Reduction in Plasmodium falciparum Pfk13 and pfg377 allele diversity through time in southern Vietnam.

BACKGROUND: Plasmodium falciparum has acquired resistance to artemisinin in Southeast Asia, with mutations in the P. falciparum Kelch-13 (Pfk13) gene associated with the resistance phenotype. The widespread use of Artemisinin-based combination therapy (ACT)s in Southeast Asia has led to the selection and spread of parasites carrying mutations in Pfk13. We characterised the allele diversity of Pfk13 and pfg377, an artemisinin-resistance neutral polymorphic gene, in parasite DNA extracted human blood from in southern Vietnam in 2003, 2012, 2015 and 2018. METHOD: This study was conducted in Bu Gia Map commune, Binh Phuoc province, Vietnam, from May 2018 to January 2019. Twenty-four samples from 2018 to 2019, 30 from 2003, 24 from 2012 and 32 from 2015 were analysed. Malaria-infected human blood was collected by finger-prick and used for molecular analysis. A nested-PCR targeting the small subunit ribosomal RNA gene was used for Plasmodium species identification, followed by amplification and nucleotide sequencing of Pfk13 and region 3 of pfg377. Archived blood samples collected in the same region in 2012 and 2015 were also analysed as above for comparison. RESULTS: The genetic diversity of Pfk13 and pfg377 was lower in 2018-2019 compared to 2012 and 2015. The number of distinct Pfk13 mutants decreased from three in 2012 and 2015, P553L, V568G and C580Y, to one, C580Y in 2018-2019. In 2018-2019, the frequency of C580Y mutant strains was 71% (17/24 isolates). All samples were wild type in 2003. In 2012 and 2015, there were single-strain infections as well as co-infections with two mutant strains or with mutant and wild strains, whereas there were no co-infections in 2018. pfg377 allele diversity decreased from five alleles in 2012 to two alleles in 2018-2019. CONCLUSION: The genetic diversity of P. falciparum was reduced at the two genetic loci surveyed in this study, Pfk13 and pfg377. In the case of the former gene, we observed an increase in the prevalence of parasites carrying the C580Y gene, known to confer reduced susceptibility to ACTs. The reduction in the diversity of pfg377 may be linked to the clonal expansion of parasite strains carrying the C580Y mutation, leading to an overall reduction in parasite genetic diversity across the population.

Circulating level of sPD-1 and PD-1 genetic variants are associated with hepatitis B infection and related liver disease progression.

BACKGROUND: Programmed cell death-1 (PD-1) variants and circulating level of soluble PD-1 are associated with susceptibility to malignant and infectious disease. This study aimed to examine the association of PD-1.5 and PD-1.9 variants, and plasma sPD-1 level with hepatitis B virus (HBV) infection and disease progression. METHODS: The study cohort consisted of adults infected with HBV (n=513) - stratified by clinical course, including chronic hepatitis B (CHB, n=173), liver cirrhosis (LC, n=134) and hepatocellular carcinoma (HCC, n=206) - and matched healthy controls (HC, n=196). The PD-1.5 (rs2227981 C/T) and PD-1.9 (rs2227982 C/T) genetic variants were genotyped by Sanger sequencing, and plasma sPD-1 levels were quantified by enzyme immunoassay. RESULTS: Plasma sPD-1 levels were significantly higher among patients infected with HBV. The highest plasma sPD-1 levels were observed in patients with CHB, followed by patients with LC and HCC. In addition, the plasma sPD-1 levels correlated positively with liver inflammation [aspartate transaminase (AST): rho=0.57, P<0.0001; alanine aminotransferase: rho=0.57, P<0.0001], and were positively correlated with liver fibrosis [AST to platelet ratio index score: rho=0.53, P<0.0001). The PD-1.9 TT genotype was less common in patients with CHB compared with patients with LC, HCC, and HCC+LC in both codominant and recessive models (P<0.01), and was found to be a risk factor for HCC predisposition {HCC vs non-HCC: odds ratio (OR) 2.0 [95% confidence interval (CI) 1.13-3.7], Padj=0.017}. The PD-1.5 CT genotype was associated with reduced risk of acquiring HCC [OR 0.6 (95% CI 0.4-0.9), Padj=0.031]. CONCLUSION: sPD-1 level was associated with liver inflammation and progression of liver fibrosis, and the PD-1.5 and PD-1.9 variants were associated with HBV infection and progression of liver disease.

Maternal Vaginal Colonization and Extended-Spectrum Beta-Lactamase-Producing Bacteria in Vietnamese Pregnant Women.

Extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) resistance to commonly prescribed drugs is increasing in Vietnam. During pregnancy, ESBL-E may predispose women to reproductive tract infections and increases the risk for neonatal morbidity. Vaginal colonization and infections by Escherichia coli and Klebsiella pneumoniae are seldom studied in Vietnam. In this study, we investigated ESBL-producing Enterobacterales in the birth canal of pregnant women. Between 2016 and 2020, vaginal swabs were collected from 3104 pregnant women (mean gestational age of 31 weeks) and inoculated onto MacConkey agar plates. Colonies were subjected to direct identification and antimicrobial susceptibility testing using the VITEK®-2 automated compact system and disk diffusion. ESBL production was determined phenotypically. E. coli, Klebsiella species were identified in 30% (918/3104) of the vaginal swabs, with E. coli being the most common (73%; 667/918). ESBL-production was detected in 47% (432/918) of Enterobacterales, with frequent multidrug-resistant phenotype. The overall prevalence of carbapenem resistance was low (8%). Over 20% of Klebsiella spp. were carbapenem-resistant. Pregnant women had a high prevalence of colonization and may transmit ESBL-E to neonates at birth, an important risk factor to be considered. The high rate of ESBL-producers and carbapenem resistance in Enterobacterales in Vietnam emphasizes the need for consequent surveillance and access to molecular typing.

Prevalence, species distribution and antifungal susceptibility of Candida albicans causing vaginal discharge among symptomatic non-pregnant women of reproductive age at a tertiary care hospital, Vietnam.

BACKGROUND: Vaginal candidiasis is frequent in women of reproductive age. Accurate identification Candida provides helpful information for successful therapy and epidemiology study; however, there are very limited data from the Vietnam have been reported. This study was performed to determine the prevalence, species distribution of yeast causing vaginal discharge and antifungal susceptibility patterns of Candida albicans among symptomatic non-pregnant women of reproductive age. METHODS: Vaginal discharge samples were collected from 462 women of reproductive age in Hanoi, Vietnam between Sep 2019 and Oct 2020. Vaginal swabs from these patients were examined by direct microscopic examination (10% KOH). CHROMagar™ Candida medium and Sabouraud dextrose agar supplemented with chloramphenicol (0.5 g/l) were used to isolate yeast, and species identification was performed using morphological tests and molecular tools (PCR and sequencing). Antifungal susceptibility testing was determined according to the Clinical and Laboratory Standards Institute guidelines (M27-A3 and M27-S4). RESULTS: The prevalence of vaginal yeast colonization in non-pregnant women was 51.3% of 462 participants. Nine different yeast species were identified. Among these isolates, C. albicans (51.37%) was the most frequent, followed by C. parapsilosis (25.88%), C. glabrata (11.37%), C. tropicalis (4.31%), C. krusei (3.92%), C. africana (1.57%), Saccharomyces cerevisiae (0.78%), C. nivariensis (1 isolates, 0.39%), and C. lusitaniae (1 isolates, 0.39%), respectively. Among C. albicans, all 46 isolates were 100% susceptible to micafungin, caspofungin, and miconazole. The susceptibility rates to amphotericine B, 5-flucytosine, fluconazole, itraconazole and voriconazole were 95.65, 91.30, 91.30, 82.61 and 86.95%, respectively. CONCLUSIONS: The prevalence of VVC among symptomatic non-pregnant women of reproductive age in Vietnam was higher than many parts of the world. The high frequency of non-albicans Candida species, which were often more resistant to antifungal agents, was a notable feature. Resistance rates of vaginal C. albicans isolates to antifungal agents was low. Our findings suggest that continued surveillance of changes in species distribution and susceptibility to antifungals should be routinely screened and treated.

Isolation, semi-synthesis, docking-based prediction, and bioassay-based activity of Dolichandrone spathacea iridoids: new catalpol derivatives as glucosidase inhibitors.

