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BackgroundPatients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer may have poor prognoses and short overall and disease-free survival. Most previous studies focused on assessing the quality of life and health-state utility of the general population of breast cancer patients. The number of studies for HER2-positive breast cancer patients is negligible. This study investigated the health-state utility and its associated factors among Vietnamese patients with HER2-positive breast cancer.MethodsWe conducted face-to-face interviews with 301 HER2-positive breast cancer patients to collect data. Their health-state utility was measured via the EQ-5D-5L instrument. The Mann-Whitney U and Kruskal-Wallis tests were employed to compare the differences in utility scores between two groups and among three groups or more, respectively. Factors associated with patients' heath-state utility were identified via Tobit regression models.ResultsPain/discomfort (56.1%) and anxiety/depression (39.5%) were the two issues that patients suffered from the most, especially among metastatic breast cancer patients. The severity of distress (depression, anxiety, and stress) in patients was relatively mild. Of 301 patients, their average utility score was 0.86±0.17 (range: 0.03-1.00), and the average EQ-visual analogue scale (VAS) score was 69.12±12.60 (range: 30-100). These figures were 0.79±0.21 and 65.20±13.20 for 102 metastatic breast cancer patients, significantly lower than those of 199 non-metastatic cancer patients (0.89±0.13 and 71.13±11.78) (pConclusionsOur findings showed a significant decrement in utility scores among metastatic breast cancer patients. Patients' health-state utility differed by their demographic characteristics (age, education level, and income) and clinical characteristics (stage of cancer and distress). Their utility scores may support further cost-effectiveness analysis in Vietnam.

IntroductionIn the context of collective efforts taken in Japan to control the spread of COVID-19, the state of emergency and social distancing have caused a negative impact on the mental health of all residents, including foreign communities in Japan. This study aimed to evaluate the level of anxiety and its associated factors among non-Japanese residents residing in Japan during the COVID-19 pandemic.MethodsA web-based survey in 13 languages was conducted among non-Japanese residents living in Japan during the COVID-19 situation. The State-Trait Anxiety Inventory assessed the level of anxiety-State (STAI-S) scores prorated from its six-item version. The multivariable logistic regression using the Akaike Information Criterion (AIC) method was performed to identify the associated factors of anxiety among participants.ResultsFrom January to March 2021, we collected 392 responses. A total of 357 valid responses were analyzed. 54.6% of participants suffered from clinically significant anxiety (CSA). In multivariable logistic model analysis, the CSA status or the high level of anxiety was associated with three factors, including having troubles/difficulties in learning or working, decreased sleep duration, and decreased overall physical health (pConclusionOur study suggests several possible risk factors of anxiety among non-Japanese residents living in Japan undergoing the COVID-19 pandemic, including the troubles or difficulties in learning or working, the decrease in sleep duration, and the decrease in overall physical health.

Convergent extension of the chordamesoderm is the best-examined gastrulation movement in Xenopus. Here we study general features of cell-cell contacts in this tissue by combining depletion of adhesion factors C-cadherin, Syndecan-4, fibronectin, and hyaluronic acid, the analysis of respective contact width spectra and contact angles, and La3+ staining of the pericellular matrix. We provide evidence that like in other gastrula tissues, cell-cell adhesion in the chordamesoderm is largely mediated by different types of pericellular matrix. Specific glycocalyx structures previously identified in Xenopus gastrula tissues are absent in chordamesoderm but other contact types like 10-20 nm wide La3+ stained structures are present instead. Knockdown of any of the adhesion factors reduces the abundance of cell contacts but not the average relative adhesiveness of the remaining ones: a decrease of adhesiveness at low contact widths is compensated by an increase of contact widths and an increase of adhesiveness proportional to width. From the adhesiveness-width relationship, we derive a model of chordamesoderm cell adhesion that involves the interdigitation of distinct pericellular matrix units. Quantitative description of pericellular matrix deployment suggests that reduced contact abundance upon adhesion factor depletion is correlated with excessive accumulation of matrix material in non-adhesive gaps and the loss of some contact types.

We characterized polysubstance use burden and associations with mental health problems across demographic subgroups of PWH. In 2018-2020, as part of a primary care-based intervention study, PWH in care at three medical centers in Kaiser Permanente Northern California were screened for depression (PHQ-9≥10), anxiety (GAD-2≥3), and substance use (Tobacco, Alcohol, Prescription medication, and other Substance use [TAPS]≥1 per substance). We used Poisson regression to estimate prevalence ratios (PRs) comparing polysubstance use prevalence (TAPS≥1 for ≥2 substances) between PWH with positive screens for depression or anxiety vs. neither, among all PWH, and stratified by race/ethnicity and age (restricted to men), adjusting for sociodemographics, CD4, and HIV load. Screened PWH (N = 2865) included 92% men, 56% White, 19% Black, and 15% Hispanic PWH, with a median age of 55 years. Overall, polysubstance use prevalence was 26.4% (95% CI 24.9%-28.1%). PWH with depression or anxiety (n = 515) had an adjusted polysubstance use PR of 1.26 (1.09-1.46) vs. PWH with neither (n = 2350). Adjusted PRs were 1.47 (1.11-1.96), 1.07 (0.74-1.54), and 1.10 (0.85-1.41) among Black, Hispanic, and White men, respectively. Adjusted PRs did not differ by age group. Interventions should consider jointly addressing mental health and substance use problems and potential drivers, e.g. stigma or socioeconomic factors.

For decades, Agrobacterium rhizogenes (now Rhizobium rhizogenes), the causative agent of hairy root disease, has been harnessed as an interkingdom DNA delivery tool for generating transgenic hairy roots on a wide variety of plants. One of the strategies involves the construction of transconjugant R. rhizogenes by transferring gene(s) of interest into previously constructed R. rhizogenes pBR322 acceptor strains; little has been done, however, to improve upon this system since its implementation. We developed a simplified method utilising bi-parental mating in conjunction with effective counterselection for generating R. rhizogenes transconjugants. Central to this was the construction of a new Modular Cloning (MoClo) compatible pBR322-derived integration vector (pIV101). Although this protocol remains limited to pBR322 acceptor strains, pIV101 facilitated an efficient construction of recombinant vectors, effective screening of transconjugants, and RP4-based mobilisation compatibility that enabled simplified conjugal transfer. Transconjugants from this system were tested on Lotus japonicus and found to be efficient for the transformation of transgenic hairy roots and supported infection of nodules by a rhizobia symbiont. The expedited protocol detailed herein substantially decreased both the time and labour for creating transconjugant R. rhizogenes for the subsequent transgenic hairy root transformation of Lotus, and it could readily be applied for the transformation of other plants.

