Mapping access to drug outlets in Vietnam: distribution of drug outlets and the sociodemographic characteristics of the communities they serve.

Background: Drug outlets are a vital first point of healthcare contact in low- and middle-income countries (LMICs), but they are often poorly regulated and counter staff may be unqualified to provide advice. This introduces the risk of easy access to potentially harmful products, including unnecessary antimicrobials. Over-the-counter antimicrobial sales are a major driver of antimicrobial resistance (AMR) in LMICs. We aimed to investigate the distribution of different types of drug outlets and their association with socio-economic factors. Methods: We mapped the location of drug outlets in 40 randomly selected geographic clusters, covering a population of 1.96 million people. Data including type of drug outlet, context, operating hours, chief pharmacist name and qualification, and business registration identification were collected from mandatory public signage. We describe the density of drug outlets and levels of staff qualifications in relation to population density, urban vs rural areas, and poverty indices. Findings: We characterised 1972 drug outlets. In the study area, there was an average of 102 outlets/per 100,000 population, compared to the global average of 25. Predictably, population density was correlated with the density of drug outlets. We found that drug outlets were less accessible in rural vs urban areas, and for the poor. Furthermore, for these populations, degree-qualified pharmacists were less accessible and public signage frequently lacked mandatory registration information. Interpretation: Drug outlets appear over-supplied in Vietnam compared to other countries. Unregistered outlets and outlets without degree-qualified pharmacists are prevalent, especially in poor and rural areas, posing a risk for inappropriate supply of antimicrobials, which may contribute to AMR, and raises questions of equitable healthcare access. Funding: This study was funded by a grant from the Australian Department of Foreign Affairs and Trade.

Influences of anthropogenic activities on water quality in the Saigon River, Ho Chi Minh City.

Water quality for the surface water along the Saigon River in Ho Chi Minh City was assessed for four groups of water samples collected at the agricultural, industrial, residential, and less impacted areas. A variety of parameters indicating water quality including physicochemical parameters, nutrients, heavy metals, and antibiotic residues were measured for both the rainy and dry seasons, two main tropical seasons in HCM City using the standard methods. The results showed that the river water in the rainy season was detected with significantly higher values of turbidity, BOD5, PO4-P, NH4-N, NO3-N; and lower values of pH, temperature, conductivity, DO, salinity, Cu, Zn, As, Ni, Hg compared to that in the dry season. Sulfamethoxazole and trimethoprim were highly detected in the industrial areas compared to the agricultural and residential areas. Multivariate analyses suggested that the industrial and residential activities were more important contributors to the pollution of the Saigon River than the agricultural activities in HCM City.

Critical transporters of methionine and methionine hydroxyl analogue supplements across the intestine: What we know so far and what can be learned to advance animal nutrition.

DL-methionine (DL-Met) and its analogue DL-2-hydroxy-4-(methylthio) butanoic acid (DL-methionine hydroxyl analogue or DL-MHA) have been used as nutritional supplements in the diets of farmed raised animals. Knowledge of the intestinal transport mechanisms involved in these products is important for developing dietary strategies. This review provides updated information of the expression, function, and transport kinetics in the intestine of known Met-linked transporters along with putative MHA-linked transporters. As a neutral amino acid (AA), the transport of DL-Met is facilitated by multiple apical sodium-dependent/-independent high-/low-affinity transporters such as ASCT2, B0AT1 and rBAT/b0,+AT. The basolateral transport largely relies on the rate-limiting uniporter LAT4, while the presence of the basolateral antiporter y+LAT1 is probably necessary for exchanging intracellular cationic AAs and Met in the blood. In contrast, the intestinal transport kinetics of DL-MHA have been scarcely studied. DL-MHA transport is generally accepted to be mediated simply by the proton-dependent monocarboxylate transporter MCT1. However, in-depth mechanistic studies have indicated that DL-MHA transport is also achieved through apical sodium monocarboxylate transporters (SMCTs). In any case, reliance on either a proton or sodium gradient would thus require energy input for both Met and MHA transport. This expanding knowledge of the specific transporters involved now allows us to assess the effect of dietary ingredients on the expression and function of these transporters. Potentially, the resulting information could be furthered with selective breeding to reduce overall feed costs.

