Overlapping Stevens-Johnson Syndrome and DRESS Syndrome Caused by Phenobarbital: A Vietnamese Case Report.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome and Stevens-Johnson Syndrome (SJS) are severe cutaneous adverse reactions to drugs. Those reactions which are rare in children can be especially severe and challenging to diagnose and manage. Herein we present a 59-month-old male who presented with a rash, fever, and multiple organ dysfunction initiation of Phenobarbital for epilepsy. Diagnosis of ovelaping SJS and DRESS syndrome had been made based on clinical manifestations accompanied with skin biopsy according to RegisSCAR diagnostic criteria. A therapy with intravenous immune globulin (IVIG), corticosteroids and supportive care was given successfully for the patient. This case underscored the significance of promptly and effectively recognizing and managing these intricate reactions.

Plastic Waste: Challenges and Opportunities to Mitigate Pollution and Effective Management.

The present world is now facing the challenge of proper management and resource recovery of the enormous amount of plastic waste. Lack of technical skills for managing hazardous waste, insufficient infrastructure development for recycling and recovery, and above all, lack of awareness of the rules and regulations are the key factors behind this massive pile of plastic waste. The severity of plastic pollution exerts an adverse effect on the environment and total ecosystem. In this study, a comprehensive analysis of plastic waste generation, as well as its effect on the human being and ecological system, is discussed in terms of source identification with respect to developed and developing countries. A detailed review of the existing waste to energy and product conversion strategies is presented in this study. Moreover, this study sheds light on sustainable waste management procedures and identifies the key challenges to adopting effective measures to minimise the negative impact of plastic waste.

Current scenario and challenges of plastic pollution in Bangladesh: a focus on farmlands and terrestrial ecosystems.

Plastic is considered one of the most indispensable commodities in our daily life. At the end of life, the huge ever-growing pile of plastic waste (PW) causes serious concerns for our environment, including agricultural farmlands, groundwater quality, marine and land ecosystems, food toxicity and human health hazards. Lack of proper infrastructure, financial backup, and technological advancement turn this hazardous waste plastic management into a serious threat to developing countries, especially for Bangladesh. A comprehensive review of PW generation and its consequences on environment in both global and Bangladesh contexts is presented. The dispersion routes of PW from different sources in different forms (microplastic, macroplastic, nanoplastic) and its adverse effect on agriculture, marine life and terrestrial ecosystems are illustrated in this work. The key challenges to mitigate PW pollution and tackle down the climate change issue is discussed in this work. Moreover, way forward toward the design and implementation of proper PW management strategies are highlighted in this study.

A new species of Vietnamophryne (Anura: Microhylidae) from Northeastern Vietnam.

A new species of the genus Vietnamophryne is described from Vietnam on the basis of two specimens collected from Tuyen Quang Province, Northeastern Vietnam. The new species is morphologically most similar to Vietnamophryne occidentalis from Thailand, however, it differs from the latter by having large black blotches in the lower jaw region, and a yellow-orange chest and belly. The genetic distance between the new species and other Vietnamophryne taxa is > 2.13% (16S mtDNA gene fragment). Vietnamophryne aurantifusca sp. nov. can be distinguished from all other species of Vietnamophryne by a combination of the following morphological characteristics: Size medium (SVL 17.618.2 mm in males); head wider than long; tympanum medium; finger I longer than half of finger II; dorsal skin relatively smooth with some round nodules, concentrated in the middle of the back, arranged along the length of the back, with a prominent ridge along the spine; Dorsum orangish-brown entirely and paler on margin of back with a small brownish ridge along the spine; sides brownish with creamy patches and orange spots; ventral surface orange, with grey marbling, most intense on the throat, ventral side of arms and thighs, and ventral surfaces of limbs dark grey with some orange spots.

Southbound - the southernmost record of Tylototriton (Amphibia, Caudata, Salamandridae) from the Central Highlands of Vietnam represents a new species.

