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BACKGROUND: Acute myeloid leukaemia (AML) is characterised by the halt in maturation of myeloid progenitor cells, combined with uncontrolled proliferation and abnormal survival, leading to the accumulation of immature blasts. In many subtypes of AML the underlying causative genetic insults are not fully described. MicroRNAs are known to be dysregulated during oncogenesis. Overexpression of miR-155 is associated with some cancers, including haematological malignancies, and it has been postulated that miR-155 has an oncogenic role. This study investigated the effects of modulating miR-155 expression in human AML cells, and its mechanism of action. RESULTS: Analysis of miR-155 expression patterns in AML patients found that Fms-like tyrosine kinase 3 (FLT3)-wildtype AML has the same expression level as normal bone marrow, with increased expression restricted to AML with the FLT3-ITD mutation. Induction of apoptosis by cytarabine arabinoside or myelomonocytic differentiation by 1,23-dihydroxyvitaminD3 in FLT3-wildtype AML cells led to upregulated miR-155 expression. Knockdown of miR-155 by locked nucleic acid antisense oligonucleotides in the FLT3-wildtype AML cells conferred resistance to cytarabine arabinoside induced apoptosis and suppressed the ability of cells to differentiate.Ectopic expression of miR-155 in FLT3-wildtype AML cells led to a significant gain of myelomonocytic markers (CD11b, CD14 and CD15), increase in apoptosis (AnnexinV binding), decrease in cell growth and clonogenic capacity.In silico target prediction identified a number of putative miR-155 target genes, and the expression changes of key transcription regulators of myeloid differentiation and apoptosis (MEIS1, GF1, cMYC, JARID2, cJUN, FOS, CTNNB1 and TRIB2) were confirmed by PCR. Assessment of expression of apoptosis-related proteins demonstrated a marked increase in cleaved caspase-3 expression confirming activation of the apoptosis cascade. CONCLUSIONS: This study provides evidence for an anti-leukaemic role for miR-155 in human FLT3-wildtype AML, by inducing cell apoptosis and myelomonocytic differentiation, which is in contrast to its previously hypothesized role as an oncogene. This highlights the complexity of gene regulation by microRNAs that may have tumour repressor or oncogenic effects depending on disease context or tissue type.
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Epigênese Genética , Leucemia Mieloide Aguda/genética , MicroRNAs/genética , Proteínas de Neoplasias/genética , Tirosina Quinase 3 Semelhante a fms/genética , Antígenos CD/genética , Antígenos CD/metabolismo , Antimetabólitos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/genética , Caspase 3/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Citarabina/farmacologia , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Células HL-60 , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , MicroRNAs/metabolismo , Mutação , Proteínas de Neoplasias/metabolismo , Transdução de Sinais , Análise de Sobrevida , Células Tumorais Cultivadas , Tirosina Quinase 3 Semelhante a fms/metabolismoRESUMO
Splenic marginal zone (MZ) B cells are a lineage distinct from follicular and peritoneal B1 B cells. They are located next to the marginal sinus where blood is released. Here they pick up antigens and shuttle the load onto follicular dendritic cells inside the follicle. On activation, MZ B cells rapidly differentiate into plasmablasts secreting antibodies, thereby mediating humoral immune responses against blood-borne type 2 T-independent antigens. As Krüppel-like factors are implicated in cell differentiation/function in various tissues, we studied the function of basic Krüppel-like factor (BKLF/KLF3) in B cells. Whereas B-cell development in the bone marrow of KLF3-transgenic mice was unaffected, MZ B-cell numbers in spleen were increased considerably. As revealed in chimeric mice, this occurred cell autonomously, increasing both MZ and peritoneal B1 B-cell subsets. Comparing KLF3-transgenic and nontransgenic follicular B cells by RNA-microarray revealed that KLF3 regulates a subset of genes that was similarly up-regulated/down-regulated on normal MZ B-cell differentiation. Indeed, KLF3 expression overcame the lack of MZ B cells caused by different genetic alterations, such as CD19-deficiency or blockade of B-cell activating factor-receptor signaling, indicating that KLF3 may complement alternative nuclear factor-κB signaling. Thus, KLF3 is a driving force toward MZ B-cell maturation.
