e-Cigarette Tobacco Flavors, Public Health, and Toxicity: Narrative Review.

BACKGROUND: Recently, the US Food and Drug Administration implemented enforcement priorities against all flavored, cartridge-based e-cigarettes other than menthol and tobacco flavors. This ban undermined the products' appeal to vapers, so e-cigarette manufacturers added flavorants of other attractive flavors into tobacco-flavored e-cigarettes and reestablished appeal. OBJECTIVE: This review aims to analyze the impact of the addition of other flavorants in tobacco-flavored e-cigarettes on both human and public health issues and to propose further research as well as potential interventions. METHODS: Searches for relevant literature published between 2018 and 2023 were performed. Cited articles about the toxicity of e-cigarette chemicals included those published before 2018, and governmental websites and documents were also included for crucial information. RESULTS: Both the sales of e-cigarettes and posts on social media suggested that the manufacturers' strategy was successful. The reestablished appeal causes not only a public health issue but also threats to the health of individual vapers. Research has shown an increase in toxicity associated with the flavorants commonly used in flavored e-cigarettes, which are likely added to tobacco-flavored e-cigarettes based on tobacco-derived and synthetic tobacco-free nicotine, and these other flavors are associated with higher clinical symptoms not often induced solely by natural, traditional tobacco flavors. CONCLUSIONS: The additional health risks posed by the flavorants are pronounced even without considering the toxicological interactions of the different tobacco flavorants, and more research should be done to understand the health risks thoroughly and to take proper actions accordingly for the regulation of these emerging products.

Rare Case of Mycobacterium Avium Complex Peritonitis in a Patient with Multiple Myeloma Undergoing Peritoneal Dialysis.

Mycobacterium avium complex (MAC) infections can present as a variety of severe diseases. While it has a predilection for immunocompromised patients such as those with Human immunodeficiency virus (HIV), it can also affect immunocompetent patients as well. One of the rare yet severe diseases that MAC infections can present is MAC peritonitis. Often hard to distinguish from other causes of peritonitis, high clinical suspicion should be maintained for those who are susceptible. Here we present an 85-year-old female with a past medical history of end-stage renal disease on peritoneal dialysis who presented with nausea and vomiting. She was found to have tenderness around her peritoneal dialysis site and was noted to have mild ascites. Her labs were significant for several electrolyte abnormalities, leukocytosis, and ascitic fluid obtained during a previous admission, and serology was positive for acid-fast bacilli. It was further revealed that the species was Mycobacterium avium complex. Initially, she started on rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE), subsequently antibiotics were changed to azithromycin, ethambutol, and rifampin after MAC identification in acid-fast bacilli culture. We aim to highlight this rare presentation of peritonitis secondary to MAC.

An Interesting Case of Methicillin-Resistant Staphylococcus aureus Prostate Abscess in an Immunocompetent Patient.

Prostate abscess is a rare complication of prostatitis, typically observed in patients with conditions such as immunodeficiency, diabetes, urinary tract abnormalities, and chronic indwelling catheters. Gram-negative bacteria such as Enterobacteriaceae are the most commonly detected organisms in prostate abscesses. Methicillin-resistant Staphylococcus aureus (MRSA) infections are rarely reported. The unique aspect of our case involves MRSA bacteria, further complicated by an MRSA prostate abscess, in a 61-year-old immunocompetent male. The patient, with a past medical history of hypertension and diabetes, presented to the emergency department complaining of nausea and vomiting for four days, with an associated subjective fever and right-sided abdominal pain. A computed tomography (CT) scan of the abdomen/pelvis with contrast showed a prostatic abscess, with abscess/phlegmon extending bilaterally into the seminal vesicles. Urine and blood cultures were positive for MRSA. Initially, Piperacillin/Tazobactam and Vancomycin were initiated. Subsequently, the treatment was switched to Daptomycin. The patient also underwent cystoscopy with urethral dilation, transurethral prostate resection, and unroofing. Although MRSA is not a typical causative agent of prostatitis, it should be considered in the differential diagnosis, especially when clinical improvement cannot be achieved with standard empirical treatment. Timely identification and appropriate treatment (such as drainage and antibiotics) are crucial for both patient survival and the prevention of complications.

