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Introduction Because blaCTX-M is responsible for resistance of bacteria to the third generation cephalosporins, location of blaCTX-M could be a good indicator for classifying bacterial isolates harboring blaCTX-M in molecular epidemiology. However, determination of blaCTX-M location has been difficult when multiple copies of ISEcp1 were found on bacterial genome. We aimed to establish a high-throughput analytical method for upstream genetic structures (UGS) of ISEcp1 to facilitate determination of blaCTX-M location. Methods Extracted DNA samples obtained from 168 Escherichia coli isolates possessing blaCTX-M were digested by restriction enzyme, HaeIII, and the digested DNA fragments were ligated with homemade barcode adaptors. Then, DNA fragments containing UGS of ISEcp1 were amplified and subjected to the Nanopore sequencer. Results Nucleotide sequences and locations of 168 UGSs obtained from the examined E. coli isolates were determined. Among the 168 determined UGSs, 150 (89.3%) UGS were confirmed on plasmid and classified into eight types. Interestingly, coding sequence of ISEcp1 transposase gene in seven of the eight types were disrupted by IS26 insertion. The remaining 18 (10.7%) UGSs were observed in identical chromosomal region. The obtained nucleotide sequences the locations of UGSs were confirmed by conventional capillary sequencer and Southern blotting, respectively, and any discrepant result was not observed with these confirmation procedures. Conclusions Our results indicated that the established method was efficient for simultaneously determining at least 100 different UGS, and suggested that the determined UGSs of ISEcp1-blaCTX-M transposition unit was useful for classification of bacterial isolates harboring blaCTX-M.

Extended spectrum β-lactamases (ESBL)-producing Escherichia coli have been found in healthy individuals in Indonesia and Vietnam. The ISEcp1-bla CTX-M transposition unit of ESBL-producing bacterial isolates has been considered responsible for the production of CTX-M type ESBL and is important for the dissemination of bla CTX-M . This study aimed to characterize the upstream genetic structure (UGS) of E. coli isolates possessing bla CTX-M-1 group and/or bla CTX-M-9 group genes obtained from healthy individuals in Indonesia and Vietnam. A total of 501 CTX-M type ESBL-producing E. coli isolates possessing bla CTX-M-1 group and/or bla CTX-M-9 group genes were obtained from healthy individuals of the two countries in 2018. UGSs of the ISEcp1-bla CTX-M transposition unit of the 501 ESBL-producing E. coli isolates were amplified by barcode-adaptor-ligation-mediated PCR and analyzed using the Nanopore sequencer. The obtained sequence information was used to classify the UGSs of the ISEcp1-bla CTX-M transposition unit. From the 501 ESBL-producing E. coli isolates, 502 UGSs were obtained, which were classified into 85 UGS types based on the sequence. ISEcp1 of 359 (71.5%) of the 502 UGSs was disrupted by gene insertion, and ISEcp1-bla CTX-M transposition unit of most (87.1%) of the determined UGSs was confirmed as plasmidic. Only 6 (7.1%) of the 85 UGS types were common to both countries. Our results indicated that many different UGSs of ISEcp1-bla CTX-M transposition units were detected in Indonesia and Vietnam; hence, we suggest that structurally different kinds of plasmids harboring bla CTX-M were separately distributed in the two countries. This article is protected by copyright. All rights reserved.

Truc Thanh Thai,1 Thinh Huu Nguyen,2 Phuong Thu Thi Pham,3 Han Hy Thi Bui,4 Tam Ngoc Minh Bui2 1Faculty of Public Health, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam; 2Training and Scientific Research Department, University Medical Center Ho Chi Minh City, Ho Chi Minh City, Vietnam; 3Hospital for Rehabilitation - Occupational Diseases at Ho Chi Minh City, Ho Chi Minh City, Vietnam; 4Woolcock Institute of Medical Research, Hanoi, VietnamCorrespondence: Truc Thanh ThaiFaculty of Public Health, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, VietnamTel +84 908 381 266Email thaithanhtruc@ump.edu.vnTam Ngoc Minh BuiTraining and Scientific Research Department, University Medical Center Ho Chi Minh City, Ho Chi Minh City, VietnamTel +84 906 951 668Email tam.bnm@umc.edu.vnPurpose: Healthcare workers (HCWs) are a crucial resource in the battle against the COVID-19 pandemic but are vulnerable to both SARS-CoV-2 infection and negative psychological consequences. This study evaluated HCWs’ emotions, stressor experiences and coping strategies during the pandemic.Methods: A cross-sectional study was conducted among HCWs at the University Medical Center in Ho Chi Minh City. The questionnaire was adapted from the MERS-CoV Staff Questionnaire to measure HCWs’ emotions, stressor experiences and coping strategies during the COVID-19 pandemic.Results: Among the 1423 participants eligible in the data analysis, the majority were female (71.1%) with a mean age of 34.2 (standard deviation 7.8) years. While most participants reported that they did their job because of their professionalism and duty as HCWs (87.4%), a high number reported feeling nervous and scared (86.0%). Most participants reported worry about transmitting SARS-CoV-2 to their families or friends (76.6%) and concern that a small mistake or lapse in concentration could infect themselves and others (76.7%). The most common coping strategies were following strict personal protective measures (95.3%), avoiding going out (92.5%) and reading about SARS-CoV-2 (92.3%). Females who had a higher educational level and less than 5-years work experience and those who worked at clinical departments and subclinical departments were more vulnerable.Conclusion: This study indicates an urgent need for psychological support for HCWs, especially for those at high risk of having stress. Interventions and support should utilize psychological resources and approaches effectively to adapt to the new situation during the COVID-19 pandemic.Keywords: stressor experience, coping strategy, motivational factors, health care worker, COVID-19

Introduction: Insomnia is a common disease in all societies and age groups. Among them, medical students are one of the population most susceptible to sleep problems. Studies from many countries have shown high prevalence of insomnia among medical students. Sleep diary is the gold standard for evaluating subjective insomnia and other sleep disorders. This research aims to study the prevalence of insomnia in Vietnamese medical students, associated factors, and their sleep patterns. Method: In a cross-sectional survey using stratified random sampling, a total of 176 medical students was recruited, each completed a self-administered questionnaire and a 7-consecutive-day sleep diary. Demographic data and lifestyle factors were obtained from the questionnaire, while sleep patterns and quality were collected from the sleep diary. We performed data analysis using SPSS ver 22, p

A high prevalence of mental disorders in adolescents has been reported worldwide, but little is known about mental health literacy in this population, particularly in developing countries. The goal of this study was to evaluate mental health literacy level and help-seeking preferences in high school students in Ho Chi Minh City, Vietnam. These two variables were also compared between students who had stress, anxiety and depression with students who did not. A cross-sectional study was conducted with 1094 students across 27 classes at three high schools. Students completed a self-report questionnaire that included validated scales such as the Depression Anxiety Stress Scale (DASS-21), the Mental Health Literacy Scale (MHLS) and the General Help-Seeking Questionnaire. Based on the DASS-21, the prevalence of students reporting symptoms of stress, depression and anxiety was 36.1%, 39.8% and 59.8%, respectively. The mean MHLS score was 104.12 (SD = 10.09) and was significantly lower in students who had symptoms of depression. The most common help-seeking preferences for mental illness were friends, classmates and relatives or family members. Help-seeking preferences were almost identical among students with stress, anxiety or depression. While Vietnamese high school students had high levels of symptoms of stress, depression and anxiety and moderate levels of mental health literacy, non-professionals were preferred as their first help-seeking choice. Our findings revealed the need for routine school-based mental health screening and referral activities as well as mental health education programs for high school students in Vietnam.

