Evaluation of Dihydroartemisinin-Piperaquine Efficacy and Molecular Markers in Uncomplicated Falciparum Patients: A Study across Binh Phuoc and Dak Nong, Vietnam.

Background and Objectives: Malaria continues to be a significant global health challenge. The efficacy of artemisinin-based combination therapies (ACTs) has declined in many parts of the Greater Mekong Subregion, including Vietnam, due to the spread of resistant malaria strains. This study was conducted to assess the efficacy of the Dihydroartemisinin (DHA)-Piperaquine (PPQ) regimen in treating uncomplicated falciparum malaria and to conduct molecular surveillance of antimalarial drug resistance in Binh Phuoc and Dak Nong provinces. Materials and Methods: The study included 63 uncomplicated malaria falciparum patients from therapeutic efficacy studies (TES) treated following the WHO treatment guidelines (2009). Molecular marker analysis was performed on all 63 patients. Methods encompassed Sanger sequencing for pfK13 mutations and quantitative real-time PCR for the pfpm2 gene. Results: This study found a marked decrease in the efficacy of the DHA-PPQ regimen, with an increased rate of treatment failures at two study sites. Genetic analysis revealed a significant presence of pfK13 mutations and pfpm2 amplifications, indicating emerging resistance to artemisinin and its partner drug. Conclusions: The effectiveness of the standard DHA-PPQ regimen has sharply declined, with rising treatment failure rates. This decline necessitates a review and possible revision of national malaria treatment guidelines. Importantly, molecular monitoring and clinical efficacy assessments together provide a robust framework for understanding and addressing detection drug resistance in malaria.

Neutrophil: Lymphocyte and Platelet: Lymphocyte ratios measured before transplantation and their correlation with new-onset diabetes post-transplantation in renal transplant recipients.

PURPOSE: Our goal was to evaluate the neutrophil:lymphocyte (NLR) and platelet:lymphocyte (PLR) ratios measured before transplantation and their correlation with new-onset diabetes after transplantation (NODAT) in renal transplant recipients. PATIENTS AND METHODS: We conducted our study in 324 adult patients consecutively admitted to Military Hospital 103, Ha Noi, Viet Nam, who received kidney allografts from living donors. These patients were followed-up during the first 2 years post-transplantation for NODAT. We examined the association between NLR and PLR measured prior to transplantation in patients with NODAT: NLR and PLR were calculated based on the results of the complete blood count. The criteria for diagnosis of a fully symptomatic NODAT case were based on the guidelines established by the American Diabetes Association and included fasting venous blood glucose and glycosylated hemoglobin A1c (HbA1c) levels, with or without an oral glucose tolerance test. RESULTS: The overall rate of NODAT during the two years after kidney transplantation was 13.6%. We found mean values of age and body mass index (BMI), and median values of NLR, PLR, high sensitivity C-reactive protein (hs-CRP) levels, and the arteriosclerosis ratio in the NODAT group to be significantly higher than those of the non-NODAT group (all p < 0.05). Furthermore, an adjusted multivariate regression analysis showed that age (area under the curve [AUC] = 0.727, p < 0.001), BMI (AUC = 0.846, p < 0.001), serum hs-CRP levels (AUC = 0.884, p < 0.001), NLR (AUC = 0.888; p < 0.001), and PLR (AUC = 0.818; p < 0.001) had predictive value for NODAT. CONCLUSION: NLR and PLR measured before transplantation were good predictors for NODAT in the first 2 years post-renal transplantation.

Developing efficient CuO nanoplate/ZnO nanoparticle hybrid photocatalysts for methylene blue degradation under visible light.

