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.

Novel dimeric Smac analogs as prospective anticancer agents.

A small library of monovalent Smac mimics with general structure NMeAla-Tle-(4R)-4-Benzyl-Pro-Xaa-cysteamide, was synthesized (Xaa=hydrophobic residue). The library was screened in vitro against human breast cancer cell lines MCF-7 and MDA-MB-231, and two most active compounds oligomerized via S-alkylation giving bivalent and trivalent derivatives. The most active bivalent analogue SMAC17-2X was tested in vivo and in physiological conditions (mouse model) it exerted a potent anticancer effect resulting in ∼23.4days of tumor growth delay at 7.5mg/kg dose. Collectively, our findings suggest that bivalent Smac analogs obtained via S-alkylation protocol may be a suitable platform for the development of new anticancer therapeutics.

Hapivirins and diprovirins: novel θ-defensin analogs with potent activity against influenza A virus.

θ-Defensins are cyclic octadecapeptides found in nonhuman primates whose broad antiviral spectrum includes HIV-1, HSV-1, severe acute respiratory syndrome coronavirus, and influenza A virus (IAV). We previously reported that synthetic θ-defensins called retrocyclins can neutralize and aggregate various strains of IAV and increase IAV uptake by neutrophils. This study describes two families of peptides, hapivirins and diprovirins, whose design was inspired by retrocyclins. The goal was to develop smaller partially cyclic peptides that retain the antiviral activity of retrocyclins, while being easier to synthesize. The novel peptides also allowed for systemic substitution of key residues to evaluate the role of charge or hydrophobicity on antiviral activity. Seventy-two hapivirin or diprovirin peptides are described in this work, including several whose anti-IAV activity equals or exceeds that of normal α- or θ-defensins. Some of these also had strong antibacterial and antifungal activity. These new peptides were active against H3N2 and H1N1 strains of IAV. Structural features imparting strong antiviral activity were identified through iterative cycles of synthesis and testing. Our findings show the importance of hydrophobic residues for antiviral activity and show that pegylation, which often increases a peptide's serum t(1/2) in vivo, can increase the antiviral activity of DpVs. The new peptides acted at an early phase of viral infection, and, when combined with pulmonary surfactant protein D, their antiviral effects were additive. The peptides strongly increased neutrophil and macrophage uptake of IAV, while inhibiting monocyte cytokine generation. Development of modified θ-defensin analogs provides an approach for creating novel antiviral agents for IAV infections.

Research trends in cybercrime victimization during 2010-2020: a bibliometric analysis.

Research on cybercrime victimization is relatively diversified; however, no bibliometric study has been found to introduce the panorama of this subject. The current study aims to address this research gap by performing a bibliometric analysis of 387 Social Science Citation Index articles relevant to cybercrime victimization from Web of Science database during the period of 2010-2020. The purpose of the article is to examine the research trend and distribution of publications by five main fields, including time, productive authors, prominent sources, active institutions, and leading countries/regions. Furthermore, this study aims to determine the global collaborations and current gaps in research of cybercrime victimization. Findings indicated the decidedly upward trend of publications in the given period. The USA and its authors and institutions were likely to connect widely and took a crucial position in research of cybercrime victimization. Cyberbullying was identified as the most concerned issue over the years and cyber interpersonal crimes had the large number of research comparing to cyber-dependent crimes. Future research is suggested to concern more about sample of the elder and collect data in different countries which are not only European countries or the USA. Cross-nation research in less popular continents in research map was recommended to be conducted more. This paper contributed an overview of scholarly status of cybercrime victimization through statistical evidence and visual findings; assisted researchers to optimize their own research direction; and supported authors and institutions to build strategies for research collaboration.

Reprint of: Why Vietnam continues to impose the death penalty for drug offences: A narrative commentary.

