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328 result(s) for "Giang, Le Minh"
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O-GlcNAc transferase regulates glioblastoma acetate metabolism via regulation of CDK5-dependent ACSS2 phosphorylation
Glioblastomas (GBMs) preferentially generate acetyl-CoA from acetate as a fuel source to promote tumor growth. O-GlcNAcylation has been shown to be elevated by increasing O-GlcNAc transferase (OGT) in many cancers and reduced O-GlcNAcylation can block cancer growth. Here, we identify a novel mechanism whereby OGT regulates acetate-dependent acetyl-CoA and lipid production by regulating phosphorylation of acetyl-CoA synthetase 2 (ACSS2) by cyclin-dependent kinase 5 (CDK5). OGT is required and sufficient for GBM cell growth and regulates acetate conversion to acetyl-CoA and lipids. Elevating O-GlcNAcylation in GBM cells increases phosphorylation of ACSS2 on Ser-267 in a CDK5-dependent manner. Importantly, we show that ACSS2 Ser-267 phosphorylation regulates its stability by reducing polyubiquitination and degradation. ACSS2 Ser-267 is critical for OGT-mediated GBM growth as overexpression of ACSS2 Ser-267 phospho-mimetic rescues growth in vitro and in vivo. Importantly, we show that pharmacologically targeting OGT and CDK5 reduces GBM growth ex vivo. Thus, the OGT/CDK5/ACSS2 pathway may be a way to target altered metabolic dependencies in brain tumors.
Chronic Immune Platelet Activation Is Followed by Platelet Refractoriness and Impaired Contractility
Autoimmune diseases, including systemic lupus erythematosus (SLE), have a high risk of thrombotic and hemorrhagic complications associated with altered platelet functionality. We studied platelets from the blood of SLE patients and their reactivity. The surface expression of phosphatidylserine, P-selectin, and active integrin αIIbβ3 were measured using flow cytometry before and after platelet stimulation. Soluble P-selectin was measured in plasma. The kinetics of platelet-driven clot contraction was studied, as well as scanning and transmission electron microscopy of unstimulated platelets. Elevated levels of membrane-associated phosphatidylserine and platelet-attached and soluble P-selectin correlated directly with the titers of IgG, anti-dsDNA-antibodies, and circulating immune complexes. Morphologically, platelets in SLE lost their resting discoid shape, formed membrane protrusions and aggregates, and had a rough plasma membrane. The signs of platelet activation were associated paradoxically with reduced reactivity to a physiological stimulus and impaired contractility that revealed platelet exhaustion and refractoriness. Platelet activation has multiple pro-coagulant effects, and the inability to fully contract (retract) blood clots can be either a hemorrhagic or pro-thrombotic mechanism related to altered clot permeability, sensitivity of clots to fibrinolysis, obstructiveness, and embologenicity. Therefore, chronic immune platelet activation followed by secondary platelet dysfunction comprise an understudied pathogenic mechanism that supports hemostatic disorders in autoimmune diseases, such as SLE.
