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1.
Rev Med Suisse ; 20(889): 1742-1746, 2024 Oct 02.
Article in French | MEDLINE | ID: mdl-39359213

ABSTRACT

Cytomegalovirus is the most common cause of congenital infection worldwide. 90 % of children infected in utero are born without symptoms, but 15 % of them will develop disorders within the first five years of life. The most common disorders affect the inner ear, resulting in sensorineural hearing loss and/or vestibular dysfunction (VD). VD is often unrecognized and confused with conditions -affecting the central nervous system. It can cause delays in psychomotor development and predispose to overall developmental delay. Early diagnosis and treatment are essential to prevent or limit these sequelae. Antiviral treatment during the pre- and neonatal periods should be considered.


Le cytomégalovirus est la cause la plus fréquente d'infection congénitale dans le monde. 90 % des enfants infectés in utero naissent sans symptôme, mais 15 % d'entre eux vont développer des atteintes au cours des cinq premières années de vie. Les plus fréquentes touchent l'oreille interne, engendrant une­surdité neurosensorielle et/ou une dysfonction vestibulaire (DV). La DV est souvent méconnue et confondue avec des atteintes du système nerveux central. Elle peut provoquer des retards du ­développement psychomoteur et prédisposer à un retard global du développement. Un diagnostic et une prise en charge précoces sont essentiels pour prévenir ou limiter ces séquelles. Un traitement antiviral en période pré et néonatale doit être considéré.


Subject(s)
Cytomegalovirus Infections , Humans , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/congenital , Cytomegalovirus Infections/complications , Infant, Newborn , Pregnancy , Hearing Loss, Sensorineural/diagnosis , Hearing Loss, Sensorineural/etiology , Hearing Loss, Sensorineural/virology , Hearing Loss, Sensorineural/epidemiology , Female , Pregnancy Complications, Infectious/diagnosis , Vestibular Diseases/diagnosis , Vestibular Diseases/epidemiology , Vestibular Diseases/etiology , Antiviral Agents/therapeutic use
2.
Future Sci OA ; 10(1): 2395244, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-39254097

ABSTRACT

The emergence of multicancer early detection (MCED) tests holds promise for improving early cancer detection and public health outcomes. However, positive MCED test results require confirmation through recommended cancer diagnostic imaging modalities. To address these challenges, we have developed a consultation and work-up protocol for definitive diagnostic results post MCED testing, named SPOT-MAS. Developed through circulating tumor DNA (ctDNA) analysis and in line with professional guidelines and advisory board consensus, this protocol standardizes information to aid general practitioners in accessing, interpreting and managing SPOT-MAS results. Clinical effectiveness is demonstrated through a series of identified cancer cases. Our research indicates that the protocol could empower healthcare professionals to confidently interpret circulating tumor DNA test results for 5 common types of cancer, thereby facilitating the clinical integration of MCED tests.


New tests can now screen for multiple types of cancer early, offering hope for better health outcomes. If one of these tests shows a positive result, doctors need to confirm it with imaging tests. We have developed a guide to help doctors understand and confirm these results. This guide could help healthcare professionals interpret results for five common types of cancer, making it easier to use these tests in regular medical practice.

3.
Nat Mater ; 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39266677

ABSTRACT

Magnetoresistance is a fundamental transport phenomenon that is essential for reading the magnetic states for various information storage, innovative computing and sensor devices. Recent studies have expanded the scope of magnetoresistances to the nonlinear regime, such as a bilinear magnetoelectric resistance (BMER), which is proportional to both electric field and magnetic field. Here we demonstrate that the BMER is a general phenomenon that arises even in three-dimensional systems without explicit momentum-space spin textures. Our theory suggests that the spin Hall effect enables the BMER provided that the magnitudes of spin accumulation at the top and bottom interfaces are not identical. The sign of the BMER follows the sign of the spin Hall effect of heavy metals, thereby evidencing that the BMER originates from the bulk spin Hall effect. Our observation suggests that the BMER serves as a general nonlinear transport characteristic in three-dimensional systems, especially playing a crucial role in antiferromagnetic spintronics.

