Implementing living-donor pediatric liver transplantation in Southern Vietnam: 15-year results and perspectives.

BACKGROUND: ND2 in Ho Chi Minh City is currently the only public center that performs PLT in Southern Vietnam. In 2005, the first PLT was successfully performed, with support from Belgian experts. This study reviews the implementation of PLT at our center and evaluates the results and challenges. METHODS: Implementation of PLT at ND2 required medico-surgical team building and extensive improvement of hospital facilities. Records of 13 transplant recipients from 2005 to 2020 were studied retrospectively. Short- and long-term complications, as well as the survival rates, were reported. RESULTS: The mean follow-up time was 8.3 ± 5.7 years. Surgical complications included one case of hepatic artery thrombosis that was successfully repaired, one case of colon perforation resulting in death from sepsis, and two cases of bile leak that were drained surgically. PTLD was observed in five patients, of whom three died. There were no cases of retransplantation. The 1-year, 5-year, and 10-year patient survival rates were 84.6%, 69.2%, and 69.2%, respectively. There were no cases of complication or death among the donors. CONCLUSION: Living-donor PLT was developed at ND2 for providing a life-saving treatment to children with end-stage liver disease. Early surgical complication rate was low, and the patient survival rate was satisfactory at 1 year. Long-term survival decreased considerably due to PTLD. Future challenges include surgical autonomy and improvement of long-term medical follow-up with a particular emphasis on prevention and management of Epstein-Barr virus-related disease.

Designing a novel heterostructure AgInS2@MIL-101(Cr) photocatalyst from PET plastic waste for tetracycline degradation.

Semiconductor-containing porous materials with a well-defined structure could be unique scaffolds for carrying out selective organic transformations driven by visible light. We herein introduce for the first time a heterostructure of silver indium sulfide (AgInS2) ternary chalcogenide and a highly porous MIL-101(Cr) metal-organic framework (MOF) synthesised from polyethylene terephthalate plastic waste. Our results demonstrate that AgInS2 nanoparticles were uniformly attached to each lattice plane of the octahedral MIL-101(Cr) structure, resulting in a nanocomposite with a high distribution of semiconductors in a porous media. We also demonstrate that the nanocomposite with up to 40% of AgInS2 doping exhibited excellent catalytic activity for tetracycline degradation under visible light irradiation (∼99% tetracycline degraded after 4 h) and predominantly maintained its performance after five cycles. These results could promote a new material circularity pathway to develop new semiconductors that can be used to protect water from further pollution.

Novel highly-multiplexed AmpliSeq targeted assay for Plasmodium vivax genetic surveillance use cases at multiple geographical scales.

Although the power of genetic surveillance tools has been acknowledged widely, there is an urgent need in malaria endemic countries for feasible and cost-effective tools to implement in national malaria control programs (NMCPs) that can generate evidence to guide malaria control and elimination strategies, especially in the case of Plasmodium vivax. Several genetic surveillance applications ('use cases') have been identified to align research, technology development, and public health efforts, requiring different types of molecular markers. Here we present a new highly-multiplexed deep sequencing assay (Pv AmpliSeq). The assay targets the 33-SNP vivaxGEN-geo panel for country-level classification, and a newly designed 42-SNP within-country barcode for analysis of parasite dynamics in Vietnam and 11 putative drug resistance genes in a highly multiplexed NGS protocol with easy workflow, applicable for many different genetic surveillance use cases. The Pv AmpliSeq assay was validated using: 1) isolates from travelers and migrants in Belgium, and 2) routine collections of the national malaria control program at sentinel sites in Vietnam. The assay targets 229 amplicons and achieved a high depth of coverage (mean 595.7 ± 481) and high accuracy (mean error-rate of 0.013 ± 0.007). P. vivax parasites could be characterized from dried blood spots with a minimum of 5 parasites/µL and 10% of minority-clones. The assay achieved good spatial specificity for between-country prediction of origin using the 33-SNP vivaxGEN-geo panel that targets rare alleles specific for certain countries and regions. A high resolution for within-country diversity in Vietnam was achieved using the designed 42-SNP within-country barcode that targets common alleles (median MAF 0.34, range 0.01-0.49. Many variants were detected in (putative) drug resistance genes, with different predominant haplotypes in the pvmdr1 and pvcrt genes in different provinces in Vietnam. The capacity of the assay for high resolution identity-by-descent (IBD) analysis was demonstrated and identified a high rate of shared ancestry within Gia Lai Province in the Central Highlands of Vietnam, as well as between the coastal province of Binh Thuan and Lam Dong. Our approach performed well in geographically differentiating isolates at multiple spatial scales, detecting variants in putative resistance genes, and can be easily adjusted to suit the needs in other settings in a country or region. We prioritize making this tool available to researchers and NMCPs in endemic countries to increase ownership and ensure data usage for decision-making and malaria policy.

