Mercury distribution, mobilization and bioavailability in polluted sediments of Scheldt Estuary and Belgian Coastal Zone.

In this study, the vertical distribution of mercury (Hg) in estuarine and marine sediment porewaters and solid phases was assessed by conventional and passive sampling techniques in the historically polluted Scheldt Estuary and Belgian Coastal Zone (BCZ). The Diffusive Gradients in Thin-films (DGT) measured labile Hg concentrations (HgLA) were mostly lower than the porewater Hg concentrations (HgPW), and they also presented different vertical distribution patterns. Still high Hg concentrations in the sediment solid phases, comparable to the historical ones, were observed. Even though pH, redox potential and dissolved sulfide concentration could influence the Hg biogeochemical behaviour, organic matter (OM) played a key role in governing Hg mobilization from sediment solid phase to porewater and in its partitioning between porewater and solid phase over depth. In the marine sediments, where OM had a marine signature, higher labile Hg concentrations in the porewater and faster resupply from the solid phase were observed. The DGT technique showed significant potential not only for the measurement of bioavailable Hg fractions in porewater, but also for the assessment of kinetic parameters governing the release of labile Hg species from the solid phase with the assistance of the DGT Induced Fluxes in Sediments (DIFS) model.

Medication Adherence in Vietnamese Patients with Cardiovascular and Endocrine-Metabolic Diseases.

(1) Background: COVID-19 has significantly affected the quality of life and the medication adherence of patients with chronic diseases. Attitudes towards the disease and preventive measures are the things that need to be considered for patient adherence to medication during the COVID-19 pandemic. We aimed to evaluate the rate and compare the medication adherence and the impact of the COVID-19 pandemic on medication adherence in Vietnamese patients with cardiovascular and endocrine−metabolic diseases. (2) Methods: A cross-sectional study was conducted on outpatients having chronic diseases such as cardiovascular or/and endocrine−metabolic diseases in some southern provinces in Vietnam. In each group of patients, medication adherence was measured and assessed with the General Medication Adherence Scale (GMAS), adjusted and validated in Vietnam. In addition, the study also investigated attitudes and practices to prevent COVID-19. (3) Results: Out of 1444 patients in our study, the level of adherence was recorded in 867 cases, accounting for 61.1%. The group of patients with only cardiovascular disease and patients with only endocrine−metabolic disease had relatively similar compliance rates of 62 and 61.1%, respectively. The leading cause of non-adherence to treatment in all three groups of patients in the study, as assessed by the GMAS, was non-adherence due to financial constraints. Our study showed that 71.6% of patients felt anxious when going to the hospital for a medical examination. However, only 53.7% identified the COVID-19 pandemic as obstructing treatment follow-up visits. The research results showed that the COVID-19 epidemic influences the patient's psychology with regard to re-examination and treatment adherence, with p coefficients of 0.003 and <0.001, respectively. (4) Conclusion: Medication adherence rates in two disease groups are close, and financial constraint is the fundamental reason for medication non-adherence. Regulatory agencies must take care of people's welfare to improve adherence in the epidemic context.

Medication Adherence of Vietnamese Outpatients with Chronic Diseases during the COVID-19 Pandemic.

The purpose of this study was to determine the medication adherence of outpatients with chronic diseases and the association between both patient attitudes and preventive practices regarding COVID-19 and their medication adherence. We performed a cross-sectional study in Vietnam. Medication adherence was determined using the translated and validated Vietnamese version of the General Medication Adherence Scale (GMAS). Patient attitudes and preventive practices regarding COVID-19 were measured using the 5K message of the Vietnam Ministry of Health (facemasks, disinfection, distance, no gatherings, health declarations). The associations between patient characteristics and medication adherence were determined by multivariable regression. The study included 1852 outpatients, and 57.6% of the patients adhered to their medications. Patients who recognized the pandemic's obstruction of medical follow-ups (OR = 1.771; 95%CI = 1.461−2.147; p < 0.001), who applied ≥2 preventive methods (OR = 1.422; 95%CI = 1.173−1.725; p = 0.001), who were employed (OR = 1.677; 95%CI = 1.251−2.248; p = 0.001), who were living in urban areas (OR = 1.336; 95%CI = 1.090−1.637; p = 0.005,) who possessed higher education levels (OR = 1.313; 95%CI = 1.059−1.629; p = 0.013), or who had ≤2 comorbidities (OR = 1.293; 95%CI = 1.044−1.600; p = 0.019) were more likely to adhere to their medications. The adherence percentage for outpatients with chronic diseases was quite low during the pandemic. Patients who did not recognize the COVID-19 pandemic's obstruction of medical follow-ups or who had poor preventive practices were less likely to adhere to medications. Healthcare providers should pay more attention to these groups to achieve desired treatment outcomes.

