Publications by authors named "Nhu Le"

165 Publications

MCM3 is a novel proliferation marker associated with longer survival for patients with tubo-ovarian high-grade serous carcinoma.

Virchows Arch 2021 Nov 15. Epub 2021 Nov 15.

Department of Quantitative Health Sciences, Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN, USA.

Tubo-ovarian high-grade serous carcinomas (HGSC) are highly proliferative neoplasms that generally respond well to platinum/taxane chemotherapy. We recently identified minichromosome maintenance complex component 3 (MCM3), which is involved in the initiation of DNA replication and proliferation, as a favorable prognostic marker in HGSC. Our objective was to further validate whether MCM3 mRNA expression and possibly MCM3 protein levels are associated with survival in patients with HGSC. MCM3 mRNA expression was measured using NanoString expression profiling on formalin-fixed and paraffin-embedded tissue (N = 2355 HGSC) and MCM3 protein expression was assessed by immunohistochemistry (N = 522 HGSC) and compared with Ki-67. Kaplan-Meier curves and the Cox proportional hazards model were used to estimate associations with survival. Among chemotherapy-naïve HGSC, higher MCM3 mRNA expression (one standard deviation increase in the score) was associated with longer overall survival (HR = 0.87, 95% CI 0.81-0.92, p < 0.0001, N = 1840) in multivariable analysis. MCM3 mRNA expression was highest in the HGSC C5.PRO molecular subtype, although no interaction was observed between MCM3, survival and molecular subtypes. MCM3 and Ki-67 protein levels were significantly lower after exposure to neoadjuvant chemotherapy compared to chemotherapy-naïve tumors: 37.0% versus 46.4% and 22.9% versus 34.2%, respectively. Among chemotherapy-naïve HGSC, high MCM3 protein levels were also associated with significantly longer disease-specific survival (HR = 0.52, 95% CI 0.36-0.74, p = 0.0003, N = 392) compared to cases with low MCM3 protein levels in multivariable analysis. MCM3 immunohistochemistry is a promising surrogate marker of proliferation in HGSC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00428-021-03232-0DOI Listing
November 2021

Nudging Handwashing among Primary School Students in the Philippines: Evidence from a Cluster Randomized Trial.

Am J Trop Med Hyg 2021 Oct 25. Epub 2021 Oct 25.

UNICEF Philippines Country Office WASH, Philippines.

Handwashing is key to preventing the transmission of various infectious diseases of which school-aged children are particularly susceptible. Traditional, information-messaging campaigns may increase handwashing awareness but have had limited success in promoting behavior change. Behavioral economics "nudges," which explicitly target the knowledge-behavior gap, is a promising alternative. We evaluate the impact of school-based nudges in the first fully powered cluster randomized controlled trial in the Philippines. Out of our sample of 132 eligible schools, we randomly assigned half to receive nudges, including contextual cues (painted footpath from toilet to handwashing station) and visible reminders (posters and eye sticker), and half to the control group. Four months after implementation, we measured handwashing with soap (HWWS) after toilet use among grades 1-6 students using direct observation and compared this outcome between treatment and control schools. We also assessed whether nudges increased soap availability. The intervention increased HWWS rates by 17.3% points (pp), [95% CI: 4.2, 30.4] in treatment schools from the control group mean of 11.7%. The effect size was comparable across gender and age groups. Access to functioning handwashing facilities with soap increased by 36% (+20.2 pp, 95% CI: 10.9, 29.4). Mediation analysis suggests the program simultaneously nudged students to wash hands with soap in classrooms that already had soap, and nudged teachers to provide soap where it was not already available. These findings demonstrate that behavioral nudges costing less than $70 per school can lead to significant increases in HWWS among students 4 months post-intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4269/ajtmh.20-0673DOI Listing
October 2021

An observational study of breakthrough SARS-CoV-2 Delta variant infections among vaccinated healthcare workers in Vietnam.

EClinicalMedicine 2021 Nov 30;41:101143. Epub 2021 Sep 30.

Hospital for Tropical Diseaes, Ho Chi Minh City, Vietnam.

Background: Data on breakthrough SARS-CoV-2 Delta variant infections in vaccinated individuals are limited.

Methods: We studied breakthrough infections among Oxford-AstraZeneca vaccinated healthcare workers in an infectious diseases hospital in Vietnam. We collected demographic and clinical data alongside serial PCR testing, measurement of SARS-CoV-2 antibodies, and viral whole-genome sequencing.

Findings: Between 11-25 June 2021 (7-8 weeks after the second dose), 69 staff tested positive for SARS-CoV-2. 62 participated in the study. Most were asymptomatic or mildly symptomatic and all recovered. Twenty-two complete-genome sequences were obtained; all were Delta variant and were phylogenetically distinct from contemporary viruses obtained from the community or from hospital patients admitted prior to the outbreak. Viral loads inferred from Ct values were 251 times higher than in cases infected with the original strain in March/April 2020. Median time from diagnosis to negative PCR was 21 days (range 8-33). Neutralizing antibodies (expressed as percentage of inhibition) measured after the second vaccine dose, or at diagnosis, were lower in cases than in uninfected, fully vaccinated controls (median (IQR): 69.4 (50.7-89.1) vs. 91.3 (79.6-94.9), p=0.005 and 59.4 (32.5-73.1) vs. 91.1 (77.3-94.2), p=0.002). There was no correlation between vaccine-induced neutralizing antibody levels and peak viral loads or the development of symptoms.

Interpretation: Breakthrough Delta variant infections following Oxford-AstraZeneca vaccination may cause asymptomatic or mild disease, but are associated with high viral loads, prolonged PCR positivity and low levels of vaccine-induced neutralizing antibodies. Epidemiological and sequence data suggested ongoing transmission had occurred between fully vaccinated individuals.

Funding: Wellcome and NIH/NIAID.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eclinm.2021.101143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481205PMC
November 2021

Accurate Distinction of Ovarian Clear Cell From Endometrioid Carcinoma Requires Integration of Phenotype, Immunohistochemical Predictions, and Genotype: Implications for Lynch Syndrome Screening.