Unraveling reproductive and maternal health challenges of women living with HIV/AIDS in Vietnam: a qualitative study
Background Human Immunodeficiency Virus (HIV) remains a significant public health concern worldwide. Women living with HIV/AIDS (WLHA) have the additional and unique need to seek sexual and reproductive health services. WLHA’s maternal health journeys can be shaped by the cultural norms and resources that exist in their society. This study sought to understand if and how WLHA’s family planning, pregnancy, and motherhood experiences could be influenced by the patriarchal culture, gender roles, and HIV stigma in Vietnam, specifically. Methods Between December 2021 and March 2022, 30 WLHA with diverse socioeconomic backgrounds and childbirth experiences were interviewed in Hanoi, Vietnam. These semi-structured interviews covered topics including HIV stigma, gender norms, pregnancy experiences, and child-rearing challenges. Interviews were audio recorded, transcribed, and analysed using ATLAS.ti. Results Qualitative analyses of participant quotes revealed how limited information on one’s health prospects and reproductive options posed a significant challenge to family planning. Societal and familial expectations as well as economic circumstances also influenced reproductive decision-making. WLHA often encountered substandard healthcare during pregnancy, labor, and delivery. Stigma and lack of provider attentiveness resulted in cases where women were denied pain relief and other medical services. Communication breakdowns resulted in failure to administer antiretroviral therapy for newborns. Motherhood for WLHA was shadowed by concerns for not only their own health, but also the wellbeing of their children, as HIV stigma affected their children at school and in society as well. Many WLHA highlighted the constructive or destructive role that family members could play in their childbirth decision-making and care-giving experiences. Conclusions Overall, this study underscores the complex ways that cultural expectations, family support, and stigma in healthcare impact WLHA. Efforts to educate and engage families and healthcare providers are warranted to better understand and address the needs of WLHA, ultimately improving their reproductive and maternal health. Plain language summary HIV-related stigma and discrimination have consequential impacts on health and quality of life for women living with HIV (WLHA). WLHA in Vietnam must navigate the additional challenges of a traditionally patriarchal and hierarchical society. Women typically face less educational and occupational opportunities and are often expected to defer to expectations of family and virtue. Stigma among family members, friends, employers, and healthcare providers poses a significant challenge to WLHA autonomy, especially as it relates to their reproductive health decision-making and maternal health experiences. This study aims to better understand the experiences of WLHA throughout family planning, pregnancy, and motherhood. The findings will hopefully shed light on strategies to empower WLHA and to combat HIV- and gender-based stigma not only in Vietnam, but also globally.
Understanding Vietnam’s drug policy for amphetamine-type stimulants misuse
Introduction The emergence of widespread amphetamine-type stimulants (ATSs) usage has created significant challenges for drug control and treatment policies in Southeast Asian countries. This study analyses the development of drug policies and examines current treatment program constraints in Vietnam to deal with ATS misuse. The aim was to gain insights that may be useful for national and international drug-related policy development and revision. Methods A desk review of national policy documents and 22 in-depth key informant interviews were conducted from 2019 to 2021. Thematic content analysis was employed to identify key themes and their connections. Results Analysis identified Vietnam’s 30-year history of developing policies and formulating strategies to reduce supply, demand, and harm from illicit drugs. With the increasing number of people who use ATS (PWUA), Vietnam has recently promoted harsh policy and law enforcement to deter drug use and supply. This policy trend prevails in many Asian countries. The three main constraints in dealing with ATS misuse emerged from punitive and restrictive drug policies. First, the general public believed that Centre-based compulsory treatment (CCT) is the only appropriate treatment for all types of illicit drug addiction despite its low-quality service provision. The rigid drug policy has led to social persuasion with impractical expectations for CCT effectiveness. Second, the emphasis on punishment and detention has hampered new drug treatment service development in Vietnam. CCT has become monopolistic in the context of impoverished services. Third, people who use drugs tend to hide their needs and avoid formal treatment and support services, resulting in declined social coherence. Conclusion While new drugs are constantly evolving, the current law enforcement approach potentially constrains expertise to adopt effective treatment services. This study suggests that the top-down policing mechanism presently hinders the development of an appropriate intervention strategy for ATS misuse and diminishes social support to service providers.
Shape changes of erythrocytes during blood clot contraction and the structure of polyhedrocytes
Polyhedral erythrocytes, named polyhedrocytes, are formed in contracted blood clots and thrombi, as a result of compression by activated contractile platelets pulling on fibrin. This deformation was shown to be mechanical in nature and polyhedrocytes were characterized using light and electron microscopy. Through three-dimensional reconstruction, we quantified the geometry of biconcave, intermediate, and polyhedral erythrocytes within contracting blood clots. During compression, erythrocytes became less oblate and more prolate than the biconcave cells and largely corresponded to convex, irregular polyhedra with a total number of faces ranging from 10 to 16. Faces were polygons with 3 to 6 sides. The majority of the faces were quadrilaterals, though not all sides were straight and not all faces were flat. There were no changes in the surface area or volume. These results describe the gradual natural deformation of erythrocytes as a part of compaction into a tightly packed array that is an important but understudied component of mature blood clots and thrombi.