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Diferenciação Celular/genética , Fatores de Transcrição Kruppel-Like/fisiologia , Células Progenitoras Linfoides/metabolismo , Células Progenitoras Linfoides/fisiologia , Linfopoese/genética , Mucosa/imunologia , Animais , Antígenos CD19/genética , Antígenos CD19/metabolismo , Células Cultivadas , Análise por Conglomerados , Feminino , Perfilação da Expressão Gênica , Técnicas de Transferência de Genes , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Tecido Linfoide/imunologia , Tecido Linfoide/metabolismo , Tecido Linfoide/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Análise em Microsséries , Mucosa/metabolismo , Mucosa/fisiologiaRESUMO
Krüppel-like factor 3 (Klf3) is a member of the Klf family of transcription factors. Klfs are widely expressed and have diverse roles in development and differentiation. In this study, we examine the function of Klf3 in B cell development by studying B lymphopoiesis in a Klf3 knockout mouse model. We show that B cell differentiation is significantly impaired in the bone marrow, spleen, and peritoneal cavity of Klf3 null mice and confirm that the defects are cell autonomous. In the bone marrow, there is a reduction in immature B cells, whereas recirculating mature cells are noticeably increased. Immunohistology of the spleen reveals a poorly structured marginal zone (MZ) that may in part be caused by deregulation of adhesion molecules on MZ B cells. In the peritoneal cavity, there are significant defects in B1 B cell development. We also report that the loss of Klf3 in MZ B cells is associated with reduced BCR signaling strength and an impaired ability to respond to LPS stimulation. Finally, we show increased expression of a number of Klf genes in Klf3 null B cells, suggesting that a Klf regulatory network may exist in B cells.
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Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/patologia , Fatores de Transcrição Kruppel-Like/deficiência , Fatores de Transcrição Kruppel-Like/genética , Linfopoese/genética , Linfopoese/imunologia , Animais , Subpopulações de Linfócitos B/metabolismo , Células da Medula Óssea/imunologia , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Peritônio/imunologia , Peritônio/metabolismo , Peritônio/patologia , Quimera por Radiação/genética , Quimera por Radiação/imunologia , Baço/imunologia , Baço/metabolismo , Baço/patologiaRESUMO
In this study, selective Nb doping (P-type) at the WS2 layer in a WS2-MoS2 lateral heterostructure via a chemical vapor deposition (CVD) method using a solution-phase precursor containing W, Mo, and Nb atoms is proposed. The different chemical activity reactivity (MoO3 > WO3 > Nb2O5) enable the separation of the growth temperature of intrinsic MoS2 to 700 °C (first grown inner layer) and Nb-doped WS2 to 800 °C (second grown outer layer). By controlling the Nb/(W+Nb) molar ratio in the solution precursor, the hole carrier density in the p-type WS2 layer is selectively controlled from approximately 1.87 × 107/cm2 at 1.5 at.% Nb to approximately 1.16 × 1013/cm2 at 8.1 at.% Nb, while the electron carrier density in n-type MoS2 shows negligible change with variation of the Nb molar ratio. As a result, the electrical behavior of the WS2-MoS2 heterostructure transforms from the N-N junction (0 at.% Nb) to the P-N junction (4.5 at.% Nb) and the P-N tunnel junction (8.1 at.% Nb). The band-to-band tunneling at the P-N tunnel junction (8.1 at.% Nb) is eliminated by applying negative gate bias, resulting in a maximum rectification ratio (105) and a minimum channel resistance (108 Ω). With this optimized photodiode (8.1 at.% Nb at Vg = -30 V), an Iphoto/Idark ratio of 6000 and a detectivity of 1.1 × 1014 Jones are achieved, which are approximately 20 and 3 times higher, respectively, than the previously reported highest values for CVD-grown transition-metal dichalcogenide P-N junctions.