Am J Surg Pathol 2021 11;45(11):1452-1463

Department of Pathology, University of Calgary.

Ovarian clear cell carcinoma (OCCC) and ovarian endometrioid carcinoma (OEC) are both associated with endometriosis but differ in histologic phenotype, biomarker profile, and survival. Our objectives were to refine immunohistochemical (IHC) panels that help distinguish the histotypes and reassess the prevalence of mismatch repair deficiency (MMRd) in immunohistochemically confirmed OCCC. We selected 8 candidate IHC markers to develop first-line and second-line panels in a training set of 344 OCCC/OEC cases. Interobserver reproducibility of histotype diagnosis was assessed in an independent testing cohort of 100 OCC/OEC initially without and subsequently with IHC. The prevalence of MMRd was evaluated using the testing cohort and an expansion set of 844 ovarian carcinomas. The 2 prototypical combinations (OCCC: Napsin A+/HNF1B diffusely+/PR-; OEC: Napsin A-/HNF1B nondiffuse/PR+) occurred in 75% of cases and were 100% specific. A second-line panel (ELAPOR1, AMACR, CDX2) predicted the remaining cases with 83% accuracy. Integration of IHC improved interobserver reproducibility (κ=0.778 vs. 0.882, P<0.0001). The prevalence of MMRd was highest in OEC (11.5%, 44/383), lower in OCCC (1.7%, 5/297), and high-grade serous carcinomas (0.7%, 5/699), and absent in mucinous (0/126) and low-grade serous carcinomas (0/50). All 5 MMRd OCCC were probable Lynch syndrome cases with prototypical IHC profile but ambiguous morphologic features: 3/5 with microcystic architecture and 2/5 with intratumoral stromal inflammation. Integration of first-line and second-line IHC panels increases diagnostic precision and enhances prognostication and triaging for predisposing/predictive molecular biomarker testing. Our data support universal Lynch syndrome screening in all patients with OEC when the diagnosis of other histotypes has been vigorously excluded.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PAS.0000000000001798DOI Listing
November 2021

Absence of SARS-CoV-2 antibodies in pre-pandemic plasma from children and adults in Vietnam.

Int J Infect Dis 2021 Oct 31;111:127-129. Epub 2021 Jul 31.

Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam. Electronic address:

We tested pre-pandemic (2015--2019) plasma samples from 148 Vietnamese children and 100 Vietnamese adults at high risk of zoonotic infections for antibodies against SARS-CoV-2 nucleocapsid and spike proteins. None was positive. The data thus demonstrated no evidence of prior serological cross-reactivity with SARS-CoV-2 that might explain the low numbers of COVID-19 in Vietnam. No pre-existing cross-reactivity might explain Vietnam success of COVID-19 control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijid.2021.07.072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324399PMC
October 2021

Coxsackievirus A16 in Southern Vietnam.

Front Microbiol 2021 24;12:689658. Epub 2021 Jun 24.

Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.

Hand, Foot and Mouth Disease (HFMD) is a major public health concern in the Asia-Pacific region. Most recent HFMD outbreaks have been caused by enterovirus A71 (EV-A71), coxsackievirus A16 (CVA16), CVA10, and CVA6. There has been no report regarding the epidemiology and genetic diversity of CVA16 in Vietnam. Such knowledge is critical to inform the development of intervention strategies. From 2011 to 2017, clinical samples were collected from in- and outpatients enrolled in a HFMD research program conducted at three referral hospitals in Ho Chi Minh City (HCMC), Vietnam. Throat or rectal swabs positive for CVA16 with sufficient viral load were selected for whole genome sequencing and evolutionary analysis. Throughout the study period, 320 CVA16 positive samples were collected from 2808 HFMD patients (11.4%). 59.4% of patients were male. The median age was 20.8 months (IQR, 14.96-31.41). Patients resided in HCMC (55.3%), Mekong Delta (22.2%), and South East Vietnam (22.5%). 10% of CVA16 infected patients had moderately severe or severe HFMD. CVA16 positive samples from 153 patients were selected for whole genome sequencing, and 66 complete genomes were obtained. Phylogenetic analysis demonstrated that Vietnamese CVA16 strains belong to a single genogroup B1a that clusters together with isolates from China, Japan, Thailand, Malaysia, France and Australia. The CVA16 strains of the present study were circulating in Vietnam some 4 years prior to its detection in HFMD cases. We report for the first time on the molecular epidemiology of CVA16 in Vietnam. Unlike EV-A71, which showed frequent replacement between subgenogroups B5 and C4 every 2-3 years in Vietnam, CVA16 displays a less pronounced genetic alternation with only subgenogroup B1a circulating in Vietnam since 2011. Our collective findings emphasize the importance of active surveillance for viral circulation in HFMD endemic countries, critical to informing outbreak response and vaccine development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2021.689658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265502PMC
June 2021

A cluster of Ankyrin and Ankyrin-TPR repeat genes is associated with panicle branching diversity in rice.

PLoS Genet 2021 06 7;17(6):e1009594. Epub 2021 Jun 7.

LMI RICE, National Key Laboratory for Plant Cell Biotechnology, Agronomical Genetics Institute, Hanoi, Vietnam.

The number of grains per panicle is an important yield-related trait in cereals which depends in part on panicle branching complexity. One component of this complexity is the number of secondary branches per panicle. Previously, a GWAS site associated with secondary branch and spikelet numbers per panicle in rice was identified. Here we combined gene capture, bi-parental genetic population analysis, expression profiling and transgenic approaches in order to investigate the functional significance of a cluster of 6 ANK and ANK-TPR genes within the QTL. Four of the ANK and ANK-TPR genes present a differential expression associated with panicle secondary branch number in contrasted accessions. These differential expression patterns correlate in the different alleles of these genes with specific deletions of potential cis-regulatory sequences in their promoters. Two of these genes were confirmed through functional analysis as playing a role in the control of panicle architecture. Our findings indicate that secondary branching diversity in the rice panicle is governed in part by differentially expressed genes within this cluster encoding ANK and ANK-TPR domain proteins that may act as positive or negative regulators of panicle meristem's identity transition from indeterminate to determinate state.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pgen.1009594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211194PMC
June 2021

Comprehensive determination of polychlorinated biphenyls and brominated flame retardants in surface sediment samples from Hanoi urban area, Vietnam: Contamination status, accumulation profiles, and potential ecological risks.

