Is fumigation enough for air conditioning units in operation theatres and Intensive care units?

Background:Strict asepsis is necessary in operating theatres (OT) and intensive care units (ICU) as the patients undergo invasive procedures. The filters of contaminated air conditioning (AC) units provide a niche for proliferation of fungi and production of fungal spores.Methods: The routine procedure for maintenance of sterile atmosphere in our hospital, i.e. fumigation and mopping walls with disinfectants often fail to address these fungal spores of the AC filters. We therefore carried out a surveillance of the ACs in ICUs and OTs to find the level of contamination with fungal spores and also to improvise on intervention strategies to tackle the problem. Over 3 months period, 34 ACs from 7 OTs and 2 ICUs were screened by taking 2 swabs from each AC which were then tested for the presence of fungal spores as per standard methods.Results: The contamination rate was 88.2% before fumigation and 76.9% after fumigation. The fungal spore contamination rate was reduced to 20% (1 out of 5 ACs) after servicing of the ACs was done. Aspergillus spp. was the most common fungal isolate.Conclusion: Based on the observations, we recommend regular servicing of the ACs as well as wet mopping of the ducts with sporicidal solution at regular intervals.

Molecular mechanisms and functional consequences of chromatin binding by the human cytomegalovirus proteins IE1 and pUL83

Interferons (IFN) are an essential component of the vertebrate innate immune system against viruses and other pathogens. Human Cytomegalovirus (HCMV), like other viruses, has developed strategies to evade the host IFN response, enabling lifelong viral persistence in the infected host. In this work, we explore how two HCMV proteins, immediate-early protein 1 (IE1), the first viral protein produced in infected cells, and pUL83, the most abundant protein in the virus particle, counteract the host IFN response in the initial stages of infection by interacting with chromatin. First, we identified the molecular mechanism by which pUL83 interacts with host chromatin using various techniques including fluorescence microscopy and in-vitro histone binding studies. The Linker domain of pUL83 (amino acids 388-479) binds with the core histones for this interaction. The Linker targets the nucleosome acidic patch formed by histones H2A-H2B via residues R₄₅₃ and R₄₅₅. It also has distinct charged residue clusters that mediate binding to all four core histones. Nucleosome targeting by IE1 and pUL83 inhibits host IFN-β and IFN-λ production, enabling HCMV to efficiently spread from the initial infected cell to its neighbouring cells, resulting in the formation of larger and more foci of infection. Our results suggest that inhibition of IFN induction by IE1-nucleosome interaction is unlikely due to changes in nucleosome occupancy, but it may rather be attributable to inhibition of NFkB binding to the IFNB1 promoter. Furthermore, we demonstrate that nucleosome binding by IE1 prevents DNA double strand break repair by non-homologous end joining. Finally, we noticed that IE1-nucleosome interaction limits HCMV reactivation in monocytic cells, allowing the virus to persist in a latent state. Overall, we propose that pUL83 and IE1 promote efficient viral spread by inhibiting IFN gene induction via a novel chromatin-based molecular mechanism involving core histones."This work was supported by a Wellcome Trust Institutional Strategic Support Fund. A part of my tuition fee was covered by a St Leonard’s College Scholarship." -- Acknowledgement

Antithrombotic Management in Ischemic Stroke with Essential Thrombocythemia: Current Evidence and Dilemmas

The final, published version of this article is available at https://doi.org/10.1159/000516471Thrombotic diseases like ischemic stroke are common complications of essential thrombocythemia (ET) due to abnormal megakaryopoiesis and platelet dysfunction. Ischemic stroke in ET can occur as a result of both cerebral arterial and venous thrombosis. Management of ET is aimed at preventing vascular complications including thrombosis. Acute management of ischemic stroke in ET is the same as that in the general population without myeloproliferative disorders. However, an ET patient with ischemic stroke is at high risk for rethrombosis and is therefore additionally managed with cytoreductive therapy and antithrombotic agents. Given abnormal platelet production in ET, there is suboptimal suppression of platelets with the standard recommended dose of aspirin for cardiovascular (CV) prevention. Hence, for optimal CV protection in ET, low-dose aspirin is recommended twice daily in an arterial thrombotic disease like atherothrombotic ischemic stroke in presence of the following risk factors: age >60 years, Janus kinase2 V617F gene mutation, and presence of CV risk factors. In the presence of the same risk factors, concurrent antiplatelet and anticoagulant therapy is suggested for venous thrombosis. However, increased risk of bleeding with dual antithrombotic agents poses a significant challenge in their use in cerebral venous thromboembolism or atrial fibrillation in presence of the above-mentioned risk factors. We discuss these dilemmas regarding antithrombotic management in ischemic stroke in ET in this case-based review of literature in the light of current evidence

Human cytomegalovirus pUL83 targets core histones to inhibit interferon synthesis and promote viral spread

Tegument protein pUL83 is the most abundant component of human cytomegalovirus (hCMV) particles. The viral protein is predicted to be composed of three domains: a pyrin association domain (PAD), a carboxy-terminal domain (CTD), and an intrinsically disordered linker domain (amino acids 388–479) located between the PAD and CTD. Although pUL83 has been shown to antagonize interferon (IFN) responses, it has not been fully elucidated how the viral protein may contribute to hCMV replication. In this study we demonstrate that pUL83 associates broadly with viral and host chromatin including condensed chromosomes during mitosis. We further show that the linker domain in pUL83 is both required and sufficient for host chromatin targeting, and that this interaction depends on two evolutionary conserved arginine residues (R453 and R455) in the viral protein. Our data indicate that the pUL83 linker domain specifically associates with human core histones (but not linker histones). Furthermore, pUL83 inhibits IFN-beta and IFN-lambda gene induction, but not expression of other cytokine genes, via a mechanism that largely depends on the linker domain including R453/455. Although earlier studies suggested that pUL83 is dispensable for productive hCMV infection in fibroblasts, we find that the viral protein is necessary for efficient plaque formation in these cells, specifically in the presence of IFN. Finally, the pUL83 linker domain including R453/455 contributes significantly to the plaque size in hCMV-infected fibroblasts. Overall, we propose that pUL83 promotes spread of hCMV by selectively inhibiting induction of IFN gene expression via a novel chromatin-based molecular mechanism involving core histones

Is fumigation enough for air conditioning units in operation theatres and Intensive care units?

Background:Strict asepsis is necessary in operating theatres (OT) and intensive care units (ICU) as the patients undergo invasive procedures. The filters of contaminated air conditioning (AC) units provide a niche for proliferation of fungi and production of fungal spores.Methods: The routine procedure for maintenance of sterile atmosphere in our hospital, i.e. fumigation and mopping walls with disinfectants often fail to address these fungal spores of the AC filters. We therefore carried out a surveillance of the ACs in ICUs and OTs to find the level of contamination with fungal spores and also to improvise on intervention strategies to tackle the problem. Over 3 months period, 34 ACs from 7 OTs and 2 ICUs were screened by taking 2 swabs from each AC which were then tested for the presence of fungal spores as per standard methods.Results: The contamination rate was 88.2% before fumigation and 76.9% after fumigation. The fungal spore contamination rate was reduced to 20% (1 out of 5 ACs) after servicing of the ACs was done. Aspergillus spp. was the most common fungal isolate.Conclusion: Based on the observations, we recommend regular servicing of the ACs as well as wet mopping of the ducts with sporicidal solution at regular intervals.