BackgroundEvaluating the prognosis of patients with aneurysmal subarachnoid hemorrhage (aSAH) who may be at risk of poor outcomes using grading systems is one way to make a better decision on treatment for these patients. This study aimed to compare the accuracy of the modified World Federation of Neurosurgical Societies (WFNS), WFNS, and Hunt and Hess (H&H) Grading Scales in predicting the outcomes of patients with aSAH.MethodsFrom August 2019 to June 2021, we conducted a multicenter prospective cohort study on adult patients with aSAH in three central hospitals in Hanoi, Vietnam. The primary outcome was the 90-day poor outcome, measured by a score of 4 (moderately severe disability) to 6 (death) on the modified Rankin Scale (mRS). We calculated the areas under the receiver operator characteristic (ROC) curve (AUROCs) to determine how well the grading scales could predict patient prognosis upon admission. We also used ROC curve analysis to find the best cut-off value for each scale. We compared AUROCs using Z-statistics and compared 90-day mean mRS scores among intergrades using the pairwise multiple-comparison test. Finally, we used logistic regression to identify factors associated with the 90-day poor outcome.ResultsOf 415 patients, 32% had a 90-day poor outcome. The modified WFNS (AUROC: 0.839 [95% confidence interval, CI: 0.795-0.883]; cut-off value≥2.50; PAUROCConclusionsIn this study, the modified WFNS, WFNS, and H&H scales all had good discriminatory abilities for the prognosis of patients with aSAH. Because of the better effect size in predicting poor outcomes, the modified WFNS scale seems preferable to the WFNS and H&H scales.

Situated in the southern end of the Annamite Mountain Range, Langbiang Plateau is a major biodiversity hotspot of southern Vietnam known for high species diversity and endemicity. To achieve effective conservation, parts of the plateau were designated as the Langbiang Biosphere Reserve, an UNESCO World Network aiming to improve relationships between inhabitants and their environments. Amongst the rich endemic flora of the plateau are three gesneriads ascribed to Primulina, a calciphilous genus with high species diversity in the vast limestone karsts stretching from southern China to northern Vietnam. However, a recent phylogenetic study questioned the generic placement of the Langbiang Primulina, corroborating with observations on the geographical distribution, habitat preference, and phyllotaxy of the three species. Based on phylogenetic analyses of nuclear ITS and plastid trnL-F DNA sequences of a comprehensive sampling covering nearly all genera of the Old World Gesneriaceae, we demonstrate that the three Langbiang Primulina species form a fully supported clade distantly related to other Primulina. As this clade is biogeographically, ecologically, morphologically, and phylogenetically distinct worthy of generic recognition, we propose to name it Langbiangia gen. nov. to highlight the rich and unique biodiversity of the Langbiang Plateau. By means of this taxonomic endeavor, we are hoping to raise the conservation awareness of this biodiversity heritage of southern Vietnam and promote the importance of Langbiang Biosphere Reserve that is crucial for achieving action-oriented global targets of the post-2020 global biodiversity framework (GBF) of the UN Convention on Biological Diversity (CBD)-effective conservation and management of at least 30% of biodiverse terrestrial, inland water, and costal and marine areas by 2030-that has been agreed at the COP15 in Montréal in December 2022.

BackgroundDiagnosing concomitant pulmonary embolism (PE) in COVID-19 patients remains challenging. As such, PE may be overlooked. We compared the diagnostic yield of systematic PE-screening based on the YEARS-algorithm to PE-screening based on clinical gestalt in emergency department (ED) patients with COVID-19.MethodsWe included all ED patients who were admitted because of COVID-19 between March 2020 and February 2021. Patients already receiving anticoagulant treatment were excluded. Up to April 7, 2020, the decision to perform CT-pulmonary angiography (CTPA) was based on physician's clinical gestalt (clinical gestalt cohort). From April 7 onwards, systematic PE-screening was performed by CTPA if D-dimer level was ≥1000 ug/L, or ≥500 ug/L in case of ≥1 YEARS-item (systematic screening cohort).Results1095 ED patients with COVID-19 were admitted. After applying exclusion criteria, 289 were included in the clinical gestalt and 574 in the systematic screening cohort. The number of PE diagnoses was significantly higher in the systematic screening cohort compared to the clinical gestalt cohort: 8.2% vs. 1.0% (3/289 vs. 47/574; p100 mg/L (OR 2.78, 95%CI 1.37-5.66, p = 0.005) were independently associated with PE.ConclusionIn ED patients with COVID-19, the number of PE diagnosis was significantly higher in the cohort that underwent systematic PE screening based on the YEARS-algorithm in comparison with the clinical gestalt cohort, with a number needed to test of 7.1 CTPAs to detect one PE.

Background Diagnosing concomitant pulmonary embolism (PE) in COVID-19 patients remains challenging. As such, PE may be overlooked. We compared the diagnostic yield of systematic PE-screening based on the YEARS-algorithm to PE-screening based on clinical gestalt in emergency department (ED) patients with COVID-19. Methods We included all ED patients who were admitted because of COVID-19 between March 2020 and February 2021. Patients already receiving anticoagulant treatment were excluded. Up to April 7, 2020, the decision to perform CT-pulmonary angiography (CTPA) was based on physician’s clinical gestalt (clinical gestalt cohort). From April 7 onwards, systematic PE-screening was performed by CTPA if D-dimer level was ≥1000 ug/L, or ≥500 ug/L in case of ≥1 YEARS-item (systematic screening cohort). Results 1095 ED patients with COVID-19 were admitted. After applying exclusion criteria, 289 were included in the clinical gestalt and 574 in the systematic screening cohort. The number of PE diagnoses was significantly higher in the systematic screening cohort compared to the clinical gestalt cohort: 8.2% vs. 1.0% (3/289 vs. 47/574; p100 mg/L (OR 2.78, 95%CI 1.37–5.66, p = 0.005) were independently associated with PE. Conclusion In ED patients with COVID-19, the number of PE diagnosis was significantly higher in the cohort that underwent systematic PE screening based on the YEARS-algorithm in comparison with the clinical gestalt cohort, with a number needed to test of 7.1 CTPAs to detect one PE.

Background Acute diarrhea is a common health problem in children, especially those under five years of age (U5). The mortality rate due to acute diarrhea among U5 children accounted for 11% in Lao PDR in 2016. No study has been done to investigate the etiologic pathogens of acute diarrhea and the risk factors associated with dehydration status among U5 children hospitalized with acute diarrhea in this region. Objectives The study aimed to evaluate the clinical characteristics, etiological agents and associated factors of dehydration status of acute diarrhea among hospitalized U5 children in Savannakhet Province, Lao PDR. Methods This retrospective study reviewed paper-based medical records with available stool examination results of 33 U5 children hospitalized with acute diarrhea in Savannakhet Provincial Hospital, Lao PDR between Jan. 2018 and Dec. 2019. Descriptive statistics were used to describe clinical characteristics and etiologic agents of acute diarrhea of the children. Nonparametric test, Pearson’s Chi-square test and Fisher exact test were used to determine the risk factors associated with level of dehydration of the participants. Results Vomiting was the most common symptom (66.6%), followed by fever (60.6%). Dehydration was found in 48.4% of subjects. Rotavirus was the most common identified pathogen with a prevalence of 55.5%. Bacterial enteric infection was identified in 15.1% of patients. There is a significantly higher prevalence of dehydration among children with acute diarrhea caused by rotavirus compared to those with negative rotavirus testing (70.0% vs. 12.5%, p = 0.02). Conclusions Rotavirus was the most prevalent pathogen of acute diarrhea among U5 children. Pediatric patients with acute diarrhea caused by rotavirus had a higher prevalence of dehydration compared to those with negative rotavirus testing.