Environ Res 2021 06 20;197:111158. Epub 2021 Apr 20.

Laboratory of Environmental Chemistry, Institute of Natural Product Chemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Hanoi, 10000, Viet Nam; Graduate University of Science and Technology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Hanoi, 10000, Viet Nam. Electronic address:

Comprehensive and updated information about polychlorinated biphenyls (PCBs) and brominated flame retardants (BFRs) in surface sediments from Hanoi, the capital city of Vietnam, is rather scarce. In this study, concentrations and profiles of 209 PCBs, 41 polybrominated diphenyl ethers (PBDEs), 2,2',4,4',5,5'-hexabromobiphenyl (BB-153), hexabromocyclododecane (HBCD), pentabromoethylbenzene (PBEB), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), and decabromodiphenyl ethane (DBDPE) were determined in sediment samples collected from the Red River and some inner-city rivers of Hanoi. Concentrations (ng/g dry weight, median and range) of pollutants decreased in the order: DBDPE (28; not detected ND - 59) ≈ PCBs (27; 1.7-50) > PBDEs (23; 0.20-61) > HBCD (1.2; ND - 5.2) > BTBPE (0.46; ND - 3.6) > BB-153 (0.004; ND - 0.014) > PBEB (ND). Pollutant levels in the inner-city river sediments were about one to two orders of magnitude higher than those measured in the Red River main stream sediments. Tri-to hexa-CBs are major homologs but detailed profiles vary between individual samples, reflecting source and/or seasonal variations. CB-11 and CB-209 were found at higher proportions in sediments than in technical PCB mixtures, suggesting their novel sources from pigments. Deca-BDE and DBDPE are the most predominant BFRs with an increasing trend predicted for DBDPE. A preliminary ecological risk assessment was conducted for these pollutants in sediments. Total PCBs and deca-BDE in a few inner-city river sediments may exhibit adverse effects on benthic organisms, but no serious risk was estimated in general.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envres.2021.111158DOI Listing
June 2021

Trace Metal Element Analysis in Some Seafood in the Coastal Zone of the Red River (Ba Lat Estuary, Vietnam) by Green Sample Preparation and Inductively Coupled Plasma-Mass Spectrometry (ICP-MS).

J Anal Methods Chem 2021 4;2021:6649362. Epub 2021 Mar 4.

Institute of Natural Product Chemistry (INPC), Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam.

Fisheries and aquaculture production in the coastal zone of Vietnam contribute significantly to the national economy. However, seafood quality and safety, especially in terms of metal contents, are of increasing concern, for both domestic and international markets. This paper presents the results of an investigation in some trace metal elements (iron (Fe), zinc (Zn), manganese (Mn), copper (Cu), arsenic (As), cadmium (Cd), and mercury (Hg)) concentrations in some fishes, crustaceans, and molluscs in the coastal zone of the Red River (in the Ba Lat estuary in Thai Binh and Nam Dinh provinces) during four sampling campaigns in 2020. All samples were treated by a green sample preparation using microwave digestion and then analyzed by inductively coupled plasma-mass spectrometry (ICP-MS). The results showed that the trace metal element concentrations in fish, crustacean, and mollusc samples decreased in the following order: Fe > Zn > Mn > Cu > As > Cd ∼ Hg. In more details, the ranges of trace metal elements in seafood samples were 13.13-202.73; 7.63-82.71; 0.48-22.73; 0.72-15.58; 0.18-5.12; 0.001-1.114; and 0.001-0.923 mg·kg for Fe, Zn, Mn, Cu, As, Cd, and Hg, respectively. The research results contribute to the dataset of the seafood (both fishery and aquacultural seafood) quality in the Red River coastal zone. Although the mean values of different trace metal elements observed in this study were lower than the allowed values of Vietnam's or European's threshold for food safety, some high concentrations were detected. The survey results suggest the need to expand the monitoring scope (frequency of monitoring, number of samples, and observed variables) for obtaining a fully comprehensive assessment of seafood quality in this region. Our results also indicate that it is necessary to manage water quality in coastal areas, especially where aquaculture activities are carried out.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/6649362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952155PMC
March 2021

Unsubstituted and Methylated PAHs in Surface Sediment of Urban Rivers in the Red River Delta (Hanoi, Vietnam): Concentrations, Profiles, Sources, and Ecological Risk Assessment.

Bull Environ Contam Toxicol 2021 Sep 24;107(3):475-486. Epub 2021 Mar 24.

Laboratory of Environmental Chemistry, Institute of Natural Product Chemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Hanoi, 10000, Vietnam.

Unsubstituted and methylated polycyclic aromatic hydrocarbons (22 PAHs and 17 Me-PAHs) were examined in surface sediments collected from the Red River and four inner-city rivers of Hanoi City, Vietnam. Concentrations of total PAHs and Me-PAHs ranged from 52 to 920 (median 710) and from 70 to 2600 (median 1000) ng/g dry weight in samples of dry and wet seasons, respectively. Significant correlation was observed between total PAHs and organic carbon contents (Spearman's ρ = 0.782; p < 0.05). PAHs were more abundant than Me-PAHs in all samples and dominated by 4-6 ring compounds. The most predominant PAHs were benzo[ghi]perylene, benzo[b/j]fluoranthene, chrysene, pyrene, fluoranthene, and phenanthrene. Methylated derivatives of naphthalene, phenanthrene, anthracene, and benz[a]anthracene were frequently detected. The patterns of PAHs indicated principal pyrogenic sources (notably gasoline exhaust) in this highly urbanized area. The occurrence of several PAHs were occasionally associated with adverse effects on benthic organisms of the inner-city rivers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00128-021-03174-yDOI Listing
September 2021

Axonal swellings are related to type 2 diabetes, but not to distal diabetic sensorimotor polyneuropathy.

