scholarly journals Blood Interferon Signatures Putatively Link Lack of Protection Conferred by the RTS,S Recombinant Malaria Vaccine to an Antigen-specific IgE Response

F1000Research ◽  
2017 ◽  
Vol 4 ◽  
pp. 919
Author(s):  
Darawan Rinchai ◽  
Scott Presnell ◽  
Marta Vidal ◽  
Sheetij Dutta ◽  
Virander Chauhan ◽  
...  

Malaria remains a major cause of mortality and morbidity worldwide. Progress has been made in recent years with the development of vaccines that could pave the way towards protection of hundreds of millions of exposed individuals. Here we used a modular repertoire approach to re-analyze a publically available microarray blood transcriptome dataset monitoring the response to malaria vaccination. We report the seminal identification of interferon signatures in the blood of subjects on days 1, 3 and 14 following administration of the third dose of the RTS,S recombinant malaria vaccine. These signatures at day 1 correlate with protection, and at days 3 and 14 to susceptibility to subsequent challenge of study subjects with live parasites. In addition we putatively link the decreased abundance of interferon-inducible transcripts observed at days 3 and 14 post-vaccination with the elicitation of an antigen-specific IgE response in a subset of vaccine recipients that failed to be protected by the RTS,S vaccine. Furthermore, profiling of antigen-specific levels of IgE in a Mozambican cohort of malaria-exposed children vaccinated with RTS,S identified an association between elevated baseline IgE levels and subsequent development of naturally acquired malaria infection during follow up. Taken together these findings warrant further investigation of the role of antigen-specific IgE in conferring susceptibility to malaria infection.

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 919 ◽  
Author(s):  
Darawan Rinchai ◽  
Scott Presnell ◽  
Damien Chaussabel

Malaria remains a major cause of mortality and morbidity worldwide. Progress has been made in recent years with the development of vaccines that could pave the way towards protection of hundreds of millions of exposed individuals. Here we used a modular repertoire approach to re-analyze a publically available microarray blood transcriptome dataset monitoring the response to malaria vaccination. We report the seminal identification of interferon signatures in the blood of subjects on days 1, 3 and 14 following administration of the third dose of the RTS,S recombinant malaria vaccine. These signatures at day 1 correlate with protection, and at days 3 and 14 to susceptibility to subsequent challenge of study subjects with live parasites. In addition we putatively link the decreased abundance of interferon-inducible transcripts observed at days 3 and 14 post-vaccination with the elicitation of an antigen specific IgE response in a subset of vaccine recipients that failed to be protected by the RTS,S vaccine.


2018 ◽  
Vol 25 (4) ◽  
pp. 481-491
Author(s):  
Joseph M Shulan ◽  
Leonid Vydro ◽  
Arthur B Schneider ◽  
Dan V Mihailescu

With increasing numbers of childhood cancer survivors who were treated with radiation, there is a need to evaluate potential biomarkers that could signal an increased risk of developing thyroid cancer. We aimed to examine the relationships between thyrotropin and thyroglobulin levels and the risk of developing thyroid nodules and cancer in a cohort of radiation-exposed children. 764 subjects who were irradiated in the neck area as children were examined and followed for up to 25 years. All subjects underwent a clinical examination, measurements of thyrotropin, thyroglobulin levels and thyroid imaging. At baseline, 216 subjects had thyroid nodules and 548 did not. Of those with nodules, 176 underwent surgery with 55 confirmed thyroid cancers. During the follow-up, 147 subjects developed thyroid nodules including 22 with thyroid cancer. Thyroglobulin levels were higher in subjects with prevalent thyroid nodules (26.1 ng/mL vs 9.37 ng/mL; P < 0.001) and in those who had an initial normal examination but later developed thyroid nodules (11.2 ng/mL vs 8.87 ng/mL; P = 0.017). There was no relationship between baseline thyrotropin levels and the prevalent presence or absence of thyroid nodules, whether a prevalent neoplasm was benign or malignant, subsequent development of thyroid nodules during follow-up or whether an incident nodule was benign or malignant. In conclusion, in radiation-exposed children, higher thyroglobulin levels indicated an increased risk of developing thyroid nodules but did not differentiate between benign and malignant neoplasms. There was no association between the baseline TSH level and the risk of developing thyroid nodules or cancer.


2011 ◽  
Vol 25 (6) ◽  
pp. 401-403 ◽  
Author(s):  
Randy M. Leung ◽  
Robert C. Kern ◽  
David B. Conley ◽  
Bruce K. Tan ◽  
Rakesh K. Chandra

Background It is universally accepted that osteomeatal complex (OMC) disease is linked to the subsequent development of chronic rhinosinusitis without nasal polyps (CRSsNPs) via postobstructive mechanisms. The role of OMC obstruction in the pathogenesis of CRSwNPs is less clear. This study was designed to identify if there is an association between OMC obstruction and inflammation of the adjacent sinuses, when patients are stratified by polyp status. This is a follow-up and expanded series of a previous pilot study from our group. Method CT scans of 144 patients with CRSsNPs and 123 patients with CRS with nasal polyps (CRSwNPs) were evaluated for each sinus and OMC. Patients had no previous surgeries for NPs. CT scans were obtained after a trial of maximal medical therapy. Results Increasing OMC involvement was associated with increasing Lund-Mackay score for both CRSsNPs and CRSwNPs. In CRSsNP patients, OMC status significantly correlated with adjacent sinus status (p < 0.0001). Meanwhile in CRSwNPs, OMC status does not correlate with adjacent sinus status (p = 0.328). Conclusion OMC obstruction in the setting of CRSwNP may be a barometer of the overall disease process, but in this scenario, paranasal sinus inflammation can not be classified as a postobstructive phenomenon. These findings question the role of minimally invasive procedures in the management of CRSwNPs.