BackgroundAcute diarrhea is a common health problem in children, especially those under five years of age (U5). The mortality rate due to acute diarrhea among U5 children accounted for 11% in Lao PDR in 2016. No study has been done to investigate the etiologic pathogens of acute diarrhea and the risk factors associated with dehydration status among U5 children hospitalized with acute diarrhea in this region.ObjectivesThe study aimed to evaluate the clinical characteristics, etiological agents and associated factors of dehydration status of acute diarrhea among hospitalized U5 children in Savannakhet Province, Lao PDR.MethodsThis retrospective study reviewed paper-based medical records with available stool examination results of 33 U5 children hospitalized with acute diarrhea in Savannakhet Provincial Hospital, Lao PDR between Jan. 2018 and Dec. 2019. Descriptive statistics were used to describe clinical characteristics and etiologic agents of acute diarrhea of the children. Nonparametric test, Pearson's Chi-square test and Fisher exact test were used to determine the risk factors associated with level of dehydration of the participants.ResultsVomiting was the most common symptom (66.6%), followed by fever (60.6%). Dehydration was found in 48.4% of subjects. Rotavirus was the most common identified pathogen with a prevalence of 55.5%. Bacterial enteric infection was identified in 15.1% of patients. There is a significantly higher prevalence of dehydration among children with acute diarrhea caused by rotavirus compared to those with negative rotavirus testing (70.0% vs. 12.5%, p = 0.02).ConclusionsRotavirus was the most prevalent pathogen of acute diarrhea among U5 children. Pediatric patients with acute diarrhea caused by rotavirus had a higher prevalence of dehydration compared to those with negative rotavirus testing.

Antibiotics are frequently prescribed for children in the outpatient setting. Although sometimes necessary, antibiotic use is associated with important downstream effects including the development of antimicrobial resistance among human and environmental microorganisms. Current outpatient stewardship efforts focus on guiding appropriate antibiotic prescribing practices among providers, but little is known about parents' understanding of antibiotics and appropriate disposal of leftover antibiotics. To help bridge this gap, we conducted a qualitative study to assess parental understanding of their children's antibiotics, their adherence to antibiotic instructions, and their disposal practices. We conducted a semi-structured interview with parents of 13 children diagnosed with acute respiratory illnesses and prescribed antibiotics in an urban outpatient clinic. We found that parents had limited understanding of how antibiotics work. Although they received instructions about antibiotic use during the healthcare visit, adherence to the prescription and appropriate disposal of antibiotics was suboptimal. Limited baseline understanding of antibiotics, their prior experiences with antibiotics, perceptions about their social networks' antibiotic use, and information provided to them by healthcare providers may influence these behaviors. Our findings can inform educational efforts of outpatient stewardship programs to help optimize parental understanding of how to use and dispose of their children's antibiotics.

Antibiotics are frequently prescribed for children in the outpatient setting. Although sometimes necessary, antibiotic use is associated with important downstream effects including the development of antimicrobial resistance among human and environmental microorganisms. Current outpatient stewardship efforts focus on guiding appropriate antibiotic prescribing practices among providers, but little is known about parents’ understanding of antibiotics and appropriate disposal of leftover antibiotics. To help bridge this gap, we conducted a qualitative study to assess parental understanding of their children’s antibiotics, their adherence to antibiotic instructions, and their disposal practices. We conducted a semi-structured interview with parents of 13 children diagnosed with acute respiratory illnesses and prescribed antibiotics in an urban outpatient clinic. We found that parents had limited understanding of how antibiotics work. Although they received instructions about antibiotic use during the healthcare visit, adherence to the prescription and appropriate disposal of antibiotics was suboptimal. Limited baseline understanding of antibiotics, their prior experiences with antibiotics, perceptions about their social networks’ antibiotic use, and information provided to them by healthcare providers may influence these behaviors. Our findings can inform educational efforts of outpatient stewardship programs to help optimize parental understanding of how to use and dispose of their children’s antibiotics.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has made it clear that combating coronavirus outbreaks benefits from a combination of vaccines and therapeutics. A promising drug target common to all coronaviruses-including SARS-CoV, MERS-CoV, and SARS-CoV-2-is the papain-like protease (PLpro). PLpro cleaves part of the viral replicase polyproteins into non-structural protein subunits, which are essential to the viral replication cycle. Additionally, PLpro can cleave both ubiquitin and the ubiquitin-like protein ISG15 from host cell substrates as a mechanism to evade innate immune responses during infection. These roles make PLpro an attractive antiviral drug target. Here we demonstrate that ubiquitin variants (UbVs) can be selected from a phage-displayed library and used to specifically and potently block SARS-CoV-2 PLpro activity. A crystal structure of SARS-CoV-2 PLpro in complex with a representative UbV reveals a dimeric UbV bound to PLpro at a site distal to the catalytic site. Yet, the UbV inhibits the essential cleavage activities of the protease in vitro and in cells, and it reduces viral replication in cell culture by almost five orders of magnitude.

Raising environmental awareness and product development are two separate and costly investments that many small and medium-sized fashion businesses cannot afford to achieve sustainability. Therefore, there is a need to determine which factors exert a more significant impact on consumer loyalty and purchase intention toward eco-friendly fashions. Thus, this study employs a mixed-methods approach with thematic analysis and the SEM-PLS technique to research how Vietnamese Gen Z’s perceptions of product-service quality, environmental awareness, and pro-environmental behavior influence their purchase intention and loyalty toward eco-friendly fashion products. Most interviewees acknowledged that they primarily gained knowledge about eco-friendly fashion through social media platforms. The qualitative results further showed that their knowledge of and attitudes toward eco-friendly fashion practices were insufficient to convince young customers to afford eco-friendly fashion products. The SEM-PLS results of 313 participants show that while customers’ perceived behavioral control plays a more significant role in stimulating purchase intention, only product-service quality factors impact loyalty. Hence, this study suggests that businesses should prioritize improving service and product quality rather than funding green marketing when targeting Vietnamese Gen Z in case of financial constraints. Government should prioritize financial and technological support for fashion firms to develop high-quality eco-friendly fashion to ensure the product availability.