Structural barriers to HIV prevention among men who have sex with men (MSM) in Vietnam: Diversity, stigma, and healthcare access
Men who have sex with men (MSM) in Vietnam experience disproportionate rates of HIV infection. To advance understanding of how structural barriers may shape their engagement with HIV prevention services, we draw on 32 in-depth interviews and four focus groups (n = 31) conducted with MSM in Hanoi between October 2015- March 2016. Three primary factors emerged: (1) Diversity, both in relation to identity and income; Vietnamese MSM described themselves as segregated into Bóng kín (hidden, often heterosexually-identified MSM) and Bóng lộ ('out,' transgender, or effeminate MSM). Lower-income, 'hidden' MSM from rural areas were reluctant to access MSM-targeted services; (2) Stigma: MSM reported being stigmatized by the healthcare system, family, and other MSM; and (3) Healthcare access: this was limited due to economic barriers and lack of MSM-friendly services. Our research suggests the need for multiple strategies to reach diverse types of MSM as well as to address barriers in access to health services such as stigma and costs. While a great deal has been written about the diversity of MSM in relation to gender performance and sexual identities, our research points to the substantial structural-level barriers that must be addressed in order to achieve meaningful and effective HIV prevention for MSM worldwide.
Patient preferences for incentives in Contingency Management interventions in methadone treatment: A best-worst scale analysis
Contingency management (CM) effectively enhances adherence and retention in methadone maintenance treatment (MMT). But implementing CM in resource-limited settings is challenging, particularly due to costs associated with providing incentives. In this study, we aimed to describe and quantify patient preferences regarding low-cost CM incentives to promote adherence and retention in MMT. We conducted a cross-sectional survey using a best-worst scale (case 1) among 216 participants ages 18 or older undergoing MMT in six clinics in Hanoi, Vietnam. The study asked participants to complete 13 sets of best-worst scaling tasks. Each task presented a subset of four incentives chosen from a total of 13 incentives. Net scores for each incentive were calculated by subtracting the total times an incentive was rated as least appealing from the total times it was rated as most appealing. Standardized scores were derived by dividing the net score by the sum of selections and then converted to weighted probabilities (WP) that ranged from 0% to 100% (example interpretation: an incentive with WP of 20% is twice as desired as an incentive with WP of 10%). The 95% confidence intervals (95% CI) were estimated using bootstrapping. The mean age of participants was 44.7 (SD = 8.0, range: 25-66). Most were male (95%), married (59%), and had not completed high school (69%). About half (50%) had been on methadone treatment for more than five years. The most preferred incentives were \"discount for monthly methadone fees\" (WP = 16.9, 95% CI: 16.0, 17.8) and \"take-home methadone privileges\" (WP = 11.3, 95% CI: 10.1, 12.6), followed by \"priority coupons for early medical examinations/consultations\". In contrast, the least preferred incentives were \"being recognized/praised in their community\" (WP = 4.5, 95% CI: 4.0, 5.0) and \"being recognized/praised at their clinic\" (WP = 4.7, 95% CI: 4.1, 5.4). Treatment fee support, take-home methadone privilege, and coupons for prioritizing checkup at clinics emerged as the most desirable incentives for patients. We recommend future CM intervention may consider using these incentives as the first-line rewards to offer to reinforce treatment adherence and retention in methadone treatment. These findings suggest potential low-cost CM strategies that could inform decision-making in MMT programs.