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BACKGROUND: Jewel orchid is the common name of several orchid species which can be alike in morphological characteristics, but variable in medicinal properties. At present, two DNA barcode loci, namely, maturase K (matK) and ribulose 1,5-biphosphate carboxylase (rbcL), are intensively utilized for plant identification. However, the discrimination effectiveness of these loci is variable among plant species. This study was carried out to compare the identifying efficacy of these two loci on jewel orchid population collected throughout Vietnam. RESULTS: The results revealed that 21 jewel orchid accessions studied were segregated into four different species with significant variations. The discrimination power of matK and rbcL markers in this jewel orchid study displayed different efficiency level. The rbcL gene has higher distinguishing potential than either matK gene alone or the combination of both genes. CONCLUSION: The findings of this project could provide valuable information that is necessary for classification, plant origin identification, breeding, and conservation program of jewel orchid in Vietnam.
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Pharmacological inhibition of MDM2/4, which activates the critical tumor suppressor p53, has been gaining increasing interest as a strategy for the treatment of acute myeloid leukemia (AML). While clinical trials of MDM2 inhibitors have shown promise, responses have been confined to largely molecularly undefined patients, indicating that new biomarkers and optimized treatment strategies are needed. We previously reported that the microRNA miR-10a is strongly overexpressed in some AML, and demonstrate here that it modulates several key members of the p53/Rb network, including p53 regulator MDM4, Rb regulator RB1CC1, p21 regulator TFAP2C, and p53 itself. The expression of both miR-10a and its downstream targets were strongly predictive of MDM2 inhibitor sensitivity in cell lines, primary AML specimens, and correlated to response in patients treated with both MDM2 inhibitors and cytarabine. Furthermore, miR-10a inhibition induced synergy between MDM2 inhibitor Nutlin-3a and cytarabine in both in vitro and in vivo AML models. Mechanistically this synergism primarily occurs via the p53-mediated activation of cytotoxic apoptosis at the expense of cytoprotective autophagy. Together these findings demonstrate that miR-10a may be useful as both a biomarker to identify patients most likely to respond to cytarabine+MDM2 inhibition and also a druggable target to increase their efficacy.
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Biomarcadores Tumorais/metabolismo , Leucemia Mieloide Aguda/metabolismo , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Citarabina/farmacologia , Feminino , Humanos , Imidazóis/farmacologia , Leucemia Mieloide Aguda/tratamento farmacológico , Camundongos , Camundongos Endogâmicos NOD , Piperazinas/farmacologiaRESUMO
van der Waals heterostructures (vdWHs) of metallic (m-) and semiconducting (s-) transition-metal dichalcogenides (TMDs) exhibit an ideal metal/semiconductor (M/S) contact in a field-effect transistor. However, in the current two-step chemical vapor deposition process, the synthesis of m-TMD on pregrown s-TMD contaminates the van der Waals (vdW) interface and hinders the doping of s-TMD. Here, NbSe2/Nb-doped-WSe2 metal-doped-semiconductor (M/d-S) vdWHs are created via a one-step synthesis approach using a niobium molar ratio-controlled solution-phase precursor. The one-step growth approach synthesizes Nb-doped WSe2 with a controllable doping concentration and metal/doped-semiconductor vdWHs. The hole carrier concentration can be precisely controlled by controlling the Nb/(W + Nb) molar ratio in the precursor solution from â¼3 × 1011/cm2 at Nb-0% to â¼1.38 × 1012/cm2 at Nb-60%; correspondingly, the contact resistance RC value decreases from 10â¯888.78 at Nb-0% to 70.60 kΩ.µm at Nb-60%. The Schottky barrier height measurement in the Arrhenius plots of ln(Isat/T2) versus q/KBT demonstrated an ohmic contact in the NbSe2/WxNb1-xSe2 vdWHs. Combining p-doping in WSe2 and M/d-S vdWHs, the mobility (27.24 cm2 V-1 s-1) and on/off ratio (2.2 × 107) are increased 1238 and 4400 times, respectively, compared to that using the Cr/pure-WSe2 contact (0.022 cm2 V-1 s-1 and 5 × 103, respectively). Together, the RC value using the NbSe2 contact shows 2.46 kΩ.µm, which is â¼29 times lower than that of using a metal contact. This method is expected to guide the synthesis of various M/d-S vdWHs and applications in future high-performance integrated circuits.
