Robust and prototypical immune responses toward influenza vaccines in the high-risk group of Indigenous Australians

Morbidity and mortality rates from seasonal and pandemic influenza occur disproportionately in high-risk groups, including Indigenous people globally. Although vaccination against influenza is recommended for those most at risk, studies on immune responses elicited by seasonal vaccines in Indigenous populations are largely missing, with no data available for Indigenous Australians and only one report published on antibody responses in Indigenous Canadians. We recruited 78 Indigenous and 84 non-Indigenous Australians vaccinated with the quadrivalent influenza vaccine into the Looking into InFluenza T cell immunity - Vaccination cohort study and collected blood to define baseline, early (day 7), and memory (day 28) immune responses. We performed in-depth analyses of T and B cell activation, formation of memory B cells, and antibody profiles and investigated host factors that could contribute to vaccine responses. We found activation profiles of circulating T follicular helper type-1 cells at the early stage correlated strongly with the total change in antibody titers induced by vaccination. Formation of influenza-specific hemagglutinin-binding memory B cells was significantly higher in seroconverters compared with nonseroconverters. In-depth antibody characterization revealed a reduction in immunoglobulin G3 before and after vaccination in the Indigenous Australian population, potentially linked to the increased frequency of the G3m21* allotype. Overall, our data provide evidence that Indigenous populations elicit robust, broad, and prototypical immune responses following immunization with seasonal inactivated influenza vaccines. Our work strongly supports the recommendation of influenza vaccination to protect Indigenous populations from severe seasonal influenza virus infections and their subsequent complications.

Influenza is a significant respiratory viral infection that causes a serious burden of disease. High morbidity and mortality rates from seasonal and pandemic influenza occur disproportionately in specific high-risk population groups, including children, the elderly, pregnant women, Indigenous people globally, and individuals with underlying comorbidities such as diabetes, immunosuppression, and lung and heart disease (1–3). Currently, antibody-based influenza vaccines targeting highly variable hemagglutinin (HA) and neuraminidase (NA) surface glycoproteins are the most effective way to combat seasonal infections. The inactivated influenza vaccine contains glycoproteins corresponding to the circulating A/H3N2 and A/H1N1 strains and one B strain from either the Victoria or Yamagata lineage (in trivalent/TIV vaccines) or both B lineage strains (in quadrivalent/QIV vaccines). Antigenic drift necessitates annual updates of the vaccine components to warrant protection, and despite this the overall vaccine effectiveness can vary vastly from −7 to 75% (4). Vaccine effectiveness not only differs between seasons but also between vaccine components, with H3N2 showing the lowest overall vaccine effectiveness and H1N1pdm09 (pH1N1) the highest (5). Several factors such as preexisting immunity, immunosenescence, and vaccine strain mismatch can influence vaccine effectiveness (6). Genetic factors such as HLA polymorphisms contributing to differences in HLA-II expression are associated with stronger or weaker vaccine responses (7). For example, individuals expressing HLA-DRB1*11:04 showed high titers postvaccination whereas HLA-DRB1*13:01 showed reduced antibody titers postvaccination (7).Our understanding of why some individuals fail to establish a protective immune response after influenza vaccination is still very limited. To determine which factors shape the immune response postvaccination, we and others have identified cellular and humoral responses that correlate with robust immune responses to influenza vaccination (8, 9). Importantly, 7 d postvaccination an increase in ICOS⁺CXCR3⁺CXCR5⁺CD4⁺ circulating T follicular helper 1 (cT_FH1) cells was observed that correlated with antibody-secreting cells (ASCs) and rises in antibody titers (9, 10).Indigenous populations experience higher rates of infections with a range of pathogens including tuberculosis (11) and influenza (12). Notification and hospitalization rates of seasonal influenza virus infections are 1.5 to 8.6 times and 1.2 to 4.3 times, respectively, higher in Indigenous compared with non-Indigenous Australians (12). With social determinants of health and comorbidities contributing to a higher disease burden (13), one key strategy proposed to improve health outcomes for Indigenous populations is immunization (14). However, only a few studies to date have examined viral immunity in Indigenous populations and most of our knowledge is based on studies in non-Indigenous populations. We have revealed host variations in HLA profiles in Indigenous populations (15, 16), suggesting that differences in HLA or other genetic factors might impact influenza vaccine responses in Indigenous Australians. Despite national funding, vaccination rates still remain low in Indigenous communities (17). A recent study from Menzies et al. revealed that more than 50% of unvaccinated Indigenous Australians stated that the “flu” vaccine would not be effective (18). To date, there are no published data to define immune responses to influenza vaccines in Indigenous Australians, while globally only one study assessed antibody responses following adjuvanted pH1N1 influenza immunization in Indigenous Canadians and showed comparable antibody levels pre- and postvaccination (19). Determining the immunological response to influenza vaccination in high-risk Indigenous populations can therefore provide a stronger scientific basis for influenza recommendations, which if appropriately communicated may increase vaccine uptake.In this study, we recruited Indigenous and non-Indigenous Australians vaccinated with the QIV between 2016 and 2018 and assessed their immunity pre- and postvaccination. We performed in-depth analyses of T and B cell activation, memory B cell formation, and antibody profiles as well as investigating host factors that could contribute to vaccine responses. Our study clearly demonstrates that Indigenous Australians mount effective and prototypical immune responses to the inactivated influenza vaccine and thus provides an immunological basis to support current vaccine recommendations in Indigenous populations.     