In several nations in Southeast Asia, illegally importing, exporting, trading, or possessing drugs is a capital offence. Like China, another communist state in Asia, Vietnam imposes its harshest legal punishments for drug-related crimes, though many international opponents have continued to call for the abolishment of these inhumane sentences. Using grey literature, reports by international observers, and informal interviews with colleagues, the present article explores the policies and provisions of Vietnam's Party-State in regulating capital punishment for drug offences, situating Vietnam's sentencing practices in the context of legislative reviews, international obligations, and humanitarian perspectives. Assessing the arguments put forward by abolitionists, retentionists, and supporters of de facto abolition allows for a more comprehensive understanding of Vietnam's stance toward the Second Optional Protocol of the International Covenant on Civil and Political Rights (ICCPR), which is aimed at abolishing the death penalty in the future. The article concludes with a call for further action, outlining some basic recommendations on how the Vietnamese can keep their promises to reduce, and ultimately abolish, impositions of the death penalty for drug-related crimes.

Why Vietnam continues to impose the death penalty for drug offences: A narrative commentary.

In several nations in Southeast Asia, illegally importing, exporting, trading, or possessing drugs is a capital offence. Like China, another communist state in Asia, Vietnam imposes its harshest legal punishments for drug-related crimes, though many international opponents have continued to call for the abolishment of these inhumane sentences. Using grey literature, reports by international observers, and informal interviews with colleagues, the present article explores the policies and provisions of Vietnam's Party-State in regulating capital punishment for drug offences, situating Vietnam's sentencing practices in the context of legislative reviews, international obligations, and humanitarian perspectives. Assessing the arguments put forward by abolitionists, retentionists, and supporters of de facto abolition allows for a more comprehensive understanding of Vietnam's stance toward the Second Optional Protocol of the International Covenant on Civil and Political Rights (ICCPR), which is aimed at abolishing the death penalty in the future. The article concludes with a call for further action, outlining some basic recommendations on how the Vietnamese can keep their promises to reduce, and ultimately abolish, impositions of the death penalty for drug-related crimes.

'We realised we needed a new approach': Government and law enforcement perspectives on the implementation and future of the drug decriminalisation policy in vietnam.

In 2009, Vietnam officially decriminalised drug use through amendments to the criminal law. The amendments outlined explicitly that illicit drug use would be seen as an administrative violation, but not a criminal offence. This legal transition has not been without implementation challenges, and police particularly have struggled to find a balance between drug law enforcement and decriminalisation. Despite being a health-orientated drug policy amendment, in practice it allows police to send suspected drug users to compulsory treatment centres without judicial oversight and people who use drugs continue to face challenges in their interface with law enforcement which can negatively impact access to harm reduction and community-based treatment programs. Using policy desk research combined with indepth interviews with 14 key informants from people representing a range of relevant Vietnamese government (n = 10) and non-government agencies (n = 4), this paper explores some insights and considerations into how decriminalisation of drug use in the amended law was implemented. We explore key informant perspectives into how the decriminalisation amendment could be implemented more effectively in order to improve health outcomes for people who use drugs in Vietnam through re-envisioned police protocols and practices. Findings show that while decriminalising drug use in Vietnam was designed as a progressive and health-orientated drug policy, the ongoing disconnect between the health intent of the policy and the police-led oversight of its implementation in the community persists. Part of this disconnect is explained by the lack of training and clear protocols that would enhance the police in their ability to contribute to the health intent of the policy rather than continue to view drug use through a drug law enforcement only lens. The paper calls for further collaboration across policing and the health and community-based organisations delivering services for people who use drugs. We suggest that through developing a deeper understanding of the interplay between policing and the implementation of harm reduction policy and programs, decriminalisation can co-exist within a broader and deeply entrenched drug control strategy in Vietnam.

Bridged Analogues for p53-Dependent Cancer Therapy Obtained by S-Alkylation.

A small library of anticancer, cell-permeating, stapled peptides based on potent dual-specific antagonist of p53-MDM2/MDMX interactions, PMI-N8A, was synthesized, characterized and screened for anticancer activity against human colorectal cancer cell line, HCT-116. Employed synthetic modifications included: S-alkylation-based stapling, point mutations increasing hydrophobicity in key residues as well as improvement of cell-permeability by introduction of polycationic sequence(s) that were woven into the sequence of parental peptide. Selected analogue, ArB14Co, was also tested in vivo and exhibited potent anticancer bioactivity at the low dose (3.0 mg/kg). Collectively, our findings suggest that application of stapling in combination with rational design of polycationic short analogues may be a suitable approach in the development of physiologically active p53-MDM2/MDMX peptide inhibitors.

Grifonin-1: a small HIV-1 entry inhibitor derived from the algal lectin, Griffithsin.