4.
Heliyon ; 10(11): e31987, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38867992

ABSTRACT

Background: Anti-SARS-CoV-2 and immunomodulatory drugs are important for treating clinically severe patients with respiratory distress symptoms. Alpha- and gamma-mangostins (AM and GM) were previously reported as potential 3C-like protease (3CLpro) and Angiotensin-converting enzyme receptor 2 (ACE2)-binding inhibitors in silico. Objective: We aimed to evaluate two active compounds, AM and GM, from Garcinia mangostana for their antivirals against SARS-CoV-2 in live virus culture systems and their cytotoxicities using standard methods. Also, we aimed to prove whether 3CLpro and ACE2 neutralization were major targets and explored whether any additional targets existed. Methods: We tested the translation and replication efficiencies of SARS-CoV-2 in the presence of AM and GM. Initial and subgenomic translations were evaluated by immunofluorescence of SARS-CoV-2 3CLpro and N expressions at 16 h after infection. The viral genome was quantified and compared with the untreated group. We also evaluated the efficacies and cytotoxicities of AM and GM against four strains of SARS-CoV-2 (wild-type B, B.1.167.2, B.1.36.16, and B.1.1.529) in Vero E6 cells. The potential targets were evaluated using cell-based anti-attachment, time-of-drug addition, in vitro 3CLpro activities, and ACE2-binding using a surrogated viral neutralization test (sVNT). Moreover, additional targets were explored using combinatorial network-based interactions and Chemical Similarity Ensemble Approach (SEA). Results: AM and GM reduced SARS-CoV-2 3CLpro and N expressions, suggesting that initial and subgenomic translations were globally inhibited. AM and GM inhibited all strains of SARS-CoV-2 at EC50 of 0.70-3.05 µM, in which wild-type B was the most susceptible strain (EC50 0.70-0.79 µM). AM was slightly more efficient in the variants (EC50 0.88-2.41 µM), resulting in higher selectivity indices (SI 3.65-10.05), compared to the GM (EC50 0.94-3.05 µM, SI 1.66-5.40). GM appeared to be more toxic than AM in both Vero E6 and Calu-3 cells. Cell-based anti-attachment and time-of-addition suggested that the potential molecular target could be at the post-infection. 3CLpro activity and ACE2 binding were interfered with in a dose-dependent manner but were insufficient to be a major target. Combinatorial network-based interaction and chemical similarity ensemble approach (SEA) suggested that fatty acid synthase (FASN), which was critical for SARS-CoV-2 replication, could be a target of AM and GM. Conclusion: AM and GM inhibited SARS-CoV-2 with the highest potency at the wild-type B and the lowest at the B.1.1.529. Multiple targets were expected to integratively inhibit viral replication in cell-based system.

5.
Rev Med Suisse ; 20(878): 1173-1177, 2024 Jun 12.
Article in French | MEDLINE | ID: mdl-38867563

ABSTRACT

Complex ear reconstruction requires specialized multidisciplinary care. Most patients present with microtia, often associated with hearing disorders. The management of these disorders is a priority, and reconstruction of the external ear remains optional. Nowadays, auricular reconstruction is based on the subcutaneous implantation of either autologous cartilage or an allogeneic implant. Autologous reconstruction requires highly specialized surgical expertise and involves harvesting rib cartilage but carries a lower risk of exposure compared to allogeneic implants. Both techniques yield good results with a high success rate and have a positive impact on the social functioning and daily life of patients.


La reconstruction complexe du pavillon auriculaire nécessite une prise en charge multidisciplinaire spécialisée. La majorité des patients nécessitant ce geste présentent une microtie, souvent associée à des troubles de l'audition. La prise en charge de ceux-ci est prioritaire et la reconstruction du pavillon reste facultative. Aujourd'hui, la reconstruction du pavillon se base sur l'implantation sous-cutanée d'une maquette de cartilage autologue ou d'un implant allogène. La reconstruction autologue demande une expertise chirurgicale hautement spécialisée et nécessite un prélèvement de cartilage costal mais présente un risque d'exposition inférieur par rapport à l'implant allogène. Les deux techniques permettent d'atteindre de bons résultats avec un taux de réussite élevé et un effet positif sur le fonctionnement social et le quotidien des patients.