CuO/ZnO nanocomposites with different components can overcome the drawbacks of previously used photocatalysts owing to their promotion in charge separation and transportation, light absorption, and the photo-oxidation of dyes. In this study, CuO nanoplates were synthesized by the hydrothermal method, while ZnO nanoparticles were fabricated by the precipitation method. A series of CuO/ZnO nanocomposites with different ZnO-to-CuO weight ratios, namely, 2 : 8, 4 : 6, 5 : 5, 6 : 4, and 8 : 2 were obtained via a mixing process. X-ray diffraction patterns confirmed the presence of hexagonal wurtzite ZnO and monoclinic CuO in the synthesized CuO/ZnO nanocomposites. Scanning electron microscopy showed the dispersion of ZnO nanoparticles on the surface of CuO nanoplates. Ultraviolet-visible absorption spectra exhibited a slight red-shift in the absorption edge of binary oxides relative to pure ZnO or CuO. All samples were employed for the photocatalytic degradation of methylene blue (MB) under visible light irradiation. The composite samples exhibited enhanced photocatalytic performance compared with pristine CuO or ZnO. This study aimed to examine the effect of the ZnO-to-CuO weight ratio on their photocatalytic performance. The results indicated that among all the synthesized nanocomposites and pristine oxides, the nanocomposite with ZnO and CuO in a proportion of 4 : 6 shows the highest photodegradation activity for the removal of MB with 93% MB photodegraded within 60 min at an initial MB concentration of 5 ppm. The photocatalytic kinetic data were described well by the pseudo-first-order model with a high correlation coefficient of 0.95. The photocatalytic mechanism of the mixed metal oxide was proposed and discussed in detail. The photodegradation characteristic of CuO/ZnO nanostructures is valuable for methylene blue degradation from aqueous solutions as well as environmental purification in various fields.

Bosma Arhinia Microphthalmia Syndrome (BAMS): First Report from Vietnam.

Bosma arhinia microphthalmia syndrome (BAMS) is a rare condition, with about 100 cases identified worldwide. It is characterized by nasal and ophthalmic abnormalities, as well as disturbances in puberty and sexual development. The cardinal sign is arhinia, though some cases have partial aplasia of the external nose. In addition, several reports have revealed abnormal brain structure, including changes to the olfactory bulbs. This case describes a 29-year-old female who has suffered from BAMS since birth. On presentation, she was noted to have congenital arhinia, bilateral microphthalmia, vision loss, mouth-breathing, an unclear speaking voice, a high arched or cleft palate, and a hypoplastic maxilla. Her paranasal sinuses were ossified and underdeveloped. This syndrome occurs rarely, both within Vietnam and worldwide. It is characterized by four major features: arrhinia, complete absence of the paranasal sinuses, eye defects, and absent sexual maturation. This case report describes the presentation of the disorder to improve otolaryngologists' understanding of BAMS. Criteria for diagnosis consist of arhinia, midface hypoplasia (with a hypoplastic maxilla), hypogonadotropic hypogonadism, and normal intellectual abilities. Additional important findings are microphthalmia with or without coloboma, anosmia, maxillary hypoplasia, a high-arched palate, and absence of paranasal sinuses and olfactory bulbs.

Urinary catecholamine excretion, cardiovascular variability, and outcomes in tetanus.

Severe tetanus is characterized by muscle spasm and cardiovascular system disturbance. The pathophysiology of muscle spasm is relatively well understood and involves inhibition of central inhibitory synapses by tetanus toxin. That of cardiovascular disturbance is less clear, but is believed to relate to disinhibition of the autonomic nervous system. The clinical syndrome of autonomic nervous system dysfunction (ANSD) seen in severe tetanus is characterized principally by changes in heart rate and blood pressure which have been linked to increased circulating catecholamines. Previous studies have described varying relationships between catecholamines and signs of ANSD in tetanus, but are limited by confounders and assays used. In this study, we aimed to perform detailed characterization of the relationship between catecholamines (adrenaline and noradrenaline), cardiovascular parameters (heart rate and blood pressure) and clinical outcomes (ANSD, mechanical ventilation required, and length of intensive care unit stay) in adults with tetanus, as well as examine whether intrathecal antitoxin administration affected subsequent catecholamine excretion. Noradrenaline and adrenaline were measured by ELISA from 24-h urine collections taken on day 5 of hospitalization in 272 patients enrolled in a 2 × 2 factorial-blinded randomized controlled trial in a Vietnamese hospital. Catecholamine results measured from 263 patients were available for analysis. After adjustment for potential confounders (i.e., age, sex, intervention treatment, and medications), there were indications of non-linear relationships between urinary catecholamines and heart rate. Adrenaline and noradrenaline were associated with subsequent development of ANSD, and length of ICU stay.

Diagnostic value of 3D T1-weighted gradient-echo and 2D T1-weighted in-phase and out-of-phase gradient-echo sequences for appendicitis diagnosis in pregnant women.