A new species of the genus Tylototriton is described from Ngoc Linh Mountain, Kon Tum Province, in the Central Highlands of Vietnam based on integrative taxonomy, namely by combining molecular and morphological evidence. Tylototritonngoclinhensissp. nov. differs from all other congeners based on morphological data, allopatric distribution, and molecular divergence. In terms of genetic divergence, Tylototritonngoclinhensissp. nov. distinctly differs from the sister species T.panhai (6.77%) and from T.ngarsuensis (12.36%) based on the mitochondrial NADH dehydrogenase subunit 2 (ND2) gene. Tylototritonngoclinhensissp. nov. is a moderate sized and robust salamander species with large cephalic edges, parotoids, and vertebral ridge orange in coloration. The new taxon differs from its congeners by a combination of the following morphological characteristics: size medium (SVL 60.8-66.5 mm, TL 57.6-61.8 mm in males, and SVL 72.5-75.6 mm, TL 62.9-67.9 mm in females); head longer than wide; parotoids very prominent and enlarged, projecting backwards; tail length shorter than snout-vent length; vertebral ridge large, high and glandular in appearance; 14 large and distinct dorsolateral glandular warts; gular fold present; tips of fore and hind limbs overlapping when adpressed along the body; tips of fingers reaching between eye and nostril when foreleg is laid forward; dorsal surface and lateral sides of the head, upper and lower lips, dorsolateral glandular warts, vertebral ridge, the peripheral area of the cloaca and the ventral edge of the tail orange in coloration; the presence of a distinct black line extending from the posterior end of the eye towards the shoulder. Tylototritonngoclinhensissp. nov. is restricted to evergreen montane forests near water bodies on Ngoc Linh Mountain. We suggest that the new species should be classified as Endangered (EN) in the IUCN Red List. This new important discovery represents the eighth Tylototriton taxon described from Vietnam, and at the same time constitutes the southernmost distributional record for the whole genus in Asia.

Dual roles of oxostephanine as an Aurora kinase inhibitor and angiogenesis suppressor.

The Aurora kinases, including Aurora A, B and C, play critical roles in cell division. They have been found overexpressed in a number of types of cancer and may thus be potential targets in cancer therapy. Several Aurora kinase inhibitors have been identified and developed. Some of these have been used in clinical trials and have exhibited certain efficacy in cancer treatment. However, none of these has yet been applied clinically due to the poor outcomes. Oxostephanine is an aporphine alkaloid isolated from several plants of the genus Stephania. This compound has been reported to inhibit Aurora kinase activity in kinase assays and in cancer cells. The present study aimed to investigate the real­time effects of oxostephanine extracted from Stephania dielsiana Y.C. Wu leaves on the growth of an ovarian cancer cell line (OVCAR­8, human ovarian carcinoma); these effects were compared to those of the well­known Aurora kinase inhibitor, VX­680. The effects of oxostephanine on stromal cells, as well as endothelial cells were also examined. The results demonstrated that oxostephanine was an Aurora kinase inhibitor through the prevention of histone H3 phosphorylation at serine 10, the mislocalization of Aurora B and the induction of aneuploidy. Moreover, this substance was selectively cytotoxic to human umbilical vein endothelial cells (hUVECs), whereas it was less cytotoxic to human fibroblasts and umbilical cord­derived mesenchymal stem cells. In addition, this compound significantly attenuated the migration and tube formation ability of hUVECs. Taken together, the present study demonstrates that oxostephanine plays dual roles in inhibiting Aurora kinase activity and angiogenesis. Thus, it may have potential for use as a drug in cancer treatment.

Will previous palliative surgery for congenital heart disease be detrimental to subsequent pig heart xenotransplantation?