Subject(s)
Plastic Surgery Procedures , Humans , Plastic Surgery Procedures/methods , Ear, External/abnormalities , Ear, External/surgery , Congenital Microtia/surgery , Congenital Microtia/therapy , Transplantation, Autologous/methods , Cartilage/transplantation , Prostheses and Implants
6.
JMIR Hum Factors ; 11: e44619, 2024 01 05.
Article in English | MEDLINE | ID: mdl-38180799

ABSTRACT

BACKGROUND: Wearable devices have been used extensively both inside and outside of the hospital setting. During the COVID-19 pandemic, in some contexts, there was an increased need to remotely monitor pulse and saturated oxygen for patients due to the lack of staff and bedside monitors. OBJECTIVE: A prototype of a remote monitoring system using wearable pulse oximeter devices was implemented at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam, from August to December 2021. The aim of this work was to support the ongoing implementation of the remote monitoring system. METHODS: We used an action learning approach with rapid pragmatic methods, including informal discussions and observations as well as a feedback survey form designed based on the technology acceptance model to assess the use and acceptability of the system. Based on these results, we facilitated a meeting using user-centered design principles to explore user needs and ideas about its development in more detail. RESULTS: In total, 21 users filled in the feedback form. The mean technology acceptance model scores ranged from 3.5 (for perceived ease of use) to 4.4 (for attitude) with behavioral intention (3.8) and perceived usefulness (4.2) scoring in between. Those working as nurses scored higher on perceived usefulness, attitude, and behavioral intention than did physicians. Based on informal discussions, we realized there was a mismatch between how we (ie, the research team) and the ward teams perceived the use and wider purpose of the technology. CONCLUSIONS: Designing and implementing the devices to be more nurse-centric from their introduction could have helped to increase their efficiency and use during the complex pandemic period.


Subject(s)
COVID-19 , Humans , Vietnam , Pandemics , Patients , Hospitals
7.
Appl Radiat Isot ; 205: 111175, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38194888

ABSTRACT

An intercomparison of neutron personal dose equivalent measured by the Harshaw thermoluminescence neutron dosimeters (TLDs) between the National Institute of Metrology of China (NIM) and the Institute for Nuclear Science and Technology of Vietnam (INST) was performed. Three sets of TLDs (each set consisting of five TLDs) were prepared for each laboratory. Each set was then irradiated to the corresponding same nominal standard value of neutron personal dose equivalent, Hp(10)n-stdi, of 1.0, 2.0, and 3.0 mSv, respectively at these two laboratories. The irradiated TLDs were then read-out at the INST using the Harshaw 4500-type TLD reader to obtain neutron personal dose equivalents at the NIM, Hp(10)n-NIMi and at the INST, Hp(10)n-INSTi, which are corresponding to different values of Hp(10)n-stdi. The TLDs' responses to different scattered components of neutrons in these two fields are also discussed. Comparisons between the corresponding pair values of Hp(10)n-NIMi and Hp(10)n-INSTi show good agreements within 10% with the standard uncertainty of 12.5% (k = 1). The measured values of Hp(10)n-NIMi and Hp(10)n-INSTi are satisfied the Trumpet curve criteria. This implies that the TLDs can be used for safety assessment of occupational neutron personal dose equivalents. This intercomparison result also confirms the capabilities of these two laboratories (i.e., NIM, INST) on deliveries of neutron personal dose equivalent standard values for calibrations.

8.
Antiviral Res ; 220: 105753, 2023 12.
Article in English | MEDLINE | ID: mdl-37967754

ABSTRACT

Dengue infection is a global health problem as climate change facilitates the spread of mosquito vectors. Infected patients could progress to severe plasma leakage and hemorrhagic shock, where current standard treatment remains supportive. Previous reports suggested that several flavonoid derivatives inhibited mosquito-borne flaviviruses. This work aimed to explore sulfonamide chalcone derivatives as dengue inhibitors and to identify molecular targets. We initially screened 27 sulfonamide chalcones using cell-based antiviral and cytotoxic screenings. Two potential compounds, SC22 and SC27, were identified with DENV1-4 EC50s in the range of 0.71-0.94 and 3.15-4.46 µM, and CC50s at 14.63 and 31.02 µM, respectively. The compounds did not show any elevation in ALT or Cr in C57BL/6 mice on the 1st, 3rd, and 7th days after being administered intraperitoneally with 50 mg/kg SC22 or SC27 in a single dose. Moreover, the SAM-binding site of NS5 methyltransferase was a potential target of SC27 identified by computational and enzyme-based assays. The main target of SC22 was in a late stage of viral replication, but the exact target molecule had yet to be identified. In summary, a sulfonamide chalcone, SC27, was a potential DENV inhibitor that targeted viral methyltransferase. Further investigation should be the study of the structure-activity relationship of SC27 derivatives for higher potency and lower toxicity.


