Adapting and Scaling a Digital Health Intervention to Improve Maternal and Child Health Among Ethnic Minority Women in Vietnam Amid the COVID-19 Context: Protocol for the dMOM Project.

BACKGROUND: Due to interconnected structural determinants including low maternal health knowledge, economic marginalization, and remoteness from low-capacity health centers, ethnic minority women in remote areas of Vietnam face severe maternal, newborn, and child health (MNCH) inequities. As ethnic minorities represent 15% of the Vietnamese population, these disparities are significant. mMOM-a pilot mobile health (mHealth) intervention using SMS text messaging to improve MNCH outcomes among ethnic minority women in northern Vietnam-was implemented from 2013-2016 with promising results. Despite mMOM's findings, exacerbated MNCH inequities, and digital health becoming more salient amid COVID-19, mHealth has not yet been scaled to address MNCH among ethnic minority women in Vietnam. OBJECTIVE: We describe the protocol for adapting, expanding, and exponentially scaling the mMOM intervention qualitatively through adding COVID-19-related MNCH guidance and novel technological components (mobile app and artificial intelligence chatbots) and quantitatively through broadening the geographical area to reach exponentially more participants, within the evolving COVID-19 context. METHODS: dMOM will be conducted in 4 phases. (1) Drawing on a review of international literature and government guidelines on MNCH amid COVID-19, mMOM project components will be updated to respond to COVID-19 and expanded to include a mobile app and artificial intelligence chatbots to more deeply engage participants. (2) Using an intersectionality lens and participatory action research approach, a scoping study and rapid ethnographic fieldwork will explore ethnic minority women's unmet MNCH needs; acceptability and accessibility of digital health; technical capacity of commune health centers; gendered power dynamics and cultural, geographical, and social determinants impacting health outcomes; and multilevel impacts of COVID-19. Findings will be applied to further refine the intervention. (3) dMOM will be implemented and incrementally scaled across 71 project communes. (4) dMOM will be evaluated to assess whether SMS text messaging or mobile app delivery engenders better MNCH outcomes among ethnic minority women. The documentation of lessons learned and dMOM models will be shared with Vietnam's Ministry of Health for adoption and further scaling up. RESULTS: The dMOM study was funded by the International Development Research Centre (IDRC) in November 2021, cofacilitated by the Ministry of Health, and is being coimplemented by provincial health departments in 2 mountainous provinces. Phase 1 was initiated in May 2022, and phase 2 is planned to begin in December 2022. The study is expected to be complete in June 2025. CONCLUSIONS: dMOM research outcomes will generate important empirical evidence on the effectiveness of leveraging digital health to address intractable MNCH inequities among ethnic minority women in low-resource settings in Vietnam and provide critical information on the processes of adapting mHealth interventions to respond to COVID-19 and future pandemics. Finally, dMOM activities, models, and findings will inform a national intervention led by the Ministry of Health. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/44720.

SGN-CD228A Is an Investigational CD228-Directed Antibody-Drug Conjugate with Potent Antitumor Activity across a Wide Spectrum of Preclinical Solid Tumor Models.

SGN-CD228A is an investigational antibody-drug conjugate (ADC) directed to melanotransferrin (CD228, MELTF, MFI2, p97), a cell-surface protein first identified in melanoma. SGN-CD228A consists of a humanized antibody, hL49, with high specificity and affinity for CD228 that is stably conjugated to 8 molecules of the clinically validated microtubule-disrupting agent monomethyl auristatin E (MMAE) via a novel glucuronide linker. We performed comprehensive IHC studies, which corroborated published RNA sequencing data and confirmed low CD228 expression in normal tissues and high expression in several cancers, including melanoma, squamous non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), colorectal cancer, and pancreatic cancer. SGN-CD228A was efficiently internalized in various tumor cell types, and its cytotoxic activity was dependent on CD228 expression and internalization and intrinsic sensitivity to the MMAE payload. Compared with the valine-citrulline dipeptide linker, the novel glucuronide linker increased the cellular retention of MMAE in vitro and conferred improved antitumor activity against melanoma cell lines in vitro and in vivo. In addition, SGN-CD228A was active across melanoma, TNBC, and NSCLC cell line- and patient-derived xenograft models with heterogeneous antigen expression. In vivo, CD228 expression was important for response to SGN-CD228A but was not well correlated across all tumor types, suggesting that other factors associated with ADC activity are important. Overall, SGN-CD228A is a CD228-directed, investigational ADC that employs innovative technology and has compelling preclinical antitumor activity. SGN-CD228A is investigated in a Phase I clinical trial (NCT04042480) in patients with advanced solid tumors.