Diabetologia 2021 04 23;64(4):923-931. Epub 2021 Jan 23.

Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.

Aims/hypothesis: Distal diabetic sensorimotor polyneuropathy (DSP) is a common complication of diabetes with many patients showing a reduction of intraepidermal nerve fibre density (IENFD) from skin biopsy, a validated and sensitive diagnostic tool for the assessment of DSP. Axonal swelling ratio is a morphological quantification altered in DSP. It is, however, unclear if axonal swellings are related to diabetes or DSP. The aim of this study was to investigate how axonal swellings in cutaneous nerve fibres are related to type 2 diabetes mellitus, DSP and neuropathic pain in a well-defined cohort of patients diagnosed with type 2 diabetes.

Methods: A total of 249 participants, from the Pain in Neuropathy Study (UK) and the International Diabetic Neuropathy Consortium (Denmark), underwent a structured neurological examination, nerve conduction studies, quantitative sensory testing and skin biopsy. The study included four groups: healthy control study participants without diabetes (n = 45); participants with type 2 diabetes without DSP (DSP-; n = 31); and participants with evidence of DSP (DSP+; n = 173); the last were further separated into painless DSP+ (n = 74) and painful DSP+ (n = 99). Axonal swellings were defined as enlargements on epidermal-penetrating fibres exceeding 1.5 μm in diameter. Axonal swelling ratio is calculated by dividing the number of axonal swellings by the number of intraepidermal nerve fibres.

Results: Median (IQR) IENFD (fibres/mm) was: 6.7 (5.2-9.2) for healthy control participants; 6.2 (4.4-7.3) for DSP-; 1.3 (0.5-2.2) for painless DSP+; and 0.84 (0.4-1.6) for painful DSP+. Swelling ratios were calculated for all participants and those with IENFD > 1.0 fibre/mm. When only those participants with IENFD > 1.0 fibre/mm were included, the axonal swelling ratio was higher in participants with type 2 diabetes when compared with healthy control participants (p < 0.001); however, there was no difference between DSP- and painless DSP+ participants, or between painless DSP+ and painful DSP+ participants. The axonal swelling ratio correlated weakly with HbA (r = 0.16, p = 0.04), but did not correlate with the Toronto Clinical Scoring System (surrogate measure of DSP severity), BMI or type 2 diabetes duration.

Conclusions/interpretation: In individuals with type 2 diabetes where IENFD is >1.0 fibre/mm, axonal swelling ratio is related to type 2 diabetes but is not related to DSP or painful DSP. Axonal swellings may be an early marker of sensory nerve injury in type 2 diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00125-020-05352-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940290PMC
April 2021

Viral Metagenomic Analysis of Cerebrospinal Fluid from Patients with Acute Central Nervous System Infections of Unknown Origin, Vietnam.

Emerg Infect Dis 2021 01;27(1):205-213

Central nervous system (CNS) infection is a serious neurologic condition, although the etiology remains unknown in >50% of patients. We used metagenomic next-generation sequencing to detect viruses in 204 cerebrospinal fluid (CSF) samples from patients with acute CNS infection who were enrolled from Vietnam hospitals during 2012-2016. We detected 8 viral species in 107/204 (52.4%) of CSF samples. After virus-specific PCR confirmation, the detection rate was lowered to 30/204 (14.7%). Enteroviruses were the most common viruses detected (n = 23), followed by hepatitis B virus (3), HIV (2), molluscum contagiosum virus (1), and gemycircularvirus (1). Analysis of enterovirus sequences revealed the predominance of echovirus 30 (9). Phylogenetically, the echovirus 30 strains belonged to genogroup V and VIIb. Our results expanded knowledge about the clinical burden of enterovirus in Vietnam and underscore the challenges of identifying a plausible viral pathogen in CSF of patients with CNS infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3201/eid2701.202723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774551PMC
January 2021

Antibiotic and antiparasitic residues in surface water of urban rivers in the Red River Delta (Hanoi, Vietnam): concentrations, profiles, source estimation, and risk assessment.

Environ Sci Pollut Res Int 2021 Mar 24;28(9):10622-10632. Epub 2020 Oct 24.

Laboratory of Environmental Chemistry, Institute of Natural Product Chemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, 10000, Vietnam.

Antibiotic residues and antimicrobial resistance in surface water are issues of global concern, especially in developing countries. In this study, the occurrence of seven antibiotics and one antiparasitic agent was determined in surface water samples collected from four rivers running through Hanoi urban area in the Red River Delta, northern Vietnam. The pharmaceuticals in water samples were analyzed by solid-phase extraction combined with liquid chromatography-tandem mass spectrometry method. The concentrations of pharmaceuticals in our samples ranged from 3050 to 16,700 (median 7800) ng/L, which were generally higher than levels found in river water from many other locations in the world. Amoxicillin, oxfendazole, and lincomycin were the most dominant and frequently detected compounds (detection rate 100%), which together accounted for 76 ± 14% of total concentrations. Sulfacetamide and sulfamethoxazole were detected at moderate concentrations in more than two-thirds of the analyzed samples. The remaining antibiotics (i.e., azithromycin, ciprofloxacin, and ofloxacin) were found at lower detection frequency and concentrations. Antibiotic concentrations in the water samples were not significantly different between the investigated rivers. Meanwhile, levels of pharmaceuticals in the samples collected in February 2020 were higher than those found in the remaining samples, largely due to the sharp decrease in sulfamethoxazole and azithromycin concentrations of the samples collected in March and April. Considerable ecological risks of antibiotics in surface water were estimated for some compounds such as amoxicillin, ciprofloxacin, and ofloxacin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-020-11329-3DOI Listing
March 2021

Antibiotics in surface water of East and Southeast Asian countries: A focused review on contamination status, pollution sources, potential risks, and future perspectives.