2002 ◽  
Vol 12 (5) ◽  
pp. 496-500 ◽  
Author(s):  
I. Kloos ◽  
S. Delaloge ◽  
P. Pautier ◽  
M. Di Palma ◽  
A. Goupil ◽  
...  

The risk of tamoxifen-related endometrial adenocarcinoma is well established with daily dose and treatment duration of adjuvant tamoxifen as risk factors. There have also been in the past years, a few descriptions of uterine nonepithelial malignancies occuring after tamoxifen. We describe five recent cases of uterine carcinosarcomas occurring under/after tamoxifen administered in an adjuvant setting. None of these patients had received prior pelvic radiation therapy. Their median age at the diagnosis of breast cancer was 58 years (41–68), and 69 years (50–84) at the diagnosis of uterine carcinosarcoma. The median length of exposure to tamoxifen was 9 years (5–20), and the median time from the initiation of tamoxifen to the diagnosis of the uterine malignancy (latency period) 9 years (7–20). All patients presented with an advanced stage (IIA-IVA). Our data, together with those of the literature, plead for a causal role of a prolonged exposure to tamoxifen on the subsequent development of uterine carcinosarcoma. The long latency period observed even in patients receiving only 5 years of treatment leads us also to consider a prolonged gynecologic follow-up of the patients.


Crisis ◽  
2016 ◽  
Vol 37 (2) ◽  
pp. 130-139 ◽  
Author(s):  
Danica W. Y. Liu ◽  
A. Kate Fairweather-Schmidt ◽  
Richard Burns ◽  
Rachel M. Roberts ◽  
Kaarin J. Anstey

Abstract. Background: Little is known about the role of resilience in the likelihood of suicidal ideation (SI) over time. Aims: We examined the association between resilience and SI in a young-adult cohort over 4 years. Our objectives were to determine whether resilience was associated with SI at follow-up or, conversely, whether SI was associated with lowered resilience at follow-up. Method: Participants were selected from the Personality and Total Health (PATH) Through Life Project from Canberra and Queanbeyan, Australia, aged 28–32 years at the first time point and 32–36 at the second. Multinomial, linear, and binary regression analyses explored the association between resilience and SI over two time points. Models were adjusted for suicidality risk factors. Results: While unadjusted analyses identified associations between resilience and SI, these effects were fully explained by the inclusion of other suicidality risk factors. Conclusion: Despite strong cross-sectional associations, resilience and SI appear to be unrelated in a longitudinal context, once risk/resilience factors are controlled for. As independent indicators of psychological well-being, suicidality and resilience are essential if current status is to be captured. However, the addition of other factors (e.g., support, mastery) makes this association tenuous. Consequently, resilience per se may not be protective of SI.


2013 ◽  
Author(s):  
Francesca Menegazzo ◽  
Melissa Rosa Rizzotto ◽  
Martina Bua ◽  
Luisa Pinello ◽  
Elisabetta Tono ◽  
...  

Author(s):  
S Ioanitescu ◽  
L Micu ◽  
A Rampoldi ◽  
N Masala ◽  
V Marcu ◽  
...  

2018 ◽  
Vol 3 (2) ◽  

There have been a few case reports of head injury leading to brain tumour development in the same region as the brain injury. Here we report a case where the patient suffered a severe head injury with contusion. He recovered clinically with conservative management. Follow up Computed Tomography scan of the brain a month later showed complete resolution of the lesion. He subsequently developed malignant brain tumour in the same region as the original contusion within a very short period of 15 months. Head injury patients need close follow up especially when severe. The link between severity of head injury and malignant brain tumour development needs further evaluation. Role of anti-inflammatory agents for prevention of post traumatic brain tumours needs further exploration.


2014 ◽  
Vol 17 (3) ◽  
pp. 146
Author(s):  
Osman Tansel Darcin ◽  
Mehmet Kalender ◽  
Ayse Gul Kunt ◽  
Okay Guven Karaca ◽  
Ata Niyazi Ecevit ◽  
...  

<p><b>Background:</b> Thoracoabdominal aortic aneurysms (TAAA) present a significant clinical challenge, as they are complex and require invasive surgery. In an attempt to prevent considerably high mortality and morbidity in open repair, hybrid endovascular repair has been developed by many authors. In this study, we evaluated the early-term results obtained from this procedure.</p><p><b>Methods:</b> From November 2010 to February 2013, we performed thoracoabdominal hybrid aortic repair in 18 patients. The mean age was 68 years (12 men, 6 women). All of the patients had significant comorbidities. Follow-up computed tomography (CT) scans were performed at 1 week, 3 months, 6 months, and annually thereafter.</p><p><b>Results:</b> All patients were operated on in a staged procedure and stent graft deployment was achieved. Procedural success was achieved in all cases. All patients were discharged with complete recovery. No endoleaks weres detected in further CT examination.</p><p><b>Conclusion:</b> Our results suggests that hybrid debranching and endovascular repair of extensive thoracoabdominal aneurysms represents a suitable therapeutic option to reduce the morbidity and mortality of TAAA repair, particularly in those typically considered at high risk for standard repair.</p>


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