Allergic reactions and adverse events associated with administration of mRNA-based vaccines. A health-care system experience.

Background: Adverse reactions, including anaphylaxis, to messenger RNA coronavirus disease 2019 (COVID-19) vaccines rarely occur. Because of the need to administer a timely second dose in subjects who reported a reaction to their first dose, a panel of health-care professionals developed a safe triage of the employees and health care providers (EHCP) at a large health-care system to consider administration of future dosing. Methods: There were 28,544 EHCPs who received their first dose of COVID-19 vaccines between December 15, 2020, and March 8, 2021. The EHCPs self-reported adverse reactions to a centralized COVID-19 command center (CCC). The CCC screened and collected information on the quality of reaction, symptoms, and timing of the onset of the reaction. Results: Of 1253 calls to the CCC, 113 were identified as requiring consideration by a panel of three (American Board of Allergy and Immunology) ABAI-certified allergists for future dosing or formal in-person assessment. Of the 113 EHCPs, 94 (83.2%) were recommended to get their second dose. Eighty of 94 received their second planned dose without a severe or immediate reaction. Of the 14 of 113 identified as needing further evaluation, 6 were evaluated by a physician and subsequently received their second dose without a serious adverse reaction. Eight of 14 did not receive their second dose. Only 5 of the 113 EHCPs reported reactions (4.4%) were recommended to not take the second dose: 3 (2.6%) because of symptoms consistent with anaphylaxis, and 2 because of neurologic complications (seizure, stroke). Conclusion: The panel demonstrated that, by consideration of reaction history alone, the ECHPs could be appropriately triaged to receive scheduled second dosing of COVID-19 vaccines without delays for in-person evaluation and allergy testing.

Food Safety of Consuming Black Soldier Fly (Hermetia illucens) Larvae: Microbial, Heavy Metal and Cross-Reactive Allergen Risks.

Black soldier fly (Hermetia illucens) larvae (BSFL) are a promising, sustainable source of nutrients, however, there is limited knowledge regarding the food safety of consuming BSFL. This study determined the safety of consuming BSFL for direct human consumption in terms of microbial, heavy metal and allergen content. Microbial counts were determined using ISO (International Organization for Standardization) methods, heavy metals were determined using inductively coupled plasma mass spectrometry and allergens were determined via Orbitrap mass spectrometry and ELISA (enzyme-linked immunosorbent assay) kits. Feed and killing method influenced the presence of Bacillus cereus (p = 0.011), and only the killing method influenced Escherichia coli (p < 0.00) and total viable count (TVC) (p < 0.00). Blanching resulted in a 3-log reduction in E. coli and a 3.4 log reduction in the TVC counts. Salmonella spp. and Listeria spp. were not detected in the BSFL samples. Heavy metals were detected although they were below maximum legal limits. Cross-reactive allergens, tropomyosin and arginine kinase, were detected in the BSFL samples, although the clinical significance requires research. The feed fed to the BSFL and blanching were found to influence the safety of consuming BSFL, highlighting the importance of incorporating sufficient decontamination steps, such as blanching, to ensure food safety.

Fibronectin is a stress responsive gene regulated by HSF1 in response to geldanamycin.

Fibronectin is an extracellular matrix glycoprotein with key roles in cell adhesion and migration. Hsp90 binds directly to fibronectin and Hsp90 depletion regulates fibronectin matrix stability. Where inhibition of Hsp90 with a C-terminal inhibitor, novobiocin, reduced the fibronectin matrix, treatment with an N-terminal inhibitor, geldanamycin, increased fibronectin levels. Geldanamycin treatment induced a stress response and a strong dose and time dependent increase in fibronectin mRNA via activation of the fibronectin promoter. Three putative heat shock elements (HSEs) were identified in the fibronectin promoter. Loss of two of these HSEs reduced both basal and geldanamycin-induced promoter activity, as did inhibition of the stress-responsive transcription factor HSF1. Binding of HSF1 to one of the putative HSE was confirmed by ChIP under basal conditions, and occupancy shown to increase with geldanamycin treatment. These data support the hypothesis that fibronectin is stress-responsive and a functional HSF1 target gene. COLA42 and LAMB3 mRNA levels were also increased with geldanamycin indicating that regulation of extracellular matrix (ECM) genes by HSF1 may be a wider phenomenon. Taken together, these data have implications for our understanding of ECM dynamics in stress-related diseases in which HSF1 is activated, and where the clinical application of N-terminal Hsp90 inhibitors is intended.

Hsp90 binds directly to fibronectin (FN) and inhibition reduces the extracellular fibronectin matrix in breast cancer cells.

Heat shock protein 90 (Hsp90) has been identified in the extracellular space and has been shown to chaperone a finite number of extracellular proteins involved in cell migration and invasion. We used chemical cross-linking and immunoprecipitation followed by tandem mass spectrometry (MS/MS) to isolate a complex containing Hsp90 and the matrix protein fibronectin (FN) from breast cancer cells. Further analysis showed direct binding of Hsp90 to FN using an in vitro co-immunoprecipitation assay, a solid phase binding assay and surface plasmon resonance (SPR) spectroscopy. Confocal microscopy showed regions of co-localisation of Hsp90 and FN in breast cancer cell lines. Exogenous Hsp90ß was shown to increase the formation of extracellular FN matrix in the Hs578T cell line, whilst knockdown or inhibition of Hsp90 led to a reduction in the levels of both soluble and insoluble FN and could be partially rescued by addition of exogenous Hsp90ß. Treatment of cells with novobiocin led to internalization of FN into vesicles that were positive for the presence of the lysosomal marker, LAMP-1. Taken together, the direct interaction between FN and Hsp90, as well as the decreased levels of both soluble and insoluble FN upon Hsp90 inhibition or knockdown, suggested that FN may be a new client protein for Hsp90 and that Hsp90 was involved in FN matrix assembly and/or stability. The identification of FN as a putative client protein of Hsp90 suggests a role for Hsp90 in FN matrix stability, which is important for a number of fundamental cellular processes including embryogenesis, wound healing, cell migration and metastasis.

Breast cancer: current developments in molecular approaches to diagnosis and treatment.

Due to the high heterogeneity of breast cancers, numerous recent patents describe improved methods of detection and classification which promise better patient prognosis and treatment. In particular, there has been a shift towards more effective genetic screening to identify specific mutations associated with breast tumours, which may lead to "personalised medicine" with improved outcomes. Two challenging areas of breast cancer research involve the development of treatments for the highly aggressive triple negative breast cancer subtype as well as the chemotherapy-resistant cancer stem cell subpopulation. In addition, despite numerous recent advances in breast cancer treatment in woman, male breast cancer remains poorly understood and there are limited therapies available which are developed specifically for men. This review serves to report on important developments in the treatment of breast malignancies patented in the past two years as well as to highlight the current gaps in the field of breast cancer therapeutics and areas which require further study.

A 6-year-old boy with fever and eosinophilia.

Tissue and blood eosinophilia can be associated with a variety of infectious, allergic, and systemic diseases. Eosinophilia can range from mild and clinically inconsequential levels to high-grade eosinophilia with severe and potentially fatal consequences. Because of its ability to degranulate and produce cytotoxic mediators such as major basic protein and eosinophil peroxidase the eosinophil has the potential to cause considerable tissue damage, including potentially fatal conditions such as endomyocardial fibrosis. The most common infectious cause of eosinophilia worldwide is the parasitic helminth; fungal infection as a cause of eosinophilia is rarer, but must also be considered in the differential diagnosis. In this article we describe a unique case of reactive eosinophilia.