ORCID Profile
0000-0003-3644-3156
Current Organisations
Oak Ridge National Laboratory
,
Royal Taruma Hospital
,
Universitas Tarumanagara Fakultas Kedokteran
,
University of Sydney - Sydney Medical School Nepean
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Publisher: Cold Spring Harbor Laboratory
Date: 11-12-2020
DOI: 10.1101/2020.12.10.20244707
Abstract: Dysregulated immune response is a key driver of disease progression in sepsis and known to be associated with impaired cellular metabolism. This association has been studied mostly in the late stage sepsis patients. Here, we investigate whether such impairment in cellular metabolism is present in uncomplicated infection patients who do not develop sepsis. Forty sepsis (fulfilled Sepsis-3 criteria) and 27 uncomplicated infection patients were recruited from the emergency department along with 20 healthy volunteers. Whole blood was collected for measurement of gene expression, cytokine levels and cellular metabolic functions (including mitochondrial respiration, oxidative stress and apoptosis). Our analysis revealed the impairment of mitochondrial respiration in uncomplicated infection and sepsis patients (p value .05), with greater degree of impairment noted in the established sepsis. The impairment was significantly correlated with increased mitochondrial oxidative stress level the latter was increased in uncomplicated infection and more so in established sepsis patients. Further analysis revealed that the oxidative stress level correlated significantly with cytokine level (tumor necrosis factor-α) and gene expression levels (CYCS, TP53, SLC24A24 and TSPO). These findings suggest that impaired immune cell metabolism is present in infection patients without presenting sepsis, thereby opening potential window for early diagnosis and intervention (e.g. antioxidant therapy) in such patients.
Publisher: Office of Scientific and Technical Information (OSTI)
Date: 2020
DOI: 10.2172/1784174
Publisher: Cold Spring Harbor Laboratory
Date: 11-2021
DOI: 10.1101/2021.10.29.21265555
Abstract: Robust biomarkers that predict disease outcomes amongst COVID-19 patients are necessary for both patient triage and resource prioritisation. Numerous candidate biomarkers have been proposed for COVID-19. However, at present, there is no consensus on the best diagnostic approach to predict outcomes in infected patients. Moreover, it is not clear whether such tools would apply to other potentially pandemic pathogens and therefore of use as stockpile for future pandemic preparedness. We conducted a multi-cohort observational study to investigate the biology and the prognostic role of interferon alpha-inducible protein 27 ( IFI27 ) in COVID-19 patients. We show that IFI27 is expressed in the respiratory tract of COVID-19 patients and elevated IFI27 expression is associated with the presence of a high viral load. We further demonstrate that systemic host response, as measured by blood IFI27 expression, is associated with COVID-19 severity. For clinical outcome prediction (e.g. respiratory failure), IFI27 expression displays a high positive (0.83) and negative (0.95) predictive value, outperforming all other known predictors of COVID-19 severity. Furthermore, IFI27 is upregulated in the blood of infected patients in response to other respiratory viruses. For ex le, in the pandemic H1N1/09 swine influenza virus infection, IFI27- like genes were highly upregulated in the blood s les of severely infected patients. These data suggest that prognostic biomarkers targeting the family of IFI27 genes could potentially supplement conventional diagnostic tools in future virus pandemics, independent of whether such pandemics are caused by a coronavirus, an influenza virus or another as yet-to-be discovered respiratory virus. We searched the scientific literature using PubMed to identify studies that used the IFI27 biomarker to predict outcomes in COVID-19 patients. We used the search terms “ IFI27 ”, “COVID-19, “gene expression” and “outcome prediction”. We did not identify any study that investigated the role of IFI27 biomarker in outcome prediction. Although ten studies were identified using the general terms of “gene expression” and “COVID-19”, IFI27 was only mentioned in passing as one of the identified genes. All these studies addressed the broader question of the host response to COVID-19 none focused solely on using IFI27 to improve the risk stratification of infected patients in a pandemic. Here, we present the findings of a multi-cohort study of the IFI27 biomarker in COVID-19 patients. Our findings show that the host response, as reflected by blood IFI27 gene expression, accurately predicts COVID-19 disease progression (positive and negative predictive values 0.83 and 0.95, respectively), outperforming age, comorbidity, C-reactive protein and all other known risk factors. The strong association of IFI27 with disease severity occurs not only in SARS-CoV-2 infection, but also in other respiratory viruses with pandemic potential, such as the influenza virus. These findings suggest that host response biomarkers, such as IFI27 , could help identify high-risk COVID-19 patients - those who are more likely to develop infection complications - and therefore may help improve patient triage in a pandemic. This is the first systemic study of the clinical role of IFI27 in the current COVID-19 pandemic and its possible future application in other respiratory virus pandemics. The findings not only could help improve the current management of COVID-19 patients but may also improve future pandemic preparedness.
Publisher: American Chemical Society (ACS)
Date: 30-04-2013
DOI: 10.1021/JA312030E
Abstract: The structure of SnO2 nanoparticles (avg. 5 nm) with a few layers of water on the surface has been elucidated by atomic pair distribution function (PDF) methods using in situ neutron total scattering data and molecular dynamics (MD) simulations. Analysis of PDF, neutron prompt gamma, and thermogravimetric data, coupled with MD-generated surface D2O/OD configurations demonstrates that the minimum concentration of OD groups required to prevent rapid growth of nanoparticles during thermal dehydration corresponds to ~0.7 monolayer coverage. Surface hydration layers not only stabilize the SnO2 nanoparticles but also induce particle-size-dependent structural modifications and are likely to promote interfacial reactions through hydrogen bonds between adjacent particles. Upon heating/dehydration under vacuum above 250 °C, nanoparticles start to grow with low activation energies, rapid increase of nanoparticle size, and a reduction in the a lattice dimension. This study underscores the value of neutron diffraction and prompt-gamma analysis, coupled with molecular modeling, in elucidating the influence of surface hydration on the structure and metastable persistence of oxide nanomaterials.
Publisher: Office of Scientific and Technical Information (OSTI)
Date: 12-2019
DOI: 10.2172/1784183
Publisher: American Chemical Society (ACS)
Date: 19-03-2013
DOI: 10.1021/JA3125959
Abstract: Atomistic molecular dynamics (MD) simulations were carried out to investigate the local dynamics of polyelectrolyte dendrimers dissolved in deuterium oxide (D2O) and its dependence on molecular charge. Enhanced segmental dynamics upon increase in molecular charge is observed, consistent with quasielastic neutron scattering (QENS) measurements. A strong coupling between the intradendrimer local hydration level and segmental dynamics is also revealed. Compelling evidence shows these findings originate from the electrostatic interaction between the hydrocarbon components of a dendrimer and the invasive water. This combined study provides fundamental insight into the dynamics of charged polyelectrolytes and the solvating water molecules.
Location: United Kingdom of Great Britain and Northern Ireland
Location: Russian Federation
Location: Germany
Location: Australia
No related grants have been discovered for Velma Herwanto.