Migrating pharyngeal foreign bodies: a series of four cases of saw-toothed fish bones

Pharyngeal foreign bodies are common problems seen at emergency rooms or ENT outpatient clinics, and fish bones are the most common foreign bodies encountered in East Asia and in Korea. One of the rare complications of a swallowed sharp fish bone is its migration from the site of entry into the subcutaneous tissues of the neck. We present four unusual cases of ingested fish bones that migrated out of the upper digestive tract to the neck. In the first case, this caused a recurrent deep neck infection for 2 years; in the second case, there was penetration of the facial artery; in the third case, there was a hematoma of the floor of the mouth; in the fourth case, there was a retropharyngeal abscess.     

New prospectives of prostate cancer gene therapy: molecular targets and animal models.

Prostate cancer is the most common cancer and the second leading cause of cancer-related death among North American men. The low cure rate for prostate cancer is associated with the fact that many patients have metastatic disease at the time of disease presentation. Currently available therapeutic modalities for prostate cancer, such as surgery, radiation, hormone therapy, and chemotherapy, have failed to cure patients because these therapies are not sufficiently tumor-specific, resulting in dose-limiting toxicity. Therefore, gene therapy may offer great promise in this regard. In this article, we summarize current advances in gene therapy technologies for the treatment of cancer in general, and future prospects for treatment of human prostate cancer metastasis. We specifically emphasize current studies for improvement, both in the efficiency and the specificity of viral and nonviral vectors, and restricted transgene expression in tumors, to achieve selective targeting with minimized host organ toxicity, based on the molecular understanding of potential regulatory differences between normal and tumor cells. Cell and animal models used to study prostate cancer growth, invasion, and metastasis, and their usefulness in preclinical evaluation of therapeutic vectors in the treatment of prostate cancer skeletal metastasis are also discussed.     

Nitric oxide prevents the IFN-gamma/LPS-induced hepatotoxicity in a protein kinase G-independent manner.

Although it has been well known that the role of LPS on hepatotoxicity is mediated through TNF-alpha, the direct cytotoxic effect of LPS on IFN-gamma-primed hepatocytes has not yet been clearly demonstrated. Here, we demonstrate that the IFN-gamma-mediated death of murine embryonic liver BNL CL2 cells is potentiated by LPS (0.5 microg/ml). In addition, an exogenous NO donor, sodium nitroprusside (SNP) significantly prevents cell death induced by IFN-gamma alone or IFN-gamma plus LPS (IFN-gamma/LPS) in a dose-dependent manner over 25 microM. SNP significantly blocked the death of BNL CL2 cells only when it was added within 12 hr after treatment of IFN-gamma and IFN-gamma/LPS. The preventive effect of SNP occurred in parallel with the suppression of caspase 3-like protease activation. We have also demonstrated that a relatively high concentration as well as an appropriate period of exposure to NO may be critical to maintain cell viability from the cytotoxic effect of IFN-gamma and IFN-gamma/LPS. Furthermore, the preventive effect of SNP on IFN-gamma/LPS-induced cell death is mediated by a protein kinase G (PKG)-independent manner.     