Zoonotic diseases from birds to humans in Vietnam: possible diseases and their associated risk factors.

In recent decades, exceeding 60% of infectious cases in human beings are originated from pathogenic agents related to feral or companion animals. This figure continues to swiftly increase due to excessive exposure between human and contaminated hosts by means of applying unhygienic farming practices throughout society. In Asia countries-renowned for lax regulation towards animal-trading markets-have experienced tremendous outbreaks of zoonotic diseases every year. Meanwhile, various epidemic surges were first reported in the residential area of China-one of the largest distributor of all animal products on the planet. Some noticeable illnesses comprising of A/H5N1 or H7N9-known as avian influenza which transmitted from poultry and also wild birds-have caused inevitable disquiet among inhabitants. Indeed, poultry farming industry in China has witnessed dynamic evolution for the past two decades, both in quantity and degree of output per individual. Together with this pervasive expansion, zoonotic diseases from poultry have incessantly emerged as a latent threat to the surrounding residents in entire Asia and also European countries. Without strict exporting legislation, Vietnam is now facing the serious problem in terms of poultry distribution between the two countries' border. Even though several disease investigations have been conducted by many researchers, the disease epidemiology or transmission methods among people remained blurred and need to be further elucidated. In this paper, our aim is to provide a laconic review of common zoonotic diseases spread in Vietnam, outstanding cases and several factors predisposing to this alarming situation.

The possible zoonotic diseases transferring from pig to human in Vietnam.

Southeast Asia is considered one of worldwide hotspots consisting many distinct zoonotic infections. With optimal condition for the development of various pathogens, Vietnam is facing serious risks of zoonotic diseases. Besides, more than 50% Vietnamese people settle in rustic areas and earn their livings through small-scale animal breeding. It is possible that zoonotic diseases can be easily spread to the population by close contact with the infected animals, their infected residues, contaminated water, soil, or other possible means of transmission. In fact, zoonotic infections-transmissible infections between vertebrate animals and humans-cover a wide range of diseases with distinctive clinical and epidemiological highlights. With insufficient understanding and swift alteration in toxicity of the pathogens, these infections have gained more concerns due to sophisticated routes of transmission and harmful threats to humans. Recently emerging viral diseases exerted potential dangers to human beings, which required many countries to impose immediate actions to prevent any complications. Vietnam has recorded several cases of zoonotic diseases, especially pig-related illnesses; however, the studies on these diseases in this country remain limited. This work aims to highlight the zoonotic diseases transferring from pigs to humans and discuss risk factors of these diseases in Vietnam.

Pharmacists' training to improve inhaler technique of patients with COPD in Vietnam.

Background: Incorrect use of inhalers is very common and subsequently leads to poor control of COPD. Among health care providers, pharmacists are in the best position to educate patients about the correct use of inhaler devices. Objective: The objective of this study was to evaluate the impact of pharmacist-led training on the improvement of inhaler technique for COPD patients in Vietnam. Patients and methods: For this pre- and post-intervention study, standardized checklists of correct use of metered-dose inhalers (MDIs) and dry powder inhalers (DPIs) were used to evaluate the inhaler technique. A scoring system (maximum score =8) was applied before and after training to guarantee assessment uniformity among pharmacists. Three methods including "face-to-face training", "teach-back" and "technique reminder label" were used. After the baseline evaluation (T0), the inhaler technique was reassessed after 1 month (T1), 3 months (T2), 6 months (T3) and 12 months (T4). Results: A total of 211 COPD patients participated in the study. Before the training, a high rate of errors was recorded. After the training, the percentage of patients using MDIs and DPIs perfectly increased significantly (p<0.05). The mean technique score for MDIs and DPIs improved from 6.0 (T0) to 7.5 (T3) and 6.9 (T4) and 6.7 (T0) to 7.6 (T3) and 7.2 (T4), respectively (p<0.05). The average training time was 6 minutes (T0) and 3 minutes (T3), respectively. Conclusion: Pharmacist-led comprehensive inhaler technique intervention program using an unbiased and simple scoring system can significantly improve the inhaler techniques in COPD patients. Our results indicated a 3-month period as the optimal time period between training and retraining for maintaining the correct inhaler technique. The training would be highly feasible and suitable for implementing in the clinical setting. Our model of pharmacist-led training should be considered as an effective solution for managing COPD patients and better utilization of health care human resources, especially in a developing country like Vietnam.