Objectives: This study compared the diagnostic value of 3D T1-weighted (T1W) gradient-echo (GRE) and 2D T1W in-phase and out-of-phase GRE sequences for appendicitis diagnosis in pregnant women. Material and Methods: This retrospective study included 25 pregnant patients with suspected appendicitis who underwent 1.5 Tesla abdominal magnetic resonance imaging and had definitive diagnoses. Four doctors approached four separate imaging groups: A (only T2-weighted image [T2WI] sequences), B (T2WI and 3D T1W GRE sequences), C (T2WI and T1W in-phase and out-of-phase GRE sequences), and D (T2WI, 3D T1W GRE, and T1W in-phase and out-of-phase GRE sequences). The kappa (κ) index was used to compare the appendicitis diagnostic results between groups. The diagnostic value of these sequences in the diagnosis of pregnancy appendicitis was also evaluated. Results: Groups A and C had average consistency with definitive diagnosis (κ = 0.6), lower than Groups B and D (κ = 0.865), indicating a high definite diagnosis consistency. Groups B and D had similarly high sensitivity (80%), specificity (100%), positive predictive value (100%), negative predictive value (95.2%), and accuracy (ACC) (96%), higher than Groups A and C (60%, 95%, 75%, 90.5%, and 88%, respectively). Conclusion: 3D T1W-GRE sequences improve appendicitis diagnosis in pregnancy compared to T2W sequences alone. Adding in and out phase GRE sequences do not increase diagnostic ACC.

Stepwise Reduction of Mycophenolate Mofetil with Conversion to Everolimus for the Treatment of Active BKV in Kidney Transplant Recipients: A Single-Center Experience in Vietnam.

Background: No specific antiviral drug can effectively treat BKV reactivation after kidney transplantation. Thus, we evaluated stepwise-reduced immunosuppression to treat BKV reactivation. Methods: 341 kidney-transplant recipients were monitored for BKV infection (BKV-viremia, BKV-viruria). Positive samples with a significant virus load were nested PCR-genotyped in the VP1 region. In 97/211 patients presenting BKV viremia ≥104 copies/mL and/or BKV viruria ≥107 copies/mL, or BKV-nephropathy immunosuppression (i.e., mycophenolate mofetil [MMF]) was reduced by 50%. If viral load did not decrease within 28 days, MMF dose was further reduced by 25%, although calcineurin-inhibitor (CNI) therapy remained unchanged. If BKV viral load did not decrease within another 28 days, MMF was withdrawn and replaced by everolimus combined with reduced CNIs. Results: Only 41/97 BKV (+) cases completed the 6-month follow-up. Among these, 29 (71%) were in the BKV-I group and 12 (29%) were in BKV-IV. BKV viruria and BKV viremia were significantly decreased from 9.32 to 6.09 log10 copies/mL, and from 3.59 to 2.45 log10 copies/mL (p < 0.001 and p = 0.024, respectively). 11/32 (34.4%) patients were cleared of BKV viremia; 2/32 (6.3%) patients were cleared of BKV in both serum and urine, and 9/9 (100%) only had BKV viruria but did not develop BKV viremia. eGFR remained stable. No patient with BKV-related nephropathy had graft loss. There was a significant inverse relationship between changes in eGFR and serum BKV load (r = −0.314, p = 0.04). Conclusions: This stepwise immunosuppressive strategy proved effective at reducing BKV viral load in kidney transplant recipients that had high BKV loads in serum and/or urine. Renal function remained stable without rejection.

Impact of Freeze Storage on the Estimation of Phenotypic Antimicrobial Resistance Prevalence in Escherichia coli Collected from Faecal Samples from Healthy Humans and Chickens.