Sci Total Environ 2021 Apr 9;764:142865. Epub 2020 Oct 9.

University of Science, Vietnam National University, 334 Nguyen Trai, Thanh Xuan, Hanoi 10000, Viet Nam.

This review provides focused insights into the contamination status, sources, and ecological risks associated with multiple classes of antibiotics in surface water from the East and Southeast Asia based on publications over the period 2007 to 2020. Antibiotics are ubiquitous in surface water of these countries with concentrations ranging from <1 ng/L to hundreds μg/L and median values from 10 to 100 ng/L. Wider ranges and higher maximum concentrations of certain antibiotics were found in surface water of the East Asian countries like China and South Korea than in the Southeast Asian nations. Environmental behavior and fate of antibiotics in surface water is discussed. The reviewed occurrence of antibiotics in their sources suggests that effluent from wastewater treatment plants, wastewater from aquaculture and livestock production activities, and untreated urban sewage are principal sources of antibiotics in surface water. Ecological risks associated with antibiotic residues were estimated for aquatic organisms and the prevalence of antibiotic resistance genes and antibiotic-resistant bacteria were reviewed. Such findings underline the need for synergistic efforts from scientists, engineers, policy makers, government managers, entrepreneurs, and communities to manage and reduce the burden of antibiotics and antibiotic resistance in water bodies of East and Southeast Asian countries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2020.142865DOI Listing
April 2021

Superspreading Event of SARS-CoV-2 Infection at a Bar, Ho Chi Minh City, Vietnam.

Emerg Infect Dis 2021 01 16;27(1). Epub 2020 Oct 16.

We report a superspreading event of severe acute respiratory syndrome coronavirus 2 infection initiated at a bar in Vietnam with evidence of symptomatic and asymptomatic transmission, based on ministry of health reports, patient interviews, and whole-genome sequence analysis. Crowds in enclosed indoor settings with poor ventilation may be considered at high risk for transmission.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3201/eid2701.203480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774544PMC
January 2021

Cardiac remodeling during the neonatal intensive care period; a window of opportunity for early prevention of heart failure?

Early Hum Dev 2020 12 26;151:105168. Epub 2020 Aug 26.

Department of Neonatology, John Hunter Children's Hospital and University of Newcastle, Newcastle, NSW, Australia. Electronic address:

Background: There is growing evidence that preterm birth is a risk factor for early heart failure as a result of cardiac remodeling during a critical period of growth and development. The aim of this study was to explore if cardiac remodeling can be detected very early after preterm birth, and if present, if those remodeling changes persist until discharge.

Methods: Echocardiography parameters of left ventricular geometry and function were prospectively obtained with echocardiography in preterm infants <30 weeks gestation at postnatal day 3 and at 36 weeks postmenstrual age (PMA). Findings were compared to available data of healthy fetuses and cardiac remodeling was classified based on changes in left ventricular volume and/or mass.

Results: 65 (37 male) preterm infants were analysed. Three days after birth, 27.7% of infants had abnormal LV geometry, with immaturity and fetal growth restriction as risk factors for these early cardiac remodeling changes. At 36 weeks PMA, after a median period of 9 weeks of neonatal intensive care, 69.2% had abnormal cardiac geometry which could be classified as dilated hypertrophic remodeling (50.0%), dilated remodeling (11.5%) and hypertrophic remodeling (7.7%).

Conclusion: Cardiac remodeling changes can be detected very early after preterm birth. However, most changes take place during the neonatal intensive care period. The findings of this study could assist in identifying a group where an early and short-term intervention has the potential to prevent a pathway of abnormal cardiac development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.earlhumdev.2020.105168DOI Listing
December 2020

Clinical, etiological and epidemiological investigations of hand, foot and mouth disease in southern Vietnam during 2015 - 2018.

PLoS Negl Trop Dis 2020 08 17;14(8):e0008544. Epub 2020 Aug 17.

Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.

Hand, foot and mouth disease (HFMD) continues to challenge Asia with pandemic potential. In Vietnam, there have been two major outbreaks occurring during 2011-2012 (>200,000 hospitalizations and >200 deaths) and more recently in 2018 (>130,000 hospitalizations and 17 deaths). Given the high burden and the complex epidemic dynamics of HFMD, synthesizing its clinical and epidemiological data remains essential to inform the development of appropriate interventions and design public health measures. We report the results of a hospital-based study conducted during 2015-2018, covering the severe HFMD outbreak recently documented in Vietnam in 2018. The study was conducted at three major hospitals responsible for receiving HFMD patients from southern Vietnam with a population of over 40 million. A total of 19 enterovirus serotypes were detected in 1196 HFMD patients enrolled in the clinical study during 2015-2018, with enterovirus A71 (EV-A71), coxsackievirus A6 (CV-A6), CV-A10 and CV-A16 being the major causes. Despite the emergence of coxsackieviruses, EV-A71 remains the leading cause of severe HFMD in Vietnam. EV-A71 was consistently detected at a higher frequency during the second half of the years. The emergence of EV-A71 subgenogroup C4 in late 2018 was preceded by its low activity during 2017-early 2018. Compared with EV-A71 subgenogroup B5, C4 was more likely to be associated with severe HFMD, representing the first report demonstrating the difference in clinical severity between subgenogroup C4 and B5, the two predominant EV-A71 subgenogroups causing HFMD worldwide. Our data have provided significant insights into important aspects of HFMD over four years (2015-2018) in Vietnam, and emphasize active surveillance for pathogen circulation remains essential to inform the local public health authorities in the development of appropriate intervention strategies to reduce the burden of this emerging infections. Multivalent vaccines are urgently needed to control HFMD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pntd.0008544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451980PMC
August 2020

Refined cut-off for TP53 immunohistochemistry improves prediction of TP53 mutation status in ovarian mucinous tumors: implications for outcome analyses.

Mod Pathol 2021 01 28;34(1):194-206. Epub 2020 Jul 28.

Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW, Australia.