Helicobacter pylori Eradication Efficacy of Therapy Based on the Antimicrobial Susceptibility in Children with Gastritis and Peptic Ulcer in Mekong Delta, Vietnam.

BACKGROUND: The efficacy of Helicobacter pylori (H. pylori) eradication therapy for children is currently low, and antibiotic resistance is a significant cause of treatment failure. The purpose of this study was to evaluate the H. pylori eradication efficacy of therapy based on antimicrobial susceptibility in pediatric patients with gastritis and peptic ulcer. METHODS: This study was conducted at Can Tho Children's Hospital and Can Tho University of Medicine and Pharmacy Hospital between March 2019 and April 2022. We performed an upper gastrointestinal endoscopy, cultured H. pylori from biopsies of gastric mucosa, determined antibiotic sensitivities to H. pylori by the E-test method, and treated eradication based on the antibiotic susceptibilities of bacteria. After at least 4 weeks of eradication therapy, we assessed the effectiveness of treatment with a breath test. RESULTS: Among 237 children recruited in this study, 48.9% were boys and 51.1% were girls, and the mean age was 10.03 ± 2.53 years. We determined that 80.6% of H. pylori were resistant to clarithromycin, as well as amoxicillin, metronidazole, levofloxacin, and tetracycline, at 71.7%, 49.4%, 45.1%, and 11.4%, respectively. The overall eradication rate of H. pylori was 83.1% (172/207). Among therapies tailored to antimicrobial susceptibility, the bismuth quadruple regimen achieved the greatest success, but the efficacy of triple therapy with esomeprazole + AMX + CLR/MTZ was low. CONCLUSIONS: Tailored eradication therapy was highly successful in our study but did not achieve over 90%. We recommend that in countries with a high prevalence of antibiotic resistance in H. pylori strains, particularly where the amoxicillin-resistance rate of H. pylori is high, therapy tailored to antimicrobial susceptibility should be used as first-line therapy, and bismuth and tetracycline should be added to enhance the eradication efficacy in children.

Clinically relevant preservation conditions for mesenchymal stem/stromal cells derived from perinatal and adult tissue sources.

The interplay between mesenchymal stem/stromal cells (MSCs) and preservation conditions is critical to maintain the viability and functionality of these cells before administration. We observed that Ringer lactate (RL) maintained high viability of bone marrow-derived MSCs for up to 72 h at room temperature (18°C-22°C), whereas adipose-derived and umbilical cord-derived MSCs showed the highest viability for 72 h at a cold temperature (4°C-8°C). These cells maintained their adherence ability with an improved recovery rate and metabolic profiles (glycolysis and mitochondrial respiration) similar to those of freshly harvested cells. Growth factor and cytokine analyses revealed that the preserved cells released substantial amounts of leukaemia inhibitory factors (LIFs), hepatocyte growth factor (HGF) and vascular endothelial growth factor-A (VEGF-A), as well as multiple cytokines (eg IL-4, IL-6, IL-8, MPC-1 and TNF-α). Our data provide the simplest clinically relevant preservation conditions that maintain the viability, stemness and functionality of MSCs from perinatal and adult tissue sources.

Succinylcholine-Induced Rhabdomyolysis in Adults: Case Report and Review of the Literature.

