Acute Progressive Visual Loss in a Case of Acute Myeloid Leukemia: Challenges in the Utility of Molecular Tests in Early Diagnose of Cytomegalovirus Retinitis

Cytomegalovirus (CMV) retinitis is one of the rare but debilitating presentations of the CMV infection in children with leukemia. Herein, we report a 12-year-old boy with acute myeloid leukemia complicated by rapid progressive visual loss during relapse of leukemia. The definite diagnosis of CMV retinitis was made after vitreous aspiration. Despite prompt treatment and ophthalmologic intervention, he died because of AML relapse. Viral infections, especially cytomegalovirus infection, may present with vague clinical pictures during any time of chemotherapy, which may not be easily distinguishable from bacterial or fungal retinitis and also chemotherapy-induced retinopathies. Clinician should consider CMV retinitis in seropositive patients especially those without detectable viremia

Using meta-analysis and machine learning to investigate the transcriptional response of immune cells to Leishmania infection.

BackgroundLeishmaniasis is a parasitic disease caused by the Leishmania protozoan affecting millions of people worldwide, especially in tropical and subtropical regions. The immune response involves the activation of various cells to eliminate the infection. Understanding the complex interplay between Leishmania and the host immune system is crucial for developing effective treatments against this disease.MethodsThis study collected extensive transcriptomic data from macrophages, dendritic, and NK cells exposed to Leishmania spp. Our objective was to determine the Leishmania-responsive genes in immune system cells by applying meta-analysis and feature selection algorithms, followed by co-expression analysis.ResultsAs a result of meta-analysis, we discovered 703 differentially expressed genes (DEGs), primarily associated with the immune system and cellular metabolic processes. In addition, we have substantiated the significance of transcription factor families, such as bZIP and C2H2 ZF, in response to Leishmania infection. Furthermore, the feature selection techniques revealed the potential of two genes, namely G0S2 and CXCL8, as biomarkers and therapeutic targets for Leishmania infection. Lastly, our co-expression analysis has unveiled seven hub genes, including PFKFB3, DIAPH1, BSG, BIRC3, GOT2, EIF3H, and ATF3, chiefly related to signaling pathways.ConclusionsThese findings provide valuable insights into the molecular mechanisms underlying the response of immune system cells to Leishmania infection and offer novel potential targets for the therapeutic goals

The pathway enrichment analysis of up and down-regulated genes between infected and healthy controls.

The circles size and color mean the gene ratio and the adjusted p-value, respectively. The top pathways are shown.</p

Venn diagram for overlap visualization between meta-analysis results and feature genes identified from the feature selection models.

Venn diagram for overlap visualization between meta-analysis results and feature genes identified from the feature selection models.</p

The xlsx file, including the A to M Tables.

BackgroundLeishmaniasis is a parasitic disease caused by the Leishmania protozoan affecting millions of people worldwide, especially in tropical and subtropical regions. The immune response involves the activation of various cells to eliminate the infection. Understanding the complex interplay between Leishmania and the host immune system is crucial for developing effective treatments against this disease.MethodsThis study collected extensive transcriptomic data from macrophages, dendritic, and NK cells exposed to Leishmania spp. Our objective was to determine the Leishmania-responsive genes in immune system cells by applying meta-analysis and feature selection algorithms, followed by co-expression analysis.ResultsAs a result of meta-analysis, we discovered 703 differentially expressed genes (DEGs), primarily associated with the immune system and cellular metabolic processes. In addition, we have substantiated the significance of transcription factor families, such as bZIP and C2H2 ZF, in response to Leishmania infection. Furthermore, the feature selection techniques revealed the potential of two genes, namely G0S2 and CXCL8, as biomarkers and therapeutic targets for Leishmania infection. Lastly, our co-expression analysis has unveiled seven hub genes, including PFKFB3, DIAPH1, BSG, BIRC3, GOT2, EIF3H, and ATF3, chiefly related to signaling pathways.ConclusionsThese findings provide valuable insights into the molecular mechanisms underlying the response of immune system cells to Leishmania infection and offer novel potential targets for the therapeutic goals.</div

QuantiFERON-TB Gold and Tuberculin Skin Test for the Diagnosis of Latent Tuberculosis Infection in Children

Background: Appropriate diagnosis and treatment of latent tuberculosis infection (LTBI) play the most important role in the control of tuberculosis. This study aimed to determine the prevalence of LTBI among healthy tuberculosis unexposed children vaccinated with BCG using the tuberculin skin test (TST) and QuantiFERON TB Gold In-Tube (QFT-GIT) and comparing the agreement between the two tests. Methods: A cross-sectional study was carried out between October 2009 and March 2010 in 24 schools and 11 daycare centers. A total of 967 children were divided into 15 age groups, with a minimum of 64 children per group. Results: The prevalence rates of LTBI with TST were 3.8%, and 2.2% with QFT-GIT. One case was positive in TST and QFT-GIT, 20 cases were QFT-GIT positive, but TST negative and 36 cases were TST positive, but QFT-GIT negative, and finally, 910 cases were negative in both. There was poor agreement between TST and QFT-GIT (1.8%, 95%, CI: 0%-5.3%, k=0.007). The specificity of QFT-GIT in the BCG vaccinated, children aged 1-15 years old, was 97.8% (97.8%, 95% CI: 96.8%-98.8%). After three months, 2/17 (11.8%) of those initially QFT-GIT negative converted, and 10/15 (66%) of those initially QFT-GIT positive reverted. Conclusion: It seems that TST and QFT-GIT are not appropriate tests for the diagnosis of LTBI among healthy tuberculosis unexposed BCG vaccinated children. There was a low reproducibility rate of QFT-GIT. The cause of the the poor agreement requires further studies

Weighted gene co-expression network analysis (WGCNA) of differentially expressed genes (DEGs).

Hierarchical cluster tree representing seven modules of co-expressed genes. The gene dendrogram was constructed by clustering dissimilarity using consensus Topological Overlap. The color row indicates the corresponding module colors. Each colored row represents a module color-coded to highlight a group of genes with strong interconnections.</p

The top significant Gene Ontology (GO) categories of the differentially expressed genes (DEGs) in three ontologies: BP, biological process; MF, molecular function; and CC, cellular component.

The top significant Gene Ontology (GO) categories of the differentially expressed genes (DEGs) in three ontologies: BP, biological process; MF, molecular function; and CC, cellular component.</p

Gene expression comparison between infected and healthy controls.

Volcano plot displaying combined effect size (x-axis) and negative log10 of the false discovery rate value (y-axis). The significant up and down-regulated genes are plotted as red dots.</p

The number of differentially expressed genes (DEGs) in different transcription factor families.

The number of up- or down-regulated are shown for each transcription factor family.</p