Many studies on phenotypic antimicrobial resistance (AMR) of bacteria from healthy populations are conducted on freeze-stored samples. However, the impact of this practice on phenotypic AMR is not known. We investigated the prevalence of phenotypic AMR in Escherichia coli from chicken (n = 10) and human (n = 11) faecal samples collected from healthy subjects, subject to freeze storage (-20 °C and -80 °C) for 1, 2, 3, and 6 months. We compared counts of E. coli and prevalence of phenotypic resistance against five antimicrobials commonly used in chicken farming (ciprofloxacin, enrofloxacin, doxycycline, gentamicin, and florfenicol) with samples processed within 24 h of collection. Prevalence of phenotypic AMR was estimated by performing differential counts on agar media with and without antimicrobials. At -20 °C, there was a considerable reduction in E. coli counts over time, and this reduction was greater for human samples (-0.630 log10 units per 100 days) compared with chicken samples (-0.178 log10 units per 100 days). For most antimicrobials, AMR prevalence estimates decreased in freeze-stored samples both in humans and chickens over time. Based on these results, we conclude that results on the prevalence of phenotypic AMR on samples from freeze-stored samples are unreliable, and only fresh samples should be used in such studies.

Assessment of the distribution and ecological risks of heavy metals in coastal sediments in Vietnam's Mong Cai area.

Coastal sediments in the Mong Cai area were collected and analyzed for grain size, heavy metals, total organic carbon, and isotopes (210Pb, 226Ra, δ15N, δ13C) to assess sediment quality. The most common sediments were fine sand in surface sediment, very fine sand in core C1, and very coarse and coarse silt in core C2. The total organic carbon was highest in C2 next to the surface and lowest in C1, with content levels of 1.81%, 0.40%, and 0.31%, respectively. The chronology in C1 was 1877-2019 (142 years, 0-5 0 cm), with an average sedimentation rate of 0.71 cm/year. In C2, the chronology was 1944-2019 (75 years, 0-14 cm), with an average sedimentation rate of 0.27 cm/year. These δ13C and δ15N in the sediment reflect the source of the organic matter mix from the marine and terrigenous sediments. All studied heavy metals were lower than the ISQGs, with the exception of As in C1 and C2, which were higher. C1 showed a decline in As over time, while C2 As levels increased between 1996 and 2019. In terms of heavy metal pollution indexes, the geoaccumulation index (Igeo) showed that C1 and C2 were unpolluted to moderately polluted with As, with Li and Pb in C2; the enrichment factor (EF) was moderately enriched with As; the contamination factor (CF) was moderately contaminated (Pb, Cd, Fe, Mo, and Li) in C2 and C1 (Cd, As, Li) and considerably contaminated (As) in C2. The risk factor (ER) of As showed a moderate potential ecological risk in C2. The degree of contamination (CD) ranged from moderate to considerable (C1, C2), and the ecological risk (RI) was low. Although CD ranged from moderate (C1) to considerable (C2), most contamination was concentrated at the bottom of the cores. RI was low. The Mong Cai sediment quality does not currently affect the coastal area's ecosystem and fauna.

Environmental management in Ramsar designated wetland areas in Vietnam: studies from U Minh Thuong and Tram Chim national parks (Mekong Delta).

This study investigated the possibility of using remotely sensed data and field surveys for understanding the environmental management practices in two Ramsar sites - U Minh Thong and Tram Chim national parks - in the Vietnamese Mekong Delta. Enhanced agriculture, infrastructure development, changes in hydrological regime, forest fires, and natural resources exploitation are the key variables that caused the depletion of these two wetland areas. Land cover, particularly vegetation coverage, has been changed considerably during the post-war period and agriculture has been intensified in the surrounding areas of U Minh Thuong and Tram Chim wetlands. The current water management strategies in U Minh Thuong and Tram Chim were designated to ensure proper water circulation during the dry and wet seasons in a way helpful to agriculture in the buffer zones and to prevent forest fires during the dry season. It is found that the water management strategies to prevent forest fires in both the parks resulted in the accumulation of toxic agrochemicals within the park during the wet season. Both U Minh Thuong and Tram Chim wetlands are invaded by alien plant species which is threatening the natural biodiversity of the area. Proper monitoring and control of invasive species is necessary for protecting the natural biodiversity of these wetland ecosystems. Proper law enforcement and an interactive and inclusive wetland management should be practiced in order to conserve these valuable wetland ecosystems.

Antimicrobial resistance in commensal Escherichia coli from humans and chickens in the Mekong Delta of Vietnam is driven by antimicrobial usage and potential cross-species transmission.