Subject(s)
Chalcone , Chalcones , Dengue Virus , Dengue , Humans , Animals , Mice , Dengue Virus/chemistry , Chalcone/pharmacology , Chalcone/therapeutic use , Chalcones/pharmacology , Methyltransferases , Mice, Inbred C57BL , Binding Sites , Dengue/drug therapy , Sulfonamides/pharmacology , Sulfonamides/therapeutic use , Antiviral Agents/therapeutic use , Viral Nonstructural Proteins , Virus Replication
9.
Malar J ; 22(1): 326, 2023 Oct 28.
Article in English | MEDLINE | ID: mdl-37898749

ABSTRACT

BACKGROUND: This study investigates the processes regarding changing malaria treatment policies in Vietnam. Moreover, it explores the feasibility of introducing triple artemisinin-based combination therapy (TACT) in Vietnam to support the national malaria control and elimination plan. METHODS: Data were collected via 12 in-depth interviews with key stakeholders, combined with a review of policy documents. RESULTS: TACT is considered as a useful backup strategy in case future treatment failures with current artemisinin-based combination therapy (ACT) would occur. Moreover, TACT is also considered as a promising strategy to prevent the re-establishment of malaria. However, regulatory procedures and implementation timelines for TACT were expected to be lengthy. Therefore, strategies to engage national decision-makers, regulators, and suppliers should be initiated soon, stipulating the benefits of TACT deployment. In Vietnam, a procedure to apply for an import permit without registration that has previously been applied to the introduction of artesunate-pyronaridine was proposed to accelerate the introduction of TACT. Global-level support through the World Health Organization recommendations and prequalification were considered critical for supporting the introduction of TACT in Vietnam. CONCLUSIONS: Appropriate approach strategies and early stakeholder engagement will be needed to accelerate the introduction of TACT in Vietnam.


Subject(s)
Antimalarials , Artemisinins , Malaria, Falciparum , Malaria , Humans , Antimalarials/therapeutic use , Malaria, Falciparum/drug therapy , Vietnam , Feasibility Studies , Plasmodium falciparum , Artemisinins/therapeutic use , Malaria/drug therapy , Malaria/prevention & control , Drug Therapy, Combination , Policy
10.
Emerg Microbes Infect ; 12(2): 2270074, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37842770

ABSTRACT

Chikungunya virus is a re-emerging arbovirus that has caused epidemic outbreaks in recent decades. Patients in older age groups with high viral load and severe immunologic response during acute infection are likely to develop chronic arthritis and severe joint pain. Currently, no antiviral drug is available. Previous studies suggested that a flavone derivative, 8-bromobaicalein, was a potential dengue and Zika replication inhibitor in a cell-based system targeting flaviviral polymerase. Here we characterized that 8-bromobaicalein inhibited chikungunya virus replication with EC50 of 0.49 ± 0.11 µM in Vero cells. The molecular target predicted at viral nsP1 methyltransferase using molecular binding and fragment molecular orbital calculation. Additionally, oral administration of 250 mg/kg twice daily treatment alleviated chikungunya-induced musculoskeletal inflammation and reduced viral load in healthy adult mice. Pharmacokinetic analysis indicated that the 250 mg/kg administration maintained the compound level above EC99.9 for 12 h. Therefore, 8-bromobaicalein should be a potential candidate for further development as a pan-arboviral drug.


Subject(s)
Arboviruses , Chikungunya Fever , Chikungunya virus , Zika Virus Infection , Zika Virus , Chlorocebus aethiops , Humans , Adult , Animals , Mice , Aged , Chikungunya Fever/drug therapy , Vero Cells , Viral Load , Chikungunya virus/physiology , Inflammation
11.
Mar Drugs ; 21(6)2023 Jun 16.
Article in English | MEDLINE | ID: mdl-37367686

ABSTRACT

Nine sesquiterpenes, including eight pentalenenes (1-8) and one bolinane derivative (9), were isolated from the culture broth of a marine-derived actinobacterium Streptomyces qinglanensis 213DD-006. Among them, 1, 4, 7, and 9 were new compounds. Their planar structures were determined by spectroscopic methods (HRMS, 1D, and 2D NMR), and the absolute configuration was established by biosynthesis consideration and electronic-circular-dichroism (ECD) calculations. All the isolated compounds were screened for their cytotoxicity against six solid and seven blood cancer cell lines. Compounds 4-6 and 8 showed a moderate activity against all of the tested solid cell lines, with GI50 values ranging from 1.97 to 3.46 µM.