Truc Thanh Thai,1 Mairwen K Jones,2 Thao Phuong Nguyen,1 Thao Van Pham,1 Han Hy Thi Bui,3 Loan Xuan Kim,1 Tap Van Nguyen4 1Faculty of Public Health, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City Vietnam; 2Faculty of Medicine & Health, The University of Sydney, Sydney, New South Wales, Australia; 3Woolcock Institute of Medical Research Vietnam, Ho Chi Minh City, Vietnam; 4Department of Medicine and Pharmacy, Tra Vinh University, Tra Vinh, VietnamCorrespondence: Truc Thanh ThaiFaculty of Public Health, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, VietnamTel +84 908381266Email thaithanhtruc@ump.edu.vnTap Van NguyenDepartment of Medicine and Pharmacy, Tra Vinh University, Tra Vinh, VietnamTel +84 914064340Email nvtap@tvu.edu.vnPurpose: Research conducted across different countries has consistently identified non-suicidal self-injury (NSSI) to be a common and significant public health problem. This study examined the prevalence, associated factors and functions of NSSI, among a large sample of Vietnamese adolescents.Methods: A total of 1316 high school students (15– 18 years old, 63.3% female) across urban and suburban areas in Ho Chi Minh City, participated in this cross-sectional study. NSSI was assessed by the Functional Assessment of Self-Mutilation.Results: Almost half (43.9%) of the adolescents engaged in at least one type of NSSI within the preceding 12-month period and more than one quarter (26.1%) engaged in multiple types of NSSI. Hitting self on purpose (23.1%), picking at a wound (17.0%), or biting self (16.7%) were the most frequent behaviours. Severe forms of NSSI such as scraping, burning or erasing skin were reported by 17.2%. The most common functions for NSSI were to stop bad feelings (56.0%), to punish self (48.7%), to get control of a situation (44.0%) and to feel relaxed (42.2%). Symptoms of depression, anxiety and stress were significant factors associated with NSSI, particularly for participants who engaged in moderate/severe NSSI and multiple types of NSSI.Conclusion: High rates of NSSI were found in Vietnamese adolescents. There is a pressing need for the development and implementation of effective interventions to reduce NSSI. Strategies that promote positive mental health and reduce symptoms of depression, anxiety and stress as well as approaches that help adolescents manage their internal emotions are likely to be beneficial.Keywords: non-suicidal self-injury, functions, high school students, adolescents, associated factors, Vietnam

Background. Preservation and restoration of skin integrity following surgery is paramount for optimal patient wound healing outcomes. Acute wounds such as incisional wounds, skin tears, trauma or burn injury cause pain, reduce quality of life and are a considerable economic burden to the Australian healthcare system. Despite considerable advances in surgical technique and even with a panacea of innovative novel wound dressings, our scientific and clinical understanding of wound healing prevention and management of acute wound complications continue to present a considerable challenge to clinicians and policy makers. Understanding the gaps in knowledge and identifying clinical practice deficits are key for prevention and management of acute wounds. Aims. This scoping review aims to (i) map current research evidence and outcomes in acute wounds management, (ii) map current research evidence and outcomes in acute wounds prevention and (iii) determine research gaps in acute wound research relevant to Australia. Methods. The framework for this scoping review will utilise the PRISMA-ScR framework developed by Tricco et al.1. We will search the following databases – Medline, CINAHL, Embase, Joanna Briggs Institute (JBI), Cochrane Library and PubMed from January 2010 to March 2021. Trial registries (e.g. ISRCTN, ANZCTR and clinicaltrials.gov) and websites and publications of professional associations for wound care will also be searched. Two reviewers will independently screen all titles, abstracts and full text for articles to include. Conflicts will be solved by a third reviewer. This scoping review will include both qualitative and quantitative studies on acute wounds conducted in Australia. We will extract data from eligible articles and results will be grouped according to area of research and synthesised in a narrative review. Ethics and dissemination. As we will use data (i.e., journal articles) from publicly available platforms this scoping review does not require ethical approval. Findings will be disseminated through a peer-reviewed journal and conference presentation and social media platforms.

High concentration of particulate matter (PM) threatens public health and the environment. Increasing traffic in the city is one of the main factors for increased PM in the air. Urban green spaces play an important role in reducing PM. In this study, the leaf surface and in-wax PM (sPM and wPM) accumulation were compared for 11 plant species widely used for landscaping in South Korea. In addition, biochemical characteristics of leaves (ascorbic acid chlorophyll content, leaf pH, and relative water content) were analyzed to determine air pollution tolerance. Plant species suitable for air quality improvement were selected based on their air pollution tolerance index (APTI) and anticipated performance index (API). Results showed a significant difference according to the accumulation of sPM and wPM and the plant species. PM accumulation and APTI showed a positive correlation. Pinus strobus showed the highest PM accumulation and APTI values, while Cercis chinensis showed the lowest. In 11 plants, API was divided into five groups. Pinus densiflora was classified as the best group, while Cornus officinalis and Ligustrum obtusifolium were classified as not recommended.

This study investigated whether screening for symptoms of mental disorders and referral to mental health services was associated with decreased depression symptoms among people living with HIV/AIDS (PLHIV) in Vietnam. Four hundred PLHIV (63.5% male, mean age 34.8 (SD = 6.8) years) at two outpatient clinics in Ho Chi Minh City were interviewed by psychiatrists and also completed the Center for Epidemiologic Studies-Depression scale (CES-D). One hundred and seventy-four (43.5%) were identified with symptoms of a range of mental illnesses, including depression, anxiety, alcohol use disorder, substance use disorder and HIV associated dementia and were referred to mental health services. Of the 174 PLHIV referred, 162 (93%) returned and completed the CES-D three months later and 125 of these 162 (77%) had attended a mental health service and undertaken treatment. A significant improvement was found in the mean CES-D scores of the 125 attenders from baseline (M = 19.0, SD = 7.5) to month three (M = 11.7, SD = 7.9, p < 0.001). PLHIV who had attended a mental health service and undertaken treatment demonstrated a greater reduction of mean scores on the CES-D compared to PLHIV who had either received a referral but not attended a mental health service to undertake treatment, or not been referred initially.

This literature review aimed to provide a narrative review of evidence on validity of clinical and microbial indicators of infection and to gain insights into the diagnosis of infection in chronic leg ulcers (CLUs). A search was conducted in Cinahl, Medline, the Cochrane Library databases, Embase, Web of Science, ScienceDirect, Pubmed, PsycINFO, ProQuest dissertations, and Google Scholar from January 1990 to July 2017. The inclusion criteria were original studies, systematic reviews, and consensus documents focused on "infection" in CLUs, English language, clinical and community settings, and human. The reviewed studies were inconsistent in criteria for infection between investigated wound types and lack of specificity regarding wound types. There were few studies investigating the criteria for diagnosis of infection in leg ulcers. The identification of leg ulcer infection still remains problematic and relies on out-of-date and not uniform evidence. Literature in this area was mostly limited to level III and IV evidence based on The Australian National Health and Medical Research Council Levels of Evidence, or expert opinion. This literature review showed seven clinical signs and symptoms that could be diagnostic for infection in CLUs, including: new, increased, or altered ulcer pain; malodour; increased ulcer area; wound breakdown, delayed or non-healing; and erythema and increased local temperature, whilst the microbial indicators used to diagnose infected leg ulcers were varied and regarded as less important.

Aims In RCT of adults with decompensated cirrhosis, GCSF mobilizes hematopoietic stem cells HSC and improves short-term outcome. An FDA-IND for sequential Kasai-GCSF treatment in biliary atresia BA was approved. This phase 1 study examines GCSF safety in Kasai subjects. Preliminary short-term outcome was evaluated. Methods GCSF (Neupogen) at 5 or 10 μg/kg (n = 3/group) was given in 3 daily doses starting on day 3 of Kasai surgery (NCT03395028). Serum CD34+ HSC cell counts, and 1-month of GCSF-related adverse events were monitored. The 6-months Phase 1 clinical outcome was compared against 10 subsequent post Phase 1 Kasai patients who did not receive GCSF. Results With GCSF, WBC and platelet count transiently increased, LFT and serum creatinine remained stable. Reversible splenic enlargement (by 8.5–20%) occurred in 5/6 subjects. HSC count increased 12-fold and 17.5-fold for the 5 μg/kg and10 ug/kg dose respectively; with respective median total bilirubin levels for GCSF vs no-GCSF groups of 55 vs 91 μM at 1 month, p = 0.05; 15 vs 37 μM at 3 months, p = 0.24); and the 6-months cholangitis frequency of 40% vs 90%, p = 0.077. Conclusions GCSF safely mobilizes HSC in Kasai infants and may improve short-term biliary drainage and cholangitis. Phase 2 efficacy outcome of GCSF adjunct therapy for sequential Kasai and GCSF is pending.

To provide an analysis of papers published by the Journal of Cancer Survivorship (JCSU) from March 1, 2007 (its inception) until December 31, 2020. Characteristics (locations, study type, cancer type, keywords assigned by original authors) of all included articles were extracted into EndNote X9 and were coded and analyzed using Excel, NVivo v.R1.3 and VOSviewer, v.1.616. Journal Impact Factor and citation counts of each manuscript were downloaded from Clarivate Journal Citation Reports and Scopus®, respectively. Published papers are predominantly from the USA, Australia, and the UK. While breast cancer continues to be the dominant cancer type, a range of different cancer types and populations with mixed-cancer types have been addressed in the journal. Cross-sectional designs were the most used. JCSU’s impact factor experienced a steady growth between 2011 and 2015 and stabilized over recent years (2016–2020), at 3.296 (1 year) and 3.830 (5 years). Keyword co-occurrence analyses indicated prominent themes including quality of life, physical activity, late effects, follow-up care, and psychosocial aspects of cancer survivorship. JCSU has made a significant contribution thus far by disseminating knowledge in cancer survivorship. This paper provides insights of JCSU’s success to date and recommends further diversification and directions for practice areas that are novel or have received less attention by the cancer survivorship community. This journal stands ready to publish new information that informs the cancer survivorship community on the multidimensional nature of cancer and facilitates translation into quality care across many different settings and across the globe.