INTRODUCTION: Pig heart xenotransplantation might act as a bridge in infants with complex congenital heart disease (CHD) until a deceased human donor heart becomes available. Infants develop antibodies to wild-type (WT, i.e., genetically-unmodified) pig cells, but rarely to cells in which expression of the 3 known carbohydrate xenoantigens has been deleted by genetic engineering (triple-knockout [TKO] pigs). Our objective was to test sera from children who had undergone palliative surgery for complex CHD (and who potentially might need a pig heart transplant) to determine whether they had serum cytotoxic antibodies against TKO pig cells. METHODS: Sera were obtained from children with CHD undergoing Glenn or Fontan operation (n = 14) and healthy adults (n = 8, as controls). All of the children had complex CHD and had undergone some form of cardiac surgery. Seven had received human blood transfusions and 3 bovine pericardial patch grafts. IgM and IgG binding to WT and TKO pig red blood cells (RBCs) and peripheral blood mononuclear cells (PBMCs) were measured by flow cytometry, and killing of PBMCs by a complement-dependent cytotoxicity assay. RESULTS: Almost all children and adults demonstrated relatively high IgM/IgG binding to WT RBCs, but minimal binding to TKO RBCs (p < 0.0001 vs WT), although IgG binding was greater in children than adults (p < 0.01). All sera showed IgM/IgG binding to WT PBMCs, but this was much lower to TKO PBMCs (p < 0.0001 vs WT) and was greater in children than in adults (p < 0.05). Binding to both WT and TKO PBMCs was greater than to RBCs. Mean serum cytotoxicity to WT PBMCs was 90% in both children and adults, whereas to TKO PBMCs it was only 20% and < 5%, respectively. The sera from 6/14 (43%) children were cytotoxic to TKO PBMCs, but no adult sera were cytotoxic. CONCLUSIONS: Although no children had high levels of antibodies to TKO RBCs, 13/14 demonstrated antibodies to TKO PBMCs, in 6 of these showed mild cytotoxicity. As no adults had cytotoxic antibodies to TKO PBMCs, the higher incidence in children may possibly be associated with their exposure to previous cardiac surgery and biological products. However, the numbers were too small to determine the influence of such past exposures. Before considering pig heart xenotransplantation for children with CHD, testing for antibody binding may be warranted.

Amolops caelumnoctis Rao amp; Wilkinson, 2007, a Junior Synonym of A. splendissimus Orlov amp; Ho, 2007 (Amphibia: Anura: Ranidae).

Amolops splendissimus Orlov and Ho, 2007 and A. caelumnoctis Rao and Wilkinson, 2007 were described almost simultaneously from either side of the China-Vietnam border. The two species share a strong morphological resemblance, and their taxonomic distinctiveness has been questioned, yet no one has confirmed the taxonomic relationship and status between the two taxa. To resolve this taxonomic issue, we collected additional topotypic and near-topotypic specimens of A. splendissimus and A. caelumnoctis from both China (A. caelumnoctis: Wenshan County, Yunnan Province; type locality Luchun County, Yunnan Province), and Vietnam (A. splendissimus: Tam Duong District, Lai Chau Province; type locality Mount Ky Quan San, Bat Xat, Lao Cai Province). Molecular analysis based on a 16S rRNA fragment revealed minimal genetic divergences between the two taxa (0.0%0.4% uncorrected p-distance), and both species are closely related to A. viridimaculatus (2.1%2.3%) and A. medogensis (3.5%3.7%). Morphological comparisons between the newly collected specimens and the original descriptions of both species further support the lack of distinctiveness of the two species, hence, we conclude that A. caelumnoctis is a junior synonym of A. splendissimus.

Anti-pig IgE and IgA Antibodies in Naive Primates and Nonhuman Primates With Pig Xenografts.

BACKGROUND: Natural preformed anti-pig IgM/IgG antibodies in primates play an important role in xenograft rejection. As it is not clear how IgE and IgA engage in the immune system in xenotransplantation, we investigated natural preformed and elicited anti-pig IgE/IgA in naive primates and after xenotransplantation in nonhuman primates. METHODS: The binding of IgM/IgG/IgE/IgA antibodies to red blood cells (RBCs) from wild-type (WT), α1,3-galactosyltransferase gene-knockout (GTKO), and GTKO/cytidine monophospho-N-acetylneuraminic acid hydroxylase gene-knockout/ß-1,4 N-acetylgalactosaminyltransferase 2 gene-knockout (ie, triple-knockout pigs) pigs were measured by flow cytometry in naive human (n = 50) and baboon (n = 14) sera. Antibody binding to WT and GTKO pig RBCs (pRBCs) was also measured in the sera of baboons (nonsensitized n = 7, sensitized n = 2) and rhesus monkeys (nonsensitized n = 2, sensitized n = 11) following WT or GTKO pig organ/tissue xenotransplantation. Deposition of IgM/IgG/IgE/IgA in the grafts was detected by immunohistochemistry. RESULTS: The majority of humans had natural preformed IgM/IgG/IgE/IgA to WT and GTKO pRBCs. In contrast, IgM/IgG/IgE/IgA to triple-knockout pRBCs were present at lower levels and frequency (P < 0.01). Baboons also had IgM/IgG/IgE/IgA antibodies against WT pRBCs, but fewer to GTKO and triple-knockout (P < 0.01). After xenotransplantation into nonhuman primates, when IgM/IgG increased, IgE/IgA also increased, but to a lesser extent. In addition to IgM/IgG, IgE or IgA deposition was observed in rejected pig xenografts. CONCLUSIONS: Primates develop serum anti-pig IgE/IgA antibodies both naturally and during xenograft rejection. The pathophysiological role, if any, of anti-pig IgE/IgA antibodies remains unknown.