Raising environmental awareness and product development are two separate and costly investments that many small and medium-sized fashion businesses cannot afford to achieve sustainability. Therefore, there is a need to determine which factors exert a more significant impact on consumer loyalty and purchase intention toward eco-friendly fashions. Thus, this study employs a mixed-methods approach with thematic analysis and the SEM-PLS technique to research how Vietnamese Gen Z's perceptions of product-service quality, environmental awareness, and pro-environmental behavior influence their purchase intention and loyalty toward eco-friendly fashion products. Most interviewees acknowledged that they primarily gained knowledge about eco-friendly fashion through social media platforms. The qualitative results further showed that their knowledge of and attitudes toward eco-friendly fashion practices were insufficient to convince young customers to afford eco-friendly fashion products. The SEM-PLS results of 313 participants show that while customers' perceived behavioral control plays a more significant role in stimulating purchase intention, only product-service quality factors impact loyalty. Hence, this study suggests that businesses should prioritize improving service and product quality rather than funding green marketing when targeting Vietnamese Gen Z in case of financial constraints. Government should prioritize financial and technological support for fashion firms to develop high-quality eco-friendly fashion to ensure the product availability.

ObjectiveThis article describes the Personalized Reimbursement Model (PRM) program methodology, limitations, achievement and perspectives in using real-world data of cancer drugs use to improve and personalize drug pricing and reimbursement in France.Materials and methodsPRM platform aggregates Electronic Pharmacy Records (EPR) data from French medical centers (PRM centers) to build retrospective cohorts of patients treated with injectable cancer drugs in a hospital setting. Data extracted on January 1st, 2020, from breast cancer (BC) patients who received trastuzumab, trastuzumab emtansin or pertuzumab since January 1st, 2011, and from lung cancer (LC) patients who received bevacizumab or atezolizumab since January 1st, 2015, enabled recovering their injectable cancer drugs history from diagnosis date until December 30th, 2019, and served as dataset for assessment.Results123 PRM centers provided data from 30,730 patients (25,660 BC and 5,070 LC patients respectively). Overall, 20,942 (82%) of BC and 4,716 (93%) of LC patients were analyzed. Completion rate was above 98% for patients characteristics, diagnostic and treatment related data. PRM centers cover 48% and 33% of BC and LC patients in-hospital therapeutic management in France, respectively. Distribution of BC and LC patients therapeutic management, by medical center category and geographic location, was similar in PRM centers to all French medical centers, ensuring the representativeness of the PRM platform.ConclusionPRM Platform enabled building a national database generating on demand Real-World Evidence based on EPR. This enabled the first performance-based risk-sharing arrangements based on PRM data, between the CEPS and Roche, for atezolizumab cancer immunotherapy in metastatic non-small cell lung cancer indication.

Supplier selection and segmentation are crucial tasks of companies in order to reduce costs and increase the competitiveness of their goods. To handle uncertainty and dynamicity in the supplier segmentation problem, this research thus proposes a new dynamic generalized fuzzy multi-criteria group decision making (MCGDM) approach from the aspects of capability and willingness and with respect to environmental issues. The proposed approach defines the aggregated ratings of alternatives, the aggregated weights of criteria, and the weighted ratings by using generalized fuzzy numbers with the effect of time weight. Next, we determine the ranking order of alternatives via a popular centroid-index ranking approach. Finally, two case studies demonstrate the efficiency of the proposed dynamic approach. The applications show that the proposed appoach is effective in solving the MCGDM in vague environment.

[This corrects the article DOI: 10.1371/journal.pone.0245187.].

Categorical judgments can systematically bias the perceptual interpretation of stimulus features. However, it remained unclear whether categorical judgments directly modify working memory representations or, alternatively, generate these biases via an inference process down-stream from working memory. To address this question we ran two novel psychophysical experiments in which human subjects had to reverse their categorical judgments about a stimulus feature, if incorrect, before providing an estimate of the feature. If categorical judgments indeed directly altered sensory representations in working memory, subjects' estimates should reflect some aspects of their initial (incorrect) categorical judgment in those trials. We found no traces of the initial categorical judgment. Rather, subjects seemed to be able to flexibly switch their categorical judgment if needed and use the correct corresponding categorical prior to properly perform feature inference. A cross-validated model comparison also revealed that feedback may lead to selective memory recall such that only memory samples that are consistent with the categorical judgment are accepted for the inference process. Our results suggest that categorical judgments do not modify sensory information in working memory but rather act as top-down expectations in the subsequent sensory recall and inference process.

Access to quality veterinary antimicrobial products contributes to efficient treatment of diseases in Vietnamese livestock and to reducing antimicrobial resistance (AMR). Poor quality antimicrobial drugs can lead to treatment failure, potentially influencing the inappropriate use of antimicrobials products, including increasing the dose, combining drugs, or changing to a broader spectrum antimicrobial. The objective of the study was to determine the actual concentration of antimicrobial active ingredient (AAI) in commercially available veterinary antimicrobial products as an indicator of their quality. A total of 144 veterinary antimicrobial products were purchased from randomly selected veterinary drug stores in 34 districts in eight provinces. For the qualitative analysis, we observed criteria linked to form, colour, and labelling information according to the Department of Animal Health regulations. For the quantitative analysis, high-performance liquid chromatography was used to determine the actual concentration of AAI in each sample. Of the 144 samples, 131 (91%) met the national standard of quality of being within ±10% of the labelled concentration. Ten antimicrobials (6.9%) contained less than half of the labelled content concentrations. Veterinary antimicrobial product quality control is an important part of addressing AMR. To support the national action plan to lower AMR, a veterinary drug quality control program should be implemented at all stages of the supply chain to assure high quality drugs and effective treatment of sick animals.

Although many researchers and policy makers have argued that social mixing could contribute to sustainable communities, most people still prefer to live in a homogeneous rather than a diverse community. Considering the large gap between the political need for social mixing and people's preference, it is essential to understand residents' perceptions and preferences regarding socially-mixed neighborhoods in order to promote sustainable community development. This study explorers residents' willingness to accept living in mixed-income communities in Korea, with attention to various levels of income mix. This study conducted an online survey of 2,000 respondents living in seven metropolitan cities in Korea, including Seoul. The study aimed to investigate residents' comfortability and willingness to move into different mixed-income communities. The results showed that residents with higher openness to diversity are more likely to accept mixed-income communities, but frequent interaction with low-income people reduces higher-income people's willingness to accept mixed-income communities. As both personal attitudes and experience are important determinants of individuals' social mix preference, a more systematic community development strategy is required to achieve successful social mixing.

Experimental autoimmune encephalomyelitis (EAE) is an established animal model of multiple sclerosis (MS). Inflammatory CD4+ T cell responses directed against CNS antigens, including myelin proteolipid protein (PLP), are key mediators of EAE. Dendritic cells (DCs) are critical for the induction of T cell responses against infectious agents. However, the importance of DCs in priming self-reactive CD4+ T cells in autoimmune disease such as MS has been unclear. To determine the requirement of DCs in PLP-specific CD4+ T cell responses and EAE, we genetically deleted CD11c+ DCs in PLP T cell receptor (TCR) transgenic SJL mice constitutively. DC deficiency did not impair the development, selection or the pathogenic function of PLP-specific CD4+ T cells in these mice, and resulted in accelerated spontaneous EAE compared to DC sufficient controls. In addition, using a genetic approach to ablate DCs conditionally in SJL mice, we show that CD11c+ DCs were dispensable for presenting exogenous or endogenous myelin antigen to PLP-specific T cells and for promoting pro-inflammatory T cell responses and severe EAE. Our findings demonstrate that constitutive or conditional ablation of CD11c+ DCs diminished self-tolerance to PLP autoantigen. They further show that in the absence of DCs, non-DCs can efficiently present CNS myelin antigens such as PLP to self-reactive T cells, resulting in accelerated onset of spontaneous or induced EAE.

