Targeting an RNA-Binding Protein Network in Acute Myeloid Leukemia

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Effectiveness of Influenza Vaccine in Hemodialyzed Patients: A Retrospective Study

Infection is one of the leading causes of mortality in dialysis patients, second only to cardiovascular disease. This retrospective study assessed the efficacy and clinical outcomes of influenza vaccination among hemodialysis (HD) patients. In the 2014–2015 season, 104 of 164 (63.6%) HD patients were vaccinated for influenza by the outpatient community health system facilities. Significantly more patients, 159 of 170 (93.8%), were vaccinated in 2015–2016 by the hospital dialysis unit staff during an inpatient HD session (P <0.001). A trend toward fewer complications from influenza infection was observed in vaccinated patients. Among HD patients with diabetes (who comprised 56% of the study population), the incidence of influenza was 17% among nonvaccinated patients vs. 6.3% among those who were vaccinated (P =0.026). The inpatient vaccination policy resulted in a greater rate of vaccination. HD patients with diabetes benefit from influenza vaccination, with a significantly lower incidence of influenza infection.     

Inequalities in Tobacco Retailer Compliance Violations Across the State of Oklahoma, 2015–2019

Objective

To evaluate the relationship between compliance check violations, and characteristics of the tobacco retailer and neighborhood social vulnerability in Oklahoma.

Design

This cross-sectional study utilized the US Food and Drug Administration (FDA) Compliance Check Inspections of Tobacco Product Retailers database for 2015–2019. These data were combined with Neighborhood social vulnerability variables using the Centers for Disease Control and Prevention (CDC) Social Vulnerability Index.

Setting

The setting of this study is the state of Oklahoma, USA.

Outcome measures

The outcome variable for this analysis was whether a sale was made to the youth during the compliance check (e.g., violation; yes/no) regardless of the outcome of the violation, and number of violations per a retailer.

Results

We observed a strong association between having a violation and retailer store type, after controlling for socioeconomic vulnerability and percentage of mobile homes. The proportion of a tobacco retailer’s violations also varied by store type.

Conclusions

More targeted enforcements and retailer education by store type may be necessary to increase compliance.

     

Mesenchymal stem cell therapy alleviates the neuroinflammation associated with acquired brain injury

Ischemic stroke and traumatic brain injury (TBI) comprise two particularly prevalent and costly examples of acquired brain injury (ABI). Following stroke or TBI, primary cell death and secondary cell death closely model disease progression and worsen outcomes. Mounting evidence indicates that long‐term neuroinflammation extensively exacerbates the secondary deterioration of brain structure and function. Due to their immunomodulatory and regenerative properties, mesenchymal stem cell transplants have emerged as a promising approach to treating this facet of stroke and TBI pathology. In this review, we summarize the classification of cell death in ABI and discuss the prominent role of inflammation. We then consider the efficacy of bone marrow–derived mesenchymal stem/stromal cell (BM‐MSC) transplantation as a therapy for these injuries. Finally, we examine recent laboratory and clinical studies utilizing transplanted BM‐MSCs as antiinflammatory and neurorestorative treatments for stroke and TBI. Clinical trials of BM‐MSC transplants for stroke and TBI support their promising protective and regenerative properties. Future research is needed to allow for better comparison among trials and to elaborate on the emerging area of cell‐based combination treatments.     

The role of polo-like kinase 3 in the response of BRAF-mutant cells to targeted anticancer therapies

The activation of oncogenic mitogen-activated protein kinase cascade via mutations in BRAF is often observed in human melanomas. Targeted inhibitors of BRAF (BRAFi), alone or as a part of a combination therapy, offer a significant benefit to such patients. Unfortunately, some cases are initially nonresponsive to these drugs, while others become refractory in the course of treatment, underscoring the need to understand and mitigate the underlying resistance mechanisms. We report that interference with polo-like kinase 3 (PLK3) reduces the tolerance of BRAF-mutant melanoma cells to BRAFi, while increased PLK3 expression has the opposite effect. Accordingly, PLK3 expression correlates with tolerance to BRAFi in a panel of BRAF-mutant cell lines and is elevated in a subset of recurring BRAFi-resistant melanomas. In PLK3-expressing cells, R406, a kinase inhibitor whose targets include PLK3, recapitulates the sensitizing effects of genetic PLK3 inhibitors. The findings support a role for PLK3 as a predictor of BRAFi efficacy and suggest suppression of PLK3 as a way to improve the efficacy of targeted therapy.     

Influenza A Virus Hemagglutinin and Other Pathogen Glycoprotein Interactions with NK Cell Natural Cytotoxicity Receptors NKp46, NKp44, and NKp30

Natural killer (NK) cells are part of the innate immunity repertoire, and function in the recognition and destruction of tumorigenic and pathogen-infected cells. Engagement of NK cell activating receptors can lead to functional activation of NK cells, resulting in lysis of target cells. NK cell activating receptors specific for non-major histocompatibility complex ligands are NKp46, NKp44, NKp30, NKG2D, and CD16 (also known as FcγRIII). The natural cytotoxicity receptors (NCRs), NKp46, NKp44, and NKp30, have been implicated in functional activation of NK cells following influenza virus infection via binding with influenza virus hemagglutinin (HA). In this review we describe NK cell and influenza A virus biology, and the interactions of influenza A virus HA and other pathogen lectins with NK cell natural cytotoxicity receptors (NCRs). We review concepts which intersect viral immunology, traditional virology and glycobiology to provide insights into the interactions between influenza virus HA and the NCRs. Furthermore, we provide expert opinion on future directions that would provide insights into currently unanswered questions.