A low-cost, flexible extruder for liposomes synthesis and application for Murrayafoline A delivery for cancer treatment.

Liposomal encapsulation is a drug delivery strategy with many advantages, such as improved bioavailability, ability to carry large drug loads, as well as controllability and specificity towards various targeted diseased tissues. Currently, most preparation techniques require an additional extrusion or filtering step to obtain monodisperse liposomes with the size of less than 100 nm. In this study, a compact liposome extruder was designed at a cost of $4.00 and used to synthesize liposome suspensions with defined particle size and high homogeneity for Murrayafoline A (Mu-A) loading and release. The synthesized MuA-loaded liposomes displayed a biphasic drug release and remained stable under the storage condition of 4°C. They also significantly reduced the viability of HepG2 cells in the cancer spheroids by 25%. The low-cost, flexible liposome extruder would allow the researchers to study liposomes and their applications in a cost-effective manner.

Plasmodium vivax morbidity after radical cure: A cohort study in Central Vietnam.

BACKGROUND: In Vietnam, the importance of vivax malaria relative to falciparum during the past decade has steadily increased to 50%. This, together with the spread of multidrug-resistant Plasmodium falciparum, is a major challenge for malaria elimination. A 2-year prospective cohort study to assess P. vivax morbidity after radical cure treatment and related risk factors was conducted in Central Vietnam. METHODS AND FINDINGS: The study was implemented between April 2009 and December 2011 in four neighboring villages in a remote forested area of Quang Nam province. P. vivax-infected patients were treated radically with chloroquine (CQ; 25 mg/kg over 3 days) and primaquine (PQ; 0.5 mg/kg/day for 10 days) and visited monthly (malaria symptoms and blood sampling) for up to 2 years. Time to first vivax recurrence was estimated by Kaplan-Meier survival analysis, and risk factors for first and recurrent infections were identified by Cox regression models. Among the 260 P. vivax patients (61% males [159/260]; age range 3-60) recruited, 240 completed the 10-day treatment, 223 entered the second month of follow-up, and 219 were followed for at least 12 months. Most individuals (76.78%, 171/223) had recurrent vivax infections identified by molecular methods (polymerase chain reaction [PCR]); in about half of them (55.61%, 124/223), infection was detected by microscopy, and 84 individuals (37.67%) had symptomatic recurrences. Median time to first recurrence by PCR was 118 days (IQR 59-208). The estimated probability of remaining free of recurrence by month 24 was 20.40% (95% CI [14.42; 27.13]) by PCR, 42.52% (95% CI [35.41; 49.44]) by microscopy, and 60.69% (95% CI [53.51; 67.11]) for symptomatic recurrences. The main risk factor for recurrence (first or recurrent) was prior P. falciparum infection. The main limitations of this study are the age of the results and the absence of a comparator arm, which does not allow estimating the proportion of vivax relapses among recurrent infections. CONCLUSION: A substantial number of P. vivax recurrences, mainly submicroscopic (SM) and asymptomatic, were observed after high-dose PQ treatment (5.0 mg/kg). Prior P. falciparum infection was an important risk factor for all types of vivax recurrences. Malaria elimination efforts need to address this largely undetected P. vivax transmission by simultaneously tackling the reservoir of P. falciparum and P. vivax infections.

Administration, Billing, and Payment for Pharmacy Student-Based Immunizations to Medicare Beneficiaries at Mobile Medicare Clinics.