Background:Data about the risk factors and pancreatic cancer in developing countries remain limited. We investigated for the first time the role of a number of risk factors (family cancer history, smoking, alcohol consumption, diabetes, inflammation disease, HBV infection) associated with pancreatic cancer among Vietnamese patients.Methods:We included all patients hospitalized at 4 Northern Vietnamese hospitals (Vietnam National Cancer Hospital, Bach Mai, Viet Duc, Thai Nguyen) and diagnosed with pancreatic cancer during the period from 2017 to 2019. Risk factors of eligible patients were collected and assessed the associations using a matched control study and logistic regression model analysis.Results:We identified 196 patients with diagnosis of pancreatic cancer of which 114 males and 82 females. The average age of the patient at the time of diagnosis was 58.28 years (standard deviation of 12.94, ranging from 25 to 87). Most of patients were diagnosed at advanced stage (85%). Smoking, diabetes, inflammation disease significantly increased the cancer risks (OR and 95% CI were 2.42 (1.38-4.37), 3.09 (1.54-6.68), 2.21 (1.42-3.45), respectively). HBV infection demonstrated a significant link with pancreatic cancer in univariate model (OR = 2.94 (1.08-9.36)), but not in multivariate model. However, cancer family history and alcohol drinkers did not show any significantly increased risk related to pancreatic cancer.Conclusions:Our finding showed smoking, diabetes, inflammation disease significantly increased the risk of pancreatic cancer in Vietnam.

Background: Tumor budding (Bd) has been demonstrated to be a promising prognostic factor in many carcinomas and in gastric cancer. It may represent an optimal additional parameter that is helpful for risk stratification in gastric adenocarcinoma. Hence, the present research was designed to predict the survival outcomes of gastric cancer in Vietnam, applying the tumor budding criteria of the International Tumor Budding Consensus Conference (ITBCC) 2016. Methods: The present study was conducted on 109 gastric cancer patients who underwent surgery but did not receive neo-adjuvant chemotherapy from 2012 to 2015. The patients’ clinicopathological features were recorded. Bd was evaluated according to the 2016 ITBCC criteria and classified as Bd1 (0–4 buds), Bd2 (5–9 buds), and Bd3 (≥10 buds) grades, in addition to being categorized into 2 main Bd groups: low (Results: Of all the patients, 22.9% were classified as Bd1, 31.2% as Bd2, and 45.9% as Bd3 grades. Furthermore, 54.1% patients were categorized into the low and 45.9% into the high Bd groups. Patients with Bd1 and Bd2 grades (the low Bd group) exhibited the best prognosis, with 5-year overall survival (OS) rates of 85.7%, 90.8%, and90.3%, respectively. Patients with Bd3 grade (the high Bd group exhibited the worst prognosis, and none of them lived for 5 years (p < 0.001). Similar to OS rates, disease-free survival (DFS) rates markedly reduced from the Bd1 to Bd3 grade: Bd1, 95.0%; Bd2, 84.7%; and Bd3, 0% (p < 0.001). Conclusion: Patients with different gastric cancer Bd grades exhibited significantly different OS and DFS rates. The present study findings suggest that the ITBCC criteria can be used to stratify Bd for the treatment and prognosis of gastric cancer patients in Vietnam.

Background Clonorchiasis, caused by the fish-borne trematode Clonorchis sinensis, is a neglected tropical disease and a public health issue in endemic countries. In Vietnam, an in-depth analysis of risk factors for the condition is missing up to now. This study aimed to determine the prevalence of C. sinensis infection and associated risk factors in rural communities in northern Vietnam. Methodology/Principal findings A cross-sectional survey was conducted in 4 communes in Yen Bai and Thanh Hoa provinces where clonorchiasis is known to be present and raw fish consumption is a common. Using a simple random sampling approach, stool was collected from 841 participants over 6 years old for coprological examination, and a questionnaire measured knowledge, attitudes, and practices with regard to clonorchiasis in 757 participants over 15 years old. Univariable and multivariable logistic regression models were run to identify risk factors for infection with C. sinensis. The overall prevalence of C. sinensis infection was 40.4%, with commune prevalences ranging between 26.5% and 53.3%. In the final model, males were significantly more likely to be infected with C. sinensis (OR 2.00; 95% CI 1.31–3.05). Recent (i.e. last year) consumption of raw fish (OR 8.00, 95% CI 4.78–13.36), low education level (OR 5.57; 95% CI 2.37–13.07), lack of treatment (OR 1.82, 95% CI 1.15–2.89), being between 19 to 39 years old (OR 6.46; 95% CI 1.25–33.37), and the presence of an unhygienic toilet (OR 2.74, 95% CI 1.53–4.92) were significantly associated with C. sinensis infection. Conclusion/Significance This study demonstrated a high prevalence of C. sinensis infection in rural communities in northern Vietnam. Thus, control measures including, mass drug administration for those communes should be applied to reduce the prevalence. Moreover, specific health education activities should be developed for risk groups in C. sinensis endemic areas., Author summary Clonorchiasis, caused by the fish-borne trematode Clonorchis sinensis, is a chronic liver infection and is classified as a neglected tropical disease, particularly in some Asian countries such as Vietnam. Light infections with C. sinensis are asymptomatic, yet heavy chronic infections are associated with clinical complications such as, bile duct obstruction, hepatic fibrosis and the most serious complication being bile duct cancer. We carried out a community-based study on C. sinensis infection in rural communities in northern Vietnam. Our results indicated that the Thac Ba lake area in Yen Bai province is a hot spot of C. sinensis infection, and that Thanh Hoa province remains an area with widespread small liver fluke infection. Eating raw fish was confirmed to be an important risk factor for C. sinensis infection in Vietnam. Presence of infection was furthermore associated with gender, age, education and hygienic practices. Mass drug administration and improved awareness campaigns for the population in these regions are needed. Setting-specific interventions targeting different risk groups should be considered to reduce the disease transmission.

Rapid diagnostic tests (RDTs) have been developed to detect influenza A virus for the swift diagnosis and management of patients. However, despite the simplicity and convenience, the low sensitivity of RDTs remains a limitation for their use in point of care testing (POCT). In this study, we developed a rapid fluorescent immunochromatographic strip test (FICT) and the performance of FICT was confirmed by the real-time reverse transcription-polymerase chain reaction (rRT-PCR) of H1N1, compared with that of RDT. The limit of detection (LOD) of FICT was improved by 16-fold compared to RDT. FICT showed 85.29% sensitivity (29/34) (95% Confidence Interval [95% CI]: 68.94 to 95.05), 100% specificity (26/26) (95% CI: 86.78 to 100.00), and a strong correlation (kappa; 0. 92) compared with rRT-PCR (20 ≤ Ct ≤ 36). In contrast, RDT (Standard Diagnostics [SD] BIOLINE Influenza Ag A/ B/ A(H1N1) Pandemic) showed 55.88% sensitivity (19/34) (95% CI: 37.87 to 72.82), 100% specificity (26/26) (95% CI: 77.07 to 100), and had a fair correlation with rRT-PCR (kappa; 0. 75). FICT had better sensitivity than RDT (P

Background: Clinically, there are many systems of visual field staging parallel exist. The agreement between glaucoma function and appearance is still uncertain. This study was to compare visual field staging classifications (as function staging) with disc damage likelihood scale (DDLS as appearance staging) in primary open angle glaucoma (POAG).Methods: Cross-section study on 55 patients (90 eyes) examined and treated in Vietnam National Institute of Ophthalmology from 9/2016 – 9/2017. The MD (mean deviation), PSD (pattern standard deviation), VFI (visual field index) indexes were recorded and were used to classify glaucoma staging according to categories of eGSS (enhance glaucoma severity staging), mGSS (modified glaucoma severity staging), HPA (Hoddaps – Palmela – Adersons), AGIS (advance glaucoma intervention study) and DDLS. Using SPSS 16.0 software, statistically significance was tested with proper tests as Chi – square test, Fisher exact test, Kappa (to assess the agreement - disagreement), Spearman Rank (to assess the level of correlation).Results: Mean visual field indexes were -11.49 dB (MD), 5.85 dB (PSD), 74.2% (VFI). Compared to the DDLS, all systems had slight agreement (K < 0.2). The disagreement percentage was highest in eGSS (70%) then followed by mGSS (50%) and HPA (48.9%). In terms of definitive diagnosis, HPA and mGSS showed a substantial agreement (K > 0.6) with AGIS which is higher than that between eGSS and AGIS (retrospectively 0.773 and 0.75 vs 0.399) with p < 0.001. In terms of staging detection, the agreement between HPA &mGSS and AGIS was substantial (K > 0.6) while that between eGSS and AGIS was fair (K < 0.4).Conclusion: mGSS and HPA tend to show the stronger agreement with standard classifications than eGSS. mGSS should be used in clinical practice and research.