Subject(s)
Antineoplastic Agents , Sesquiterpenes , Streptomyces , Molecular Structure , Antineoplastic Agents/chemistry , Streptomyces/chemistry , Sesquiterpenes/chemistry
12.
Plants (Basel) ; 12(9)2023 Apr 30.
Article in English | MEDLINE | ID: mdl-37176920

ABSTRACT

Part of the Indo-Chinese peninsula and located on the northwest edge of the Coral Triangle in the South China Sea, the Vietnamese coastal zone is home to a wealthy marine biodiversity associated with the regional geological setting and history, which supports a large number of marine ecosystems along a subtropical to tropical gradient. The diversity of coastal benthic marine primary producers is also a key biological factor supporting marine biological diversity. The present review provides: (1) an updated checklist of the Vietnamese marine flora, (2) a review of molecular-assisted alpha taxonomic efforts, (3) an analysis of marine floral biodiversity spatial distribution nationally and regionally (South China Sea), (4) a review of the impact of anthropogenic and environmental stressors on the Vietnamese marine flora, and (5) the efforts developed in the last decade for its conservation. Based on the studies conducted since 2013 and the nomenclatural changes that occurred during this period, an updated checklist of benthic marine algae and seagrasses consisted in a new total of 878 species, including 439 Rhodophyta, 156 Ochrophyta, 196 Chlorophyta, 87 Cyanobacteria, and 15 phanerogam seagrasses. This update contains 54 new records and 5 new species of macroalgae. The fairly poor number of new records and new species identified in the last 10 years in a "mega-diverse" country can be largely attributed to the limited efforts in exploring algal biodiversity and the limited use of genetic tools, with only 25.4% (15 species) of these new records and species made based on molecular-assisted alpha taxonomy. The South Central Coast supports the highest species diversity of marine algae, which coincides with the largest density of coral reefs along the Vietnamese coast. Vietnam holds in the South China Sea one of the richest marine floras, imputable to the country's geographical, geological, and climatic settings. However, Vietnam marine floral biodiversity is under critical threats examined here, and current efforts are insufficient for its conservation. A methodical molecular-assisted re-examination of Vietnam marine floral biodiversity is urgently needed, complemented with in-depth investigations of the main threats targeting marine flora and vulnerable taxa, and finally, conservation measures should be urgently implemented.

14.
Mar Drugs ; 21(3)2023 Mar 06.
Article in English | MEDLINE | ID: mdl-36976216

ABSTRACT

Two new alkaloids, streptopyrroles B and C (1 and 2), were discovered through a chemical investigation of the ethyl acetate (EtOAc) extract from a marine-derived actinomycete, Streptomyces zhaozhouensis, along with four known analogs (3-6). The structures of the new compounds were elucidated by spectroscopic analysis (HR-ESIMS, 1D, and 2D NMR) and a comparison of their experimental data with literature values. The new compounds were evaluated for their antimicrobial activity by standard broth dilution assay, and the tested compounds showed significant activity against Gram-positive bacteria with minimum inhibitory concentration (MIC) values ranging from 0.7 to 2.9 µM, and kanamycin was used as a positive control with MIC values ranging from <0.5 to 4.1 µM. Additionally, 1, 3, and 5 were evaluated for their cytotoxicity against six tumor cell lines by sulforhodamine B (SRB) assay, and these compounds displayed cytotoxic activities against all the tested cell lines, with concentration causing 50% cell growth inhibition (GI50) values ranging from 4.9 to 10.8 µM, while a positive control, adriamycin, showed GI50 values of 0.13-0.17 µM.


