Though SARS-CoV-2 infections are yet to be completely characterised in a host-pathogen interaction context, some of the mechanisms governing the interaction between the novel betacoronavirus and the human host, have been brought to light in satisfactory detail. Among the emerging evidence, postulates regarding potential benefits of innate immune memory and heterologous immunity have been put under discussion. Innate immune memory entails epigenetic reprogramming of innate immune cells caused by vaccination or infections, whereas heterologous immunity denotes cross-reactivity of T cells with unrelated epitopes and bystander CD8+ activation. Familiarization of the host immune system with a certain pathogen, educates monocytes, macrophages and other innate cells into phenotypes competent for combating unrelated pathogens. Indeed, the resolution at which non-specific innate immune memory occurs, is predominant at the level of enhanced cytokine secretion as a result of epigenetic alterations. One vaccine whose non-specific effects have been documented and harnessed in treating infections, cancer and autoimmunity, is the Bacillus Calmette–Guérin (BCG) vaccine currently used for immunization against pulmonary tuberculosis (TB). The BCG vaccine induces a diverse cytokine secretion profile in immunized subjects, which in turn may stimulate epigenetic changes mediated by immunoreceptor signalling. Herein, we provide a concise summarization of previous findings regarding the effects of the BCG vaccine on innate immune memory and heterologous immunity, supplemented with clinical evidence of the non-specific effects of this vaccine on non-mycobacterial infections, cancer and autoimmunity. This interpretative synthesis aims at providing a plausible immunological and immunogenetic model by which BCG vaccination may, in fact, be beneficial for the current efforts in combating COVID-19.
Human pulmonary tuberculosis represents an unfortunately placed and persistent thorn in global health; asymptomatically infecting nearly a third of the global population, with roughly 10 million new cases and 1.5 million deaths annually. It continues to hold a place among the top ten causes of death in the world and remains the leading infectious cause of death by a single pathogen. Among the numerous reasons for such statistics is the relatively poor efficacy of the near-century-old BCG vaccine. In spite of it being the only approved vaccine for TB, its benefit is predominantly observed in preventing paediatric miliary TB and TB meningitis, whilst it offers considerably limited protection against infection in adults. The advent of mRNA vaccine technologies has passed the critical tribulations for current demand of Coronavirus disease 2019, and in so validating the argument on employing the technology as an effective response to TB as it suggests fulfilment of the necessary criteria: induction of robust, determined innate response with a favourable safety profile across a wider population. To this end, the novel mRNA vaccines were proven to elicit immune responses against bacterial pathogens; by virtue, the technology may be applied in bacterial infection treatment. Meanwhile, no approved mRNA prophylactics for bacterial infections exist yet. Within this work, we propose a novel vaccine design for TB that harvests the potential of mRNA vaccine technology. This was achieved by using a barrage of in silico tools for epitope identification, construct design and rigorous physicochemical evaluation and immune response predictions. The vaccine itself was design for the purpose of immunizing previously unexposed patients, along with individuals that have asymptomatic TB. Additionally, immune response simulations have predicted an immune response relatively in agreement with the natural, beneficial, response to M.tb infection, rather than the detrimental variety.
BACKGROUND: Patient monitors are medical devices used to monitor vital parameters such as heart rate, respiratory rate, blood pressure, blood oxygen saturation, and body temperature during inpatient treatment. As such, patient monitors provide physicians with information necessary to adjust the treatment as well as evaluate the overall status and recovery of the patient. Measurements made by intrinsic sensors of patient monitors must be compliant and provide reliable readings in order to ensure safety and optimal quality of care to the patients. OBJECTIVE: This paper proposes a novel method for conformity assessment testing of patient monitors in healthcare institutions for post-market surveillance purposes. METHOD: The method was developed on the basis of metrology characteristics of sensors used to monitor vital parameters observed by patient monitors and evaluation of their vital safety and performance parameters. In addition to the evaluation of essential safety and visual integrity of patient monitors, their performance in terms of accuracy of the readings is evaluated. RESULTS: The developed method was validated between 2018 and 2021 in healthcare institutions of all levels. The results obtained during validation suggest that conformity assessment testing of patient monitors as a method used during PMS contributes to significant improvement in devices’ accuracy and reliability. CONCLUSION: A standardized approach in conformity assessment testing of patient monitors during PMS, besides increasing reliability of the devices, is the first step in digital transformation of management of these devices in healthcare institutions opening possibility for use of artificial intelligence.
Tuberculosis persists among the top 10 causes of death globally; causing 1.7 million deaths and 10 million new infections in 2018. Approximately 1/3 of the global population is infected with Mycobacterium tuberculosis; 10% of which are expected to develop active TB at some point in their life. The high burden of tuberculosis in the world is owed to lack of adherence to treatment, diminishment in treatment options and post-infection bacterial metabolic dormancy called latent TB (LTB), along with logistic, financial and political obstacles impeding successful TB control programs globally. Infections with M. tuberculosis leave no component of the immune system unengaged, hallmarked with granulomatous pathology as a function of the adaptive immune system. The hallmark of infection is a granulomatous pathological course, with the purpose of containing the difficult-to-kill bacilli, although the nature of the granuloma remains moot. The cells responsible for granuloma formation are professional alveolar macrophages, which seem to have both a beneficial and detrimental role in TB immunopathology. Herein, we discuss relevant immunological intricacies of macrophages in TB, ranging from immunogenetics, receptor-mediated uptake, macrophage-mediated immunopathology and the infamous tuberculosis granuloma.
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