Scrub typhus, caused by Orientia tsutsugamushi, is a common fever in parts of Southern and Southeast Asia. As delayed diagnosis of scrub typhus leads to inappropriate treatment and high mortality rates, of up to 70%, sensitive and rapid detection of O. tsutsugamushi is required for timely and appropriate treatment. Molecular assays, such as PCR and real-time PCR, have been shown to be more sensitive than conventional immunoassay, however, they are only available in centralized laboratories. In contrast to PCR assays, Recombinase Polymerase Amplification (RPA) is conducted under a constant temperature ranging from 24°C to 45°C. Therefore, this technology is very promising for nucleic acid testing in the field, and in resource-limited areas. An RPA assay for the detection of O. tsutsugamushi based on the target gene encoding for the 47 kDa outer membrane protein has been reported, but the primer and probe sequences of this assay are suboptimal for detection of the majority of recently published sequences of O. tsutsugamushi isolates from Southeast Asia. We have established a real-time RPA assay with primer and probe sequences that are optimized for most Southeast Asia's isolates of O. tsutsugamushi. As a result, the new RPA assay showed better performance than the previous assay in detecting O. tsutsugamushi in clinical samples of scrub typhus cases found in Vietnam. The specificity of RPA assay was also evaluated using genomic DNA from microorganisms commonly encountered in the differential diagnosis of scrub typhus, and blood samples from healthy controls and O. tsutsugamushi negative confirmed cases.

Functionalization of BODIPY dyes with TPP substituents endowed them with mitochondria-targeting capabilities. The uniodinated BODIPY control displayed good biocompatibility, low cytotoxicity in the dark, and exceptional cellular imaging capabilities; however, it did not exhibit photodynamic therapeutic properties upon excitation at 530 nm. Dual functional photosensitizers were obtained in the case of mono- and di-iodinated BODIPY derivatives, which exhibited mitochondria-targeting capabilities and provided clear fluorescence confocal bioimages, while efficiently generating high levels of singlet oxygen species and displaying photodynamic therapeutic activity toward two cancer cell lines following LED irradiation. Overall, the results presented herein demonstrate the considerable potential for the use of TPP-functionalized BODIPY dyes as viable agents for fluorescence-imaging-guided photodynamic therapy (PDT) for cancer treatment.

Mutations and amplification of the fms-like receptor tyrosine kinase FLT3 gene, such as those found in MV-4-11 cells, are common in acute myeloid leukemia (AML). Such mutations result in aberrant activation of FLT3, increased growth and survival of tumor cells, and the development of refractory forms of AML with poor patient outcomes. In addition, AXL receptor tyrosine kinase imparts chemotherapeutic resistance in AML. MV-4-11 is a human biphenotypic B myelomonocytic leukemia with t(4;11)(q21;q23) chromosomal translocation commonly found in AML patients; it possesses a homozygous in-frame tandem repeat insertion in the FLT3 allele resulting in constitutively phosphorylated FLT3. Commonly employed preclinical orthotopic models of AML are primarily evaluated based on morbidity and mortality, which provide limited real time information on tumor burden and dissemination. The purpose of this study is to develop a MV-4-11 mouse model that allows the quantification and anatomical localization of the AML cells by monitoring bioluminescent signal in live animals and to utilize this model to investigate the efficacy of a FLT3/AXL inhibitor, gilteritinib. This poster describes a) the production of luciferase-expressing human MV-4-11 (MV-4-11-luc) cells via lentiviral transduction, b) the characterization of MV-4-11-luc progression in two models of immunocompromised mice, c) the efficacy of the FLT3/AXL kinase inhibitor gilteritinib against systemic MV-4-11-luc compared with two standard AML therapies, cytarabine and cyclophosphamide and d) the development of a humanized MV-4-11 tumor bearing model in NCG mice. Bioluminescence imaging revealed dose dependent tumor growth localized to the hind limbs and peritoneal cavity, which disseminated and intensified over time. Characteristic moribundity associated with disease progression was observed in this model. By comparison, robust growth of both parental and luc-transduced MV-4-11 was also observed in the highly immunodeficient NCG mice with or without prior myeloablation. Efficacy studies in NCG mice bearing parental or luciferase-tagged MV-4-11 cells demonstrated potent anti-tumor activity using the FLT3/AXL inhibitor. Bioluminescent imaging of orthotopic MV-4-11-luc xenografts in immunocompromised mice is a quantitative and sensitive method that provides anatomical context for assessing the efficacy of AML therapeutics. Ongoing and future work is focused on a) genetic profiling of MV-4-11 tumors after treatment with gilteritinib, b) further characterization of a humanized MV-4-11 model to evaluate immune-modulating therapeutics, and c) utilizing the model to evaluate activity of cell therapies that target AML. Citation Format: Na Li, Vivek Mahajan, Lindsay Butler, Elizabeth Rainbolt, Shasta Kidder, Kay Meshaw, Diana Gietl, Susan Yeyeodu, Anya Avrutskaya, Jing Wan, Thi Bui, Chassidy Hall, David P. Harris. Inhibition of FLT3 and AXL by gilteritinib controls systemic tumor growth in luciferase-transduced MV-4-11 acute myeloid leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2933.

Greater than 50% of all cancer patients receive radiation therapy at some point during their cancer treatment to control solid tumor growth (Harrington 2011). In addition to the direct action of radiation on tumor cell proliferation, radiation also has the potential to stimulate an anti-tumor immune response (Weichselbaum 2017). The success of immune checkpoint therapies such as anti-PD-1, anti-PD-L1, and anti-CTLA-4 inhibitory antibodies has driven large investment into the discovery of novel immune-oncology therapies. While the clinical response to immune checkpoint inhibitors can be profound for those patients that respond, there still exists a large percentage of patients that do not see benefit. In order to expand the number of patients that may respond to immune checkpoint inhibition, combination with radiation therapy needs to be tested and in fact a large number of preclinical and clinical studies are being conducted (for review see Asna 2019). Preclinical syngeneic tumor models are a critical means to assess new immunotherapies and drive preclinical programs. E0771 is a medullary breast adenocarcinoma cell line originally isolated from a spontaneous tumor and can be implanted subcutaneously in C57BL/6 mice (Ewens 2005). In order to characterize the E0771 syngeneic breast tumor model for future studies with radiation and immunotherapy, we assessed the efficacy changes in response to various schedules of radiation doses with and without either anti-PD-1 or anti-CTLA-4 antibody therapies. In addition, we analyzed the tumor infiltrating immune cell populations following radiation therapy. E0771 is sensitive to radiation therapy with a clear dose response. Radiation administered either as a single dose, hypofractionated, or hyperfractionated gave similar tumor responses. Flow cytometry analysis shows a higher infiltration of T regulatory cells compared with CD8+ T cells at baseline, which is exacerbated by irradiation. The CD8/Treg ratio is reversed with the addition of anti-CTLA-4 treatment to radiation and resulted in curative responses for 9 of 10 mice in the combination group. Citation Format: Patrick Fadden, Thi Bui, Kelli Davis, David Hurtado, Emily Sugg, Abigail Svancarek, Ian Belle, Chassidy Hall. Radiation therapy and immune checkpoint inhibitor combinations in the E0771 medullary breast adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1558.

Objectives People with diabetes are at high risk of polypharmacy owing to complex treatment of diabetes and comorbidities. Polypharmacy is associated with increased risk of adverse reactions and decreased compliance. Therefore, the objectives of this study were to assess polypharmacy in people with type 2 diabetes (T2D) and associated diabetes-related factors in rural areas in Vietnam. Method People with T2D (n = 806) who had received treatment for diabetes at a district hospital were invited to participate in a questionnaire-based cross-sectional survey. Polypharmacy was defined as ≥5 types of medicine and assessed as a) prescription medicine and non-prescription/over the counter (OTC) medicine and b) prescription medicine and non-prescription/OTC, herbal and traditional medicine, and dietary supplement. Multiple logistic regression was used to investigate the association between polypharmacy and diabetes specific factors: duration, comorbidities and diabetes-related distress. Results Of the people with T2D, 7.8% had a medicine use corresponding to polypharmacy (prescription medicine and non-prescription/OTC), and 40.8% when herbal and traditional medicine, and dietary supplement were included. Mean number of medicine intake (all types of medicines and supplements) were 3.8±1.5. The odd ratios (ORs) of polypharmacy (medicine and supplements) increased with diabetes duration (5 years OR = 1.74; 95%CI: 1.14–2.64 as compared to ≤1-year duration of diabetes), number of comorbidities (1–2 comorbidities: OR = 2.0; 95%CI: 1.18–3.42; ≥3 comorbidities: OR = 2.63;95%CI: 1.50–4.61 as compared to no comorbidities), and suffering from diabetes-related distress (OR = 1.49; 95%CI: 1.11–2.01) as compared to those without distress. Conclusions In rural northern Vietnam, persons with longer duration of T2D, higher number of comorbidities and diabetes-related stress have higher odds of having a medicine use corresponding to polypharmacy. A high proportion of people with T2D supplement their prescription, non-prescription/OTC medicine with herbal and traditional medicine and dietary supplements.