Subject(s)
Actinobacteria , Alkaloids , Anti-Infective Agents , Antineoplastic Agents , Anti-Bacterial Agents/chemistry , Anti-Infective Agents/pharmacology , Anti-Infective Agents/metabolism , Antineoplastic Agents/chemistry , Magnetic Resonance Spectroscopy , Actinobacteria/metabolism , Alkaloids/pharmacology , Alkaloids/metabolism , Microbial Sensitivity Tests
15.
Front Neurol ; 14: 1085926, 2023.
Article in English | MEDLINE | ID: mdl-36959819

ABSTRACT

Introduction: Vestibular deficits are considered rare in children, but the lack of systematic screening leads to underdiagnosis. It has been demonstrated that chronic vestibular dysfunction impacts the normal psychomotor development of children. Early identification is needed to allow for clinical management, ensuring better global development. For this purpose, our research group has developed the Geneva Balance Test (GBT), aiming to objectively quantify the balance capacity of children over a broad age range, to screen for bilateral vestibulopathy (BV), and to quantify the improvement of balance abilities in children. Methods: To determine the capacity of the GBT to quantify the balance capacity of children with BV, we conducted an observational prospective study with three populations: 11 children with BV, and two age-matched control groups composed of (1) 15 healthy subjects without the vestibular or auditory disorder (HS) and (2) 11 pediatric cochlear implant recipients (CIs) without vestibular disorders. Results of the three populations have been compared in three different age sub- groups (3-5, 6-9, and ≥10 years), and with results of a short, modified version of the Bruininks-Oseretsky test of Motor proficiency Ed. 2 (mBOT-2). Results: Statistical analyses demonstrated significant differences in the scores of the GBT between children aged 3-5, 6-9, and ≥10 years with BV and in both control populations (HS and CI). BV scores reflected poorer balance capacities at all ages. Children in the youngest CI sub-group (3-5 years) showed intermediate GBT scores but reached HS scores at 6-9 years, reflecting an improvement in their balance capacities. All the results of the GBT were significantly correlated with mBOT-2 results, although only a few BV completed the entire mBOT-2. Discussion: In this study, the GBT allowed quantifying balance deficits in children with BV. The BOT-2 test is not validated for children <4.5 years of age, and the GBT seems to be better tolerated in all populations than the mBOT-2. Furthermore, mBOT-2 results saturated, reaching maximum values by 6-9 years whereas the GBT did not, suggesting that the GBT could be a useful tool for monitoring the development of balance capacities with age and could be used in the follow-up of children with severe vestibular disorders.

16.
J Crit Care ; 76: 154286, 2023 08.
Article in English | MEDLINE | ID: mdl-36965223

ABSTRACT

PURPOSE: We aimed to identify a gene signature that discriminates between sepsis and aseptic inflammation in patients administered antibiotics in the intensive care unit and compare it to commonly utilised sepsis biomarkers. METHODS: 91 patients commenced on antibiotics were retrospectively diagnosed as having: (i) blood culture positive sepsis; (ii) blood culture negative sepsis; or (iii) aseptic inflammation. Bloods were collected after <24 h of antibiotic commencement for both gene expression sequencing analysis and measurement of previously identified biomarkers. RESULTS: 53 differentially expressed genes were identified that accurately discriminated between blood culture positive sepsis and aseptic inflammation in a cohort of patients given antibiotics [aROC 0.97 (95% CI, 0.95-0.99)]. This gene signature was validated in a publicly available database. The gene signature outperformed previously identified sepsis biomarkers including C-reactive protein [aROC 0.72 (95% CI, 0.57-0.87)], NT-Pro B-type Natriuretic Peptide [aROC 0.84 (95% CI, 0.73-0.96)], and Septicyte™ LAB [aROC 0.8 (95% CI, 0.68-0.93)], but was comparable to Procalcitonin [aROC 0.96 (95% CI, 0.9-1)]. CONCLUSIONS: A gene expression signature was identified that accurately discriminates between sepsis and aseptic inflammation in patients given antibiotics in the intensive care unit.