Dolichandrone spathacea iridoids are promising anti-diabetic inhibitors towards α-glucosidase protein (PDB-3W37) and oligo-1,6-glucosidase protein (PDB-3AJ7). Five catalpol iridoids (1, 2, 10, 13, 14) were isolated from mangrove plant D. spathacea, and their derivatives (3, 4, 5, 6, 7, 8, 9, 11, 12, 15) were obtained from reduction, acetylation, O-alkylation, acetonisation, or hydrolysation starting from naturally isolated compounds. They were identified by spectral methods such as IR, MS, and 1D and 2D NMR. Their glucosidase-related (3W37 and 3AJ7) inhibitability and physiological compatibility were predicted by molecular docking simulation and prescreened based on Lipinski's rule of five. Experimental α-glucosidase inhibition of 1-15 was evaluated using enzyme assays. Compounds 3, 4, 5, 6, and 9 are new iridoid derivatives, introduced to the literature for the first time, while all fifteen compounds 1-15 are studied for molecular docking for the first time. Regarding protein 3W37, the five strongest predicted inhibitors assemble in the order 2 > 10 > 1 > 9 > 14. In respect to 3AJ7, the corresponding order is 14 > 2 > 10 > 5 > 1 = 9. Lipinski's criteria suggest 10 as the candidate with the most potential for oral administration. The in vitro bioassay revealed that compound 10 is the most effective inhibitor with a respective IC50 value of 0.05 µM, in the order 10 > 2 > 14 > 13 > 1. The computational and experimental results show good consistency. The study opens an alternative approach for diabetes treatment based on inhibitability of natural and semi-synthesised catalpol iridoid derivatives towards carbohydrate-hydrolases.

A case of traumatic anterior cerebral artery-cavernous sinus fistula.

Direct anterior cerebral artery-cavernous sinus fistula is an extremely rare complication of head trauma. We describe a male patient (age 49 years) with a history of head trauma 15 years ago who was hospitalised for a bulging red eye and tinnitus. Digital subtraction angiography showed a direct anterior cerebral artery (fork junction A1 - prior passage)-cavernous sinus fistula. The patient was treated with arterial endovascular intervention, complete sealing of the fistula orifice using coils. He was discharged 5 days later with no symptoms of a bulging red eye, ringing in the ears, or nerve paralysis. Re-examination after 3 months of stable clinical features did not show recurrent fistula. In conclusion, anterior cerebral artery-cavernous sinus fistula is an extremely rare lesion, and arterial endovascular intervention using coils is a safe and effective method for treatment of such lesion.

The impact of sexual harassment on obesity in female adolescents: An update and perspective to control.

BACKGROUND AND AIMS: Sexual victimization, happened during childhood and beyond, is known to be a substantial contributing factor for obesity development later in life. This work aims to bring about updated information on the relationship between sexual harassment and obesity. METHODS: Based on an intensive scientific literature review in Google Scholar, Pubmed databases, the total of 106 studies (N = 141,199) were assessed including 52 studies on the connection between negative lifetime impacts and obesity, 11 studies on post-traumatic stress disorder (PTSD) symptoms with proposed biological mechanisms related to obesity, 15 studies on the relationship between major depressive disorder (MDD) symptoms and obesity, 11 studies on the body dismorphic disorder (BDD) and 17 studies on the binge eating disorder (BED) were also examined to evaluate the association of obesity and traumatic life experiences. RESULTS: Although 40-70% of all cases related to obesity have been considered to be hereditary, many experts argue that deviations in the environment contribute to excessive food intake and depressed physical activity in numerous Western countries. Several studies have identified that childhood sexual abuse (CSA) may be nearly as common as obesity. However, just a few researchers have taken notice of the possible connection between these two. CONCLUSIONS: By mentioning some possible obesity-related psychological disorders in response to CSA, we present updated information on the relationship between sexual harassment and obesity.

Magnetoelectric Vortex Magnetic Field Sensors Based on the Metglas/PZT Laminates.

This paper describes the route, from simulations toward experiments, for optimizing the magnetoelectric (ME) geometries for vortex magnetic field sensors. The research is performed on the base of the Metglas/Piezoelectric (PZT) laminates in both open and closed magnetic circuit (OMC and CMC) geometries with different widths (W), lengths (L), and diameters (D). Among these geometries, the CMC laminates demonstrate advantages not only in their magnetic flux distribution, but also in their sensitivity and in their independence of the position of the vortex center. In addition, the ME voltage signal is found to be enhanced by increasing the magnetostrictive volume fraction. Optimal issues are incorporated to realize a CMC-based ME double sandwich current sensor in the ring shape with D × W = 6 mm × 1.5 mm and four layers of Metglas. At the resonant frequency of 174.4 kHz, this sensor exhibits the record sensitivity of 5.426 V/A as compared to variety of devices such as the CMC ME sensor family, fluxgate, magnetoresistive, and Hall-effect-based devices. It opens a potential to commercialize a new generation of ME-based current and (or) vortex magnetic sensors.

Massive Dissecting Aneurysm in the Basilar Tip Artery Treated with Intra-aneurysm and Basilar Artery Coiling.