[This corrects the article DOI: 10.1371/journal.pone.0093608.].

IntroductionAtopic dermatitis is a common skin disease characterized by altered cutaneous immunity in which patients often exhibit lower skin microbiota diversity compared to healthy skin and are prone to colonization by Staphylococcus aureus. Apple cider vinegar has been shown to have antibacterial effects; however, its effects on the skin microbiome have not previously been well-described.ObjectivesWe aimed to examine the effects of topical dilute apple cider vinegar soaks on Staphylococcus aureus abundance, skin bacterial microbiome composition, and skin bacterial microbiome diversity in atopic dermatitis participants compared to healthy skin.MethodsEleven subjects with atopic dermatitis and 11 healthy controls were enrolled in this randomized, non-blinded, single-institution, split-arm pilot study. Subjects soaked one forearm in dilute apple cider vinegar (0.5% acetic acid) and the other forearm in tap water for 10 minutes daily. Skin bacteria samples were collected from subjects' volar forearms before and after 14 days of treatment. 16S sequencing was used to analyze Staphylococcus aureus abundance and skin bacterial microbiome composition, and alpha diversity of microbiota were determined using Shannon diversity index.ResultsThere was no difference in skin bacterial microbiome in atopic dermatitis subjects after 2 weeks of daily water or apple cider vinegar treatments (p = 0.056 and p = 0.22, respectively), or in mean abundance of S. aureus on apple cider vinegar-treated forearms (p = 0.60). At 2 weeks, the skin bacterial microbiomes of healthy control subjects were not significantly different from the skin bacterial microbiome of atopic dermatitis subjects (p = 0.14, 0.21, 0.12, and 0.05).ConclusionsOur results suggest that daily soaks in 0.5% apple cider vinegar are not an effective method of altering the skin bacterial microbiome in atopic dermatitis. Further studies are needed to explore the effects of different concentrations of apple cider vinegar on skin microflora and disease severity.Trial numberUVA IRB-HSR #19906.

This study aims to make a critical review of provincial competitiveness index (PCI) in the Central Highlands of Vietnam. In this regard, the research examines relationships between PCI and the possible attraction of enterprises operating in the region, thereafter, proposes some policy recommendations to improve business environment in the region. The secondary dataset of PCI and enterprise were incorporate with primary data collected from qualitative methods to explore the effect of PCI on enterprise attraction. The results show that the enterprises which have been operating in the Central Highlands accounted for 2.2% of the total with invested capital and accounted for 1.1% of whole country in 2018. PCI highly correlates with the number of enterprises, the employees and the capital of enterprises. Consequently, in order to attract enterprises, local governments in the region need to improve sub-indexes thereby improving general PCI scores.

Highly methylated Long Interspersed Nucleotide Elements 1 (LINE-1) constitute approximately 20% of the human genome, thus serving as a surrogate marker of global genomic DNA methylation. To date, there is still lacking a consensus about the precise location in LINE-1 promoter and its methylation threshold value, making challenging the use of LINE-1 methylation as a diagnostic, prognostic markers in cancer. This study reports on a technical standardization of bisulfite-based DNA methylation analysis, which ensures the complete bisulfite conversion of repeated LINE-1 sequences, thus allowing accurate LINE-1 methylation value. In addition, the study also indicated the precise location in LINE-1 promoter of which significant variance in methylation level makes LINE-1 methylation as a potential diagnostic biomarker for lung cancer. A serial concentration of 5-50-500 ng of DNA from 275 formalin-fixed paraffin-embedded lung tissues were converted by bisulfite; methylation level of two local regions (at nucleotide position 300-368 as LINE-1.1 and 368-460 as LINE-1.2) in LINE-1 promoter was measured by real time PCR. The use of 5 ng of genomic DNA but no more allowed to detect LINE-1 hypomethylation in lung cancer tissue (14.34% versus 16.69% in non-cancerous lung diseases for LINE-1.1, p < 0.0001, and 30.28% versus 32.35% for LINE-1.2, p < 0.05). Our study thus highlighted the optimal and primordial concentration less than 5 ng of genomic DNA guarantees the complete LINE-1 bisulfite conversion, and significant variance in methylation level of the LINE-1 sequence position from 300 to 368 allowed to discriminate lung cancer from non-cancer samples.

BackgroundThe prevalence of risk factors for poor outcomes from aneurysmal subarachnoid hemorrhage (SAH) varies widely and has not been fully elucidated to date in Vietnam. Understanding the risk and prognosis of aneurysmal SAH is important to reduce poor outcomes in Vietnam. The aim of this study, therefore, was to investigate the rate of poor outcome at 90 days of ictus and associated factors from aneurysmal SAH in the country.MethodsWe performed a multicenter prospective cohort study of patients (≥18 years) presenting with aneurysmal SAH to three central hospitals in Hanoi, Vietnam, from August 2019 to August 2020. We collected data on the characteristics, management, and outcomes of patients with aneurysmal SAH and compared these data between good (defined as modified Rankin Scale (mRS) of 0 to 3) and poor (mRS, 4-6) outcomes at 90 days of ictus. We assessed factors associated with poor outcomes using logistic regression analysis.ResultsOf 168 patients with aneurysmal SAH, 77/168 (45.8%) were men, and the median age was 57 years (IQR: 48-67). Up to 57/168 (33.9%) of these patients had poor outcomes at 90 days of ictus. Most patients underwent sudden-onset and severe headache (87.5%; 147/168) and were transferred from local to participating central hospitals (80.4%, 135/168), over half (57.1%, 92/161) of whom arrived in central hospitals after 24 hours of ictus, and the initial median World Federation of Neurological Surgeons (WFNS) grading score was 2 (IQR: 1-4). Nearly half of the patients (47.0%; 79/168) were treated with endovascular coiling, 37.5% (63/168) were treated with surgical clipping, the remaining patients (15.5%; 26/168) did not receive aneurysm repair, and late rebleeding and delayed cerebral ischemia (DCI) occurred in 6.1% (10/164) and 10.4% (17/163) of patients, respectively. An initial WFNS grade of IV (odds ratio, OR: 15.285; 95% confidence interval, CI: 3.096-75.466) and a grade of V (OR: 162.965; 95% CI: 9.975-2662.318) were independently associated with poor outcomes. Additionally, both endovascular coiling (OR: 0.033; 95% CI: 0.005-0.235) and surgical clipping (OR: 0.046; 95% CI: 0.006-0.370) were inversely and independently associated with poor outcome. Late rebleeding (OR: 97.624; 95% CI: 5.653-1686.010) and DCI (OR: 15.209; 95% CI: 2.321-99.673) were also independently associated with poor outcome.ConclusionsImprovements are needed in the management of aneurysmal SAH in Vietnam, such as increasing the number of aneurysm repairs, performing earlier aneurysm treatment by surgical clipping or endovascular coiling, and improving both aneurysm repairs and neurocritical care.

