Human cytomegalovirus modulates mTORC1 to redirect mRNA translation within quiescently infected monocytes.

Human cytomegalovirus (HCMV) utilizes peripheral blood monocytes as a means to systemically disseminate throughout the host. Following viral entry, HCMV stimulates non-canonical Akt signaling leading to the activation of mTORC1 and the subsequent translation of select antiapoptotic proteins within infected monocytes. However, the full extent to which the HCMV-initiated Akt/mTORC1 signaling axis reshapes the monocyte translatome is unclear. We found HCMV entry alone was able to stimulate widescale changes to mRNA translation levels and that inhibition of mTOR, a component of mTORC1, dramatically attenuated HCMV-induced protein synthesis. Although monocytes treated with normal myeloid growth factors also exhibited increased levels of translation, mTOR inhibition had no effect, suggesting HCMV activation of mTOR stimulates the acquisition of a unique translatome within infected monocytes. Indeed, polyribosomal profiling of HCMV-infected monocytes identified distinct prosurvival transcripts that were preferentially loaded with ribosomes when compared to growth factor-treated cells. Sirtuin 1 (SIRT1), a deacetylase that exerts prosurvival effects through regulation of the PI3K/Akt pathway, was found to be highly enriched following HCMV infection in an mTOR-dependent manner. Importantly, SIRT1 inhibition led to the death of HCMV-infected monocytes while having minimal effect on uninfected cells. SIRT1 also supported a positive feedback loop to sustain Akt/mTORC1 signaling following viral entry. Taken together, HCMV profoundly reshapes mRNA translation in an mTOR-dependent manner to enhance the synthesis of select factors necessary for the survival of infected monocytes.IMPORTANCEHuman cytomegalovirus (HCMV) infection is a significant cause of morbidity and mortality among the immunonaïve and immunocompromised. Peripheral blood monocytes are a major cell type responsible for disseminating the virus from the initial site of infection. In order for monocytes to mediate viral spread within the host, HCMV must subvert the naturally short lifespan of these cells. In this study, we performed polysomal profiling analysis, which demonstrated HCMV to globally redirect mRNA translation toward the synthesis of cellular prosurvival factors within infected monocytes. Specifically, HCMV entry into monocytes induced the translation of cellular SIRT1 to generate an antiapoptotic state. Defining the precise mechanisms through which HCMV stimulates survival will provide insight into novel anti-HCMV drugs able to target infected monocytes.

Knowledge and Attitude Regarding Human Monkeypox Virus Infection among Nurses: A Cross-Sectional Study.

Introduction: Monkeypox (Mpox) is an infectious illness that can spread to humans through infected humans, animals, or contaminated objects. In 2022, the monkeypox virus spread to over 60 countries, raising significant public health concerns. Nurses play a vital role in patient care and have critical responsibilities in managing infected patients and being aware of the potential impact on the general population. Objective: This study aimed to investigate the knowledge and attitudes (KAs) of Bangladeshi nurses regarding monkeypox infectious disease. Methods: A cross-sectional study was conducted between October 2022 and March 2023 to evaluate the KA of nurses. Semi-structured and self-administered questionnaires were used, distributed via Google Form, and a convenient sampling technique was implemented. The dataset was analyzed using the Chi-square test, multivariable logistic regression, and Pearson correlation coefficient. Results: A total of 1047 datasets were included in the final analysis. Overall, 57.97% of the participants demonstrated good knowledge, and 93.12% of the respondents had a positive attitude towards monkeypox disease. Female nurses exhibited better knowledge (adjusted odds ratio (AOR) 1.36; 95% confidence interval (CI) 0.88-1.98) and a more positive attitude (AOR 1.64; 95% CI 1.12-3.00) than male nurses. Furthermore, a strong correlation was observed between good knowledge of monkeypox disease and a positive attitude (r = 0.76, p < 0.001), while poor knowledge moderately correlated with a negative attitude (r = 0.53, p < 0.001). Conclusions: Given the need for further improvement in KA, we recommend implementing additional training programs to enhance the abilities and motivation of nurses in effectively managing patients affected by monkeypox.

A Haemophilic Dengue Patient with Pleural Effusion and Earache.