TP53 mutations are implicated in the progression of mucinous borderline tumors (MBOT) to mucinous ovarian carcinomas (MOC). Optimized immunohistochemistry (IHC) for TP53 has been established as a proxy for the TP53 mutation status in other ovarian tumor types. We aimed to confirm the ability of TP53 IHC to predict TP53 mutation status in ovarian mucinous tumors and to evaluate the association of TP53 mutation status with survival among patients with MBOT and MOC. Tumor tissue from an initial cohort of 113 women with MBOT/MOC was stained with optimized IHC for TP53 using tissue microarrays (75.2%) or full sections (24.8%) and interpreted using established criteria as normal or abnormal (overexpression, complete absence, or cytoplasmic). Cases were considered concordant if abnormal IHC staining predicted deleterious TP53 mutations. Discordant tissue microarray cases were re-evaluated on full sections and interpretational criteria were refined. The initial cohort was expanded to a total of 165 MBOT and 424 MOC for the examination of the association of survival with TP53 mutation status, assessed either by TP53 IHC and/or sequencing. Initially, 82/113 (72.6%) cases were concordant using the established criteria. Refined criteria for overexpression to account for intratumoral heterogeneity and terminal differentiation improved concordance to 93.8% (106/113). In the expanded cohort, 19.4% (32/165) of MBOT showed evidence for TP53 mutation and this was associated with a higher risk of recurrence, disease-specific death, and all-cause mortality (overall survival: HR = 4.6, 95% CI 1.5-14.3, p = 0.0087). Within MOC, 61.1% (259/424) harbored a TP53 mutation, but this was not associated with survival (overall survival, p = 0.77). TP53 IHC is an accurate proxy for TP53 mutation status with refined interpretation criteria accounting for intratumoral heterogeneity and terminal differentiation in ovarian mucinous tumors. TP53 mutation status is an important biomarker to identify MBOT with a higher risk of mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41379-020-0618-9DOI Listing
January 2021

Tattoos and Hematologic Malignancies in British Columbia, Canada.

Cancer Epidemiol Biomarkers Prev 2020 10 22;29(10):2093-2095. Epub 2020 Jul 22.

BC Cancer, Vancouver, British Columbia, Canada.

Background: Tattoos may cause a variety of adverse reactions in the body, including immune reactions and infections. However, it is unknown whether tattoos may increase the risk of lymphatic cancers such as non-Hodgkin lymphoma (NHL) and multiple myeloma.

Methods: Participants from two population-based case-control studies were included in logistic regression models to examine the association between tattoos and risk of NHL and multiple myeloma.

Results: A total of 1,518 participants from the NHL study (737 cases) and 742 participants from the multiple myeloma study (373 cases) were included in the analyses. No statistically significant associations were found between tattoos and risk of NHL or multiple myeloma after adjusting for age, sex, ethnicity, education, body mass index, and family history.

Conclusions: We did not identify any significant associations between tattoos and risk of multiple myeloma, NHL, or NHL subtypes in these studies.

Impact: Though biologically plausible, tattoos were not associated with increased risk of NHL or multiple myeloma in this study. Future studies with greater detail regarding tattoo exposure may provide further insights.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-20-0515DOI Listing
October 2020

Clinical and pathological associations of PTEN expression in ovarian cancer: a multicentre study from the Ovarian Tumour Tissue Analysis Consortium.

Br J Cancer 2020 09 18;123(5):793-802. Epub 2020 Jun 18.

Department of Oncology, Strangeways Research Laboratory, University of Cambridge, Cambridge, England.

Background: PTEN loss is a putative driver in histotypes of ovarian cancer (high-grade serous (HGSOC), endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous (LGSOC)). We aimed to characterise PTEN expression as a biomarker in epithelial ovarian cancer in a large population-based study.

Methods: Tumours from 5400 patients from a multicentre observational, prospective cohort study of the Ovarian Tumour Tissue Analysis Consortium were used to evaluate associations between immunohistochemical PTEN patterns and overall survival time, age, stage, grade, residual tumour, CD8+ tumour-infiltrating lymphocytes (TIL) counts, expression of oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) by means of Cox proportional hazard models and generalised Cochran-Mantel-Haenszel tests.

Results: Downregulation of cytoplasmic PTEN expression was most frequent in ENOC (most frequently in younger patients; p value = 0.0001) and CCOC and was associated with longer overall survival in HGSOC (hazard ratio: 0.78, 95% CI: 0.65-0.94, p value = 0.022). PTEN expression was associated with ER, PR and AR expression (p values: 0.0008, 0.062 and 0.0002, respectively) in HGSOC and with lower CD8 counts in CCOC (p value < 0.0001). Heterogeneous expression of PTEN was more prevalent in advanced HGSOC (p value = 0.019) and associated with higher CD8 counts (p value = 0.0016).

Conclusions: PTEN loss is a frequent driver in ovarian carcinoma associating distinctly with expression of hormonal receptors and CD8+ TIL counts in HGSOC and CCOC histotypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41416-020-0900-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463007PMC
September 2020

The Natural History and Transmission Potential of Asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

Clin Infect Dis 2020 12;71(10):2679-2687

Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.

Background: Little is known about the natural history of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Methods: We conducted a prospective study at a quarantine center for coronavirus disease 2019 in Ho Chi Minh City, Vietnam. We enrolled quarantined people with reverse-transcription polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infection, collecting clinical data, travel and contact history, and saliva at enrollment and daily nasopharyngeal/throat swabs (NTSs) for RT-PCR testing. We compared the natural history and transmission potential of asymptomatic and symptomatic individuals.