Drug Harm Reduction in Vietnam: A Review of Stakeholders’ Perspectives and Implications for Future Interventions
Objectives. To determine how harm reduction should be applied in low-resource countries such as Vietnam by exploring the perspectives of people who use drugs (PWUD), health care professionals, and policymakers regarding methadone treatment and harm reduction strategies. Methods. We conducted 2 qualitative studies in Vietnam between 2016 and 2021. We interviewed 62 PWUD and 22 experts in drug policy development and drug treatment programs, conducted observations at methadone clinics and harm reduction program meetings, and analyzed drug policy documents. Results. PWUD considered methadone treatment only as a transition to a drug-free life. Policymakers deemed harm reduction ineffective and continued to enforce arrest and incarceration of PWUD. Drug intervention programs are not yet geared to providing specialized services. Effective communication strategies and information on evidence-based harm reduction models are inadequate to help policymakers make the right decisions. Conclusions. Harm reduction principles have not been fully adopted in Vietnam. A harm reduction strategy based on a more humanistic approach that goes beyond a biomedicalized approach is urgently needed in Vietnam and other countries in the Global South. (Am J Public Health. 2022;112(S2):S182–S190. https://doi.org/10.2105/AJPH.2022.306764 )
Differential Nutrient Inadequacy Among Vietnamese Youth: Results of a Multi-Location and Multi-Group 24-Hour Recall Survey
Background: Vietnam is undergoing a rapid nutrition transition, yet evidence on nutrient intake and inadequacy among adolescents and young adults remains limited. This study aimed to assess nutrient intakes and patterns of inadequacy among Vietnamese youth aged 16–25 years across population groups and regions. Methods: A cross-sectional study was conducted among 1005 participants from five provinces in northern, central, and southern Vietnam. Dietary intake was assessed using a two-stage 24 h recall, and nutrient inadequacy was evaluated using Estimated Average Requirement (EAR), Acceptable Macronutrient Distribution Range (AMDR), and Estimated Energy Requirement (EER) reference standards. Results: Energy and macronutrient intakes differed across groups. University students had the lowest energy intake, while young workers consumed the highest proportion of carbohydrates. Calcium inadequacy exceeded 95% in all subgroups. Regional disparities were observed, with lower intakes of several micronutrients in the South. Compared with high school students, university students showed higher risks of inadequate protein and vitamin A intake, whereas young workers exhibited lower risks of inadequate carbohydrate and folate intake but a higher risk of vitamin A inadequacy. Conclusions: Vietnamese youth exhibited substantial micronutrient inadequacies with marked variation across groups and regions. These findings underscore the need for targeted nutrition interventions tailored to specific youth contexts.
Sexual and Psychosocial Risk Burdens Associated With Online Sex Seeking Among Young Men Who Have Sex With Men: Cross-Sectional Study
The heightened HIV vulnerability associated with men who have sex with men (MSM) who find sex online in Western and East Asian countries may pose similar concerns for MSM in Southeast Asia. However, this line of research is underexamined among Southeast Asian MSM, especially in Southeast Asian cities with a high HIV prevalence among young MSM, such as Ho Chi Minh City, Vietnam. This study aimed to characterize the sexual behavioral and psychosocial correlates of online sex seeking in a sample of largely gay-identified young MSM in Ho Chi Minh City, Vietnam, and examine the relationships among social support, outness, and last instance of condomless anal sex while not on preexposure prophylaxis (PrEP) for HIV or antiretroviral therapy (ART). The analysis included specific attention paid to the use of different types of online sex platforms, which may contribute to the understanding of online sex seeking. Patterns of online sex seeking in a cross-sectional sample of young MSM (N=1005) were identified using latent class analysis. Multinomial logistic regressions and Poisson regressions with robust variance were used to estimate the associations between patterns of online sex seeking and other participant characteristics. We found four latent classes of MSM with distinct profiles of online platform use for sex seeking: (1) negligible app users, (2) gay app users, (3) poly app users, and (4) low-cost app users. Patterns of online sex seeking moderated the protective effects of social support and outness on last instance of condomless anal sex while not on PrEP or ART. When stratified by level of social support and outness, only gay app users were associated with a protective effect on last instance of condomless anal sex while not on PrEP or ART when social support and outness were high, respectively. Low-cost app users were marginally associated with a higher prevalence of condomless anal sex while not on PrEP or ART when the level of outness was low. Young Vietnamese MSM who find sex partners online have distinct patterns of app use, with contrasting sexual and psychosocial health burdens that indicate that online sex seeking is a socially patterned behavior. HIV prevention programs and tailored digital interventions should consider the different exposures to social influences associated with patterns of social networking app use as they could moderate the effectiveness of the delivered programs and interventions for reducing HIV vulnerability in young MSM.