Genome-guided exploration of metabolic features of Streptomyces peucetius ATCC 27952: past, current, and prospect.

Streptomyces peucetius ATCC 27952 produces two major anthracyclines, doxorubicin (DXR) and daunorubicin (DNR), which are potent chemotherapeutic agents for the treatment of several cancers. In order to gain detailed insight on genetics and biochemistry of the strain, the complete genome was determined and analyzed. The result showed that its complete sequence contains 7187 protein coding genes in a total of 8,023,114 bp, whereas 87% of the genome contributed to the protein coding region. The genomic sequence included 18 rRNA, 66 tRNAs, and 3 non-coding RNAs. In silico studies predicted ~ 68 biosynthetic gene clusters (BCGs) encoding diverse classes of secondary metabolites, including non-ribosomal polyketide synthase (NRPS), polyketide synthase (PKS I, II, and III), terpenes, and others. Detailed analysis of the genome sequence revealed versatile biocatalytic enzymes such as cytochrome P450 (CYP), electron transfer systems (ETS) genes, methyltransferase (MT), glycosyltransferase (GT). In addition, numerous functional genes (transporter gene, SOD, etc.) and regulatory genes (afsR-sp, metK-sp, etc.) involved in the regulation of secondary metabolites were found. This minireview summarizes the genome-based genome mining (GM) of diverse BCGs and genome exploration (GE) of versatile biocatalytic enzymes, and other enzymes involved in maintenance and regulation of metabolism of S. peucetius. The detailed analysis of genome sequence provides critically important knowledge useful in the bioengineering of the strain or harboring catalytically efficient enzymes for biotechnological applications.

Prolyl-hydroxylase inhibition induces SDF-1 associated with increased CXCR4+/CD11b+ subpopulations and cardiac repair.

SDF-1/CXCR4 activation facilitates myocardial repair. Therefore, we aimed to activate the HIF-1α target genes SDF-1 and CXCR4 by dimethyloxalylglycine (DMOG)-induced prolyl-hydroxylase (PH) inhibition to augment CXCR4+ cell recruitment and myocardial repair. SDF-1 and CXCR4 expression was analyzed under normoxia and ischemia ± DMOG utilizing SDF-1-EGFP and CXCR4-EGFP reporter mice. In bone marrow and heart, CXCR4-EGFP was predominantly expressed in CD45+/CD11b+ leukocytes which significantly increased after myocardial ischemia. PH inhibition with 500 µM DMOG induced upregulation of SDF-1 mRNA in human microvascular endothelial cells (HMEC-1) and aortic vascular smooth muscle cells (HAVSMC). CXCR4 was highly elevated in HMEC-1 but almost no detectable in HAVSMC. In vivo, systemic administration of the PH inhibitor DMOG without pretreatment upregulated nuclear HIF-1α and SDF-1 in the ischemic mouse heart associated with increased recruitment of CD45+/CXCR4-EGFP+/CD11b+ cell subsets. Enhanced PH inhibition significantly upregulated reparative M2 like CXCR4-EGFP+ CD11b+/CD206+ cells compared to inflammatory M2-like CXCR4-EGFP+ CD11b+/CD86+ cells associated with reduced apoptotic cell death, increased neovascularization, reduced scar size, and an improved heart function after MI. In summary, our data suggest increased PH inhibition as a promising tool for a customized upregulation of SDF-1 and CXCR4 expression to attract CXCR4+/CD11b+ cells to the ischemic heart associated with increased cardiac repair. KEY MESSAGES: DMOG-induced prolyl-hydroxylase inhibition upregulates SDF-1 and CXCR4 in human endothelial cells. Systemic application of DMOG upregulates nuclear HIF-1α and SDF-1 in vivo. Enhanced prolyl-hydroxylase inhibition increases mainly CXCR4+/CD11b+ cells. DMOG increased reparative M2-like CD11b+/CD206+ cells compared to M1-like cells after MI. Enhanced prolyl-hydroxylase inhibition improved cardiac repair and heart function.

Genetic evidence for the involvement of glycosyltransferase PdmQ and PdmS in biosynthesis of pradimicin from Actinomadura hibisca.