Evidence for GTKO/ß4GalNT2KO Pigs as the Preferred Organ-source for Old World Nonhuman Primates as a Preclinical Model of Xenotransplantation.

BACKGROUND: Triple-knockout (TKO) pigs (in which expression of the 3 known pig carbohydrate xenoantigens has been deleted) are likely to be an optimal source of organs for transplantation into human recipients, many of whom do not have natural antibodies against TKO pig cells. However, old world monkeys, for example, baboons, have natural antibodies directed to TKO cells (to a "fourth" xenoantigen that is exposed after TKO). METHODS: We measured (1) anti-pig IgM/IgG binding, and (2) complement-dependent cytotoxicity (CDC), by flow cytometry to α1,3-galactosyltransfearse gene-knockout (GTKO), GTKO/ß4GalNT2KO (that do not express the "fourth" xenoantigen), and TKO pig peripheral blood mononuclear cells (PBMCs) using 72 baboon sera (30 specific pathogen-free [SPF], and 42 non-SPF baboons). RESULTS: Mean IgM antibody binding to GTKO/ß4GalNT2KO pig PBMCs was significantly lower than to GTKO or TKO pig PBMCs (P < 0.01). Mean IgG antibody binding to GTKO/ß4GalNT2KO pig PBMCs was significantly lower than to TKO PBMCs (P < 0.01). Mean CDC of GTKO/ß4GalNT2KO pig PBMCs was significantly lower than of GTKO or TKO pig PBMCs (P < 0.01). SPF baboon serum IgM and IgG binding to, and CDC of, GTKO/ß4GalNT2KO or TKO PBMCs were significantly lower than non-SPF baboon sera (P < 0.01). CONCLUSIONS: Although TKO pigs form the basis for proposed clinical trials of xenotransplantation, it is difficult to identify baboons with a low or negative CDC to TKO pigs. For pig-to-baboon organ transplantation, the use of GTKO/ß4GalNT2KO pigs would be preferable. The use of SPF baboons as recipients might be a minor advantage.

Lipid droplets can promote drug accumulation and activation.

Genetic screens in cultured human cells represent a powerful unbiased strategy to identify cellular pathways that determine drug efficacy, providing critical information for clinical development. We used insertional mutagenesis-based screens in haploid cells to identify genes required for the sensitivity to lasonolide A (LasA), a macrolide derived from a marine sponge that kills certain types of cancer cells at low nanomolar concentrations. Our screens converged on a single gene, LDAH, encoding a member of the metabolite serine hydrolase family that is localized on the surface of lipid droplets. Mechanistic studies revealed that LasA accumulates in lipid droplets, where it is cleaved into a toxic metabolite by LDAH. We suggest that selective partitioning of hydrophobic drugs into the oil phase of lipid droplets can influence their activation and eventual toxicity to cells.

Human CTLA4-Ig therapy can give false-positive anti-pig antibody results in primates after xenotransplantation.