Polyphosphate uses mTOR, pyrophosphate, and Rho GTPase components to potentiate bacterial survival in Dictyostelium.

IMPORTANCE: Although most bacteria are quickly killed after phagocytosis by a eukaryotic cell, some pathogenic bacteria escape death after phagocytosis. Pathogenic Mycobacterium species secrete polyP, and the polyP is necessary for the bacteria to prevent their killing after phagocytosis. Conversely, exogenous polyP prevents the killing of ingested bacteria that are normally killed after phagocytosis by human macrophages and the eukaryotic microbe Dictyostelium discoideum. This suggests the possibility that in these cells, a signal transduction pathway is used to sense polyP and prevent killing of ingested bacteria. In this report, we identify key components of the polyP signal transduction pathway in D. discoideum. In cells lacking these components, polyP is unable to inhibit killing of ingested bacteria. The pathway components have orthologs in human cells, and an exciting possibility is that pharmacologically blocking this pathway in human macrophages would cause them to kill ingested pathogens such as Mycobacterium tuberculosis.

A phosphatidylinositol phosphate kinase inhibits Ras activation and regulates chemorepulsion in Dictyostelium discoideum.

During developmental and immune responses, cells move towards or away from some signals. Although much is known about chemoattraction, chemorepulsion (the movement of cells away from a stimulus) remains poorly understood. Proliferating Dictyostelium discoideum cells secrete a chemorepellent protein called AprA. Examining existing knockout strains, we previously identified proteins required for AprA-induced chemorepulsion, and a genetic screen suggested that the enzyme phosphatidylinositol phosphate kinase A (PIPkinA, also known as Pik6) might also be needed for chemorepulsion. Here, we show that cells lacking PIPkinA are not repelled by AprA, and that this phenotype is rescued by expression of PIPkinA. To bias cell movement, AprA inhibits Ras activation at the side of the cell closest to the source of AprA, and we find that PIPkinA is required for AprA to inhibit Ras activation. PIPkinA decreases levels of phosphatidylinositol 4-phosphate [PI(4)P] and phosphatidylinositol (3,4,5)-trisphosphate [PI(3,4,5)P3], and possibly because of these effects, potentiates phagocytosis and inhibits cell proliferation. Cells lacking PIPkinA show normal AprA binding, suggesting that PIPkinA regulates chemorepulsion at a step between the AprA receptor and AprA inhibition of Ras activation.

Dictyostelium discoideum cells retain nutrients when the cells are about to outgrow their food source.

Dictyostelium discoideum is a unicellular eukaryote that eats bacteria, and eventually outgrows the bacteria. D. discoideum cells accumulate extracellular polyphosphate (polyP), and the polyP concentration increases as the local cell density increases. At high cell densities, the correspondingly high extracellular polyP concentrations allow cells to sense that they are about to outgrow their food supply and starve, causing the D. discoideum cells to inhibit their proliferation. In this report, we show that high extracellular polyP inhibits exocytosis of undigested or partially digested nutrients. PolyP decreases plasma membrane recycling and apparent cell membrane fluidity, and this requires the G protein-coupled polyP receptor GrlD, the polyphosphate kinase Ppk1 and the inositol hexakisphosphate kinase I6kA. PolyP alters protein contents in detergent-insoluble crude cytoskeletons, but does not significantly affect random cell motility, cell speed or F-actin levels. Together, these data suggest that D. discoideum cells use polyP as a signal to sense their local cell density and reduce cell membrane fluidity and membrane recycling, perhaps as a mechanism to retain ingested food when the cells are about to starve. This article has an associated First Person interview with the first author of the paper.

Annotating Putative D. discoideum Proteins Using I-TASSER.

Using Gene Ontology annotation in any aspect or using any evidence code, we found that approximately 14% percent of predicted D. discoideum proteins have no GO annotations and no obvious similarity to any annotated protein across diverse organisms. We have been systematically examining these unannotated protein sequences using software that predicts a protein structure and then compares the predicted structure to known structures.