© 2017 International Council of Nurses Aim: To identify the practice patterns of the Australian registered nurse workforce according to position title and to map these disparate titles across all jurisdictions of the country. Introduction: Effective nursing workforce planning can contribute to improved patient care and increased effectiveness and efficiency of healthcare systems. Background: The prevailing approach to nursing workforce planning focuses on number of nursing staff needed in relation to the number of patients. The level of expertise and skill mix of registered nurses as a variable in workforce planning is rarely considered. Methods: A national cross-sectional electronic survey of registered nurses in Australia was conducted using the validated Advanced Practice Role Delineation tool developed from the Strong Model of Advanced Practice. The study involved a sample of 5599 registered nurses. Results: Sixty-six nursing position titles nationally were mapped using cluster analysis technique and gave rise to seven clusters of equivalent Australian jurisdictional nursing position titles and practice profiles. Discussion: Effective workforce policy and planning is reliant upon access to reliable evidence. This research is an international first in that it has provided comprehensive knowledge of the clinical level and practice profiles of a national nursing workforce. Implications for nursing policy: Effective, patient-centred workforce planning must consider both the numerical and expertise mix of a nursing workforce. This research provides Australian health service and policy planners with evidence-base knowledge of the nursing workforce. Internationally, this research establishes a platform from which to develop validated tools and established processes to support replication of this research.

The aim of the present study was to investigate the effect of vascular endothelial growth factor (VEGF) on the meiotic and developmental competence of porcine oocytes from small follicles (SF; 0.5–3 mm diameter). When cumulus–oocyte complexes (COCs) from medium-sized follicles (MF; 3–6 mm diameter) and SF were cultured for IVM, the maturation rates were significantly higher for oocytes from MF than SF. Concentrations of VEGF in the medium were significantly higher for COCs cultured from MF than SF. When COCs from SF were exposed to 200 ng mL–1 VEGF during the first 20 h of IVM, the maturation rate improved significantly and was similar to that of oocytes derived from MF. The fertilisability of oocytes was also significantly higher than that of VEGF-free SF controls. Following parthenogenetic activation, the blastocyst formation rate improved significantly when SF COC culture was supplemented with 200 ng mL–1 VEGF, with the rate similar to that of oocytes from MF. The results of the present study indicate that VEGF markedly improves the meiotic and developmental competence of oocytes derived from SF, especially at a concentration of 200 ng mL–1 during the first 20 h of IVM.

The screening and monitoring of residual antibiotics in pork meat were conducted in Ho Chi Minh City, Vietnam, from 2014 to 2015. One hundred samples collected from a wholesale market were screened on-site using a microbiological kit, and eighteen samples were determined as positive for residual antibiotics. Once transferred to the lab, all the samples were analyzed for 28 antibiotics using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Sulfamethazine residues (11–1600 μg/kg) were detected in 23 samples by LC-MS/MS. Notably, 11 samples with sulfamethazine concentrations ranging from 310 to 1600 μg/kg were detected as “positive” in the initial screening, whereas 12 other samples with sulfamethazine levels below 200 μg/kg were screened as “negative”. No other targeted antibiotics were identified among the remaining positive samples. These results show the potential and limitations of a monitoring system combining on-site microbiological tests and an LC-MS/MS method.

The present study was undertaken to examine the apoptotic status and meiotic progression of oocytes from small follicle (SF; 0.5-2 mm in diameter) and medium follicle (MF; 3-6 mm in diameter) when the oocytes were denuded before, during, and after IVM. Cumulus-oocyte complexes (COCs) were collected from SF or MF of prepubertal gilt ovaries. Before or 20 hours after the start of IVM culture, some oocytes were denuded and cultured for IVM. At the end of IVM, apoptotic status and meiotic progression of the oocytes were compared with oocytes matured in the presence of cumulus cells (CCs) by Annexin-V/PI assay and 4',6-Diamidino-2-phenylindole staining. Apoptotic status of the oocytes was only affected by time when the oocytes were denuded. In both oocytes from SF and MF, although the incidence of early and late apoptotic oocytes was significantly higher when the CCs were removed before IVM, the rate was significantly lower when CCs were removed 20 and 44 hours after the start of IVM. The incidence of mature oocytes was significantly affected by both the origin of COCs and time when oocytes were denuded from the COCs. Although the percentage of mature oocytes was higher in MF than SF, maturation rates were significantly higher when oocytes were denuded 20 hours, as compared with 0 and 44 hours after the start of IVM. However, the percentage of mature oocytes with a morphologically normal spindle was significantly higher when oocytes were denuded 44 hours, rather than 22 hours of IVM. In conclusion, removing CCs 20 hours after the start of IVM seems to promote meiotic progression of the oocytes to the metaphase-II stage even when the COCs were collected from SF, although factor(s) from or communication with CCs during IVM may need to obtain a morphologically normal spindle in mature oocytes.

Background: Since chronic hyperglycemia-related damage to small blood vessels results in complications, patients with longer durations of type 2 diabetes mellitus (T2DM) are more likely to develop microvascular complications, such as retinopathy, neuropathy and nephropathy, which are very harmful to the health of humans. Therefore, this study aimed to assess the prevalence of diabetes-related microvascular complications and to explore their risk factors in patients with T2DM in Tianjin, China. Methods: This observational, cross-sectional study was conducted at 8 hospitals in urban and suburban regions of Tianjin, China. The information collected from the subjects mainly included demographic characteristics, anthropometric measurements and clinical information. Univariate and multivariate logistic regression was used to identify the possible risk factors for microvascular complications (retinopathy, neuropathy and nephropathy). Results: A total of 4,490 patients with T2DM from 8 hospitals in Tianjin, China were selected from November 2015 to January 2016. Of the study subjects, 2,270 (50.6%) were males. The median age was 64.0±13.0 years. The percentage of patients with T2DM who had at least one microvascular complication was 34.5%. The prevalence rates of neuropathy, retinopathy, and nephropathy were 23.5%, 17.4%, and 10.8%, respectively. The results of the multivariate logistic regression showed that the duration of diabetes, insulin use, and the presence of hypertension and dyslipidemia were the main risk factors for developing microvascular complications of T2DM. Conclusions: The incidence of diabetes complications in Tianjin is high. Increasing the control of risk factors can reduce the occurrence of complications to reduce the disease burden and improve the quality of life of patients.

Aims and objectives : To validate the ability of factors to predict infection in adults with chronic leg ulcers over a 12-week period. Background: Leg ulcers affect ~3% of older adults and are often hard to heal. Infection is a leading contributor for delayed healing, causing delayed wound healing, increased hospitalisation, increased healthcare costs and reduced patient quality of life. The importance of early identification of infection has been highlighted for decades, yet little is known about factors that are associated with increased risk of infection in this specific population. Design : A longitudinal, prospective observational study in a single centre. Methods : Between August 2017 and May 2018, a total of 65 adults with chronic leg ulcers were prospectively observed for a 12-week period. Patients were recruited from an outpatient wound clinic at a tertiary hospital in Australia. Data were collected from recruitment (baseline) and each visit (weekly or fortnightly) up until 12 weeks. Descriptive statistics were calculated for all variables. A Cox proportional hazards regression model was used to identify predictive factors for infection. The TRIPOD guidelines for reporting were followed (See Data S1). Results : The sample consisted of 65 adults with chronic leg ulcers, and 9.2% of these had their ulcer infected at baseline. Two predictive factors, using walking aids and gout, were found to be significantly related to increased likelihood of developing infection within 12 weeks. Conclusion : The present study showed that patients who either used walking aids or were diagnosed with gout were at greater risk of infection compared to those without these factors. Relevance to clinical practice: These findings provide new information for clinicians in early identification of patients at risk of infection, and for patients in enhancing their awareness of their own risk.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have been found to contribute, predominantly, to increasing costs of COPD&mdash, a major public health issue. This study aimed to fill the gap in literature concerning costs of AECOPD in Vietnam, by examining the direct cost of AECOPD hospitalization and determining potentially associated factors. A cross-sectional study was conducted at the Respiratory Center of Bach Mai Hospital, Hanoi. A total of 57 participants were selected. Information regarding sociodemographic features, clinical characteristics, and hospitalization costs were collected. A multivariate generalized linear regression model was utilized to determine the factors associated with hospitalization costs. The mean total and daily hospitalization cost were 18.3 million VND (SD = 12.9) and 2.5 million VND (SD = 3.2), respectively. Medication cost accounted for 53.9% of hospitalization cost (from 44.0% in the Global Initiative for Chronic Obstructive Lung Disease Classification A (GOLD A) to 55.3% in GOLD C). Patients having GOLD D COPD (Coef. = 5.78, 95% CI = 0.73&ndash, 10.83), higher age (Coef. = 0.37, 95% CI = 0.13&ndash, 0.61), and higher duration of hospitalization (Coef. = 1.91, 95% CI = 1.28&ndash, 2.53) had higher hospitalization costs (p &lt, 0.05). This study suggested that interventions to screen COPD patients as well as provide timely treatment should be conducted widely in the community in order to avoid any unnecessary hospitalization cost, consequently reducing the economic burden of COPD.