An MDM2 inhibitor achieves synergistic cytotoxic effects with adenoviruses lacking E1B55kDa gene on mesothelioma with the wild-type p53 through augmenting NFI expression.

A majority of mesothelioma specimens were defective of p14 and p16 expression due to deletion of the INK4A/ARF region, and the p53 pathway was consequently inactivated by elevated MDM2 functions which facilitated p53 degradaton. We investigated a role of p53 elevation by MDM2 inhibitors, nutlin-3a and RG7112, in cytotoxicity of replication-competent adenoviruses (Ad) lacking the p53-binding E1B55kDa gene (Ad-delE1B). We found that a growth inhibition by p53-activating Ad-delE1B was irrelevant to p53 expression in the infected cells, but combination of Ad-delE1B and the MDM2 inhibitor produced synergistic inhibitory effects on mesothelioma with the wild-type but not mutated p53 genotype. The combination augmented p53 phosphorylation, activated apoptotic but not autophagic pathway, and enhanced DNA damage signals through ATM-Chk2 phosphorylation. The MDM2 inhibitors facilitated production of the Ad progenies through augmented expression of nuclear factor I (NFI), one of the transcriptional factors involved in Ad replications. Knocking down of p53 with siRNA did not increase the progeny production or the NFI expression. We also demonstrated anti-tumor effects by the combination of Ad-delE1B and the MDM2 inhibitors in an orthotopic animal model. These data collectively indicated that upregulation of wild-type p53 expression contributed to cytotoxicity by E1B55kDa-defective replicative Ad through NFI induction and suggested that replication-competent Ad together with augmented p53 levels was a therapeutic strategy for p53 wild-type mesothelioma.

Maternal and neonatal outcomes related to Zika virus in pregnant women in Southern Vietnam: An epidemiological and virological prospective analysis.

BACKGROUND: In 2016-2017, 68 women in Southern Vietnam had RT-PCR confirmed Zika virus (ZIKV) infection during pregnancy. We report here the outcomes of the pregnancies and the virological analyses related to this outbreak. METHODS: We collected clinical and epidemiological information from the women who were enrolled in the study. Medical records related to the pregnancy in 2016-2017 were retrieved for those who were not able to be enrolled in the study. Children born to women with ZIKV infection during pregnancy were also enrolled. Serum samples were evaluated for presence of ZIKV antibodies. Phylogenetic analyses were performed on Zika virus genomes sequenced from the 2016-2017 serum samples. FINDINGS: Of the 68 pregnancies, 58 were livebirths and 10 were medically terminated. Four of the medical records from cases of fetal demise were able to be retrieved, of which one was consistent with congenital ZIKV infection. Of the 58 women with a livebirth, 21 participated in the follow-up investigation. All but two women had serologic evidence of ZIKV infection. Of the 21 children included in the study (mean age: 30.3 months), 3 had microcephaly at birth. No other clinical abnormalities were reported and no differences in neurodevelopment were observed compared to a control group. Phylogenetic analysis revealed a clade within the ZIKV Asian lineage and branch at the root of samples from the 2013-2014 French Polynesian outbreak. The prM S139N mutation was not observed. INTERPRETATION: We have been able to demonstrate a clade within the ZIKV Asian lineage implicated in adverse pregnancy outcomes in Southern Vietnam. FUNDING: INCEPTION project (PIA/ANR-16-CONV-0005) and a grant received from BNP Paribas Simplidon.

Rotavirus genotype trends from 2013 to 2018 and vaccine effectiveness in southern Vietnam.

OBJECTIVES: Rotavirus (RV) genotypes vary geographically, and this can affect vaccine effectiveness (VE). This study investigated the genotype distribution of RV and explored VE before introducing the RV vaccine to the national immunization programme in Vietnam. METHODS: This hospital-based surveillance study was conducted at Children's Hospital 1, Ho Chi Minh City in 2013-2018. Stool samples and relevant data, including vaccination history, were collected from children aged <5 years who were hospitalized with gastroenteritis. RV was detected using enzyme immunoassays and then genotyped. Children aged ≥6 months were included in the VE analysis. RESULTS: Overall, 5176 children were included in this study. RV was detected in 2421 children (46.8%). RV positivity decreased over the study period and was associated with age, seasonality, location and previous vaccination. Among 1105 RV-positive samples, G3P[8] was the most prevalent genotype (43.1%), followed by G8P[8] (19.7%), G1P[8] (12.9%) and G2P[4] (12.9%). Overall VE was 69.7% [95% confidence interval (CI) 53.3-80.6%] in fully vaccinated children and 58.6% (95% CI 44.1-69.4%) in children who had received at least one dose of RV vaccine. VE was highest for G3P[8] (95% CI 75.1-84.5%) and lowest for G2P[4] (95% CI 32.4-57.2%). CONCLUSIONS: RV remains a major cause of acute gastroenteritis requiring hospitalization in southern Vietnam. The RV vaccine is effective, but its effectiveness varies with RV genotype.

