Mechanisms of reactivation of latent tuberculosis infection due to SIV coinfection

HIV is a major driver of tuberculosis (TB) reactivation. Depletion of CD4+ T cells is assumed to be the basis behind TB reactivation in individuals with latent tuberculosis infection (LTBI) coinfected with HIV. Nonhuman primates (NHPs) coinfected with a mutant simian immunodeficiency virus (SIVΔGY) that does not cause depletion of tissue CD4+ T cells during infection failed to reactivate TB. To investigate the contribution of CD4+ T cell depletion relative to other mechanisms of SIV-induced reactivation of LTBI, we used CD4R1 antibody to deplete CD4+ T cells in animals with LTBI without lentiviral infection. The mere depletion of CD4+ T cells during LTBI was insufficient in generating reactivation of LTBI. Instead, direct cytopathic effects of SIV resulting in chronic immune activation, along with the altered effector T cell phenotypes and dysregulated T cell homeostasis, were likely mediators of reactivation of LTBI. These results revealed important implications for TB control in HIV-coinfected individuals

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Use of the iTClamp versus standard suturing techniques for securing chest tubes: A randomized controlled cadaver study

Objectives: Tube thoracostomy (TT) is a common yet potentially life-saving trauma procedure. After successful placement however, securing a TT through suturing is a skillset that requires practice, risking that the TT may become dislodged during prehospital transport. The purpose of this study was to examine if the iTClamp was a simpler technique with equivalent effectiveness for securing TTs. Materials and methods: In a cadaver model, a 1.5 inch incision was utilized along the upper border of the rib below the 5th intercostal space at the anterior axillary line. TTs (sizes 28Fr, 32Fr, 36Fr and 40Fr) were inserted and secured with both suturing and iTClamp techniques according to the preset randomization. TT were then functionally tested for positive and negative pressure as well as the force required to remove the TT (pull test-up to 5 lbs). Time to secure the TT was also recorded. Results: When sutured is placed by a trained surgeon, the sutures and iTClamp were functionally equivalent for holding a positive and negative pressure. Mean pull force for both sutures and iTClamp exceeded the 5 lb threshold; there was no significant difference between the groups. Securing the TT with the iTClamp was significantly faster (p < 0.0001) with the iTClamp having a mean application time of 37.0 ± 22.8 s and using a suture had a man application time of 96.3 ± 29.0 s. Conclusion: The iTClamp was effective in securing TTs. The main benefit to the iTClamp is that minimal skill is required to adequately secure a TT to ensure that it does not become dislodged during transport to a trauma center. Keywords: Chest tube, Tube thoracostomy, Securing chest tube

Genetic Diversity of Cryptosporidium spp. from Bangladeshi Children▿

The genetic diversity of Cryptosporidium spp. from infected children was characterized for the first time in Bangladesh. Seven C. hominis and C. parvum subtype families (including a new family, IIm) and 15 subtypes (including 2 new subtypes) were identified. The dominance of specific families and subtypes was different from that in other countries

Antiviral drug screen identifies DNA-damage response inhibitor as potent blocker of SARS-CoV-2 replication.

SARS-CoV-2 has currently precipitated the COVID-19 global health crisis. We developed a medium-throughput drug-screening system and identified a small-molecule library of 34 of 430 protein kinase inhibitors that were capable of inhibiting the SARS-CoV-2 cytopathic effect in human epithelial cells. These drug inhibitors are in various stages of clinical trials. We detected key proteins involved in cellular signaling pathways mTOR-PI3K-AKT, ABL-BCR/MAPK, and DNA-damage response that are critical for SARS-CoV-2 infection. A drug-protein interaction-based secondary screen confirmed compounds, such as the ATR kinase inhibitor berzosertib and torin2 with anti-SARS-CoV-2 activity. Berzosertib exhibited potent antiviral activity against SARS-CoV-2 in multiple cell types and blocked replication at the post-entry step. Berzosertib inhibited replication of SARS-CoV-1 and the Middle East respiratory syndrome coronavirus (MERS-CoV) as well. Our study highlights key promising kinase inhibitors to constrain coronavirus replication as a host-directed therapy in the treatment of COVID-19 and beyond as well as provides an important mechanism of host-pathogen interactions