From July 2017 to Jan 2019, a total of 572 retail fresh vegetables were collected to clarify the contamination of Salmonella in the Mekong Delta, Vietnam. Salmonella was isolated from 74 (12.9%) of 572 samples. The isolation rate of Salmonella from retail fresh vegetables in the rainy season (15.3%) was significantly higher than that in the dry season (7.6%) (P

Exposing to adverse childhood experiences (ACEs) has been identified as one of the major contributing factors to poor mental health and suicide in adolescents. However, little is known about this relationship in Vietnamese adolescents. This study aimed to evaluate the effect of ACEs on depression, psychological distress and suicidal thought among Vietnamese adolescents across different areas in Vietnam. Cross-sectional surveys were conducted among 4957 secondary school and high school students aged 13-20 in urban area, rural area, border area and mountainous area. The students were asked to complete a self-report questionnaire which included the Center for Epidemiological studies - Depression, the Kessler-10 and ACE questionnaire from the WHO Adverse Childhood Experiences Study. Suicidal thought was evaluated by a single question from the U.S. Youth Risk Behavior Survey. Among 4720 students included in the analysis, 54.4% were female. The prevalence of depression, psychological distress and suicidal thought was 22.9%, 30.6% and 10.9% respectively. About 86% of participants experienced at least one type of ACEs and nearly 56% reported multiple types of ACEs. Students with four or more types of ACEs had 6.98 (95% CI 5.09 -9.56), 4.72 (95 % CI 3.58-6.23) and 6.43 (95 % CI 4.45-9.30) times higher in odds of having depression, psychological distress and suicidal thought respectively. In conclusion, ACEs are common in Vietnamese adolescents and are strongly associated with depression, psychological distress and suicidal thought. Our finding indicates urgent needs for interventions targeting both ACEs and depression, psychological distress in Vietnamese adolescents.

Liposomes are considered an ideal biomimetic environment and are potential functional carriers for important molecules such as steroids and sterols. With respect to the regulation of self-assembly via sterol insertion, several pathways such as the sterol biosynthesis pathway are affected by the physicochemical properties of the membranes. However, the behavior of steroid or sterol molecules (except cholesterol (Chl)) in the self-assembled membranes has not been thoroughly investigated. In this study, to analyze the fundamental behavior of steroid molecules in fluid membranes, Chl, lanosterol, and ergosterol were used as representative sterols in order to clarify how they regulate the physicochemical properties of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) liposomes. Membrane properties such as surface membrane fluidity, hydrophobicity, surface membrane polarity, inner membrane polarity, and inner membrane fluidity were investigated using fluorescent probes, including 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene, 8-anilino-1-naphthalenesulfonic acid, 6-propionyl-2-(dimethylamino) naphthalene, 6-dodecanoyl-2-dimethylaminonaphthalene, and 1,6-diphenyl-1,3,5-hexatriene. The results indicated that each sterol derivative could regulate the membrane properties in different ways. Specifically, Chl successfully increased the packing of the DOPC/Chl membrane proportional to its concentration, and lanosterol and ergosterol showed lower efficiencies in ordering the membrane in hydrophobic regions. Given the different binding positions of the probes in the membranes, the differences in membrane properties reflected the relationship between sterol derivatives and their locations in the membrane.

Antibiotic residues in aquatic products in Vietnam were investigated. A total of 511 fish and shrimp samples were collected from markets in Ho Chi Minh City (HCMC), Thai Binh (TB), and Nha Trang (NT) from July 2013 to October 2015. The samples were extracted with 2% formic acid in acetonitrile and washed with dispersive C18 sorbent. Thirty-two antibiotics were analyzed by LC-MS/MS. Of the 362 samples from HCMC, antibiotic residues were found in 53 samples. Enrofloxacin was commonly detected, at a rate of 10.8%. In contrast, samples from TB and NT were less contaminated: only 1 of 118 analyzed samples showed residues in TB and only 1 of 31 showed residues in NT. These differences were attributed to the local manufacturing/distribution systems. To understand the current status of antibiotic use and prevent adverse effects that may be caused by their overuse, continual monitoring is required.

Targeting CTLA-4 has shown remarkable long-term benefits and thus remains a valuable approach for combating cancers of many types. A number of preclinical models have been developed over the years to evaluate the efficacy of immune checkpoint blockade in promoting antitumor immunity. In particular, knock-in (KI) humanized mouse models offer the possibility to study clinical grade immune checkpoint inhibitors (ICI) in the context of a fully functional immune system. Here we show the response to ipilimumab in a newly developed hCTLA-4 KI humanized mouse model. Our results demonstrate significant tumor growth inhibition as well as complete tumor regressions in the MC38 colorectal cancer model following treatment with ipilimumab. We have extended these studies by re-challenging the tumor-free surviving animals with tumors cells implanted opposite to the original tumor site. We established that all re-challenged hCTLA-4 KI mice remained tumor free suggesting potent T cell memory was maintained. To identify the immune cells and cytokines that could be responsible for the durable responses, we used multiparameter flow cytometry to characterize and compare blood, spleen and tumors tissues from the control, ipilimumab and mCTLA-4 treated mice. Comprehensive multichromatic phenotyping and functional intracellular cytokine staining (ICS) using validated 18-color flow cytometry panels showed a significant increase in CD8+ T cell frequencies when mice were treated with anti-hCTLA-4 but not with the mouse counterpart or the isotype control. Importantly, hCTLA-4 blockade reduced the regulatory T cell (FoxP3+ Treg) frequency and increased leukocyte infiltration into the tumor in the hCTLA-4 treated mice but not in the other two treated groups. Although equivalent numbers of CD4+ and CD8+ total T lymphocytes where found in the blood of all groups after each treatment, the quality of the T cell responses was found to be significantly different. CD45+ lymphocytes from the blood analyzed from the hCTLA-4 treated mice showed significant increases in both central memory (CM) CD8+ and CD4+ T cells consistent with increased anti-tumor efficacy seen in these mice. Furthermore, treatment of MC38 tumor-bearing mice with ipilimumab enhanced significantly the secretion of IFNγ from CD8+ and CD4+ T cells and the proliferation of both T cell populations as shown by the upregulation of Ki67 staining. These results indicate that immune cells were actively proliferating and had the appropriate effector functions to impact tumor growth. Altogether, the data presented here demonstrates that hCTLA-4 KI humanized mice are a robust model for evaluating the immune-modulatory effects and the activity of clinical grade ICI against tumors. Citation Format: Elizabeth Reap, Fabiane SÔNEGO, Emily O'Koren, Martin Gaëlle, Anya Avrutskaya, Jacob Hauser, Robin Ball, Thi Bui, Ian Belle, Chassidy Hall, Paula L. Miliani De Marval, Kader Thiam. Enhanced anti-tumor lymphocyte function and frequencies measured by multichromatic flow cytometry in human CTLA-4 knock-in mice in a colorectal carcinoma model after treatment with ipilimumab [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5635.

Background: Data about the risk factors and cancer types in developing countries remains limited. We investigate for the first time the role of a number of risk factors (family cancer history, smoking, alcohol consumption, diabetes, hypertension) associated with pancreatic cancer among Vietnamese patients. Methods: Patients hospitalized at 4 hospitals (K, Bach Mai, Viet Duc, Thai Nguyen) and diagnosed with pancreatic cancer (confirmed by histopathology and/or MRI/CT scan) in the period from January 2017 to May 2019 were included in the study. Some risk factors of the patients were collected and compared with a healthy age- and gender-matched (1:1) control group. Results: We have identified 196 patients with diagnosis of pancreatic cancer of which 114 males and 82 females. The average age of the patient at the time of diagnosis was 58.28 years (standard deviation of 12.94, ranging from 25 to 87). A positive family history, smoking and hypertension disease of pancreatic cancer significantly reduced the risk (OR and 95% CI were 0.06 [0.02 - 0.18], 0.53 [0.27 - 1.00], 0.1 [0.04 - 0.25], respectively). A past or present history of diabetes significantly increased the cancer risk (OR = 2.76 [1.34 - 6.05]), especially in female (OR = 5.68 [1.49 - 28.69]). Current alcohol drinkers showed a significantly increased risk of pancreatic cancer (OR = 2.23 [1.20 - 4.25]). Conclusions: Our finding showed that diabetes significantly increased the risk of pancreatic cancer in Vietnam, especially in women. An alcohol intake habit also increased the risk of pancreatic cancer. Further studies are required for fully understood the other risk factors related to this type of cancer. Citation Format: Tu V. Dao, Thuan V. Tran, Dung K. Nguyen, Oanh T. Bui, Quang T. Nguyen, Huong T. Tran. Risk factors of pancreatic cancer in Vietnam: A matched case-control hospital-based study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2368.