Results: Between 10 March and 4 April 2020, 14 000 quarantined people were tested for SARS-CoV-2; 49 were positive. Of these, 30 participated in the study: 13 (43%) never had symptoms and 17 (57%) were symptomatic. Seventeen (57%) participants imported cases. Compared with symptomatic individuals, asymptomatic people were less likely to have detectable SARS-CoV-2 in NTS collected at enrollment (8/13 [62%] vs 17/17 [100%]; P = .02). SARS-CoV-2 RNA was detected in 20 of 27 (74%) available saliva samples (7 of 11 [64%] in the asymptomatic group and 13 of 16 [81%] in the symptomatic group; P = .56). Analysis of RT-PCR positivity probability showed that asymptomatic participants had faster viral clearance than symptomatic participants (P < .001 for difference over the first 19 days). This difference was most pronounced during the first week of follow-up. Two of the asymptomatic individuals appeared to transmit SARS-CoV-2 to 4 contacts.

Conclusions: Asymptomatic SARS-CoV-2 infection is common and can be detected by analysis of saliva or NTSs. The NTS viral loads fall faster in asymptomatic individuals, but these individuals appear able to transmit the virus to others.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciaa711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314145PMC
December 2020

Combined CCNE1 high-level amplification and overexpression is associated with unfavourable outcome in tubo-ovarian high-grade serous carcinoma.

J Pathol Clin Res 2020 10 11;6(4):252-262. Epub 2020 May 11.

Department of Pathology and Laboratory Medicine, University of Calgary, Foothills Medical Center, Calgary, AB, Canada.

CCNE1 amplification is a recurrent alteration associated with unfavourable outcome in tubo-ovarian high-grade serous carcinoma (HGSC). We aimed to investigate whether immunohistochemistry (IHC) can be used to identify CCNE1 amplification status and to validate whether CCNE1 high-level amplification and overexpression are prognostic in HGSC. A testing set of 528 HGSC samples stained with two optimised IHC assays (clones EP126 and HE12) was subjected to digital image analysis and visual scoring. DNA and RNA chromogenic in situ hybridisation for CCNE1 were performed. IHC cut-off was determined by receiver operating characteristics (ROC). Survival analyses (endpoint ovarian cancer specific survival) were performed and validated in an independent validation set of 764 HGSC. Finally, combined amplification/expression status was evaluated in cases with complete data (n = 1114). CCNE1 high-level amplification was present in 11.2% of patients in the testing set and 10.2% in the combined cohort. The optimal cut-off for IHC to predict CCNE1 high-level amplification was 60% positive tumour cells with at least 5% strong staining cells (sensitivity 81.6%, specificity 77.4%). CCNE1 high-level amplification and overexpression were associated with survival in the testing and validation set. Combined CCNE1 high-level amplification and overexpression was present in 8.3% of patients, mutually exclusive to germline BRCA1/2 mutation and significantly associated with a higher risk of death in multivariate analysis adjusted for age, stage and cohort (hazard ratio = 1.78, 95 CI% 1.38-2.26, p < 0.0001). CCNE1 high-level amplification combined with overexpression identifies patients with a sufficiently poor prognosis that treatment alternatives are urgently needed. Given that this combination is mutually exclusive to BRCA1/2 germline mutations, a predictive marker for PARP inhibition, CCNE1 high-level amplification combined with overexpression may serve as a negative predictive test for sensitivity to PARP inhibitors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cjp2.168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578325PMC
October 2020

Performance of Metagenomic Next-Generation Sequencing for the Diagnosis of Viral Meningoencephalitis in a Resource-Limited Setting.

Open Forum Infect Dis 2020 Mar 8;7(3):ofaa046. Epub 2020 Feb 8.

Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.

Background: Meningoencephalitis is a devastating disease worldwide. Current diagnosis fails to establish the cause in ≥50% of patients. Metagenomic next-generation sequencing (mNGS) has emerged as pan-pathogen assays for infectious diseases diagnosis, but few studies have been conducted in resource-limited settings.

Methods: We assessed the performance of mNGS in the cerebrospinal fluid (CSF) of 66 consecutively treated adults with meningoencephalitis in a tertiary referral hospital for infectious diseases in Vietnam, a resource-limited setting. All mNGS results were confirmed by viral-specific polymerase chain reaction (PCR). As a complementary analysis, 6 viral PCR-positive samples were analyzed using MinION-based metagenomics.

Results: Routine diagnosis could identify a virus in 15 (22.7%) patients, including herpes simplex virus (HSV; n = 7) and varicella zoster virus (VZV; n = 1) by PCR, and mumps virus (n = 4), dengue virus (DENV; n = 2), and Japanese encephalitis virus (JEV; n = 1) by serological diagnosis. mNGS detected HSV, VZV, and mumps virus in 5/7, 1/1, and 1/4 of the CSF positive by routine assays, respectively, but it detected DENV and JEV in none of the positive CSF. Additionally, mNGS detected enteroviruses in 7 patients of unknown cause. Metagenomic MinION-Nanopore sequencing could detect a virus in 5/6 PCR-positive CSF samples, including HSV in 1 CSF sample that was negative by mNGS, suggesting that the sensitivity of MinION is comparable with that of mNGS/PCR.

Conclusions: In a single assay, metagenomics could accurately detect a wide spectrum of neurotropic viruses in the CSF of meningoencephalitis patients. Further studies are needed to determine the value that real-time sequencing may contribute to the diagnosis and management of meningoencephalitis patients, especially in resource-limited settings where pathogen-specific assays are limited in number.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ofid/ofaa046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7051036PMC
March 2020

Single or two drug combination therapy as initial treatment for low risk, gestational trophoblastic neoplasia. A Canadian analysis.

Gynecol Oncol 2020 05 4;157(2):367-371. Epub 2020 Mar 4.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N3M5, Canada.

Introduction: Low risk gestational trophoblastic neoplasia, WHO prognostic score of 0 to 6, is highly curable. There is no consensus on the optimal chemotherapy. Common regimens are q2wk actinomycin-D (ACT-D), weekly intramuscular methotrexate (MTX) or multi-day MTX. Combination MTX/ACT-D is rarely used.

Methods: A four centre, retrospective cohort study was carried out comparing commonly used regimens: weekly MTX, q2weekly ACT-D and q2 weekly MTX and ACT-D.