Findings and lessons from establishing Zika virus surveillance in southern Viet Nam, 2016.

OBJECTIVE: To document the evolution and optimization of the Zika virus (ZIKV) disease surveillance system in southern Viet Nam in 2016 and to describe the characteristics of the identified ZIKV-positive cases. METHODS: We established a sentinel surveillance system to monitor ZIKV transmission in eight sites in eight provinces and expanded the system to 71 sites in 20 provinces in southern Viet Nam in 2016. Blood and urine samples from patients who met the case definition at the sentinel sites were tested for ZIKV using real-time reverse transcription polymerase chain reaction at the Pasteur Institute in Ho Chi Minh City (PI-HCMC). We conducted descriptive analysis and mapped the ZIKV-positive cases. RESULTS: In 2016, 2190 specimens from 20 provinces in southern Viet Nam were tested for ZIKV at PI-HCMC; 626 (28.6%), 484 (22.1%), 35 (1.6%) and 1045 (47.7%) tests were conducted in the first, second, third and fourth quarters of the year, respectively. Of these tested specimens, 214 (9.8%) were ZIKV positive with 212 (99.1%) identified in the fourth quarter. In the fourth quarter, the highest positivity rate was those in age groups 30-39 years (30.0%) and 40-59 years (31.6%). Of the 214 ZIKV-positive patients, 210 (98.1%) presented with rash, 194 (90.7%) with fever, 149 (69.6%) with muscle pain, 123 (57.5%) with joint pain and 66 (30.8%) with conjunctivitis. DISCUSSION: The surveillance system for ZIKV disease underwent several phases of optimization in 2016, guided by the most up-to-date local data. Here we demonstrate an adaptable surveillance system that detected ZIKV-positive cases in southern Viet Nam.

A spatial-temporal statistical analysis of health seasonality: explaining HFMD infections within a children population along the Vietnamese south central coast.

BACKGROUND: Various neglected tropical diseases show spatially changing seasonality at small areas. This phenomenon has received little scientific attention so far. Our study contributes to advancing the understanding of its drivers. This study focuses on the effects of the seasonality of increasing social contacts on the incidence proportions at multiple district level of the childhood hand-foot-mouth disease in Da Nang city, Viet Nam from 2012 to 2016. METHODS: We decomposed the nonstationary time series of the incidence proportions for the nine spatial-temporal (S-T) strata in the study area, where S indicates the spatial and T the temporal stratum. The long-term trends and the seasonality are presented by the Fourier series. To study the effects of the monthly average ambient temperature and the period of preschooling, we developed a spatial-temporal autoregressive model. RESULTS: Seasonality of childhood hand-foot-mouth disease incidence proportions shows two peaks in all spatial strata annually: large peaks synchronously in April and small ones asynchronously during the preschooling period. The peaks of the average temperature are asynchronous with the seasonal peaks of the childhood hand-foot-mouth disease incidence proportions in the period between January and May, with the negative values of the regression coefficients for all spatial strata, respectively: [Formula: see text]. The increasingly cumulative preschooling period and the seasonal component of the incidence proportions are negatively correlated in the period between August and December, with the negative values of the regression coefficients for all temporal strata, respectively: [Formula: see text]. CONCLUSIONS: The study shows that social contact amongst children under five years of age is the important driving factor of the dynamics of the childhood hand-foot-mouth disease outbreaks in the study area. The preschooling season when children's contact with each other increases stimulates the geographical variation of the seasonality of childhood hand-foot-mouth disease infections at small areas in the study area.

A p53-stabilizing agent, CP-31398, induces p21 expression with increased G2/M phase through the YY1 transcription factor in esophageal carcinoma defective of the p53 pathway.