Using the 9th round of European Social Survey (ESS), we explored the relationship between Europeans' basic values and their attitudes towards immigrants. Employing a latent class analysis (LCA), we classified the respondents based on three items capturing the extent to which participants would support allowing three groups of immigrants to enter and live in their countries: immigrants of same ethnic groups, immigrants of different ethnic groups, and immigrants from poorer countries outside Europe. Four classes of Europeans with mutually exclusive response patterns with respect to their inclusive attitudes towards immigrants were found. The classes were named Inclusive (highly inclusive), Some (selective), Few (highly selective), and Exclusive (highly exclusive). Next, using a network technique, a partial correlation network of 10 basic human values was estimated for each class of participants. The four networks were compared to each other based on three network properties namely: global connectivity, community detection, and assortativity coefficient. The global connectivity (the overall level of interconnections) between the 10 basic values was found to be mostly invariant across the four networks. However, results of the community detection analysis revealed a more complex value structure among the most inclusive class of Europeans. Further, according to the assortativity analysis, as expected, for the most inclusive Europeans, values with similar motivational backgrounds were found to be interconnected most strongly to one another. We further discussed the theoretical and practical implications of our findings.

BackgroundSince the COVID-19 pandemic began, there have been concerns related to the preparedness of healthcare workers (HCWs). This study aimed to describe the level of awareness and preparedness of hospital HCWs at the time of the first wave.MethodsThis multinational, multicenter, cross-sectional survey was conducted among hospital HCWs from February to May 2020. We used a hierarchical logistic regression multivariate analysis to adjust the influence of variables based on awareness and preparedness. We then used association rule mining to identify relationships between HCW confidence in handling suspected COVID-19 patients and prior COVID-19 case-management training.ResultsWe surveyed 24,653 HCWs from 371 hospitals across 57 countries and received 17,302 responses from 70.2% HCWs overall. The median COVID-19 preparedness score was 11.0 (interquartile range [IQR] = 6.0-14.0) and the median awareness score was 29.6 (IQR = 26.6-32.6). HCWs at COVID-19 designated facilities with previous outbreak experience, or HCWs who were trained for dealing with the SARS-CoV-2 outbreak, had significantly higher levels of preparedness and awareness (pInterpretationThere was an unsurprising high level of awareness and preparedness among HCWs who participated in COVID-19 training courses. However, disparity existed along the lines of gender and type of HCW. It is unknown whether the difference in COVID-19 preparedness that we detected early in the pandemic may have translated into disproportionate SARS-CoV-2 burden of disease by gender or HCW type.

One of the earliest and most prevalent barriers to successful reproduction is polyspermy, or fertilization of an egg by multiple sperm. To prevent these supernumerary fertilizations, eggs have evolved multiple mechanisms. It has recently been proposed that zinc released by mammalian eggs at fertilization may block additional sperm from entering. Here, we demonstrate that eggs from amphibia and teleost fish also release zinc. Using Xenopus laevis as a model, we document that zinc reversibly blocks fertilization. Finally, we demonstrate that extracellular zinc similarly disrupts early embryonic development in eggs from diverse phyla, including Cnidaria, Echinodermata, and Chordata. Our study reveals that a fundamental strategy protecting human eggs from fertilization by multiple sperm may have evolved more than 650 million years ago.

Outbreaks of emerging coronaviruses in the past two decades and the current pandemic of a novel coronavirus (SARS-CoV-2) that emerged in China highlight the importance of this viral family as a zoonotic public health threat. To gain a better understanding of coronavirus presence and diversity in wildlife at wildlife-human interfaces in three southern provinces in Viet Nam 2013-2014, we used consensus Polymerase Chain Reactions to detect coronavirus sequences. In comparison to previous studies, we observed high proportions of positive samples among field rats (34.0%, 239/702) destined for human consumption and insectivorous bats in guano farms (74.8%, 234/313) adjacent to human dwellings. Most notably among field rats, the odds of coronavirus RNA detection significantly increased along the supply chain from field rats sold by traders (reference group; 20.7% positivity, 39/188) by a factor of 2.2 for field rats sold in large markets (32.0%, 116/363) and 10.0 for field rats sold and served in restaurants (55.6%, 84/151). Coronaviruses were also detected in rodents on the majority of wildlife farms sampled (60.7%, 17/28). These coronaviruses were found in the Malayan porcupines (6.0%, 20/331) and bamboo rats (6.3%, 6/96) that are raised on wildlife farms for human consumption as food. We identified six known coronaviruses in bats and rodents, clustered in three Coronaviridae genera, including the Alpha-, Beta-, and Gammacoronaviruses. Our analysis also suggested either mixing of animal excreta in the environment or interspecies transmission of coronaviruses, as both bat and avian coronaviruses were detected in rodent feces on wildlife farms. The mixing of multiple coronaviruses, and their apparent amplification along the wildlife supply chain into restaurants, suggests maximal risk for end consumers and likely underpins the mechanisms of zoonotic spillover to people.

Cluster of differentiation (CD) 166 or activated leukocyte cell adhesion molecule (ALCAM) is a transmembrane molecule known to be an intercellular adhesion factor. The expression and function of ALCAM in medulloblastoma (MB), a pediatric brain tumor with highly advanced molecular genetics, remains unclear. Therefore, this study aimed to clarify the significance and functional role of ALCAM expression in MB. ALCAM expression in 45 patients with MB was evaluated by immunohistochemical analysis of formalin-fixed paraffin-embedded clinical specimens and the relationship between ALCAM expression and pathological type/molecular subgroup, such as WNT, SHH, Group 3, and Group 4, was examined. Eight ALCAM positive (18%), seven partially positive (16%), and 30 negative (67%) cases were detected. All seven cases of the WNT molecular subgroup were ALCAM positive and ALCAM expression strongly correlated with this subgroup (P < 0.0001). In addition, functional studies using MB cell lines revealed ALCAM expression affected proliferation and migration as a positive regulator in vitro. However, ALCAM silencing did not affect survival or the formation of leptomeningeal dissemination in an orthotopic mouse model, but did induce a malignant phenotype with increased tumor cell invasion at the dissemination sites (P = 0.0029). In conclusion, our results revealed that ALCAM exhibited highly specific expression in the WNT subgroup of MB. Furthermore, we demonstrated that the cell kinetics of MB cell lines can be altered by the expression of ALCAM.