Objectives: To investigate phenotypic antimicrobial resistance (AMR) in relation to antimicrobial use (AMU) and potential inter-species transmission among Escherichia coli from humans and chickens located in the same households in the Mekong Delta of Vietnam. Methods: We collected data on AMU and faecal swabs from humans (N = 426) and chickens (N = 237) from 237 small-scale farms. From each sample, one E. coli strain was isolated and tested for its susceptibility against 11 antimicrobials by Sensititre AST. The association between AMR and AMU was investigated by logistic regression modelling. Using randomization, we compared the degree of similarity in AMR patterns between human and chicken E. coli from the same farms compared with isolates from different farms. Results: The AMU rate was ∼19 times higher in chickens (291.1 per 1000 chicken-days) than in humans (15.1 per 1000 person-days). Isolates from chickens also displayed a higher prevalence of multidrug resistance (63.3%) than those of human origin (55.1%). AMU increased the probability of resistance in isolates from human (ORs between 2.1 and 5.3) and chicken (ORs between 1.9 and 4.8). E. coli from humans and chickens living on same farms had a higher degree of similarity in their AMR patterns than isolates from humans and chicken living on different farms. Conclusions: We demonstrated the co-influence of AMU and potential transmission on observed phenotypic AMR patterns among E. coli isolates from food-producing animals and in-contact humans. Restricting unnecessary AMU alongside limiting interspecies contact (i.e. increasing hygiene and biocontainment) are essential for reducing the burden of AMR.

The prevalence of SARS-CoV-2 antibodies in quarantine workers and high-risk communities in Vietnam.

Objective: The aim of this study was to determine the seroprevalence of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) antibodies in high-risk communities and quarantine workers in Vietnam. Methods: The prevalence of SARS-CoV-2 antibodies was measured in household contacts, close contacts, community members, and migrant workers from two sub-communes in which COVID-19 outbreaks occurred in early 2021: Bac Ma 1 and Tien. The prevalence of SARS-CoV-2 antibodies was also evaluated among quarantine workers at two facilities responsible for quarantining of contacts of COVID-19 cases. Results: Among 2069 participants from the two sub-communes, six individuals (0.3%) had detectable SARS-CoV-2 antibodies despite no history of COVID-19. This included one Vietnamese migrant worker, two community members, two household contacts, and one close contact of known COVID-19 cases. Among 50 workers at two COVID-19 quarantine facilities, including 15 health care workers (HCWs), one of the HCWs tested positive for SARS-CoV-2 antibodies (1/50, 2.0%) despite no known disease. Conclusion: The prevalence of SARS-CoV-2 antibodies was low in Vietnamese 'hotspots', suggesting limited community transmission.

Genomic Mutations of BK Polyomavirus in Patients after Kidney Transplantation: A Cross-Sectional Study in Vietnam.

OBJECTIVES: The purpose of this study was to identify the SNP sites and determine the BKV genotype circulating in kidney-transplant Vietnamese recipients based on the VP1 gene region. METHODS: 344 samples were collected from post-kidney-transplant recipients at the 103 Vietnam Military Hospital to investigate the number of BKV infections. Positive samples with a sufficient virus concentration were analyzed by nested PCR in the VP1 region, sequencing detected genotyping and single-nucleotide polymorphism. RESULTS: BKV infection was determined in 214 patients (62.2%), of whom 11 (5.1%) were diagnosed with BKV-associated nephropathy. Among the 90 BKV-I strains sequenced, 89 (98.88%) were strains of I/b-1 and 1 (1.12%) was strain I/b-2. The 60 BKV-IV strains had a greater diversity of subgroups, including 40% IV/a-1, 1.66% IV/a-2, 56.68% IV/c-1, and 1.16% IV/c-2. Additionally, of 11 cases diagnosed with BKVN, seven belonged to subgroup I/b-1 (63.6%) and four to subgroup IV/c-1 (36.4%). Moreover, 22 specific SNPs that were genotype I or IV were determined in this Vietnamese population. Specifically, at position 1745, for the Vietnamese BKV-IV strains, the SNP position (A→G) appeared in 57/60 samples (95%). This causes transformation of the amino acid N→S. This SNP site can enable detection of genotype IV in Vietnam. It represents a unique evolution pattern and mutation that has not been found in other international strains. CONCLUSION: The BKV-I genotype was more common than BKV-IV; however, mutations that occur on the VP1 typing region of BKV-IV strains were more frequent than in BKV-I strains.

