident within the first 30 days after randomization. Worsening of symptom scores in surviving patients was consistently more common in the enalapril group. LCZ696 led to an early and sustained reduction in biomarkers of myocardial wall stress and injury (N-terminal pro-B-type natriuretic peptide and troponin) versus enalapril.
Angiotensin-neprilysin inhibition prevents the clinical progression of surviving patients with heart failure more effectively than angiotensin-converting enzyme inhibition.
http://www.clinicaltrials.gov. Unique identifier: NCT01035255.
In cases of fulminant amoebic colitis we have determined the interactions between Entamoeba histolytica trophozoites and immune cells in order to better understand the pathophysiology of amoebic ...colitis. Eleven specimens of amoebic colitis and five specimens of colon without amoebic lesions were studied. Trophozoites and immune cells were located by topographic stains, histochemistry and immunohistochemistry. Trophozoites were seen in both damaged and undamaged areas of the colonic mucosa. Specimens of fulminant amoebic colitis showed: (a) an increase in IgA+, IgG+ B cells and neutrophils; (b) a reduction in IgM+ B cells, CD8+ T cells, macrophages, eosinophils and mast cells; and (c) no change in the number of NK and CD4+ T cells. The cellular infiltrate in amoebic colitis may represent the combined effects of amoebic monocyte locomotion inhibitory factor and switching of IgM+ B cells to IgG+ and IgA+ plasma cells, induced by amoebic antigens. Tissue damage in the absence of trophozoites may result from ischaemia or host immune responses.
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