BackgroundThis study aimed to help the Namibian government understand the impact of Treat All implementation (started on April 1, 2017) on key antiretroviral therapy (ART) outcomes, and how this transition impacts progress toward the UNAIDS's 90-90-90 HIV targets.MethodsWe collected clinical records from two separate cohorts (before and after treat-all) of ART patients in 10 high- and medium-volume facilities in 6 northern Namibia districts. Each cohort contains 12-month data on patients' scheduled appointments and visits, health status, and viral load results. We also measured patients' wait time and perceptions of service quality using exit interviews with 300 randomly selected patients (per round). We compared ART outcomes of the two cohorts: ART initiation within 7 days from diagnosis, loss to follow-up (LTFU), missed scheduled appointments for at least 30 days, and viral suppression using unadjusted and adjusted analyses.ResultsAmong new ART clients (on ART for less than 3 months or had not yet initiated treatment as of the start date for the ART record review period), rapid ART initiation (within 7 days from diagnosis) was 5.2 times higher after Treat All than that among clients assessed before the policy took effect [AOR: 5.2 (3.8-6.9)]. However, LTFU was higher after Treat All roll-out compared to before Treat All [AOR: 1.9 (1.3-2.8)]. Established ART clients (on ART treatment for at least three months at the start date of the ART record review period) had over 3 times greater odds of achieving viral suppression after Treat All roll-out compared to established ART clients assessed before Treat All [AOR: 3.1 (1.6-5.9)].Conclusions and recommendationsThe findings indicate positive effect of the "Treat All" implementation on ART initiation and viral suppression, and negative effect on LTFU. Additionally, by April 2018, Namibia seems to have reached the UNAIDS's 90-90-90 targets.

Caesarean section (CS) can prevent maternal and neonatal mortality and morbidity. However, it involves risks and high costs that can be a burden, especially in low and middle income countries. The aim of this study is to assess its magnitude and correlates among women of reproductive age in the urban and rural areas of Vietnam. We analyzed microdata from the national Multiple Indicator Cluster Survey (MICS) conducted in 2014 by using a representative sample of households at the national level in both urban and rural areas. A total of 1,350 women who delivered in institutional settings in the two years preceding the survey were included. Frequency and percentage distributions of the variables were performed. Bivariate and multivariate logistic regression analyses were undertaken to identify the factors associated with CS. Odds ratios with a 95% confidence interval were used to ascertain the direction and strength of the associations. The overall CS rate among the women who delivered in healthcare facilities in Vietnam has rapidly increased and reached a high level (29.2%). After controlling for significant characteristics, living in urban areas doubles the likelihood of undergoing a CS (OR = 1.98; 95% CI 1.48 to 2.67). Maternal age at delivery over 35 years is a major positive correlate of CS. Beyond this common phenomenon, different distinct lines of socioeconomic and demographic cleavage operate in urban compared with rural areas. The differences regarding the correlates of CS according to the place of residence suggest that specific measures should be taken in each setting to allow women to access childbirth services that are appropriate to their needs.

Interferon α (IFNα) counteracts viral infections by activating various IFNα-stimulated genes (ISGs). These genes encode proteins that block viral transport into the host cell and inhibit viral replication, gene transcription and translation. Due to the existence of 14 different, highly homologous isoforms of mouse IFNα, an IFNα knockout mouse has not yet been established by genetic knockout strategies. An scFv intrabody for holding back IFNα isoforms in the endoplasmic reticulum (ER) and thus counteracting IFNα secretion is reported. The intrabody was constructed from the variable domains of the anti-mouse IFNα rat monoclonal antibody 4EA1 recognizing the 5 isoforms IFNα1, IFNα2, IFNα4, IFNα5, IFNα6. A soluble form of the intrabody had a KD of 39 nM to IFNα4. It could be demonstrated that the anti-IFNα intrabody inhibits clearly recombinant IFNα4 secretion by HEK293T cells. In addition, the secretion of IFNα4 was effectively inhibited in stably transfected intrabody expressing RAW 264.7 macrophages and dendritic D1 cells. Colocalization of the intrabody with IFNα4 and the ER marker calnexin in HEK293T cells indicated complex formation of intrabody and IFNα4 inside the ER. Intracellular binding of intrabody and antigen was confirmed by co-immunoprecipitation. Complexes of endogenous IFNα and intrabody could be visualized in the ER of Poly (I:C) stimulated RAW 264.7 macrophages and D1 dendritic cells. Infection of macrophages and dendritic cells with the vesicular stomatitis virus VSV-AV2 is attenuated by IFNα and IFNβ. The intrabody increased virus proliferation in RAW 264.7 macrophages and D1 dendritic cells under IFNβ-neutralizing conditions. To analyze if all IFNα isoforms are recognized by the intrabody was not in the focus of this study. Provided that binding of the intrabody to all isoforms was confirmed, the establishment of transgenic intrabody mice would be promising for studying the function of IFNα during viral infection and autoimmune diseases.

Sanfilippo syndrome type B (Sanfilippo B; Mucopolysaccharidosis type IIIB) occurs due to genetic deficiency of lysosomal alpha-N-acetylglucosaminidase (NAGLU) and subsequent lysosomal accumulation of heparan sulfate (HS), which coincides with devastating neurodegenerative disease. Because NAGLU expressed in Chinese hamster ovary cells is not mannose-6-phosphorylated, we developed an insulin-like growth factor 2 (IGF2)-tagged NAGLU molecule (BMN 250; tralesinidase alfa) that binds avidly to the IGF2 / cation-independent mannose 6-phosphate receptor (CI-MPR) for glycosylation independent lysosomal targeting. BMN 250 is currently being developed as an investigational enzyme replacement therapy for Sanfilippo B. Here we distinguish two cellular uptake mechanisms by which BMN 250 is targeted to lysosomes. In normal rodent-derived neurons and astrocytes, the majority of BMN250 uptake over 24 hours reaches saturation, which can be competitively inhibited with IGF2, suggestive of CI-MPR-mediated uptake. Kuptake, defined as the concentration of enzyme at half-maximal uptake, is 5 nM and 3 nM in neurons and astrocytes, with a maximal uptake capacity (Vmax) corresponding to 764 nmol/hr/mg and 5380 nmol/hr/mg, respectively. Similar to neurons and astrocytes, BMN 250 uptake in Sanfilippo B patient fibroblasts is predominantly CI-MPR-mediated, resulting in augmentation of NAGLU activity with doses of enzyme that fall well below the Kuptake (5 nM), which are sufficient to prevent HS accumulation. In contrast, uptake of the untagged recombinant human NAGLU (rhNAGLU) enzyme in neurons, astrocytes and fibroblasts is negligible at the same doses tested. In microglia, receptor-independent uptake, defined as enzyme uptake resistant to competition with excess IGF2, results in appreciable lysosomal delivery of BMN 250 and rhNAGLU (Vmax = 12,336 nmol/hr/mg and 5469 nmol/hr/mg, respectively). These results suggest that while receptor-independent mechanisms exist for lysosomal targeting of rhNAGLU in microglia, BMN 250, by its IGF2 tag moiety, confers increased CI-MPR-mediated lysosomal targeting to neurons and astrocytes, two additional critical cell types of Sanfilippo B disease pathogenesis.

