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Glioblastoma (GBM) is the most invasive and deadliest brain cancer in adults. Its inherent heterogeneity has been designated as the main cause of treatment failure. Thus, a deeper understanding of the diversity that shapes GBM pathobiology is of utmost importance. Single-cell RNA sequencing (scRNA-seq) technologies have begun to uncover the hidden composition of complex tumor ecosystems. Herein, a semi-systematic search of reference literature databases provided all existing publications using scRNA-seq for the investigation of human GBM. We compared and discussed findings from these works to build a more robust and unified knowledge base. All aspects ranging from inter-patient heterogeneity to intra-tumoral organization, cancer stem cell diversity, clonal mosaicism, and the tumor microenvironment (TME) are comprehensively covered in this report. Tumor composition not only differs across patients but also involves a great extent of heterogeneity within itself. Spatial and cellular heterogeneity can reveal tumor evolution dynamics. In addition, the discovery of distinct cell phenotypes might lead to the development of targeted treatment approaches. In conclusion, scRNA-seq expands our knowledge of GBM heterogeneity and helps to unravel putative therapeutic targets. [ABSTRACT FROM AUTHOR]

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A new green method has been developed for the extraction of the pseudo-total content of the heavy metals Ni, Cu, Cr, Pb, and Cd from marine sediments using a mixture of biodegradable micellar media (SDS, Triton X-100) as extractants and graphite furnace atomic absorption spectrometry (GFAAS) for their determination. This work is the first one that uses only surfactants as extractants, without the addition of chelating agents to increase the extraction efficiency of the method, proving to be effective in the extraction of metals from these types of matrices. The proposed method has shown high recovery percentages for all the metals considered (＞68%), good linearity and reproducibility (RSD ＜ 5.9%), as well as detection limits ranging from 0.06 to 2.78 μg g−1. The method was applied to the determination of the heavy metals under study in samples with different physicochemical properties. Finally, our results were compared with those obtained using microwave assisted extraction – graphite furnace atomic absorption spectrometry (MAE/GFAAS) described in ISO 11047:1998 obtaining comparable results. [ABSTRACT FROM AUTHOR]

Introduction. The Pediatric Asthma Health Outcome Measure (PAHOM) was designed to measure quality-adjusted life years (QALYs) in children with asthma. Our objective was to compare parent- and child-reported PAHOM scores to each other, to parent-reported scores on the Juniper Asthma Control Questionnaire (ACQ), and to physician-rated asthma control. Methods. A convenience sample of primarily African-American parent-child dyads (N = 261) was recruited from asthma clinics between May 2008 and May 2010. Correlations and differences in scores between the instruments and respondents were compared across variables of interest. The sensitivity and specificity of each, relative to physician-rated asthma control, were estimated. Results. Mean (SD) parent- and child-reported PAHOM scores were significantly different, 0.91 (0.13) and 0.95 (0.08), respectively, (p < .01) and were weakly correlated (0.24). Parent-reported PAHOM and parent-reported ACQ, 5-item version (ACQ5) scores were moderately correlated (-0.69). Both the parent- and child-reported PAHOM scores distinguished between physician-rated well-controlled and not well-controlled asthma (p < .01 and p < .01, respectively). When compared with physician-rated asthma control, the areas under the receiver operating characteristic (ROC) curves for the parent-reported PAHOM and the ACQ5 were similar (p = .11), but both performed better than the child-reported PAHOM (both p < .01). Discussion. The validity of the PAHOM is supported by its moderate correlation with the ACQ and its association with physician-rated asthma control. Although intended to be administered to children, parent-reported scores were better predictors of physician-rated asthma control. Conclusions. A validation study in a more economically and ethnically diverse population is needed. Until then, we recommend the PAHOM to be administered to both parents and children. [ABSTRACT FROM AUTHOR]

Background: Cardiac inflammation in heart failure is characterized by the presence of damage-associated molecular patterns, myeloid cells, and T cells. Cardiac damage-associated molecular patterns provide continuous proinflammatory signals to myeloid cells through TLRs (toll-like receptors) that converge onto the adaptor protein MyD88 (myeloid differentiation response 88). These induce activation into efficient antigen-presenting cells that activate T cells through their TCR (T-cell receptor). T-cell activation results in cardiotropism, cardiac fibroblast transformation, and maladaptive cardiac remodeling. T cells rely on TCR signaling for effector function and survival, and while they express MyD88 and damage-associated molecular pattern receptors, their role in T-cell activation and cardiac inflammation is unknown., Methods: We performed transverse aortic constriction in mice lacking MyD88 in T cells and analyzed remodeling, systolic function, survival, and T-cell activation. We profiled wild type versus Myd88 -/- mouse T cells at the transcript and protein level and performed several functional assays., Results: Analysis of single-cell RNA-sequencing data sets revealed that MyD88 is expressed in mouse and human cardiac T cells. MyD88 deletion in T cells resulted in increased levels of cardiac T-cell infiltration and fibrosis in response to transverse aortic constriction. We discovered that TCR-activated Myd88 -/- T cells had increased proinflammatory signaling at the transcript and protein level compared with wild type, resulting in increased T-cell effector functions such as adhesion, migration across endothelial cells, and activation of cardiac fibroblast. Mechanistically, we found that MyD88 modulates T-cell activation and survival through TCR-dependent rather than TLR-dependent signaling., Conclusions: Our results outline a novel intrinsic role for MyD88 in limiting T-cell activation that is central to tune down cardiac inflammation during cardiac adaptation to stress., Competing Interests: Disclosures None.

Primary immunodeficiencies (PID) are a heterogeneous group of inherited disorders, the etiology are the defects in the development or function of the immune system. The principal PID manifestations are the infections in early age, malignancy and diseases of immune dysregulation as autoimmunity and allergy. PIDs are genetics disorders and most of them are inherited as autosomal recessive, also this group of diseases is more prevalent in males and in childhood. The antibody immunodeficiency is the PID more common in adults. The more frequent disorders are the infections in the respiratory tract, abscesses, candidiasis, diarrhea, BCGosis etc. Initial approach included a complete blood count and quantification of immunoglobulins. The delay in diagnosis could be explained due to a perception that the recurrent infections are normal process or think that they are exclusively of childhood. The early diagnosis of PID by primary care physicians is important to opportune treatment and better prognosis.