BACKGROUND: Measurement of serum anti-pig antibodies is an important parameter in immune monitoring after pig-to-nonhuman primate xenotransplantation. Pig aortic endothelial cells (pAECs) are commonly used for this purpose. However, human (h) CTLA4-Ig (abatacept/belatacept) could bind to pCD80/86 on the cells, and a secondary antibody (i.e., anti-human IgG) may recognize hCTLA4-Ig (in the absence of serum anti-pig IgG antibody binding to pAECs), potentially leading to misinterpretation of the results. Our aim was to determine whether hCTLA4-Ig binding to pAECs is associated with false-positive results. METHODS: Sera were obtained from (i) naïve baboons (n = 3) and (ii) baboons (n = 2) that had undergone pig artery patch transplantation with/without hCTLA4Ig therapy. Serum IgM and IgG binding to (i) AECs, (ii) red blood cells (RBCs), and (iii) CD3+T cells in peripheral blood mononuclear cells (PBMCs) from an α1,3-galactosyltransferase gene-knockout pig expressing human CD46 (GTKO/hCD46) was measured by flow cytometry in the presence or absence of hCTLA-4Ig. Complement-dependent cytotoxicity (CDC) of wild-type (WT) pAECs by hCTLA4Ig was measured by flow cytometry. RESULTS: Sera containing hCTLA4-Ig demonstrated significantly increased IgG (but not IgM) binding to pAECs (relative geometric mean [rGM] = 1.8) compared to sera without hCTLA-4Ig (rGM =1.3) (p < .01). In contrast, there was no increased binding to pRBCs or CD3+T cells. hCTLA4-Ig did not result in cytotoxicity of WT pAECs. CONCLUSIONS: pAECs might not be an optimal cell to investigate anti-pig IgG binding when hCTLA4-Ig is administered to the recipient, as a false-positive result may result from hCTLA4-Ig binding to the pAECs. CD3+T cells would be preferable targets (compared to pRBCs) because they express both carbohydrate and MHC class I/II antigens.

Quantitative mapping of protein-peptide affinity landscapes using spectrally encoded beads.

Transient, regulated binding of globular protein domains to Short Linear Motifs (SLiMs) in disordered regions of other proteins drives cellular signaling. Mapping the energy landscapes of these interactions is essential for deciphering and perturbing signaling networks but is challenging due to their weak affinities. We present a powerful technology (MRBLE-pep) that simultaneously quantifies protein binding to a library of peptides directly synthesized on beads containing unique spectral codes. Using MRBLE-pep, we systematically probe binding of calcineurin (CN), a conserved protein phosphatase essential for the immune response and target of immunosuppressants, to the PxIxIT SLiM. We discover that flanking residues and post-translational modifications critically contribute to PxIxIT-CN affinity and identify CN-binding peptides based on multiple scaffolds with a wide range of affinities. The quantitative biophysical data provided by this approach will improve computational modeling efforts, elucidate a broad range of weak protein-SLiM interactions, and revolutionize our understanding of signaling networks.

The burden of cervical cancer in Vietnam: Synthesis of the evidence.

There is currently no national cervical screening or HPV immunization program in Vietnam. This study aims to synthesize available data on the burden of disease and to project the burden of cervical cancer to 2049 if no major interventions are implemented. We reviewed published data sources on risk factors for HPV prevalence, high-grade lesions, cervical cancer incidence and mortality in Vietnam from 1990 to 2017. We then used the available data to project the number of new cervical cancer cases for the period 2013-2049. Data on cervical cancer incidence and mortality in Vietnam are limited; two Vietnamese cancer registries have been reported on by the International Agency for Research on Cancer, which cover urban populations representing ∼20% of the national population. The reported age-standardized cervical cancer incidence in Hanoi was 6.7 (1993-1997), compared to 28.8 and 14.1 per 100,000 women in Ho Chi Minh City (1995-1998 and 2009-2012, respectively). Cancer mortality data are not uniformly available from cancer registries or mortality surveys in Vietnam because cause of death has not been routinely ascertained. Based on available urban population registry data, estimated rates in the rural population, and forward projection of existing trends, we estimate that without any further intervention, the number of new cases will increase from 6930 (range 5671-8493) in 2012 to 8562 (range 5775-12,762) in 2049, giving a total of 379,617 (range 276,879-542,941) new cases over the period 2013-2049. These findings help underpin the case for the delivery of HPV vaccination and cervical screening in Vietnam, and support similar initiatives in other low- and middle-income countries.