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BACKGROUND: Early detection of autism spectrum disorders (ASDs) is essential given the under-reported cases in low- and middle-income countries. This first national representative survey was conducted to explore the prevalence of ASDs amongst 18 and 30 months in seven provinces in Vietnam. DESIGN AND METHODS: During 2017- 2018, a national cross-sectional and population-based survey for autism spectrum disorder (ASD) amongst 40,243 children aged 18 to 30 months was conducted in 7 provinces representing the socio-economic regions of Vietnam. M-CHAT was used to screen children and then confirmed by diagnostic assessment using DSM-IV criteria. RESULTS: The prevalence of ASDs amongst children aged 18 and 30 months in Vietnam was high (0.758% or 1 in 132 children). Urban setting, male gender, and hereditable genes were associated with ASD prevalence. CONCLUSIONS: ASDs amongst children aged 18 and 30 months in Vietnam tend to be increasing and are similar to this rate in other middle-income countries but lower than that in Western countries. This under-recognized public health problem amongst children should be addressed by early detection and intervention for families with affected children.
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Importance: Many health care systems lack the efficiency, preparedness, or resources needed to address the increasing number of patients with type 2 diabetes, especially in low- and middle-income countries. Objective: To examine the effects of a quality improvement intervention comprising information and communications technology and contact with nonphysician personnel on the care and cardiometabolic risk factors of patients with type 2 diabetes in 8 Asia-Pacific countries. Design, Setting, and Participants: This 12-month multinational open-label randomized clinical trial was conducted from June 28, 2012, to April 28, 2016, at 50 primary care or hospital-based diabetes centers in 8 Asia-Pacific countries (India, Indonesia, Malaysia, the Philippines, Singapore, Taiwan, Thailand, and Vietnam). Six countries were low and middle income, and 2 countries were high income. The study was conducted in 2 phases; phase 1 enrolled 7537 participants, and phase 2 enrolled 13 297 participants. Participants in both phases were randomized on a 1:1 ratio to intervention or control groups. Data were analyzed by intention to treat and per protocol from July 3, 2019, to July 21, 2020. Interventions: In both phases, the intervention group received 3 care components: a nurse-led Joint Asia Diabetes Evaluation (JADE) technology-guided structured evaluation, automated personalized reports to encourage patient empowerment, and 2 or more telephone or face-to-face contacts by nurses to increase patient engagement. In phase 1, the control group received the JADE technology-guided structured evaluation and automated personalized reports. In phase 2, the control group received the JADE technology-guided structured evaluation only. Main Outcomes and Measures: The primary outcome was the incidence of a composite of diabetes-associated end points, including cardiovascular disease, chronic kidney disease, visual impairment or eye surgery, lower extremity amputation or foot ulcers requiring hospitalization, all-site cancers, and death. The secondary outcomes were the attainment of 2 or more primary diabetes-associated targets (glycated hemoglobin A1c <7.0%, blood pressure <130/80 mm Hg, and low-density lipoprotein cholesterol <100 mg/dL) and/or 2 or more key performance indices (reduction in glycated hemoglobin A1c≥0.5%, reduction in systolic blood pressure ≥5 mm Hg, reduction in low-density