Programmed cell death-1, PD-1, is dysregulated in T cells from children with new onset type 1 diabetes

Programmed death cell 1 (PD-1) is an inhibitor of T cell activation and is also functionally linked to glycolysis. We hypothesized that PD-1 expression is defective in activated T cells from children with type 1 diabetes (T1D), resulting in abnormal T cell glucose metabolism

Comics as a Medium for Parent Health Education: Improving Understanding of Normal 9-Month-Old Developmental Milestones

Multimodal literacy, a product of modern technology, can aid in the recall of simple-to-complex information for both children and adults. Health education information presented using educational comics takes advantage of multimodal formats and designs based on theoretical models of learning. In this study, we utilized a quasi-experimental design with both pre- and post-intervention testing. The parents of every other patient that attended the well-child appointments of their child aged <9 months were invited to participate in this study. Participants were drawn from three pediatric clinics, with a total of 280 parents included in the study. Each parent completed a pre-intervention test consisting of an eight-item questionnaire regarding the developmental milestones of a 9-month-old child. After responding to the questionnaire, the parents received a comic about a 9-month-old child reaching age-appropriate developmental milestones. Four to six weeks after the comics were provided to the parents, they responded to the same questionnaire by phone, which consisted of the same eight questions plus an additional question regarding possible additional uses of the comic. Parents significantly increased their recall of information of developmental milestones when the pre- and post-intervention test results were compared, with a significance of p < 0.001 at a 95% confidence level. Additional uses of the comic reported by parents included calling their pediatrician with doubts about their own child's appropriate achievement of milestones, and lending the comics to relatives or friends. The educational comic appeared to assist parents in making meaningful connections between the simplified pictures and the developmental milestones of their child. Comics may provide an alternative for parental education using this multimodal format to explain simple-to-complex issues

Epidemiology of Invasive Fungal Infections in Latin America

The pathogenic role of invasive fungal infections (IFIs) has increased during the past two decades in Latin America and worldwide, and the number of patients at risk has risen dramatically. Working habits and leisure activities have also been a focus of attention by public health officials, as endemic mycoses have provoked a number of outbreaks. An extensive search of medical literature from Latin America suggests that the incidence of IFIs from both endemic and opportunistic fungi has increased. The increase in endemic mycoses is probably related to population changes (migration, tourism, and increased population growth), whereas the increase in opportunistic mycoses may be associated with the greater number of people at risk. In both cases, the early and appropriate use of diagnostic procedures has improved diagnosis and outcome

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Programmed cell death-1, PD-1, is dysregulated in T cells from children with new onset type 1 diabetes.

Programmed death cell 1 (PD-1) is an inhibitor of T cell activation and is also functionally linked to glycolysis. We hypothesized that PD-1 expression is defective in activated T cells from children with type 1 diabetes (T1D), resulting in abnormal T cell glucose metabolism.In this pilot study, we enrolled children with new onset T1D within 2 weeks of diagnosis (T1D), unaffected siblings of T1D (SIBS), unaffected, unrelated children (CTRL), children with new onset, and untreated Crohn disease (CD). We repeated the assays 4-6 months post-diagnosis in T1D (T1D follow up). We analyzed anti-CD3/-CD28-stimulated peripheral blood mononuclear cells (PBMC) subsets for PD-1 expression by flow cytometry at baseline and after 24 h in culture. We measured cytokines in the culture medium by multiplex ELISA and glycolytic capacity with a flux analyzer.We enrolled 37 children. T cells derived from subjects with T1D had decreased PD-1 expression compared to the other study groups. However, in T1D follow-up T cells expressed PD-1 similarly to controls, but had no differences in PBMC cytokine production. Nonetheless, T1D follow up PBMCs had enhanced glycolytic capacity compared to T1D.Activated T cells from T1D fail to upregulate PD-1 upon T-cell receptor stimulation, which may contribute to the pathogenesis of T1D. T1D follow up PBMC expression of PD-1 normalizes, together with a significant increase in glycolysis compared to T1D. Thus, insulin therapy in T1D children is associated with normal PD1 expression and heightened glycolytic capacity in PBMC

Opitz GBBB syndrome with total anomalous pulmonary venous connection: A new MID1 gene variant

Abstract Background Opitz GBBB syndrome (GBBB) is an X‐linked disease characterized by midline defects, including congenital heart defects. We present our diagnostic approach to the identification of GBBB in a consanguineous family in which two males siblings were concordant for a total anomalous connection of pulmonary veins and minor facial dysmorphias. Methods Targeted exome sequencing analysis of a 380‐gene panel associated with cardiovascular disease was performed on the propositus. Interpretative analysis of the exome results was conducted, and 3D models of the protein changes were generated. Results We identified a NM_000381.4:c.608G>A;p.(Arg203Gln) change in MID1, affecting the conformation of the B‐box 2 domain of the protein, with a zinc finger structure and associated protein interactions. This clinical phenotype is consistent with GBBB; however, the type of congenital heart disease observed in this case has not been previously reported. Conclusion A new likely pathogenic variant on MID1 c.608G>A was found to be associated with Opitz GBBB syndrome

PBMCs from T1D follow up had enhanced glycolytic capacity compared to T1D.

<p><b>A</b>. ECAR (mpH/min) in PBMCs from T1D (black circles) and T1D Follow up (open circles) after adding glucose, oligomycin and 2-DG. <b>B</b>. Integration of area under the curve showing comparisons in ECAR between T1D and T1D Follow up with additives, as shown.</p

Demographic information.

<p>Demographic information.</p

Cytokine production is not increased in T1D compared to T1D follow up.

<p>Cells were cultured for 24 h with and without stimulation with anti CD3/CD28, the supernatant collected and assayed by multiplex cytokine ELISA. Data were log-transformed to obtain normal distributions. <b>A. T1D NS (grey circles) vs S (black circles)</b> Cytokines that showed statistically significant different in T1D between unstimulated and stimulated PBMCs. <b>B. T1D F/U NS (grey circles) vs S (black circles)</b> Cytokine concentration in PBMCs from T1D Follow up. <b>C. T1D S (black circles) vs T1D F/U S (black squares)</b> Comparison of cytokine expression on stimulated PBMCs from subjects with T1D and T1D Follow up. (* indicate p < 0.05).</p

PD-1 expression recovers in T1D follow up.

<p><b>A</b>. Subpopulations of T cells, one that down regulates PD-1 and the other that upregulates PD-1 <b>B</b>. Expression of PD-1 in T cells from T1D after 4–6 months post diagnosis (T1D Follow up) (* indicate p < 0.05). Top left CD3⁺ CD4⁺ lymphocyte gate, top right CD3⁺ CD8⁺ lymphocyte gate, bottom left CD3⁺ CD4⁺ large gate, and bottom right CD3⁺ CD8⁺ large gate.</p