Notes

A singular Actinobacterial Cutinase That contain the Non-Catalytic Polymer-Binding Site.
More than 25% of patients with COVID-19 were asymptomatic.•Among patients with COVID-19, 26.1% presented anosmia, and 22.6% complained of ageusia with median duration of 7 days.•Mean duration of SARS-CoV-2 viral shedding was 24.5 days.•Irrespective of clinical manifestations, all patients with COVID-19 showed prolonged viral shedding.Objectives Interferons (IFNs) play multifunctional roles in host defense against infectious diseases by inducing IFN-stimulated genes (ISGs). However, little is known about how ISGs regulate host immune response to Mycobacterium tuberculosis (Mtb) infection, the major cause of tuberculosis (TB). Methods We thus profiled the potential effects and mechanisms of eight Mtb-induced ISGs on Mtb infection by RNA interference in human macrophages (Mφs) derived from peripheral blood monocytes (hMDMs) and THP-1 cell line derived Mφs (THP-1-Mφs). Results MxA silencing significantly decreased intracellular Mtb infection in Mφs. Mechanistically, MxA silencing promoted inflammatory cytokines IL-1β, IL-6 and TNF-α production, and induced NF-κB p65 activation. Pharmacological inhibition of NF-κB p65 activation or gene silencing of NF-κB p65 blocked the increased production of IL-1β, IL-6 and TNF-α and restored Mtb infection by MxA silencing. Furthermore, pharmacological inhibition of TAK1 and IKKα/β blocked NF-κB p65 activation and subsequent production of pro-inflammatory cytokines by MxA silencing. Isoniazid (INH) treatment and MxA silencing could promote TAK1-IKKα/β-NF-κB signaling pathway activation and combat Mtb infection independently. Conclusions Our results reveal a novel role of MxA in regulating TAK1-IKKα/β-NF-κB signaling activation and production of antimicrobial inflammatory cytokines upon Mtb infection, providing a potential target for clinical treatment of TB.Background Reactive arthritis, irritable bowel syndrome (IBS), Guillain-Barré syndrome, ulcerative colitis, and Crohn's disease may be sequelae of Campylobacter or non-typhoidal Salmonella (NTS) infections. Proton pump inhibitors (PPI) and antibiotics may increase the risk of gastrointestinal infections (GII); however, their impact on sequelae onset is unclear. We investigated the incidence of sequelae, their association with antibiotics and PPI prescription, and assessed the economic impact on the NHS. Methods Data from the Clinical Practice Research Datalink for patients consulting their GP for Campylobacter or NTS infection, during 2000-2015, were linked to hospital, mortality, and Index of Multiple Deprivation data. We estimated the incidence of sequelae and deaths in the 12 months following GII. We conducted logistic regression modelling for the adjusted association with prescriptions. We compared differences in resource use and costs pre- and post-infection amongst patients with and without sequelae. Findings Of 20,471 patients with GII (Campylobacter 17,838), less than 2% (347) developed sequelae, with IBS (268) most common. Amongst Campylobacter patients, those with prescriptions for PPI within 12 months before and cephalosporins within 7-days before/after infection had elevated risk of IBS (adjusted odds ratio [aOR] 2.1, 1.5-2.9) and (aOR 3.6, 1.1-11.7) respectively. Campylobacter sequelae led to ∼ £1.3 million, (£750,000, £1.7 million) in additional annual NHS expenditure. Interpretation Sequelae of Campylobacter and NTS infections are rare but associated with increased NHS costs. Prior prescription of PPI may be a modifiable risk factor. Ademetionine nmr Incidence of sequelae, healthcare resource use and costs are essential parameters for future burden of disease studies.Parasites of the genus Plasmodium infect a wide range of mammalian hosts including humans, primates, bats and arboreal rodents. A hallmark of Plasmodium spp. is the very narrow host range, indicative of matching parasite-host coevolution. Accordingly, their respective genomes harbour many unique genes and gene families that typically encode proteins involved in host cell recognition and remodelling. Whether and to what extent conserved proteins that are shared across Plasmodium spp. also exert distinct species-specific roles remains largely untested. Here, we present detailed functional profiling of the female gametocyte-specific ATP-binding cassette transporter gABCG2 in the murine parasite Plasmodium berghei and compare our findings with data from the orthologous gene in the human parasite Plasmodium falciparum. We show that P. berghei gABCG2 is female-specific and continues to be expressed in zygotes and ookinetes. In contrast to a distinct localization to Iipid-rich gametocyte-specific spots as observed in P. falciparum, the murine malaria parasite homolog is found at the parasite plasma membrane. Plasmodium berghei lacking gABCG2 displays fast asexual blood-stage replication and increased proportions of female gametocytes, consistent with the corresponding P. falciparum knock-out phenotype. Strikingly, cross-species replacement of gABCG2 in either the murine or the human parasite did not restore normal growth rates. The lack of successful complementation despite high conservation across Plasmodium spp. is an indicator of distinct adaptations and tight parasite-host coevolution. Hence, incompatibility of conserved genes in closely related Plasmodium spp. might be more common than previously anticipated.Background Patients who present to the hospital for infectious complications of intravenous opioid use are at high risk for against medical advice discharge and readmissions. The role of medication assisted treatment for inpatients is not clear. We aimed to assess outcomes before and after rollout of an inpatient buprenorphine-based opioid use disorder protocol, as well as to assess outcomes in general for medication assisted therapy. Methods This was a retrospective observational cohort study at our community hospital in New Hampshire. The medical record was searched for inpatients with a complication of intravenous opioid use. We searched for admissions 11 months before and after the November 2018 buprenorphine protocol rollout. Results Rates of medication assisted therapy usage and buprenorphine linkage increased significantly after protocol rollout. Rates of against medical advice discharge did not decrease after protocol rollout, nor did readmissions. However, when evaluating the entire group of patients regardless of date of presentation or protocol use, against medical advice discharge rates were dramatically lower for patients receiving medication assisted therapy compared to those receiving supportive care only (30.
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