Training student pharmacists to administer vaccinations requires a substantial investment in vaccines, supplies, and time. Few schools of pharmacy seek out or receive any reimbursement for the provision of vaccines, despite the fact it is a covered service. This study sought to implement, deliver, and demonstrate an innovative, financially sustainable curriculum-based immunization program by trained pharmacy students as part of their experiential learning. Thirty-nine community health clinics targeting Medicare beneficiaries were conducted throughout Northern/Central California during Medicare's fall open enrollment periods between 2014⁻2016. American Pharmacists Association (APhA)-trained student pharmacists (under licensed pharmacist supervision) administered 1777 vaccinations. Vaccines were billed via a secure Health Insurance Portability and Accountability Act of 1996 (HIPAA)-compliant web-based portal. The total net income was $11,905 and $8032 for 2015 and 2016, respectively. Return on investment was greatest for the influenza vaccine > Tdap > pneumococcal. Pharmacy students are already being trained to provide immunizations and can utilize their skills to deliver financially viable public health programs.

Marked age-dependent prevalence of symptomatic and patent infections and complexity of distribution of human Plasmodium species in central Vietnam.

In Vietnam, Plasmodium falciparum and P. vivax are responsible for most malaria infections, and P. malariae and P. ovale infections are rarely reported. Nevertheless, species-specific polymerase chain reaction analysis on 2,303 blood samples collected during a cross-sectional survey conducted in a forest area of central Vietnam identified 223 (9.7%) P. falciparum, 170 (7.4%) P. vivax, 95 (4.1%) P. malariae, and 19 (0.8%) P. ovale mono-infections and 164 (7.1%) mixed infections. Of the 671 Plasmodium-positive samples by polymerase chain reaction, only 331 were detected by microscopy. Microscopy poorly diagnosed P. malariae, P. ovale, and mixed infections. Clinical and sub-clinical infections occurred in all age groups. The risk for infection and disease decreased with age, probably because of acquired partial immunity. The common occurrence of sub-patent infections seems to indicate that the malaria burden is underestimated and that diagnostic and therapeutic policies should be adapted accordingly.

Downregulation of cytosolic prostaglandin E2 synthase results in decreased nociceptive behavior in rats.

Nociception-evoked prostaglandin E2 (PGE2) release in the spinal cord contributes considerably to the development of hyperalgesia and allodynia. Biosynthesis of PGE2 involves the conversion of arachidonic acid to PGH2 by cyclooxygenases (COXs), followed by an isomerization of PGH2 to PGE2 by PGE2 synthases (PGESs). The roles of COX-1, COX-2, and the inducible microsomal PGES-1 have been studied in models of pain and inflammation. In contrast, in nociceptive processes, very little is known about the role of cytosolic PGES (cPGES), which has been described as being functionally coupled to COX-1. Here we show by in situ hybridization and immunohistological analysis that COX-1 and cPGES are constitutively expressed in neuronal and non-neuronal cells of the dorsal and ventral horns in the spinal cord of adult rats. The protein levels of both enzymes were not regulated by nociceptive stimuli; however, reduction of cPGES in rat spinal cord with intrathecal application of cPGES antisense oligonucleotides reduced the nociceptive behavior in zymosan-evoked thermal hyperalgesia and in the formalin assay. The data indicate that cPGES plays an important role in mediating early responses during spinal nociceptive processing.

Protein associated with Myc (PAM) is involved in spinal nociceptive processing.

PAM (protein associated with Myc) is a potent inhibitor of adenylyl cyclases (ACs) which is primarily expressed in neurones. Here we describe that PAM is highly expressed in dorsal horn neurones and motoneuron of the spinal cord, as well as in neurones of dorsal root ganglia in adult rats. PAM mRNA expression is differentially regulated during development in both spinal cord and dorsal root ganglia of rats, being strongest during the major respective synaptogenic periods. In adult rats, PAM expression was up-regulated in the spinal cord after peripheral nociceptive stimulation using zymosan and formalin injection, suggesting a role for PAM in spinal nociceptive processing. Since PAM inhibited Galphas-stimulated AC activity in dorsal root ganglia as well as spinal cord lysates, we hypothesized that PAM may reduce spinal nociceptive processing by inhibition of cAMP-dependent signalling. Accordingly, intrathecal treatment with antisense but not sense oligonucleotides against PAM increased basal and Galphas-stimulated AC activity in the spinal cord and enhanced formalin-induced nociceptive behaviour in adult rats. Taken together our findings demonstrate that PAM is involved in spinal nociceptive processing.