The effect of interrupted anti-retroviral treatment on the reconstitution of memory and naive T cells during tuberculosis treatment in HIV patients with active pulmonary tuberculosis

Background: The reconstitution of cellular immune components contributes to clinical outcome of HIV and Mycobacterium tuberculosis (MTB) infection. Interruption of anti-retroviral therapy (ART) could lead to perturbations in reconstitution of T cells in HIV/ tuberculosis (TB) patients. Objectives: To ascertain the effect of interrupted ART on reconstitution of CD4+ and CD8+ T sub-sets in TB patients.Methods: Participants with HIV (CD4>350 cells/μL) and TB were recruited under a larger phase 3 open label randomised controlled clinical trial. The CD45RO and CD62L markers were measured on CD4+ and CD8+ cells by flow cytometry. Samples were analysed at baseline, 3, 6, 12 months.Results: There was a significant increase of naive CD8+ cells (p = 0.003) and a decrease in effector CD8+ cells (p = 0.004) among participants in ART/TB treatment arm during the first 6 months. Withdrawing ART led to naive CD8+ cells reduction (p=0.02) to values close to baseline. An increase of naive CD8+ cells after 6 months of TB treatment in TB alone treatment arm (p=0.01) was observed. A trend towards increment of naive CD4+ sub sets in either treatment arms was observed.Conclusion: Interrupting ART alters CD8+ but not CD4+ sub-sets in patients with less advanced HIV infection and TB.Keywords: Interrupted anti-retroviral treatment, memory and naive T cells, HIV patients, active pulmonary tuberculosis

Tuberculosis Treatment in HIV Infected Ugandans with CD4 Counts >350 Cells/mm3 Reduces Immune Activation with No Effect on HIV Load or CD4 Count

Both HIV and TB cause a state of heightened immune activation. Immune activation in HIV is associated with progression to AIDS. Prior studies, focusing on persons with advanced HIV, have shown no decline in markers of cellular activation in response to TB therapy alone.) and pulmonary TB. HIV load, CD4 count, and markers of immune activation (CD38 and HLA-DR on CD4 and CD8 T cells) were measured prior to starting, during, and for 6 months after completion of standard 6 month anti-tuberculosis (TB) therapy in 38 HIV infected Ugandans with smear and culture confirmed pulmonary TB.Expression of CD38, and co-expression of CD38 and HLA-DR, on CD8 cells declined significantly within 3 months of starting standard TB therapy in the absence of anti-retroviral therapy, and remained suppressed for 6 months after completion of therapy. In contrast, HIV load and CD4 count remained unchanged throughout the study period.

The effect of interrupted anti-retroviral treatment on the reconstitution of memory and naive T cells during tuberculosis treatment in HIV patients with active pulmonary tuberculosis.

Background: The reconstitution of cellular immune components contributes to clinical outcome of HIV and Mycobacterium tuberculosis (MTB) infection. Interruption of anti-retroviral therapy (ART) could lead to perturbations in reconstitution of T cells in HIV/ tuberculosis (TB) patients. Objectives: To ascertain the effect of interrupted ART on reconstitution of CD4+ and CD8+ T sub-sets in TB patients. Methods: Participants with HIV (CD4>350 cells/\ub5L) and TB were recruited under a larger phase 3 open label randomised controlled clinical trial. The CD45RO and CD62L markers were measured on CD4+ and CD8+ cells by flow cytometry. Samples were analysed at baseline, 3, 6, 12 months. Results: There was a significant increase of naive CD8+ cells (p = 0.003) and a decrease in effector CD8+ cells (p = 0.004) among participants in ART/TB treatment arm during the first 6 months. Withdrawing ART led to naive CD8+ cells reduction (p=0.02) to values close to baseline. An increase of naive CD8+ cells after 6 months of TB treatment in TB alone treatment arm (p=0.01) was observed. A trend towards increment of naive CD4+ sub sets in either treatment arms was observed. Conclusion: Interrupting ART alters CD8+ but not CD4+ sub-sets in patients with less advanced HIV infection and TB

Helena’s Many Daughters: More Mitogenome Diversity behind the Most Common West Eurasian mtDNA Control Region Haplotype in an Extended Italian Population Sample

The high number of matching haplotypes of the most common mitochondrial (mt)DNA lineages are considered to be the greatest limitation for forensic applications. This study investigates the potential to solve this constraint by massively parallel sequencing a large number of mitogenomes that share the most common West Eurasian mtDNA control region (CR) haplotype motif (263G 315.1C 16519C). We augmented a pilot study on 29 to a total of 216 Italian mitogenomes that represents the largest set of the most common CR haplotype compiled from a single country. The extended population sample confirmed and extended the huge coding region diversity behind the most common CR motif. Complete mitogenome sequencing allowed for the detection of 163 distinct haplotypes, raising the power of discrimination from 0 (CR) to 99.6% (mitogenome). The mtDNAs were clustered into 61 named clades of haplogroup H and did not reveal phylogeographic trends within Italy. Rapid individualization approaches for investigative purposes are limited to the most frequent H clades of the dataset, viz. H1, H3, and H7

Neurodevelopment and recovery from wasting

BACKGROUND AND OBJECTIVES Acute illness with malnutrition is a common indication for hospitalization among children in low- and middle-income countries. We investigated the association between wasting recovery trajectories and neurodevelopmental outcomes in young children 6 months after hospitalization for an acute illness. METHODS Children aged 2 to 23 months were enrolled in a prospective observational cohort of the Childhood Acute Illness & Nutrition Network, in Uganda, Malawi, and Pakistan between January 2017 and January 2019. We grouped children on the basis of their wasting recovery trajectories using change in mid–upper arm circumference for age z-score. Neurodevelopment was assessed with the Malawi Developmental Assessment Tool (MDAT development-for-age z-score [DAZ]) at hospital discharge and after 6 months. RESULTS We included 645 children at hospital discharge (mean age 12.3 months ± 5.5; 55% male); 262 (41%) with severe wasting, 134 (21%) with moderate wasting, and 249 (39%) without wasting. Four recovery trajectories were identified: high–stable, n = 112; wasted–improved, n = 404; severely wasted–greatly improved, n = 48; and severely wasted–not improved, n = 28. The children in the severely wasted–greatly improved group demonstrated a steep positive MDAT-DAZ recovery slope. This effect was most evident in children with both wasting and stunting (interaction wasted–improved × time × stunting: P < .001). After 6 months, the MDAT DAZ in children with wasting recovery did not differ from community children. In children who never recovered from wasting, there remained a significant delay in MDAT DAZ scores. CONCLUSIONS Neurodevelopment recovery occurred in parallel with wasting recovery in children convalescing from acute illness and was influenced by stunting

Effects of a motivating operation manipulation on the maintenance of mands

Item does not contain fulltextWe assessed the maintenance of newly acquired mands under presession reinforcer access (reinforcer efficacy abolished) and no presession reinforcer access (reinforcer efficacy established) conditions with 3 children with autism spectrum disorder. Results suggested that the no presession access condition established the value of the reinforcer and evoked responding relative to the presession access condition. Results are discussed in the context of implications for assessing maintenance of previously acquired skills.5 p