Human versus equine intramuscular antitoxin, with or without human intrathecal antitoxin, for the treatment of adults with tetanus: a 2 × 2 factorial randomised controlled trial.

BACKGROUND: Intramuscular antitoxin is recommended in tetanus treatment, but there are few data comparing human and equine preparations. Tetanus toxin acts within the CNS, where there is limited penetration of peripherally administered antitoxin; thus, intrathecal antitoxin administration might improve clinical outcomes compared with intramuscular injection. METHODS: In a 2  × 2 factorial trial, all patients aged 16 years or older with a clinical diagnosis of generalised tetanus admitted to the intensive care unit of the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, were eligible for study entry. Participants were randomly assigned first to 3000 IU human or 21 000 U equine intramuscular antitoxin, then to either 500 IU intrathecal human antitoxin or sham procedure. Interventions were delivered by independent clinicians, with attending clinicians and study staff masked to treatment allocations. The primary outcome was requirement for mechanical ventilation. The analysis was done in the intention-to-treat population. The study is registered at ClinicalTrials.gov, NCT02999815; recruitment is completed. FINDINGS: 272 adults were randomly assigned to interventions between Jan 8, 2017, and Sept 29, 2019, and followed up until May, 2020. In the intrathecal allocation, 136 individuals were randomly assigned to sham procedure and 136 to antitoxin; in the intramuscular allocation, 109 individuals were randomly assigned to equine antitoxin and 109 to human antitoxin. 54 patients received antitoxin at a previous hospital, excluding them from the intramuscular antitoxin groups. Mechanical ventilation was given to 56 (43%) of 130 patients allocated to intrathecal antitoxin and 65 (50%) of 131 allocated to sham procedure (relative risk [RR] 0·87, 95% CI 0·66-1·13; p=0·29). For the intramuscular allocation, 48 (45%) of 107 patients allocated to human antitoxin received mechanical ventilation compared with 48 (44%) of 108 patients allocated to equine antitoxin (RR 1·01, 95% CI 0·75-1·36, p=0·95). No clinically relevant difference in adverse events was reported. 22 (16%) of 136 individuals allocated to the intrathecal group and 22 (11%) of 136 allocated to the sham procedure experienced adverse events related or possibly related to the intervention. 16 (15%) of 108 individuals allocated to equine intramuscular antitoxin and 17 (16%) of 109 allocated to human antitoxin experienced adverse events related or possibly related to the intervention. There were no intervention-related deaths. INTERPRETATION: We found no advantage of intramuscular human antitoxin over intramuscular equine antitoxin in tetanus treatment. Intrathecal antitoxin administration was safe, but did not provide overall benefit in addition to intramuscular antitoxin administration. FUNDING: The Wellcome Trust.

Comprehensive design method of a soft multifocal contact lens with NURBS.

This study presents a comprehensive method for designing a multifocal contact lens (MCL) with Snell's law and non-uniform rational B-spline (NURBS) curves. Instead of using thin lens approximation, general mathematical formulas have been developed to achieve the accurate coordinates of points on the anterior lens surface profile of the MCL to meet various given optical power distributions. Then the NURBS curve is adjusted to fit these data points to obtain the smooth front lens surface profile. This method not only improves the accuracy of the optical power profiles of MCLs but also reduces the spherical aberration in near/distance optical zones. The experimental results show that the power profiles of soft MCLs agree with those of the simulation results and original design requirements. The proposed method has been proven for the MCL design, and it can be feasibly applied in complex optical lens designs.

Prevalence of carbapenem resistance and its potential association with antimicrobial use in humans and animals in rural communities in Vietnam.