Pradimicins are potent antifungal antibiotics with effective inhibitory effects against HIV-1. Pradimicin A consists of an unusual dihydrobenzo[α]naphthacenequinone aglycone substituted with a combination of D-alanine and two sugar moieties. Detailed genetic studies revealed most steps in pradimicin A biosynthesis, but the glycosylation mechanism remained inconclusive. The biosynthetic gene cluster of pradimicin A contains two putative glycosyltransferases, pdmQ and pdmS. However, the exact involvement of each gene in biosynthesis and the particular steps required for precise structural modification was unknown. In this study, the exact role of each gene was evaluated by insertional inactivation and complementation studies. Analysis of the metabolite from both of the disruption mutants revealed abolishment of pradimicin A and complementation resulted in the recovery of production. After deletion of pdmQ, pradimicin B was found to accumulate, whereas deletion of pdmS resulted in the accumulation of aglycone of pradimicin. Together, these results suggest that pdmS is responsible for the attachment of thomosamine to form pradimicin B which in turn is glycosylated by pdmQ to form pradimicin A. These results allowed us to deduce the exact order of terminal tailoring by glycosylation and provided insight into the mechanism of pradimicin A biosynthesis.

Structural modification of herboxidiene by substrate-flexible cytochrome P450 and glycosyltransferase.

Herboxidiene is a natural product produced by Streptomyces chromofuscus exhibiting herbicidal activity as well as antitumor properties. Using different substrate-flexible cytochrome P450s and glycosyltransferase, different novel derivatives of herboxidiene were generated with structural modifications by hydroxylation or epoxidation or conjugation with a glucose moiety. Moreover, two isomers of herboxidiene containing extra tetrahydrofuran or tetrahydropyran moiety in addition to the existing tetrahydropyran moiety were characterized. The hydroxylated products for both of these compounds were also isolated and characterized from S. chromofuscus PikC harboring pikC from the pikromycin gene cluster of Streptomyces venezuelae and S. chromofuscus EryF harboring eryF from the erythromycin gene cluster of Saccharopolyspora erythraea. The compounds generated were characterized by high-resolution quadrupole-time-of-flight electrospray ionization mass spectrometry (HR-QTOF-ESI/MS) and (1)H- and (13)C-nuclear magnetic resonance (NMR) analyses. The evaluation of antibacterial activity against three Gram-positive bacteria, Micrococcus luteus, Bacillus subtilis, and Staphylococcus aureus, indicated that modification resulted in a transition from anticancer to antibacterial potency.

On the potential for CO2 mineral storage in continental flood basalts - PHREEQC batch- and 1D diffusion-reaction simulations.

Continental flood basalts (CFB) are considered as potential CO2 storage sites because of their high reactivity and abundant divalent metal ions that can potentially trap carbon for geological timescales. Moreover, laterally extensive CFB are found in many place in the world within reasonable distances from major CO2 point emission sources.Based on the mineral and glass composition of the Columbia River Basalt (CRB) we estimated the potential of CFB to store CO2 in secondary carbonates. We simulated the system using kinetic dependent dissolution of primary basalt-minerals (pyroxene, feldspar and glass) and the local equilibrium assumption for secondary phases (weathering products). The simulations were divided into closed-system batch simulations at a constant CO2 pressure of 100 bar with sensitivity studies of temperature and reactive surface area, an evaluation of the reactivity of H2O in scCO2, and finally 1D reactive diffusion simulations giving reactivity at CO2 pressures varying from 0 to 100 bar.Although the uncertainty in reactive surface area and corresponding reaction rates are large, we have estimated the potential for CO2 mineral storage and identified factors that control the maximum extent of carbonation. The simulations showed that formation of carbonates from basalt at 40 C may be limited to the formation of siderite and possibly FeMg carbonates. Calcium was largely consumed by zeolite and oxide instead of forming carbonates. At higher temperatures (60 - 100 C), magnesite is suggested to form together with siderite and ankerite. The maximum potential of CO2 stored as solid carbonates, if CO2 is supplied to the reactions unlimited, is shown to depend on the availability of pore space as the hydration and carbonation reactions increase the solid volume and clog the pore space. For systems such as in the scCO2 phase with limited amount of water, the total carbonation potential is limited by the amount of water present for hydration of basalt.