Subject(s)
Sepsis , Transcriptome , Humans , Retrospective Studies , Biomarkers , Sepsis/diagnosis , Sepsis/genetics , Inflammation , Intensive Care Units , Anti-Bacterial Agents/therapeutic use
17.
Sci Rep ; 13(1): 4891, 2023 03 25.
Article in English | MEDLINE | ID: mdl-36966240

ABSTRACT

Dengue and Zika viruses are mosquito-borne flaviviruses burdening millions every year with hemorrhagic fever and neurological symptoms. Baicalein was previously reported as a potential anti-flaviviral candidate and halogenation of flavones and flavanones potentiated their antiviral efficacies. Here, we reported that a chemically modified 8-bromobaicalein effectively inhibited all dengue serotypes and Zika viruses at 0.66-0.88 micromolar in cell-based system. The compound bound to dengue serotype 2 conserved pocket and inhibited the dengue RdRp activity with 6.93 fold more than the original baicalein. Moreover, the compound was mildly toxic against infant and adult C57BL/6 mice despite administering continuously for 7 days. Therefore, the 8-bromobaicalein should be investigated further in pharmacokinetics and efficacy in an animal model.


Subject(s)
Dengue Virus , Dengue , Flavivirus , Zika Virus Infection , Zika Virus , Animals , Mice , Dengue/drug therapy , Mice, Inbred C57BL
18.
Cancer Invest ; : 1-17, 2023 Feb 06.
Article in English | MEDLINE | ID: mdl-36719061

ABSTRACT

The SPOT-MAS assay "Screening for the Presence Of Tumor by Methylation And Size" detects the five most common cancers in Vietnam by evaluating circulating tumor DNA in the blood. Here, we validated its performance in a prospective multi-center clinical trial, K-DETEK. Our analysis of 2795 participants from 14 sites across Vietnam demonstrates its ability to detect cancers in asymptomatic individuals with a positive predictive value of 60%, with 83.3% accuracy in detecting tumor location. We present a case report to support further using SPOT-MAS as a complementary method to achieve early cancer detection and provide the opportunity for early treatment.

19.
Sci Rep ; 12(1): 21646, 2022 12 14.
Article in English | MEDLINE | ID: mdl-36517573

ABSTRACT

Flavone has recently been proved as a promising scaffold for the development of a novel drug against dengue fever, one of the major health threats globally. However, the structure-activity relationship study of flavones on the anti-dengue activity remains mostly limited to the natural-occuring analogs. Herein, 27 flavone analogs were successfully synthesized, of which 5 analogs (5e, 5h, 5o, 5q, and 5r) were novel. In total, 33 analogs bearing a diverse range of substituents were evaluated for their efficacy against DENV2-infected LLC/MK2 cells. The introduction of electron-withdrawing groups on ring B such as Br (5m) or NO2 (5n and 5q) enhanced the activity significantly. In particular, the tri-ester 5d and di-ester 5e exhibited low toxicity against normal cell, and exceptional DENV2 inhibition with the EC50 as low as 70 and 68 nM, respectively, which is over 300-fold more active compared to the original baicalein reference. The viral targets for these potent flavone analogs were predicted to be NS5 MTase and NS5 RdRp, as suggested by the likelihood ratios from the molecular docking study. The great binding interaction energy of 8-bromobaicalein (5f) confirms the anti-dengue activity at atomistic level. The physicochemical property of all the synthetic flavone analogs in this study were predicted to be within the acceptable range. Moreover, the QSAR model showed the strong correlation between the anti-dengue activity and the selected molecular descriptors. This study emphasizes the great potential of flavone as a core structure for further development as a novel anti-dengue agent in the future.


Subject(s)
Flavones , Molecular Docking Simulation , Flavones/chemistry , Structure-Activity Relationship , Esters
20.
ACS Omega ; 7(45): 41687-41695, 2022 Nov 15.
Article in English | MEDLINE | ID: mdl-36406494

ABSTRACT

Nanosilica is a versatile nanomaterial suitable as, e.g., drug carriers in medicine, fillers in polymers, and fertilizer/pesticide carriers and potentially a bioavailable source of silicon in agriculture. The enhanced biological activity of nanosilica over quartz sand has been noted before; it is directly related to the altered physicochemical properties of the nanoparticles compared to those of the bulk material. Therefore, it is feasible to use nanosilica as a form of plant stimulant. Nanosilica synthesis is a relatively cheap routine process on the laboratory scale; however, it is not easily scalable. Largely for this reason, studies of nanosilica fertilizers are scarce. This study will focus on industrial-scale silica nanoparticle production and the application of nanosilica as a plant stimulant in maize. A variant of the sol-gel method is used to successfully synthesize nanosilica particles starting from silica sand. The resulting particles are in the size range of 16-37 nm with great purity. The potential of nanosilica as a plant stimulant is demonstrated with the increased quantity and quality of maize crops.

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