Bronchiectasis and other chronic lung diseases in adolescents living with HIV.

: The incidence of pulmonary infections has declined dramatically with improved access to antiretroviral therapy (ART) and cotrimoxazole prophylaxis, but chronic lung disease (CLD) is an increasingly recognized but poorly understood complication in adolescents with perinatally acquired HIV. : There is a high prevalence of chronic respiratory symptoms, abnormal spirometry and chest radiographic abnormalities among HIV-infected adolescents in sub-Saharan Africa, wherein 90% of the world's HIV-infected children live. The incidence of lymphocytic interstitial pneumonitis, the most common cause of CLD in the pre-ART era, has declined with increased ART access. Small airways disease, particularly constrictive obliterative bronchiolitis and bronchiectasis, are emerging as leading causes of CLD among HIV-infected adolescents in low-income and middle-income countries. Asthma may be more common in high-income settings. Likely risk factors for CLD include recurrent pulmonary infections, air pollution, HIV-related immune dysfunction, and untreated HIV infection, particularly during critical stages of lung development. : Globally, the importance of HIV-associated CLD as a cause of morbidity and mortality is increasing, especially as survival has improved dramatically with ART and growing numbers of children living with HIV enter adolescence. Further research is urgently needed to elucidate the natural history and pathogenesis of CLD, and to determine optimal screening, diagnostic and treatment strategies.<br/

Rebuttal to Hasty and Vijg: ‘Accelerating aging by mouse reverse genetics: a rational approach to understanding longevity’

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72056/1/j.1474-9728.2004.00084.x.pd

The identification in adult bone marrow of pluripotent and restricted stem cells of the myeloid and lymphoid systems

The precise relationship between the stem cells for the lymphoid system and those for the blood-forming system is unclear. While it is generally assumed that the hemopoietic stem cell, the spleen colony-forming unit (CFU-S), is also the stem cell for the lymphoid system, there is little evidence for this hypothesis. To investigate the stem cells in these two systems, we irradiated bone marrow cells to induce unique chromosome aberrations in the stem cell population and injected them at limiting dilution into stem cell-deficient recipients. Several months (between 3 and 11) were allowed for the injected cells to repopulate the hemopoietic system. At that time, the bone marrow, spleen, and thymus were examined for a high frequency of cells having the same unique chromosome aberration. The presence of such markers shows that the marker was induced in a cell with extensive proliferative capacity, i.e., a stem cell. In addition, the splenic lymphocytes were stimulated with phytohemagglutinin (PHA) or lipopolysaccharide (LPS) to search for unique chromosomes in dividing T and B cells, respectively. Finally, bone marrow cells were injected into secondary irradiated recipients to determine if the marker occurred in CFU-S and to determine whether or not the same tissue distributions of marked cells could be propogated by bone marrow cells in a second recipient. After examination of 28 primary recipients, it was possible to identify three unique patterns of stem cell regeneration. In one set of mice, a unique chromosome marker was observed in CFU-S and in PHA- and LPS-stimulated cultures. These mice provide direct evidence for a pluripotent stem cell in bone marrow. In addition, two restricted stem cells were identified by this analysis. In three recipients, abnormal karyotypes were found only in myeloid cells and not in B and T lymphocytes. These mice presumably received a marked stem cell restricted to differentiate only into myeloid progeny. In three other recipients, chromosome aberrations were found only in PHA-stimulated cells; CFU-S and cells from LPS cultures did not have cells with the unique chromosome. This pattern suggests that bone marrow contains cells committed to differentiation only into T lymphocytes. For each of the three types of stem cells, secondary recipients had the same cellular distribution of marked cells as the primary recipients. This observation provides further evidence that unique markers can be induced in both pluripotent and restricted stem cells

Zine: Policing (Dis)Ability

https://www.exhibit.xavier.edu/state_sanctioned_violence/1024/thumbnail.jp

Extensive cerebrovascular disease and stroke with prolonged prodromal symptoms as first presentation of perinatally-acquired human immunodeficiency virus infection in a young adult.