Background: Vietnam and Southeast Asia are hotspots for antimicrobial resistance; however, little is known on the prevalence of carriage of carbapenem resistance in non-hospitalized humans and in animals. Carbapenem-resistant Enterobacteriaceae (CRE), particularly Escherichia coli (CREC) and Klebsiella pneumoniae (CRKP) and also Acinetobacter baumannii (CRAB) are emerging threats worldwide. Methods: We investigated healthy humans (n = 652), chickens (n = 237), ducks (n = 150) and pigs (n = 143) in 400 small-scale farms in the Mekong Delta of Vietnam. Samples (rectal swabs, faecal swabs) were investigated for carriage of CRE/CRAB and were further characterized phenotypically and genotypically. Results: In the Mekong Delta of Vietnam, the prevalence of CRE isolates in human rectal swabs was 0.6%, including 4 CREC and 1 CRKP. One pig was infected with CREC (prevalence 0.7%). CRAB was isolated from chickens (n = 4) (prevalence 2.1%) and one duck (prevalence 0.7%). CRKP was isolated from a human who was also colonized with CREC. The CRKP strain (ST16), from an 80 year-old person with pneumonia under antimicrobial treatment, genetically clustered with clinical strains isolated in a hospital outbreak in southern Vietnam. The prevalence of CRE was higher among humans that had used antimicrobials within 90 days of the sampling date than those had not (4.2% versus 0.2%) (P = 0.005). All CRE/CRAB strains were MDR, although they were susceptible to colistin and neomycin. The carbapenemase genes identified in study strains were bla NDM and bla OXA. Conclusions: The finding of a CRKP strain clustering with previous hospital outbreak raises concerns about potential transmission of carbapenem-resistant organisms from hospital to community settings or vice-versa.

Triple therapy with artemether-lumefantrine plus amodiaquine versus artemether-lumefantrine alone for artemisinin-resistant, uncomplicated falciparum malaria: an open-label, randomised, multicentre trial.

BACKGROUND: Late treatment failures after artemisinin-based combination therapies (ACTs) for falciparum malaria have increased in the Greater Mekong subregion in southeast Asia. Addition of amodiaquine to artemether-lumefantrine could provide an efficacious treatment for multidrug-resistant infections. METHODS: We conducted an open-label, randomised trial at five hospitals or health centres in three locations (western Cambodia, eastern Cambodia, and Vietnam). Eligible participants were male and female patients aged 2-65 years with uncomplicated Plasmodium falciparum malaria. Patients were randomly allocated (1:1 in blocks of eight to 12) to either artemether-lumefantrine alone (dosed according to WHO guidelines) or artemether-lumefantrine plus amodiaquine (10 mg base per kg/day), both given orally as six doses over 3 days. All received a single dose of primaquine (0·25 mg/kg) 24 h after the start of study treatment to limit transmission of the parasite. Parasites were genotyped, identifying artemisinin resistance. The primary outcome was Kaplan-Meier 42-day PCR-corrected efficacy against recrudescence of the original parasite, assessed by intent-to-treat. Safety was a secondary outcome. This completed trial is registered at ClinicalTrials.gov (NCT03355664). FINDINGS: Between March 18, 2018, and Jan 30, 2020, 310 patients received randomly allocated treatment; 154 received artemether-lumefantrine alone and 156 received artemether-lumefantrine plus amodiaquine. Parasites from 305 of these patients were genotyped. 42-day PCR-corrected treatment efficacy was noted in 151 (97%, 95% CI 92-99) of 156 patients with artemether-lumefantrine plus amodiaquine versus 146 (95%, 89-97) of 154 patients with artemether-lumefantrine alone; hazard ratio (HR) for recrudescence 0·6 (95% CI 0·2-1·9, p=0·38). Of the 13 recrudescences, 12 were in 174 (57%) of 305 infections with pfkelch13 mutations indicating artemisinin resistance, for which 42-day efficacy was noted in 89 (96%) of 93 infections with artemether-lumefantrine plus amodiaquine versus 73 (90%) of 81 infections with artemether-lumefantrine alone; HR for recrudescence 0·44 (95% CI 0·14-1·40, p=0·17). Artemether-lumefantrine plus amodiaquine was generally well tolerated, but the number of mild (grade 1-2) adverse events, mainly gastrointestinal, was greater in this group compared with artemether-lumefantrine alone (vomiting, 12 [8%] with artemether-lumefantrine plus amodiaquine vs three [2%] with artemether-lumefantrine alone, p=0·03; and nausea, 11 [7%] with artemether-lumefantrine plus amodiaquine vs three [2%] with artemether-lumefantrine alone, p=0·05). Early vomiting within 1 h of treatment, requiring retreatment, occurred in no patients of 154 with artemether-lumefantrine alone versus five (3%) of 156 with artemether-lumefantrine plus amodiaquine, p=0·06. Bradycardia (≤54 beats/min) of any grade was noted in 59 (38%) of 154 patients with artemether-lumefantrine alone and 95 (61%) of 156 with artemether-lumefantrine plus amodiaquine, p=0·0001. INTERPRETATION: Artemether-lumefantrine plus amodiaquine provides an alternative to artemether-lumefantrine alone as first-line treatment for multidrug-resistant P falciparum malaria in the Greater Mekong subregion, and could prolong the therapeutic lifetime of artemether-lumefantrine in malaria-endemic populations. FUNDING: Bill & Melinda Gates Foundation, Wellcome Trust.