lipoprotein cholesterol ≥19 mg/dL, and reduction in body weight ≥3.0%). Results: A total of 20â¯834 patients with type 2 diabetes were randomized in phases 1 and 2. In phase 1, 7537 participants (mean [SD] age, 60.0 [11.3] years; 3914 men [51.9%]; 4855 patients [64.4%] from low- and middle-income countries) were randomized, with 3732 patients allocated to the intervention group and 3805 patients allocated to the control group. In phase 2, 13 297 participants (mean [SD] age, 54.0 [11.1] years; 7754 men [58.3%]; 13 297 patients [100%] from low- and middle-income countries) were randomized, with 6645 patients allocated to the intervention group and 6652 patients allocated to the control group. In phase 1, compared with the control group, the intervention group had a similar risk of experiencing any of the primary outcomes (odds ratio [OR], 0.94; 95% CI, 0.74-1.21) but had an increased likelihood of attaining 2 or more primary targets (OR, 1.34; 95% CI, 1.21-1.49) and 2 or more key performance indices (OR, 1.18; 95% CI, 1.04-1.34). In phase 2, the intervention group also had a similar risk of experiencing any of the primary outcomes (OR, 1.02; 95% CI, 0.83-1.25) and had a greater likelihood of attaining 2 or more primary targets (OR, 1.25; 95% CI, 1.14-1.37) and 2 or more key performance indices (OR, 1.50; 95% CI, 1.33-1.68) compared with the control group. For attainment of 2 or more primary targets, larger effects were observed among patients in low- and middle-income countries (OR, 1.50; 95% CI, 1.29-1.74) compared with high-income countries (OR, 1.20; 95% CI, 1.03-1.39) (P = .04). Conclusions and Relevance: In this 12-month clinical trial, the use of information and communications technology and nurses to empower and engage patients did not change the number of clinical events but did reduce cardiometabolic risk factors among patients with type 2 diabetes, especially those in low- and middle-income countries in the Asia-Pacific region. Trial Registration: ClinicalTrials.gov Identifier: NCT01631084.
Assuntos
Sistemas de Apoio a Decisões Clínicas , Diabetes Mellitus Tipo 2/terapia , Autogestão , Tecnologia , Idoso , Amputação Cirúrgica/estatística & dados numéricos , Sudeste Asiático , Pressão Sanguínea , Fatores de Risco Cardiometabólico , Doenças Cardiovasculares/epidemiologia , LDL-Colesterol/metabolismo , Países em Desenvolvimento , Diabetes Mellitus Tipo 2/metabolismo , Pé Diabético/epidemiologia , Nefropatias Diabéticas/epidemiologia , Retinopatia Diabética/epidemiologia , Gerenciamento Clínico , Medicina Baseada em Evidências , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Mortalidade , Neoplasias/epidemiologia , Participação do Paciente , Melhoria de Qualidade , Insuficiência Renal Crônica/epidemiologia , Medição de Risco , Taiwan , Cooperação e Adesão ao TratamentoRESUMO
BACKGROUND: Health education through music video plays a vital role in raising a person's knowledge, attitudes, and behaviors positively connected to health during COVID-19 pandemic. OBJECTIVE: This study aimed to estimate the prevalence of COVID-19-related music-video-watching and examine associated factors among the Vietnamese population. METHODS: A cross-sectional study in Vietnam was conducted in February 2021 via the Internet. RESULTS: Among 658 participants, the prevalence of COVID-19-related music-video-watching was 89.1% among people. In the multivariable regression models, significant factors for COVID-19-related music-video-watching were living area, types of housemate, age groups, and current occupation. CONCLUSIONS: Lessons on health education to fight against the COVID-19 pandemic in Vietnam could be useful for similar settings in the world.