Restoration of p53 functions is one of the therapeutic strategies for esophageal carcinoma which is often defective of the p53 pathway. We examined effects of CP-31398 which potentially increased expression of wild-type p53 or converted mutated p53 to the wild-type. We used 9 kinds of human squamous esophageal carcinoma cells with different p53 genotypes and examined expression of p53 and the related molecules in CP-31398-treated cells. Cisplatin, a DNA damaging agent, induced cleavages of PARP and caspase-3 without increase of p53 levels, indicating that the p53 down-stream pathway was disrupted in these cells. CP-31398 induced growth retardation but the cytotoxic effects were irrelevant to p53 genotype. CP-31398 influenced expression of p53 and the downstream molecules in a cell-dependent manner, but constantly increased p21 expression at the transcriptional level with decreased YY1 expression. Knockdown experiments with siRNA demonstrated that the CP-31398-mediated p21 up-regulation was unrelated with p53 expression but was associated with YY1 expression. We also showed that CP-31398-induced cell cycle changes including increase of G2/M populations was attributable to the up-regulated p21. These data collectively indicated that CP-31398 augmented endogenous p21 levels and induced cell cycle changes through regulation of YY1, and that YY1 was a novel target of CP-31398 in p53 dysfunctional cells.

Heat shock protein 90 inhibitors augment endogenous wild-type p53 expression but down-regulate the adenovirally-induced expression by inhibiting a proteasome activity.

Heat shock protein 90 (HSP90) inhibitors suppressed MDM4 functions which mediated p53 ubiquitination, and blocked a chaperon function which influenced expression of the client proteins. We examined cytotoxic effects of the inhibitors, 17-allylamino-17-demetheoxygeldanamycin (17-AAG) and 17-dimethylaminoethylamino-17-demethoxy-geldanamycin (17-DMAG), on mesothelioma and investigated combinatory effects of the inhibitors and adenoviruses expressing the wild-type p53 gene (Ad-p53). A majority of mesothelioma lacks p14 and p16 expression, which leads to defective p53 pathway despite bearing the wild-type p53 genotype. The HSP90 inhibitors up-regulated endogenous wild-type p53 expression and induced cell death. Furthermore, the inhibitors increased the endogenous p53 levels that were induced by cisplatin. Nevertheless, the HSP90 inhibitors suppressed Ad-p53-induced exogenous p53 expression primarily at a posttranscriptional level and inhibited the Ad-p53-mediated cell death. HSP90 inhibitors suppressed ubiquitination processes which were involved in p53 degradation, but a proteasome inhibitor, MG-132, prevented the HSP90 inhibitors-induced p53 down-regulation. In contrast, an inhibitor for HSP70 with a chaperon function, pifithrin-µ, did not produce the p53 down-regulation. The HSP90 inhibitors did not suppress expression of Ad receptor molecules but rather increased expression of green fluorescence protein transduced by the same Ad vector. These data collectively indicated that an HSP90 inhibitor possessed a divalent action on p53 expression, as an activator for endogenous wild-type p53 through inhibited ubiquitination and a negative regulator of exogenously over-expressed p53 through the proteasome pathway.

An image cytometric technique is a concise method to detect adenoviruses and host cell proteins and to monitor the infection and cellular responses induced.

BACKGROUND: Genetically modified adenoviruses (Ad) with preferential replications in tumor cells have been examined for a possible clinical applicability as an anti-cancer agent. A simple method to detect viral and cellular proteins is valuable to monitor the viral infections and to predict the Ad-mediated cytotoxicity. METHODS: We used type 5 Ad in which the expression of E1A gene was activated by 5'-regulatory sequences of genes that were augmented in the expression in human tumors. The Ad were further modified to have the fiber-knob region replaced with that derived from type 35 Ad. We infected human mesothelioma cells with the fiber-replaced Ad, and sequentially examined cytotoxic processes together with an expression level of the viral E1A, hexon, and cellular cleaved caspase-3 with image cytometric and Western blot analyses. RESULTS: The replication-competent Ad produced cytotoxicity on mesothelioma cells. The infected cells expressed E1A and hexon 24 h after the infection and then showed cleavage of caspase-3, all of which were detected with image cytometry and Western blot analysis. Image cytometry furthermore demonstrated that increased Ad doses did not enhance an expression level of E1A and hexon in an individual cell and that caspase-3-cleaved cells were found more frequently in hexon-positive cells than in E1A-positive cells. Image cytometry thus detected these molecular changes in a sensitive manner and at a single cell level. We also showed that an image cytometric technique detected expression changes of other host cell proteins, cyclin-E and phosphorylated histone H3 at a single cell level. CONCLUSIONS: Image cytometry is a concise procedure to detect expression changes of Ad and host cell proteins at a single cell level, and is useful to analyze molecular events after the infection.