Cryopreservation of Mycobacterium tuberculosis Complex Cells

Successful long-term preservation of Mycobacterium tuberculosis cells is important for sample transport, research, biobanking, and the development of new drugs, vaccines, biomarkers, and diagnostics. In this report, Mycobacteriumbovis bacillus Calmette-Guérin and M. tuberculosis H37Ra were used as models of M. tuberculosis complex strains to study cryopreservation of M. tuberculosis complex cells in diverse sample matrices at different cooling rates. Cells were cryopreserved in diverse sample matrices, namely, phosphate-buffered saline (PBS), Middlebrook 7H9 medium with or without added glycerol, and human sputum. The efficacy of cryopreservation was quantified by microbiological culture and microscopy with BacLight LIVE/DEAD staining. In all sample matrices examined, the microbiological culture results showed that the cooling rate was the most critical factor influencing cell viability. Slow cooling (a few degrees Celsius per minute) resulted in much higher M. tuberculosis complex recovery rates than rapid cooling (direct immersion in liquid nitrogen) (P < 0.05). Among the three defined cryopreservation media (PBS, 7H9, and 7H9 plus glycerol), there was no significant differential effect on viability (P = 0.06 to 0.87). Preincubation of thawed M. tuberculosis complex cells in 7H9 broth for 20 h before culture on solid Middlebrook 7H10 plates did not help the recovery of the cells from cryoinjury (P = 0.14 to 0.71). The BacLight LIVE/DEAD staining kit, based on Syto 9 and propidium iodide (PI), was also applied to assess cell envelope integrity after cryopreservation. Using the kit, similar percentages of “live” cells with intact envelopes were observed for samples cryopreserved under different conditions, which was inconsistent with the microbiological culture results. This implies that suboptimal cryopreservation might not cause severe damage to the cell wall and/or membrane but instead cause intracellular injury, which leads to the loss of cell viability.     

Endoscope-Assisted Microsurgical Removal of an Epidermoid Tumor within the Cavernous Sinus

Epidermoid tumor of the cavernous sinus is rare. The aim of this case report is to discuss the role of neuroendoscopes in the removal of such lesions. A 21-year-old man presented with 6-year history of progressive headache, diplopia, and visual disturbance. Work-up revealed an epidermoid tumor located in the right cavernous sinus. An extradural transcavernous approach was utilized via a traditional frontotemporal craniotomy with endoscopic assistance. The postoperative course was uneventful with immediate improvement of the patient''s headache. Postoperative magnetic resonance imaging demonstrated complete removal of the tumor. There were no signs of recurrence during a 2-year follow-up period. The endoscope is a useful tool for removing epidermoid tumors from the cavernous sinus and enhances visualization of areas that would otherwise be difficult to visualize with microscopes alone. Endoscopes also help minimize the retraction of neurovascular structures.     

A Study on Image Quality Management in PACS Used by Korean Hospitals

This study evaluated a method to maintain the optimal image quality in clinical practice for image quality management in a picture archiving and communication system (PACS) that uses typical technology for digital medical images. This study conducted a survey of 25 hospitals in Seoul and metropolitan areas that had installed PACS to examine the reality of image quality management. Sixteen diagnostic monitors were used as calibration tools to compare and analyze the external illuminance uniformity and grayscale standard display function (GSDF) values at each frequency. According to the survey results, most of the hospitals did not have any particular rules or standardized methods for image quality control. In a PACS, the calibration frequency was examined within the allowable limits of error for each week and month. The calibration was not affected by the difference in brightness of the environment for reading an image. The GSDF measurement values were quite different from the standard values. In conclusion, to improve the image quality of the digital system, it is important to make good use of the system and maintain the image quality. Therefore, it is critical to capitalize on the method suggested in this study and maintain the optimal image quality to guarantee a high level of observer satisfaction.