BACKGROUND: Griffithsin, a 121-residue protein isolated from a red algal Griffithsia sp., binds high mannose N-linked glycans of virus surface glycoproteins with extremely high affinity, a property that allows it to prevent the entry of primary isolates and laboratory strains of T- and M-tropic HIV-1. We used the sequence of a portion of griffithsin's sequence as a design template to create smaller peptides with antiviral and carbohydrate-binding properties. METHODOLOGY/RESULTS: The new peptides derived from a trio of homologous ß-sheet repeats that comprise the motifs responsible for its biological activity. Our most active antiviral peptide, grifonin-1 (GRFN-1), had an EC50 of 190.8±11.0 nM in in vitro TZM-bl assays and an EC(50) of 546.6±66.1 nM in p24gag antigen release assays. GRFN-1 showed considerable structural plasticity, assuming different conformations in solvents that differed in polarity and hydrophobicity. Higher concentrations of GRFN-1 formed oligomers, based on intermolecular ß-sheet interactions. Like its parent protein, GRFN-1 bound viral glycoproteins gp41 and gp120 via the N-linked glycans on their surface. CONCLUSION: Its substantial antiviral activity and low toxicity in vitro suggest that GRFN-1 and/or its derivatives may have therapeutic potential as topical and/or systemic agents directed against HIV-1.

Oxpholipin 11D: an anti-inflammatory peptide that binds cholesterol and oxidized phospholipids.

BACKGROUND: Many gram-positive bacteria produce pore-forming exotoxins that contain a highly conserved, 12-residue domain (ECTGLAWEWWRT) that binds cholesterol. This domain is usually flanked N-terminally by arginine and C-terminally by valine. We used this 14-residue sequence as a template to create a small library of peptides that bind cholesterol and other lipids. METHODOLOGY/RESULTS: Several of these peptides manifested anti-inflammatory properties in a predictive in vitro monocyte chemotactic assay, and some also diminished the pro-inflammatory effects of low-density lipoprotein in apoE-deficient mice. The most potent analog, Oxpholipin-11D (OxP-11D), contained D-amino acids exclusively and was identical to the 14-residue design template except that diphenylalanine replaced cysteine-3. In surface plasmon resonance binding studies, OxP-11D bound oxidized (phospho)lipids and sterols in much the same manner as D-4F, a widely studied cardioprotective apoA-I-mimetic peptide with anti-inflammatory properties. In contrast to D-4F, which adopts a stable alpha-helical structure in solution, the OxP-11D structure was flexible and contained multiple turn-like features. CONCLUSION: Given the substantial evidence that oxidized phospholipids are pro-inflammatory in vivo, OxP-11D and other Oxpholipins may have therapeutic potential.

Retrocyclins kill bacilli and germinating spores of Bacillus anthracis and inactivate anthrax lethal toxin.

Theta-defensins are cyclic octadecapeptides encoded by the modified alpha-defensin genes of certain nonhuman primates. The recent demonstration that human alpha-defensins could prevent deleterious effects of anthrax lethal toxin in vitro and in vivo led us to examine the effects of theta-defensins on Bacillus anthracis (Sterne). We tested rhesus theta-defensins 1-3, retrocyclins 1-3, and several analogues of RC-1. Low concentrations of theta-defensins not only killed vegetative cells of B. anthracis (Sterne) and rendered their germinating spores nonviable, they also inactivated the enzymatic activity of anthrax lethal factor and protected murine RAW-264.7 cells from lethal toxin, a mixture of lethal factor and protective antigen. Structure-function studies indicated that the cyclic backbone, intramolecular tri-disulfide ladder, and arginine residues of theta-defensins contributed substantially to these protective effects. Surface plasmon resonance studies showed that retrocyclins bound the lethal factor rapidly and with high affinity. Retrocyclin-mediated inhibition of the enzymatic activity of lethal factor increased substantially if the enzyme and peptide were preincubated before substrate was added. The temporal discrepancy between the rapidity of binding and the slowly progressive extent of lethal factor inhibition suggest that post-binding events, perhaps in situ oligomerization, contribute to the antitoxic properties of retrocyclins. Overall, these findings suggest that theta-defensins provide molecular templates that could be used to create novel agents effective against B. anthracis and its toxins.