Results: 412 patients - 196 MTX/ACT-D, 107 MTX, 109 ACT-D - were treated between October 1994 and January 2019. Initial regimen failure (secondary to resistance or toxicity) occurred in 37% (MTX), 21% (ACT-D) and 5% (MTX/ACT-D). Relapse after completion of primary therapy (initial plus switch to another therapy if needed) was rare (0-5%). All eventually were cured. Mean number of cycles required to achieve remission were 10.1 (MTX), 7 (ACT-D) and 5.6 (MTX/ACT-D) with corresponding mean treatment durations of 3.12, 2.9 and 2.26 months. Dosage reductions occurred in 3% (MTX), 0% (ACT-D) and 29% (MTX/ACT-D). Higher failure rates occurred with WHO prognostic scores of 5 to 6 and HCG levels ≥10,000.

Summary: Initial regimen failure ie the need to switch to an alternative treatment was more common with MTX. ACT-D and MTX/ACT-D were similar within prognostic score 0-4 or HCG < 10,000. ACT-D then appears the better initial choice with its superior convenience. Above these levels primary failure rates are less with MTX/ACT-D, making it a better choice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygyno.2020.02.005DOI Listing
May 2020

Neutralizing Antibodies against Enteroviruses in Patients with Hand, Foot and Mouth Disease.

Emerg Infect Dis 2020 02;26(2):298-306

Hand, foot and mouth disease (HFMD) is an emerging infection with pandemic potential. Knowledge of neutralizing antibody responses among its pathogens is essential to inform vaccine development and epidemiologic research. We used 120 paired-plasma samples collected at enrollment and >7 days after the onset of illness from HFMD patients infected with enterovirus A71 (EV-A71), coxsackievirus A (CVA) 6, CVA10, and CVA16 to study cross neutralization. For homotypic viruses, seropositivity increased from <60% at enrollment to 97%-100% at follow-up, corresponding to seroconversion rates of 57%-93%. Seroconversion for heterotypic viruses was recorded in only 3%-23% of patients. All plasma samples from patients infected with EV-A71 subgenogroup B5 could neutralize the emerging EV-A71 subgenogroup C4. Collectively, our results support previous reports about the potential benefit of EV-A71 vaccine but highlight the necessity of multivalent vaccines to control HFMD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3201/eid2602.190721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986819PMC
February 2020

Synergistic apoptosis of human gastric cancer cells by bortezomib and TRAIL.

Int J Med Sci 2019 20;16(11):1412-1423. Epub 2019 Sep 20.

Ilsong Institute of Life Science, Hallym University, Anyang, Kyonggi-do, 14066, Republic of Korea.

Resistance against tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell death of cancer cells is a major obstacle in clinical application of TRAIL. Variable response to TRAIL of gastric cancer cells, synergy of TRAIL with bortezomib and potential mechanisms behind the phenomena were investigated in this study. The response to TRAIL varied among six gastric cancer cell lines, which correlated with the expression of apoptotic TRAIL receptors. Analysis of TCGA gene expression data showed that DR4 expression correlated with DR5 in gastric cancer. Although higher expression of DR4 was significantly associated with lower T, N and TNM stages, neither DR4 nor DR5 expression meaningfully influenced overall survival rate. Combined treatment of TRAIL with bortezomib resulted in strong synergistic response with enhanced activation of caspases-8, -9 and -3, and increased Annexin V-binding cell fractions in TRAIL-resistant SNU-216 cells. Bortezomib increased the expression of p21, but p21 silencing did not restore cell viability significantly. Bortezomib also increased DR5 expression and knockdown of DR5 expression significantly recovered cell viability reduced by the combination treatment. Bortezomib decreased phosphorylation of ERK1/2, but increased that of JNK. Treatment with either an ERK1/2 inhibitor U0126 or a JNK inhibitor SP600125 rescued SNU-216 from dying of bortezomib or combined treatment. However, upregulation of DR5 by bortezomib was knocked down only by inhibition of ERK1/2 activation significantly, but not by JNK activity inhibition. In summary, upregulation of DR5 by bortezomib is of critical significance in the synergy of bortezomib with TRAIL in apoptosis of TRAIL-resistant SNU-216 and that activity of ERK1/2 is required in the bortezomib-induced DR5 overexpression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/ijms.34398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6818207PMC
March 2020

Cardiovascular risk scoring and magnetic resonance imaging detected subclinical cerebrovascular disease.

Eur Heart J Cardiovasc Imaging 2020 06;21(6):692-700

Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada.

Aims: Cardiovascular risk factors are used for risk stratification in primary prevention. We sought to determine if simple cardiac risk scores are associated with magnetic resonance imaging (MRI)-detected subclinical cerebrovascular disease including carotid wall volume (CWV), carotid intraplaque haemorrhage (IPH), and silent brain infarction (SBI).

Methods And Results: A total of 7594 adults with no history of cardiovascular disease (CVD) underwent risk factor assessment and a non-contrast enhanced MRI of the carotid arteries and brain using a standardized protocol in a population-based cohort recruited between 2014 and 2018. The non-lab-based INTERHEART risk score (IHRS) was calculated in all participants; the Framingham Risk Score was calculated in a subset who provided blood samples (n = 3889). The association between these risk scores and MRI measures of CWV, carotid IPH, and SBI was determined. The mean age of the cohort was 58 (8.9) years, 55% were women. Each 5-point increase (∼1 SD) in the IHRS was associated with a 9 mm3 increase in CWV, adjusted for sex (P < 0.0001), a 23% increase in IPH [95% confidence interval (CI) 9-38%], and a 32% (95% CI 20-45%) increase in SBI. These associations were consistent for lacunar and non-lacunar brain infarction. The Framingham Risk Score was also significantly associated with CWV, IPH, and SBI. CWV was additive and independent to the risk scores in its association with IPH and SBI.

Conclusion: Simple cardiovascular risk scores are significantly associated with the presence of MRI-detected subclinical cerebrovascular disease, including CWV, IPH, and SBI in an adult population without known clinical CVD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ehjci/jez226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237958PMC
June 2020
-->