PURPOSE: A case of succinylcholine (SCh) and sevoflurane as a probable cause of rhabdomyolysis in an adult is presented, along with a review of the relevant literature and strategies for prevention. SUMMARY: A nondiabetic, morbidly obese 32-year-old female developed rhabdomyolysis after administration of SCh and sevoflurane for diagnostic procedures of 30 minutes' duration. Thirty-three hours following anesthesia, the patient developed diffuse muscle tenderness and progressive weakness with a creatinine kinase (CK) of 4319 U/L. Urinalysis findings indicated contamination, a white blood cells of 12.1 × 103/µL was stress induced, while all other labs were normal. Following 26 hours of intravenous fluids, the patient's CK decreased to 1243 U/L, with pain responsive to acetaminophen and improved mobility, resulting in discharge. With a lack of reasonable alternative causes and a temporal association of symptoms, procedural medication-induced rhabdomyolysis was suspected. Based on Naranjo scale evaluation, SCh and sevoflurane were probable causes of rhabdomyolysis. We reviewed the literature for SCh-induced rhabdomyolysis among adults and found 10 cases. The majority of patients received halogenated anesthesia (HA) and prophylaxis for SCh myopathy, with no known personal or family history of neuromuscular disorders (NMD) reported. CONCLUSION: Rhabdomyolysis was observed in a woman following the administration of SCh and sevoflurane for diagnostic procedures lasting 30 minutes. While avoidance is possible in adults with histories of NMDs, a high index of suspicion for occurrence of rhabdomyolysis is needed whenever combining SCh with HA in all adults.

A Vietnamese human genetic variation database.

Large scale human genome projects have created tremendous human genome databases for some well-studied populations. Vietnam has about 95 million people (the 14th largest country by population in the world) of which more than 86% are Kinh people. To date, genetic studies for Vietnamese people mostly rely on genetic information from other populations. Building a Vietnamese human genetic variation database is a must for properly interpreting Vietnamese genetic variants. To this end, we sequenced 105 whole genomes and 200 whole exomes of 305 unrelated Kinh Vietnamese (KHV) people. We also included 101 other previously published KHV genomes to build a Vietnamese human genetic variation database of 406 KHV people. The KHV database contains 24.81 million variants (22.47 million single nucleotide polymorphisms (SNPs) and 2.34 million indels) of which 0.71 million variants are novel. It includes more than 99.3% of variants with a frequency of >1% in the KHV population. Noticeably, the KHV database revealed 107 variants reported in the human genome mutation database as pathological mutations with a frequency above 1% in the KHV population. The KHV database (available at https://genomes.vn) would be beneficial for genetic studies and medical applications not only for the Vietnamese population but also for other closely related populations.

Perceptions and experiences of perinatal mental disorders in rural, predominantly ethnic minority communities in northern Vietnam.

BACKGROUND: Preliminary research has suggested that perinatal mental disorders (PMDs), including post-partum depression, are prevalent in Vietnam. However the extent to which these disorders are recognized at the community level remains largely undocumented in the literature. PMDs have also never been investigated within Vietnam's significant ethnic minority populations, who are known to bear a greater burden of maternal and infant health challenges than the ethnic majority. OBJECTIVE: To investigate knowledge and perceptions of PMDs and their treatments at the community level in a rural, predominantly ethnic minority region of northern Vietnam. METHODS: Qualitative semi-structured interviews were conducted on the topic of common PMDs. Participant groups were primary health workers (PHWs) working at local community health centers, and pregnant or postpartum women enrolled in a program for maternal and infant health that was not mental health related. Interviews included vignette scenarios that asked respondents to interpret cases of women experiencing PMDs, as well as open-ended questions about mental disorders and their treatments. RESULTS: Twelve PHWs and 14 perinatal women completed the study. Major themes that emerged from the interviews included (1) Family relationships impact psychological well-being, (2) Nutrition contributes to perinatal mental health, (3) Both traditional and western medicine play roles in perinatal health, (4) There was a lack of personal experience with women experiencing PMDs, (5) Descriptions of mental health symptoms focused on behaviours, and (6) Community care is the primary mental health support. CONCLUSIONS: PHWs reported having almost never treated a woman with a PMD. However, anecdotal evidence from the women interviewed suggests that there are incidents of mental disorders during the perinatal period that go largely unaddressed. Willingness to present to primary care appears to be high, and presents an opportunity to address this need by training PHWs in effective screening, treatment, and referral. Such training should account for culturally specific presentations of mental disorders as well as the importance of the patient's social context. To the best of the author's knowledge, this research presents the first evidence of a PMD burden within Vietnam's ethnic minority communities.