PURPOSE Noncommunicable diseases (NCDs), including cancer, have emerged as a major public health problem in Vietnam; however, NCD research in Vietnam is limited, primarily because of inadequate research infrastructures, funding, and well-trained investigators. To address these challenges, we established a US-Vietnam-China partnership to plan for building the V-CORE (Vietnam Center of Research Excellence on Cancer and Other Noncommunicable Diseases) with the support of a grant from the US National Cancer Institute. The objectives of this program are to assess the need and current NCD research capabilities and infrastructure in Vietnam and to develop and pilot test research capacity building/enrichment programs, including conducting two research projects for demonstration. METHODS AND RESULTS Through a need- and capacity-assessment workshop, with participation of stakeholders in NCD research and prevention in Vietnam, we identified top priorities and gaps and needs in cancer and other NCD research in Vietnam. We organized two site visits for Vietnam National Cancer Institute delegates to observe epidemiologic research field operations, core laboratories, and biorepositories at Vanderbilt University Medical Center and Vanderbilt Epidemiology Center, as well as at several partner institutes in Shanghai, People’s Republic of China. We organized an in-country workshop on the principles and methodology of epidemiology and biostatistics. We sponsored overseas training for 4 Vietnamese scholars. We conducted two demonstration projects: a case-control study involving 501 patients with breast cancer and 468 controls, and a community survey for diabetes and other metabolic conditions involving 1,035 urban and rural residents of Vietnam. We also jointly sponsored with Vietnam National Cancer Institute an international conference on cancer research and prevention in 2017, and jointly published 11 papers. CONCLUSION Within a 3-year period, we have built a productive collaborative network and laid a solid foundation for building the V-CORE in Vietnam. We strive to maintain and expand the collaboration and bring the success of the National Cancer Institute grant work to full fruition.

The clinical success of immune checkpoint therapies such as PD-1, PD-L1, and CTLA-4 inhibitory antibodies has stimulated interest in a wide range of approaches to cancer immunotherapy. Development of these new modalities requires robust, well characterized preclinical animal models to evaluate efficacy and potential toxicities. Preclinical efficacy assessments of novel immune-oncology therapies requires a functional immune system which limits the usefulness of traditional xenograft models and drive the use of humanized (human immune cell engrafted animals) and syngeneic model systems. Syngeneic mouse tumors are popular model systems in which to evaluate these novel therapies due the presence of fully intact mouse immune system and ease of accessibility. The MC38 mouse colon cancer model is popular for efficacy assessment studies due to its responsiveness to typical immune checkpoint inhibitors (ICI). We endeavored to characterize the kinetic immune response to checkpoint inhibitors (anti-PD-1 + anti-CTLA-4) in MC38 tumors using flow cytometry and gene expression analysis. Gene expression analysis provided a signature of gene changes that correlate to immune driven changes in tumor growth and may be used in preclinical pharmacodynamics studies as evidence of mode of action for other novel immune-oncology therapies. In addition, gene over-representation analysis highlighted the presence and involvement of B cell populations in the MC38 tumor environment which was supported by IHC data that show distinctive B cell staining in what resemble tumor associated tertiary lymphoid structures. These findings provide a greater understanding of the ICI response in the MC38 tumor model and may inform mode of action study designs for other novel immuno-oncology therapies. Citation Format: Patrick Fadden, Thi Bui, Kelli Davis, David Hurtado, Ian Belle, Katherine Krontz, Jacob Hauser, Cristina Sokolowski, Na Li, Kyle Takayama, Paula Miliani de Marval, David Harris, Edgar Wood. A kinetic analysis of tumor gene expression and cellular changes following immune checkpoint inhibition in the MC38 colon carcinoma model [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr A015. doi:10.1158/1535-7163.TARG-19-A015

The evidence base for cognitive behavioral therapy (CBT) is promising for the treatment of anger in both adults and children in most European and Western countries. The goal of the current study was to explore the effectiveness of this therapeutic approach for anger problems in Vietnam as a non-Western culture and non-English speaking country. A randomized controlled trial was undertaken with 40 adolescents for three months, using different CBT techniques. A medium effect size of .64 (Cohen's d) was found for a CBT intervention. Anger management skills of older adolescents (aged from 14 to 16) improved more than those of younger adolescents (aged from 12 to 13). The findings of the current study replicated previous studies regarding the high cost-effectiveness of CBT intervention for anger problems in children and adolescents. Furthermore, the suitability of the group CBT format for the treatment of anger within this study was consistent with other studies as well. This adds valuable evidence to the paucity of CBT literature on culturally responsive CBT in diverse populations. Despite this, more research is needed to produce evidence-based CBT for other Asian countries as well as other populations.

Aim: This study aimed to validate the relationships between possible predictive factors and clinically diagnosed infection in adult patients with chronic leg ulcers. Methods: This study used a sample of 636 adult participants whose ulcers were diagnosed as either venous, arterial or mixed aetiology leg ulcers and had no clinical signs of infection at recruitment. Data were extracted from recruitment to 12 weeks from six longitudinal prospective studies from 2004 to 2015. Survival analysis was used to investigate mean time-to-infection, including the Kaplan-Meier method and the Cox proportional-hazards regression model. Results: The sample included 74.7% venous, 19.6% mixed and 5.7% arterial leg ulcers. There were 101 (15.9%) participants diagnosed with infection at least once within 12 weeks of follow-up. Mean time-to-infection was 10.89 weeks (95% CI = 10.66-11.12). After adjustment for potential confounders, a Cox proportional hazards regression model found that depression, using walking aids, calf ankle ratio

Objective To improve an adherence documentation tool utilised by Australian Clinical Pharmacists in hospitals. Method Surveys and a focus group session were methods employed to study the perceptions of clinical pharmacists and medical officers on the ‘Medication Management Plan (MedMAP)’ as an adherence documentation tool and the perceived limitations, if any, of the form. Key findings The MedMAP had limitations which could potentially affect patient care in hospitals. The modified form was successfully trialled over a period of two weeks with favourable results. Conclusion The study identified the shortcomings of the MedMAP form and further underlined the importance of continual auditing of pivotal adherence documentation tools in hospital.

Maternal death is one of the highest causes of global mortality. Governments have long used regulation to improve maternal health but concurrent fiscal-decentralisation reforms can undermine clinical performance. This article focuses on public Vietnamese hospitals to explore how regulatory compliance is pursued in decentralised health facilities, since Vietnam has seen increasing autonomisation of public hospitals in the last decade while simultaneously experiencing marked reductions in the maternal mortality ratio. Our analysis suggests that autonomisation has allowed regional regulatory regimes to emerge and that regulatory compliance must compete with other priorities. Compliance can therefore be rethought as a negotiation having implications for how government and maternal health advocates persuade self-sufficient hospitals to take on wider health-system goals.

The development of a sensitive and rapid diagnostic test is needed for early detection of avian influenza (AI) H7 subtype. In this study, novel monoclonal antibodies (mAbs) against influenza A H7N9 recombinant hemagglutinin (rHA)1 were developed and applied to a Europium nanoparticle–based rapid fluorescent immunochromatographic strip test (FICT) to improve the sensitivity of the rapid diagnostic system. Two antibodies (2F4 and 6D7) exhibited H7 subtype specificity in a dot-FICT assay by optimization of the conjugate and the pH of the lysis buffer. The subtype specificity was confirmed by an immunofluorescence assay and Western blot analysis. The limit of detection of the FICT employing novel mAbs 31 ng/mL for H7N9 rHA1 and 40 hemagglutination units/mL for H7 subtype virus. Sensitivity was improved 25-fold using Europium as confirmed by comparison of colloidal gold-based rapid diagnostic kit using the 2F4 and 6D7 mAbs.