A 26-year-old black African woman presented with an acute onset of hemiparesis and visual symptoms. This had been preceded several months by symptoms which were apparently psychiatric in nature. She had no apparent risk for cerebrovascular disease. Neurological evaluation revealed a striking burden of cerebrovascular disease for her age, including the rare stroke syndrome of basilar artery occlusion. Human immunodeficiency virus (HIV) infection was identified during clinical assessment. This was judged to be perinatally acquired, as there was no history of sexual debut or blood transfusion; her mother was taking antiretroviral therapy and she had facial planar warts and underlying bronchiectasis. Therefore, it has been concluded that presentation of stroke should prompt HIV testing in young people and perinatally-acquired infection can present in adulthood

Harnessing recombinase polymerase amplification for rapid multi-gene detection of SARS-CoV-2 in resource-limited settings

The COVID-19 pandemic is challenging diagnostic testing capacity worldwide. The mass testing needed to limit the spread of the virus requires new molecular diagnostic tests to dramatically widen access at the point-of-care in resource-limited settings. Isothermal molecular assays have emerged as a promising technology, given the faster turn-around time and minimal equipment compared to gold standard laboratory PCR methods. However, unlike PCR, they do not typically target multiple SARS-CoV-2 genes, risking sensitivity and specificity. Moreover, they often require multiple steps thus adding complexity and delays. Here we develop a multiplexed, 1-2 step, fast (20-30 minutes) SARS-CoV-2 molecular test using reverse transcription recombinase polymerase amplification to simultaneously detect two conserved targets - the E and RdRP genes. The agile multi-gene platform offers two complementary detection methods: real-time fluorescence or dipstick. The analytical sensitivity of the fluorescence test was 9.5 (95% CI: 7.0-18) RNA copies per reaction for the E gene and 17 (95% CI: 11-93) RNA copies per reaction for the RdRP gene. The analytical sensitivity for the dipstick was 130 (95% CI: 82-500) RNA copies per reaction. High specificity was found against common seasonal coronaviruses, SARS-CoV and MERS-CoV model samples. The dipstick readout demonstrated potential for point-of-care testing in decentralised settings, with minimal or equipment-free incubation methods and a user-friendly prototype smartphone application. This rapid, simple, ultrasensitive and multiplexed molecular test offers valuable advantages over gold standard tests and in future could be configurated to detect emerging variants of concern

Predicting Risky Drinking Outcomes Longitudinally: What Kind of Advance Notice Can We Get?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65954/1/j.1530-0277.2006.00033.x.pd

Longitudinal Research on Alcohol Problems: The Flow of Risk, Problems, and Disorder over Time

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65764/1/j.1530-0277.1996.tb01753.x.pd

Negotiating the archive

Collaborative artists Carson & Miller’s project with the Scottish National Gallery of Modern Art utilizes their established practice of play. The project explores the physical and conceptual spaces of this museum’s archive. Carson & Miller’s play encompasses a variety of games; between themselves, as well as games that have drawn in visitors and staff. These games have proven to be a fruitful strategy for piercing the archive; its physical presence, its mass and meaning, its availability to the visitor. This article is informed by Roland Barthes’ punctum and explores how these archive games have opened up opportunities for interaction, handling and touch in its physical, sensual and intellectual senses

Maternal nutrition at conception modulates DNA methylation of human metastable epialleles.

In experimental animals, maternal diet during the periconceptional period influences the establishment of DNA methylation at metastable epialleles in the offspring, with permanent phenotypic consequences. Pronounced naturally occurring seasonal differences in the diet of rural Gambian women allowed us to test this in humans. We show that significant seasonal variations in methyl-donor nutrient intake of mothers around the time of conception influence 13 relevant plasma biomarkers. The level of several of these maternal biomarkers predicts increased/decreased methylation at metastable epialleles in DNA extracted from lymphocytes and hair follicles in infants postnatally. Our results demonstrate that maternal nutritional status during early pregnancy causes persistent and systemic epigenetic changes at human metastable epialleles