ERG Activates the YAP1 Transcriptional Program and Induces the Development of Age-Related Prostate Tumors.

The significance of ERG in human prostate cancer is unclear because mouse prostate is resistant to ERG-mediated transformation. We determined that ERG activates the transcriptional program regulated by YAP1 of the Hippo signaling pathway and found that prostate-specific activation of either ERG or YAP1 in mice induces similar transcriptional changes and results in age-related prostate tumors. ERG binds to chromatin regions occupied by TEAD/YAP1 and transactivates Hippo target genes. In addition, in human luminal-type prostate cancer cells, ERG binds to the promoter of YAP1 and is necessary for YAP1 expression. These results provide direct genetic evidence of a causal role for ERG in prostate cancer and reveal a connection between ERG and the Hippo signaling pathway.

Targeted inhibition of cell-surface serine protease Hepsin blocks prostate cancer bone metastasis.

The development of effective therapies inhibiting prostate cancer progression and metastasis may substantially impact prostate cancer mortality and potentially reduce the rates of invasive treatments by enhancing the safety of active surveillance strategies. Hepsin (HPN) is a cell surface serine protease amplified in a subset of human sarcomas (7.2%), as well as in ovarian (10%), lung adeno (5.4%), lung squamous cell (4.5%), adenoid cystic (5%), breast (2.6%), uterine (1.7%) and colon (1.4%) carcinomas. While HPN is not amplified in prostate cancer, it is one of the most prominently overexpressed genes in the majority of human prostate tumors and genetic experiments in mice indicate that Hepsin promotes prostate cancer metastasis, particularly metastasis to the bone marrow. We report here the development, analysis and animal trial of the small-molecule Hepsin inhibitor HepIn-13. Long-term exposure to HepIn-13 inhibited bone, liver and lung metastasis in a murine model of metastatic prostate cancer. These findings indicate that inhibition of Hepsin with small-molecule compounds could provide an effective tool for attenuation of prostate cancer progression and metastasis.

Cigarette smoking and drinking behavior of migrant adolescents and young adults in Hanoi, Vietnam.

PURPOSE: There has been a large migration from rural to urban areas in much of the developing world. In the past, this was less true in Vietnam, which remains largely agricultural; however, since the 1990s, economic reforms and loosening of government policies that had previously limited movement have led to a large increase in this rural to urban population movement. Risky health behaviors have been found among migrants in many other settings. The purpose of this research was to determine whether migrant adolescents and young adults in the city of Hanoi are more or less likely than local ones to engage in cigarette smoking and alcohol drinking health risk behaviors, to identify factors associated with these behaviors, and to suggest interventions to reduce these health risk behaviors among the study population. METHODS: A cross-sectional survey of 4,550 adolescents and young adults aged 15-24 years was conducted in urban Hanoi in 2006. This study examines current use of cigarettes and alcohol by migration status using multivariate logistic regressions. RESULTS: Cigarette smoking and drinking alcohol are male phenomena. The prevalence of cigarette smoking and alcohol drinking is high among adolescents and young adults in Hanoi and is more common among migrants who came from rural areas of other provinces than nonmigrants in the city. However, multivariate analysis revealed that migrants were neither more likely to smoke cigarettes nor drink alcohol than nonmigrants after controlling for other factors, such as age, full-time worker status, depression, and having close friends who smoke and/or drink. CONCLUSIONS: The results suggest that interventions aiming at smoking and/or drinking reduction should pay more attention to adolescents, especially males, changing health risk behaviors at school and at work, and peer influence than their migration status.

Recurrent intussusception in infants.