Leg ulcers are hard to heal. Infection causes delayed healing, negatively impacting patients’ quality of life, the healthcare system, and society. Early recognition of patients at high risk of infection is essential to prevent complications and reduce negative impacts. However, at present, factors associated with infection in this population are not yet clearly understood. The study aimed to identify factors that were significantly associated with infection in chronic leg ulcers. A sample of 561 patients with chronic leg ulcers, who were previously recruited at outpatient clinics and community settings within Australia between 2008 and 2015, were selected for the current analysis. The prevalence of infection in the sample at study recruitment was 7.8%. A multivariate logistic regression model was used to identify factors associated with infection. The study identified 7 factors that were significantly independently associated with infection, including depression, chronic pulmonary disease, anti‐coagulant use, calf ankle circumference ratio

The residual levels of antibiotics in Vietnamese eggs were monitored from 2014 to 2015. A total of 111 egg packages, distributed by 11 different companies, were collected from supermarkets in Ho Chi Minh City and the levels of 28 antibiotics were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) screening method. Sixteen samples tested positive for antibiotics; a total of eight compounds (enrofloxacin, ciprofloxacin, norfloxacin, sulfadimethoxine, sulfamethazine, sulfamonomethoxine, tilmicosin and trimethoprim) were detected. Enrofloxacin was detected in eight samples, with two samples exhibiting concentrations exceeding 1,000 µg kg−1. Tilmicosin was detected in three samples at a range of 49–568 µg kg−1. We observed that two of the 11 companies frequently sold antibiotic-contaminated eggs (detection rates of 56 and 60%), suggesting that a number of companies do not regulate the use of antibiotics in egg-laying hens. Our findings indicate that livestock farmers require instr...

Tapinarof (GSK2894512) is a naturally derived topical treatment with demonstrated efficacy for patients with psoriasis and atopic dermatitis, although the biologic target and mechanism of action had been unknown. We demonstrate that the anti-inflammatory properties of tapinarof are mediated through activation of the aryl hydrocarbon receptor (AhR). We show that tapinarof binds and activates AhR in multiple cell types, including cells of the target tissue—human skin. In addition, tapinarof moderates proinflammatory cytokine expression in stimulated peripheral blood CD4+ T cells and ex vivo human skin, and impacts barrier gene expression in primary human keratinocytes; both of these processes are likely to be downstream of AhR activation based on current evidence. That the anti-inflammatory properties of tapinarof derive from AhR agonism is conclusively demonstrated using the mouse model of imiquimod-induced psoriasiform skin lesions. Topical treatment of AhR-sufficient mice with tapinarof leads to compound-driven reductions in erythema, epidermal thickening, and tissue cytokine levels. In contrast, tapinarof has no impact on imiquimod-induced skin inflammation in AhR-deficient mice. In summary, these studies identify tapinarof as an AhR agonist and confirm that its efficacy is dependent on AhR.

Over the past decade there has been an increasing demand in the use of syngeneic models for evaluating the efficacy of checkpoint inhibition-based cancer immunotherapies. During tumor development, immune cells can became unresponsive to the presence of tumor cells due to chronic activation and expression of the programmed cell death protein-1 (PD-1) or the T-lymphocyte-associated antigen 4 (CTLA4) in T-cells or the presence of FoxP3+ Treg cells resulting in tumor immune-tolerance. Our previous studies have demonstrated that murine anti-PD-1 and CTLA-4 therapy can effectively re-activate the antitumor response against multiple syngeneic tumor models. While these models proved instrumental for evaluating murine immune-checkpoint inhibitors (ICI), there is a clear need for additional mouse models to evaluate the efficacy of ICI specific for human targets. To address this need, we describe the development of a humanized PD-1 knock-in (KI) mouse model. This mouse model has the advantage of expressing the human PD-1 protein in the context of a fully functional immune system. We also show the response to clinically relevant immune checkpoint inhibitors in two preclinical tumor models. We evaluated the anti-tumor activity of pembrolizumab in the MC38 colorectal carcinoma and the GL261 glioblastoma models. We observed significant tumor growth inhibition and growth delay in the MC38 tumor model when treated with pembrolizumab monotherapy, but not when treated with the murine counterpart (anti-PD-1 clone RPM1-14). To extend our validation studies to other tumor models, we implanted GL261 glioblastoma orthotopically in the brain of PD-1 KI mice and achieved a significant increased life span in the group treated with pembrolizumab compared to both the control group and the group treated with murine anti-PD-1 antibody. The immune profile from control and treated these animals were also characterized in these studies by flow cytometry. In summary, the results shown here underscore the value of the humanized PD-1 knock-in (KI) mouse model as a tool to evaluate human specific immune-checkpoint based therapeutics alone and in combination with other agents. Citation Format: Anya Avrutskaya, Fabiane Sonego, Jacob Hauser, Emily O’Koren, Gaëlle Martin, Julie Chaix, Robin Ball, Thi Bui, Ian Belle, Chassidy Hall, Kader Thiam, Paula L. Miliani De Marval. Validation of humanized PD-1 knock-in mice as an emerging model to evaluate human specific PD-1 therapeutics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-063.

To prevent uncontrolled immune cell activation and limit the potential for auto reactivity, T cell responses are subject to multiple levels of regulatory control. In peripheral tissues, tolerance is maintained by regulatory networks and immunosuppressive mechanisms which restrict T cell activity. These same mechanisms can however contribute to failure to mount productive and sustained anti-tumor responses. Therapeutic intervention with immune checkpoint blockade therapy (ICT) restrains negative regulation, re-engages the immune system and promotes enhanced effector responses. Following the success of immunotherapy in certain solid tumors, Nivolumab was the first checkpoint inhibitor approved for treatment of lymphoma, and this approach is now being evaluated in other types of hematological malignancies. Therefore, we developed and characterized an immunocompetent disseminated mouse model for AML using CD11blo CD49b+ PD-L1+, luciferase-transduced C1498 tumor cells. Tumor growth, evidenced by luciferase expression, was progressive and widespread with metastatic development in peripheral organs and tissues and led to increased myeloid (gMDSC, mMDSC, Macrophage, DC) populations in the tumor bearing tissues, characteristic of myeloid leukemia. An efficacious response to therapy was observed, with anti-PD-L1 showing greater overall efficacy than anti-PD-1 and enhancement with combination anti-CTLA-4 therapy. To gain a mechanistic understanding of efficacy, we performed an extensive spatial (blood, spleen, bone marrow, and ovaries) and temporal (after 1st, 3rd and 5th dose of ICT) immune cell profile analysis using flow cytometry, immuno-histochemistry and microarray gene expression in response to mono and combination ICT. In blood, the response to combination immunotherapy was characterized by an initial increase in CD4 T cells (conventional and Tregs), consistent with early priming events after 1st dose of ICT. As the response developed, T cells in blood and spleen expressed elevated Ki67, Granzyme B and CTLA-4 after 3rd and 5th dose of ICT, consistent with development of an established activated effector response. Correspondingly, the NK cell population decreased in spleen and increased in the blood correlating with mobilization of effector response. Similarly, we observed a decrease in CD4 and CD8 cells in spleen, suggesting egress from blood into the sites of neoplasm e.g. ovaries and liver. Besides the lymphoid effector response, we also observed an increase in inhibitory feedback in response to ICT in both blood and spleen. This reflected in increased mMDSC and macrophages population in the blood and an increased PD1+ and CTLA4+ CD4 and CD8 cells in spleen. Citation Format: Harris David, Lindsay Usher, Thi Bui, Ian Belle, Elizabeth Rainbolt, Shasta Kidder, Kay Meshaw, Chassidy Hall, Vivek Mahajan. Spatiotemporal changes in effector immunity in response to checkpoint blockade immune therapy in acute myeloid leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-191.

Immune focused interventions remain a high priority for many drug discovery efforts, spurred on by the success of immune checkpoint therapies such as anti-PD-1, anti-PD-L1, and anti-CTLA-4 inhibitory antibodies. Preclinical efficacy assessments of novel immune-oncology therapies requires a functional immune system which limits the usefulness of traditional xenograft models and drive the use of humanized (human immune cell engrafted animals) and syngeneic model systems. Syngeneic mouse tumors are popular model systems in which to evaluate these novel therapies due the presence of fully intact mouse immune system and ease of accessibility. The MC38 mouse colon cancer model is popular for efficacy assessment studies due to its responsiveness to typical immune checkpoint inhibitors. We endeavored to characterize the immune response to checkpoint inhibitors in MC38 tumors using flow cytometry, gene expression analysis, and immunohistochemistry (IHC). Gene expression analysis provided a signature of gene changes that correlate to immune driven changes in tumor growth and may be used in preclinical pharmacodynamics studies as evidence of mode of action for other novel immune-oncology therapies. In addition, gene overrepresentation analysis highlighted the presence and involvement of B cell populations in the MC38 tumor environment which was supported by IHC data that show distinctive B cell staining in what resemble tumor associated tertiary lymph structures. These finding suggests that MC38 may provide a good model system for evaluating therapies that can modulate or impact tumor infiltrating B cell populations. Citation Format: Patrick Fadden, Thi Bui, David Hurtado, Kelli Davis, Ian Belle, Kathrine Krontz, Jacob Hauser, Na Li, Kyle Takayama, Cristina Sokolowski, Edgar Wood. Characterization of the immune checkpoint inhibitor response in the MC38 murine colon cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-060.