INTRODUCTION: Deconstructive versus reconstructive technique remains controversial on the management of acute basilar tip artery dissection. AIM: We introduced a case report of massive dissecting aneurysm in the basilar tip artery treated with intra-aneurysm and basilar artery coiling. RESULTS: A 30-year-old male presented with sudden headache and severe vomiting. Radiographic study showed a large unruptured dissecting aneurysm in the basilar tip artery involving bilateral P1 segment. This aneurysm was treated with intra-aneurysm and basilar artery coiling. Patient was discharge after 7 days without any neurological deficits. Post-operatively, the patient received 75 mg aspirin and 75 mg clopidogrel PO per day for 3 months - then 75 mg aspirin per day for up to 1 year. Angiographic follow-up at 3 months showed a complete occlusion of aneurysmal sac and basilar tip artery without any deficits (mRS 0). Cerebral arteriography at 6 months follow-up confirmed a stable occlusion of aneurysmal sac with a minor recurrence of aneurysm in left P1 segment. CONCLUSION: Intra-aneurysm and basilar artery coiling is valuable alternative technique to treat complex basilar tip dissecting aneurysm in case of infeasible reconstructive technique. Clinical presentation, aneurysm characteristics and collateral circulation have to be investigated on each case to adopt this technique.

Benzimidazole Derivatives as Novel Zika Virus Inhibitors.

We have synthesized 50 benzimidazole (BMZ) derivatives with 1,2-phenylenediamines and aromatic aldehydes under mild oxidation conditions by using inexpensive, nontoxic inorganic salt sodium metabisulfite in a one-pot condensation reaction and screened their ability to interfere with Zika virus (ZIKV) infection utilizing a cell-based phenotypic assay. Seven BMZs inhibited an African ZIKV strain with a selectivity index (SI=CC50 /EC50 ) of 9-37. Structure-activity relationship analysis demonstrated that substitution at the C-2, N-1, and C-5 positions of the BMZ ring were important for anti-ZIKV activity. The hybrid structure of BMZ and naphthalene rings was a structural feature responsible for the high anti-ZIKV activity. Importantly, BMZs inhibited ZIKV in human neural stem cells, a physiologically relevant system considering the severe congenital anomalies, like microcephaly, caused by ZIKV infection. Compound 39 displayed the highest antiviral efficacy against the African ZIKV strain in Huh-7 (SI>37) and neural stem cells (SI=12). Compound 35 possessed the highest activity in Vero cells (SI=115). Together, our data indicate that BMZs derivatives have to be considered for the development of ZIKV therapeutic interventions.

Monitoring fine root growth to identify optimal fertilization timing in a forest plantation: A case study in Northeast Vietnam.

Fertilizer is applied widely to improve the productivity of plantations. Traditionally, fertilization is conducted in spring and/or in the early rainy season, and it is believed to support the growth of planted trees in the growing season. Little attention to date has been paid on identification of the optimal timing of fertilization and fertilizer dose. In this study, application of the fine root monitoring technique in identifying optimal fertilization timing for an Acacia plantation in Vietnam is described. The study used two fertilizer doses (100 and 200 g NPK/tree) and three fertilization timings (in spring; in the early rainy season; and based on the fine root monitoring technique to identify when the fine roots reach their growth peak). As expected fertilization timings significantly affected growth and above-ground biomass (AGB) of the plantation. Fertilization based on the fine root monitoring technique resulted in the highest growths and AGB, followed by fertilization in the early rainy season and then in spring. Applying fertilizer at 200 g NPK/tree based on the fine root monitoring technique increased diameter at breast height (DBH) by 16%, stem height by 8%, crown diameter (Dc) by 16%, and AGB by 40% as compared to early rainy season fertilization. Increases of 32% DBH, 23% stem height, 44% Dc, and 87% AGB were found in fertilization based on fine root monitoring technique compared to spring fertilization. This study concluded that forest growers should use the fine root monitoring technique to identify optimal fertilization timing for higher productivity.

Osteopontin is involved in Th1-mediated immunity against Plasmodium falciparum infection in a holoendemic malaria region in Vietnam.

We examined the role of osteopontin (OPN) in immunity against Plasmodium falciparum infection. We measured the mRNA levels for OPN and several cytokines in RNA preparations extracted from dried blood on filter paper obtained from falciparum malaria patients in Vietnam. Expression of OPN mRNA was detected in 134 of 161 patients. The expression of both interleukin-12 p40 and interferon-gamma mRNAs in the group positive for OPN mRNA was significantly higher than that in the group negative for OPN mRNA. The level of parasitemia in the OPN mRNA-positive group was much lower than that in the negative one. These results suggest that OPN might suppress multiplication of the parasites through T helper 1 cells-mediated immune responses.