AIM: Clinical features to identify infants at increased risk of recurrence after a primary episode of intussusception (IS) are poorly defined. METHODS: Prospective study of the clinical presentation, treatment and outcome in infants <2 years presenting with acute IS to the National Hospital of Pediatrics, Hanoi, over a 14-month period (1 November 2002 to 31 December 2003). A retrospective review of medical records was performed to verify complete patient ascertainment. RESULTS: Five hundred ninety-eight children were recruited, including 513 (86%) with a primary episode only and 53 (9%) with ≥1 recurrent episodes. Another 32 (5%) infants presented with recurrent IS, but the primary episode of IS occurred outside the study period. Estimated recurrence risk at 6 months following a primary episode was 14%. A pathological lead point was rare in primary (n= 1) and recurrent IS (n= 1). Most infants were successfully treated with enema reduction. CONCLUSIONS: This study describes the natural history of recurrent IS in infants and may assist in interpreting data from post-marketing surveillance following introduction of rotavirus vaccines.

Identification of secreted glycoproteins of human prostate and bladder stromal cells by comparative quantitative proteomics.

BACKGROUND: Functional development of the prostate is governed by stromal mesenchyme induction and epithelial response. Stromal/epithelial signaling can be mediated through direct cell-cell contact and diffusible factors and their cell surface receptors. These inducers are likely secreted or membrane-associated extracellular proteins. Given the importance of intercellular communication, it is possible that diseases like cancer could arise from a loss of this communication. One approach to gain a molecular understanding of stromal cells is to identify, as a first step, secreted stromal signaling factors. We proposed to do this by comparative analysis between bladder and prostate. METHODS: Secreted proteins were identified from cultured normal prostate and bladder stromal mesenchyme cells by glycopeptide-capture method followed by mass spectrometry. Differences in protein abundance between prostate and bladder were quantified from calculated peptide ion current area (PICA) followed by Western validation. Functional and pathway analyses of the proteins were carried out by Gene Ontology (GO) and Teranode software. RESULTS: This analysis produced a list of 116 prostate and 84 bladder secreted glycoproteins with ProteinProphet probability scores > or =0.9. Stromal proteins upregulated in the prostate include cathepsin L, follistatin-related protein, neuroendocrine convertase, tumor necrosis factor receptor, and others that are known to be involved in signal transduction, extracellular matrix interaction, differentiation and transport. CONCLUSIONS: We have identified a number of potential proteins for stromal signaling and bladder or prostate differentiation program. The prostate stromal/epithelial signaling may be accomplished through activation of the ECM-receptor interaction, complement and coagulation cascades, focal adhesion and cell adhesion pathways.

Influenza A H5N1 clade 2.3.4 virus with a different antiviral susceptibility profile replaced clade 1 virus in humans in northern Vietnam.

BACKGROUND: Prior to 2007, highly pathogenic avian influenza (HPAI) H5N1 viruses isolated from poultry and humans in Vietnam were consistently reported to be clade 1 viruses, susceptible to oseltamivir but resistant to amantadine. Here we describe the re-emergence of human HPAI H5N1 virus infections in Vietnam in 2007 and the characteristics of the isolated viruses. METHODS AND FINDINGS: Respiratory specimens from patients suspected to be infected with avian influenza in 2007 were screened by influenza and H5 subtype specific polymerase chain reaction. Isolated H5N1 strains were further characterized by genome sequencing and drug susceptibility testing. Eleven poultry outbreak isolates from 2007 were included in the sequence analysis. Eight patients, all of them from northern Vietnam, were diagnosed with H5N1 in 2007 and five of them died. Phylogenetic analysis of H5N1 viruses isolated from humans and poultry in 2007 showed that clade 2.3.4 H5N1 viruses replaced clade 1 viruses in northern Vietnam. Four human H5N1 strains had eight-fold reduced in-vitro susceptibility to oseltamivir as compared to clade 1 viruses. In two poultry isolates the I117V mutation was found in the neuraminidase gene, which is associated with reduced susceptibility to oseltamivir. No mutations in the M2 gene conferring amantadine resistance were found. CONCLUSION: In 2007, H5N1 clade 2.3.4 viruses replaced clade 1 viruses in northern Vietnam and were susceptible to amantadine but showed reduced susceptibility to oseltamivir. Combination antiviral therapy with oseltamivir and amantadine for human cases in Vietnam is recommended.