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Basal insulin therapy can improve glycemic control in people with type 2 diabetes. However, timely initiation, optimal titration, and proper adherence to prescribed basal insulin regimens are necessary to achieve optimal glycemic control. Even so, glycemic control may remain suboptimal in a significant proportion of patients. Unique circumstances in Asia (eg, limited resources, management of diabetes primarily in nonspecialist settings, and patient populations that are predominantly less educated) coupled with the limitations of current basal insulin options (eg, risk of hypoglycemia and dosing time inflexibility) amplify the challenge of optimal basal insulin therapy in Asia. Significant progress has been made with long-acting insulin analogs (insulin glargine 100 units/mL and insulin detemir), which provide longer coverage and less risk of hypoglycemia over intermediate-acting insulin (Neutral Protamine Hagedorn insulin). Furthermore, recent clinical evidence suggests that newer long-acting insulin analogs, new insulin glargine 300 units/mL and insulin degludec, may address some of the unmet needs of current basal insulin options in terms of risk of hypoglycemia and dosing time inflexibility. Nevertheless, more can be done to overcome barriers to basal insulin therapy in Asia, through educating both patients and physicians, developing better patient support models, and improving accessibility to long-acting insulin analogs. In this study, we highlight the unique challenges associated with basal insulin therapy in Asia and, where possible, propose strategies to address the unmet needs by drawing on clinical experiences and perspectives in Asia.
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Three new species of Aporcelaimoides from natural habitats in Vietnam are studied, described and illustrated, including line drawings, LM and/or SEM pictures. Aporcelaimoidesbrevistylum sp. n. is characterized by its body 1.95-2.90 mm long, lip region offset by deep constriction and 17-18 µm broad, ventral side of mural odontostyle 11-14 µm long with aperture occupying 62-71% of its length, neck 663-767 µm long, pharyngeal expansion occupying 58-66% of total neck length, uterus a simple tube 85-182 µm long, pars refringens vaginae absent, V = 55-63, tail short and rounded (34-46 µm, c = 49-76, c' = 0.6-0.8), spicules 67-86 µm long, and one ventromedian supplement out the range of spicules. Aporcelaimoidesminor sp. n. is distinguished in having body 2.09-2.61 mm long, lip region offset by deep constriction and 19-20 µm broad, mural odontostyle 14-16 µm long at its ventral side with aperture occupying 73-84% of its length, neck 579-649 µm long, pharyngeal expansion occupying 57-66% of total neck length, uterus a simple tube 44-69 µm long, pars refringens vaginae well developed, V = 48-56, female tail very short, rounded conoid or truncate (14-26 µm, c = 90-146, c' = 0.3-0.6), and male unknown. Aporcelaimoidessilvaticum sp. n. is characterized by its body 2.09-2.60 mm long, lip region offset by depression and 17-18 µm broad, mural odontostyle 11-12 µm long at its ventral side with aperture occupying 60-66% of its length, neck 597-720 µm long, pharyngeal expansion occupying 58-64% of total neck length, uterus a simple tube 128-243 µm long, pars refringens vaginae well developed, V = 58-60, tail short and rounded (27-37 µm, c = 67-94, c' = 0.6-0.7), spicules 64-75 µm long, and two or three widely spaced ventromedian supplements bearing hiatus. The genus Aporcelaimoides is restored, its diagnosis emended, and three species of Sectonema, namely Sectonemaamazonicum, Sectonemahaguei and Sectonemamoderatum, transferred to it. An updated list of its species, a key to their identification and a tabular compendium with the most important morphometric features are also presented.
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This paper focuses on the interactions between medical professionals in Hanoi, Vietnam and their HIV-positive patients who desire children. Drawing on ethnographic research, we argue that despite ongoing state and civil society efforts to reduce discrimination against people living with HIV (PLHIV), doctors do stigmatize patients who choose to reproduce, even if the patients are found to have carefully considered all associated risks. While the effects of the Social Evils Campaign linger, the doctors' prejudicial stance towards PLHIV's reproductive desires and risks also reflects the messages communicated by the more recent governmental campaign on Population Quality. The result of this stigmatization is a stratification of reproduction among the Vietnamese citizenry whereby PLHIV are considered obstacles to 'the cleanliness of the race'.