About 2.5 billion people are living at a higher risk of dengue fever in hundreds of tropical and sub-tropical countries. Treatment of dengue fever is quite complicated and challenging because of the lack of effective treatment approaches. We herein report a rare case of a 25-year-old female with a past medical history of haemophilia A, suffering from dengue fever, pleural effusion, earache, myalgia, headache, and vomiting. Dengue was confirmed by the non-structural protein 1 (NS1) antigen and immunoglobulin M (IgM) antibody test. She had low blood pressure (80/60 mmHg), frequent vomiting, and low platelet count during hospitalization. Moreover, a genetic disorder like haemophilia with plasma leakage and earache made the patient's condition worse. However, by repeated platelet infusion, the platelet counts elevated and the patient was discharged from the hospital after nine days. Complete recovery was achieved after 27 days. This is a rare case of dengue; physicians should be aware of the severity of the disease and its management tactics. More discussion and research need to be carried out to develop an effective and optimized treatment and management options to reduce the mortality and morbidity due to dengue fever with a co-morbid disease.

Assessing climate-induced agricultural vulnerable coastal communities of Bangladesh using machine learning techniques.

The agricultural arena in the coastal regions of South-East Asian countries is experiencing the mounting pressures of the adverse effects of climate change. Controlling and predicting climatic factors are difficult and require expensive solutions. The study focuses on identifying issues other than climatic factors using the Livelihood Vulnerability Index (LVI) to measure agricultural vulnerability. Factors such as monthly savings of the farmers, income opportunities, damage to cultivable lands, and water availability had significant impacts on increasing community vulnerability with regards to agricultural practice. The study also identified the need for assessing vulnerability after certain intervals, specifically owing to the dynamic nature of the coastal region where the factors were found to vary among the different study areas. The development of a climate-resilient livelihood vulnerability assessment tool to detect the most significant factors to assess agricultural vulnerability was done using machine learning (ML) techniques. The ML techniques identified nine significant factors out of 21 based on the minimum level of standard deviation (0.03). A practical application of the outcome of the study was the development of a mobile application. Custom REST APIs (application programming interface) were developed on the backend to seamlessly sync the app to a server, thus ensuring the acquisition of future data without much effort and resources. The paper provides a methodology for a unique vulnerability assessment technique using a mobile application, which can be used for the planning and management of resources by different stakeholders in a sustainable way.

Antibiotic use for pneumonia among children under-five at a pediatric hospital in Dhaka city, Bangladesh.

BACKGROUND: Pneumonia has been the leading cause of morbidity and mortality among children under 5 for more than 3 decades, particularly in low-income countries like Bangladesh. The World Health Organization (WHO) developed a pneumonia case management strategy which included the use of antibiotics for both primary and hospital-based care. This study aims to describe antibiotic usage for treating pneumonia in children in a private pediatric teaching hospital in Dhaka, Bangladesh. METHODS: We conducted this cross-sectional study among children <5 years old who were admitted to a private pediatric hospital in Dhaka with a diagnosis of pneumonia in November 2012. RESULTS: We enrolled 80 children during the study period. Among them, 28 (35.4%) were underweight, 14 (17.7%) were moderately underweight, and 13 (16.5%) were severely under-weight. On the basis of WHO classification (2005), 43 children (54%) had severe pneumonia and 37 (46%) had very severe pneumonia, as diagnosed by the research physician. Among the prescribed antibiotics in the hospital, parenteral ceftriaxone was the most common 40 (50%), followed by cefotaxime plus amikacin 14 (17.5%), cefuroxime 7 (8.8%), ceftazidime plus amikacin 6 (7.5%), ceftriaxone plus amikacin 3 (3.8%), meropenem 2 (2.5%), cefepime 2 (2.5%), and cefotaxime 2 (2.5%). CONCLUSION: Despite the WHO pneumonia treatment strategy, the inappropriate use of higher-generation cephalosporin and carbapenem was high in the study hospital. The results underscore the noncompliance with the WHO guidelines of antibiotic use and the importance of enforcing regulatory policy of the rational use of antibiotics for treating hospitalized children with pneumonia. Following these guidelines may help prevent increased antimicrobial resistance.