Genetic Vaccination as a Flexible Tool to Overcome the Immunological Complexity of Invasive Fungal Infections

The COVID-19 pandemic has highlighted genetic vaccination as a powerful and cost-effective tool to counteract infectious diseases. Invasive fungal infections (IFI) remain a major challenge among immune compromised patients, particularly those undergoing allogeneic hematopoietic bone marrow transplantation (HSCT) or solid organ transplant (SOT) both presenting high morbidity and mortality rates. Candidiasis and Aspergillosis are the major fungal infections among these patients and the failure of current antifungal therapies call for new therapeutic aids. Vaccination represents a valid alternative, and proof of concept of the efficacy of this approach has been provided at clinical level. This review will analyze current understanding of antifungal immunology, with a particular focus on genetic vaccination as a suitable strategy to counteract these diseases.

Antineoplastic agents used in pediatric hematopoietic bone marrow transplantation: a review about pharmacology and pharmaceutical issues.

This article proposes the characterization of the main chemotherapeutic agents used in hematopoietic stem cell transplantation in pediatric patients, carrying out a review of the main pharmacological and pharmacokinetic characteristics that are peculiar to children, as well as technical aspects for the handling, prescription, and administration of each one of these. It is extremely important that all professionals know how to recognize the characteristics of each drug and how its peculiarities impact the quality of patient's treatment, being able to predict and propose necessary interventions for potential problems of therapy, which can be identified and measured.

FDG-PET vs. chemical shift MR imaging in differentiating intertrabecular metastasis from hematopoietic bone marrow hyperplasia

Purpose To evaluate the utility of SUVmax on FDG-PET and chemical shift imaging (CSI) on MRI in the differentiation of intertrabecular metastasis (ITM) from hematopoietic bone marrow hyperplasia (HBMH). Patients and methods We retrospectively evaluated 54 indeterminate focal bone marrow lesions in 44 patients detected on FDG-PET. The lesions were assigned to the metastasis group (M group, 29 lesions of 24 patients) and the non-metastasis group (non-M group, 25 lesions of 20 patients) based on the follow-up or the histopathological studies. The lesions were assessed with the maximum standardized uptake value (SUVmax) on FDG-PET CT images and signal change ratio (SCR) on CSI. Results The median SUVmax were 5.62 and 2.91; the median SCR were − 0.08 and − 34.8 in M and non-M groups respectively, with significant difference (p < 0.001). With ROC curve analysis, the optimal cutoff value of SUVmax was 4.48 with a sensitivity of 72.4%, a specificity of 100%, and AUC of 0.905. The cutoff value of SCR was − 6.15 with a sensitivity of 82.8%, a specificity of 80%, and AUC of 0.818. Conclusion FDG-PET and CSI on MRI are useful in distinguishing ITM from HBMH. Though their sensitivities are similar, the specificity of FDG-PET was higher than that of MRI.

An intact gut microbiome protects genetically predisposed mice against leukemia

The majority of childhood leukemias are precursor B-cell acute lymphoblastic leukemias (pB-ALLs) caused by a combination of prenatal genetic predispositions and oncogenic events occurring after birth. Although genetic predispositions are frequent in children (&gt;1% to 5%), fewer than 1% of genetically predisposed carriers will develop pB-ALL. Although infectious stimuli are believed to play a major role in leukemogenesis, the critical determinants are not well defined. Here, by using murine models of pB-ALL, we show that microbiome disturbances incurred by antibiotic treatment early in life were sufficient to induce leukemia in genetically predisposed mice, even in the absence of infectious stimuli and independent of T cells. By using V4 and full-length 16S ribosomal RNA sequencing of a series of fecal samples, we found that genetic predisposition to pB-ALL (Pax5 heterozygosity or ETV6-RUNX1 fusion) shaped a distinct gut microbiome. Machine learning accurately (96.8%) predicted genetic predisposition using 40 of 3983 amplicon sequence variants as proxies for bacterial species. Transplantation of either wild-type (WT) or Pax5+/– hematopoietic bone marrow cells into WT recipient mice revealed that the microbiome is shaped and determined in a donor genotype–specific manner. Gas chromatography-mass spectrometry (GC-MS) analyses of sera from WT and Pax5+/– mice demonstrated the presence of a genotype-specific distinct metabolomic profile. Taken together, our data indicate that it is a lack of commensal microbiota rather than the presence of specific bacteria that promotes leukemia in genetically predisposed mice. Future large-scale longitudinal studies are required to determine whether targeted microbiome modification in children predisposed to pB-ALL could become a successful prevention strategy.

RESEARCH AND EVALUATION OF THE TOXICITY PARAMETERS OF NANO-DISPERSED MAGNESIUM OXIDE IN REPEATED INHALATION EXPOSURE

A repeated inhalation exposure of Wistar rats to an aerosol of aqueous suspension of nano-dispersed magnesium oxide (5-100 nm) with actual concentration of 0,485 ± 0,121 mg/m3 has been studied. There was a significant increase in the activity of alanine aminotransferase, as well as the number of leukocytes and platelets, thrombocrit. At the same time, a significant decrease in stab neutrophils and monocytes has been noted. In animals of the experimental group, acute plethora has been found in the tissues of the brain, heart, lungs, liver, pancreas, and kidneys. Subarachnoid hemorrhages in the brain; hemorrhagic heart attacks and hyperplasia of lung tissue; hyperplasia of the myeloid germ of hematopoietic bone marrow and lymphoid tissue of the small intestine; eosinophilia of infiltrate in the stomach and large intestine have been established. The results obtained make it possible to increase the effectiveness of substantiating preventive measures for workers and population exposed to inhalation exposure to nanoparticles of magnesium oxide.