PMMA Bone Cements Modified with Silane-Treated and PMMA-Grafted Hydroxyapatite Nanocrystals: Preparation and Characterization.

In this study, vinyltrimethoxysilane-treated hydroxyapatite (vHAP) and PMMA-grafted HAP (gHAP) were successfully prepared from original HAP (oHAP). Three kinds of HAP (oHAP, vHAP and g HAP) were used as additives for the preparation of three groups of HAP-modified PMMA bone cements (oHAP-BC, vHAP-BC and gHAP-BC). The setting, bending and compression properties of the bone cements were conducted according to ISO 5833:2002. The obtained results showed that the maximum temperature while curing the HAP-modified bone cements (HAP-BCs) decreased from 64.9 to 60.8 °C and the setting time increased from 8.1 to 14.0 min, respectively, with increasing HAP loading from 0 to 15 wt.%. The vHAP-BC and gHAP-BC groups exhibited higher mechanical properties than the required values in ISO 5833. Electron microscopy images showed that the vHAP and gHAP nanoparticles were dispersed better in the polymerized PMMA matrix than the oHAP nanoparticles. FTIR analysis indicated the polar interaction between the PO4 groups of the HAP nanoparticles and the ester groups of the polymerized PMMA matrix. Thermal gravimetric analysis indicated that mixtures of ZrO2/HAPs were not able to significantly improve the thermal stability of the HAP-BCs. DSC diagrams showed that the incorporation of gHAP to PMMA bone cement with loadings lower than 10 wt.% can increase Tg by about 2.4 °C.

Nanotechnology-based drug delivery for central nervous system disorders.

Drug delivery to central nervous system (CNS) diseases is very challenging since the presence of the innate blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier that impede drug delivery. Among new strategies to overcome these limitations and successfully deliver drugs to the CNS, nanotechnology-based drug delivery platform, offers potential therapeutic approach for the treatment of some common neurological disorders like Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease. This review aimed to highlight advances in research on the development of nano-based therapeutics for their implications in therapy of CNS disorders. The challenges during clinical translation of nanomedicine from bench to bed side is also discussed.

Radiation Synthesis of Selenium Nanoparticles Capped with ß-Glucan and Its Immunostimulant Activity in Cytoxan-Induced Immunosuppressed Mice.

Selenium nanoparticles (SeNPs) with diameters from 64.8 to 110.1 nm were successfully synthesized by γ-irradiation of solutions containing Se4+ and water-soluble yeast ß-glucan. The size and size distribution of SeNPs were analyzed by dynamic light scattering (DLS). Analytical X-ray diffraction (XRD) pattern results confirmed the crystal structure of the Se nanoparticles and Fourier transform infrared (FTIR) spectroscopy revealed that ß-glucan could interact with SeNPs through steric (Se…O) linkages leading to a homogeneous and translucent solution state for 60 days without any precipitates. In vivo tests in cytoxan-induced immunosuppressed mice revealed that the daily supplementation of SeNPs/ß-glucan at concentrations of 6 mg per kg body weight of tested mice significantly stimulated the generation of cellular immune factors (white blood cells, neutrophil, lymphocyte, B cells, CD4+ cells, CD34+ cells and natural killer cells) and humoral immune indexes (IgM, IgG, TNF-α, IFN-γ and IL-2) in peripheral blood, bone marrow and spleen of the immunosuppressed mice. The obtained results indicated that radiation-synthesized SeNPs/ß-glucan may be a candidate for further evaluation as an agent for the prevention of immunosuppression in chemotherapy.