The availability of large amounts of high-throughput genomic, transcriptomic and epigenomic data has provided opportunity to understand regulation of the cellular transcriptome with an unprecedented level of detail. As a result, research has advanced from identifying gene expression patterns associated with particular conditions to elucidating signalling pathways that regulate expression. There are over 1,000 transcription factors (TFs) in vertebrates that play a role in this regulation. Determining which of these are likely to be controlling a set of genes can be assisted by computational prediction, utilising experimentally verified binding site motifs. Here we present CiiiDER, an integrated computational toolkit for transcription factor binding analysis, written in the Java programming language, to make it independent of computer operating system. It is operated through an intuitive graphical user interface with interactive, high-quality visual outputs, making it accessible to all researchers. CiiiDER predicts transcription factor binding sites (TFBSs) across regulatory regions of interest, such as promoters and enhancers derived from any species. It can perform an enrichment analysis to identify TFs that are significantly over- or under-represented in comparison to a bespoke background set and thereby elucidate pathways regulating sets of genes of pathophysiological importance.

BACKGROUND AND AIM:Vietnam's burden of liver cancer is largely due to its high prevalence of chronic hepatitis B virus (HBV) infection. This study aimed to examine healthcare workers' (HCWs) knowledge, attitude and practices regarding HBV prevention and management. METHODS:A cross-sectional survey among health care workers working at primary and tertiary facilities in two Northern provinces in Vietnam in 2017. A standardized questionnaire was administered to randomly selected HCWs. Multivariate regression was used to identify predictors of the HBV knowledge score. RESULTS:Among the 314 participants, 75.5% did not know HBV infection at birth carries the highest risk of developing chronic infection. The median knowledge score was 25 out of 42 (59.5%). About one third (30.2%) wrongly believed that HBV can be transmitted through eating or sharing food with chronic hepatitis B patients. About 38.8% did not feel confident that the hepatitis B vaccine is safe. Only 30.1% provided correct answers to all the questions on injection safety. Up to 48.2% reported they consistently recap needles with two hands after injection, a practice that would put them at greater risk of needle stick injury. About 24.2% reported having been pricked by a needle at work within the past 12 months. More than 40% were concerned about having casual contact or sharing food with a person with chronic hepatitis B infection (CHB). In multivariate analysis, physicians scored significantly higher compared to other healthcare professionals. Having received training regarding hepatitis B within the last two years was also significantly associated with a better HBV knowledge score. CONCLUSIONS:Findings from the survey indicated an immediate need to implement an effective hepatitis B education and training program to build capacity among Vietnam's healthcare workers in hepatitis B prevention and control and to dispel hepatitis B stigma.

There has been marked improvement in leukemia survival, particularly among children in recent time. However, the long-term trends in survival among adult leukemia patients and the associated sex and racial survival disparities are not well understood. We, therefore, evaluated the secular trends in survival improvement of leukemia patients from 1973 through 2014, using Surveillance Epidemiology and End-Result Survey Program (SEER) data. ICD-O-3 morphology codes were used to group leukemia into four types: acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML). Survival analysis for each leukemia type stratified by race/ethnicity, age, sex was performed to generate relative survival probability estimates for the baseline time period of 1973 through 1979. Hazard ratios (HR) and respective 95% confidence intervals (CIs) for survival within subsequent 10-year time periods by race, age and sex were calculated using Cox proportional hazard models. Of the 83,255 leukemia patients for the current analysis, the 5-year survival of patients with ALL, AML, CLL, and CML during 1973-1979 were 42.0%, 6.5%, 66.5%, and 20.9%, respectively. Compared to the baseline, there were substantial improvements of leukemia-specific survival in 2010-2014 among African-American (81.0%) and Asian (80.0%) patients with CML and among 20-49 year of age with CLL (96.0%). African-American patients, those with AML and those older than 75 years of age had the lowest survival improvements. Asians experienced some of the largest survival improvements during the study period. Others, including African-American and the elderly, have not benefited as much from advances in leukemia treatment.

Background and aimInfection at birth due to mother-to-child (MTC) transmission is the most common cause of chronic hepatitis B virus (HBV) infection in Vietnam. This study was undertaken to examine the knowledge, attitudes, and practices of pregnant women and mothers in Vietnam concerning HBV prevention and immunization.MethodsA cross-sectional survey was conducted in Quang Ninh and Hoa Binh provinces in 2017. A standardized questionnaire was administered to women when they received care at primary and tertiary maternal health clinics. Multivariate regression was used to identify predictors of HBV knowledge and practices.ResultsAmong the 380 women surveyed, 50.3% were pregnant and 49.7% were postpartum. Despite 70.3% of participants reported having received information about HBV during their pregnancy, only 10.8% provided correct answers to all questions regarding HBV transmission routes and preventive measures. Around half of the participants incorrectly believed that HBV is transmitted through sneezing, contaminated water or sharing foods with chronic HBV patients. Although 86.1% of participants believed that HBV vaccination is necessary for infants, only 66.1% responded they were definitely willing to have their own child vaccinated within 24 hours. More than a third of participants expressed concern about having casual contacts or sharing foods with chronic HBV patients. In multivariate analysis, having received information about HBV during their pregnancy was significantly associated with better HBV knowledge score. Delivery at provincial level clinics was a strong predictor for perinatal HBV screening and hepatitis B birth dose administration.ConclusionsThe results highlight the need to prioritize educating pregnant women and mothers in future public health campaigns in order to increase knowledge, reduce misperception, and improve hepatitis B vaccine birth dose coverage in Vietnam.

IntroductionRisk of developing a malignancy when born premature is unknown. We hypothesised that risk of certain cancers might be increased in youth born preterm versus term. We therefore performed a systematic review and meta-analysis to evaluate the incidence of malignancy in the context of preterm birth, according to various cancer types.MethodsThe study was designed per MOOSE and PRISMA guidelines. Articles were identified through November 2015. Observational studies exploring the association between childhood malignancy and birth characteristics were included. Of the 1658 records identified, 109 full text articles were evaluated for eligibility. Random effects meta-analyses were conducted on 10/26 studies retained; 95% confidence intervals were computed and adjusted following sensitivity analysis. Publication bias was evaluated using funnel plots, Begg's and Egger's tests.ResultsNo differences in risk of primary central nervous system tumor [OR 1.05; 95% CI 0.93-1.17, 5 studies, 580 cases] and neuroblastoma [OR 1.09; 95% CI 0.90-1.32, 5 studies, 211 cases] were observed in individuals born ConclusionsChildren born premature may be at increased risk for hepatoblastoma but there is no strong evidence of an increased risk of primary central nervous system tumours or neuroblastoma. There is insufficient evidence to conclude whether prematurity modulates the risk of other childhood cancers.

BackgroundOptical coherence tomography is commonly used to measure the retinal nerve fibre layer thickness in both normal and diseased eyes; however, variation among normal eyes is common and may limit the usefulness of the results. The aim of this study was to explore the interocular asymmetries in retinal nerve fibre layer thickness in a group of normal eyes and to investigate the influence of blood vessel diameter on local retinal nerve fibre layer thickness.MethodsIn this prospective study, retinal nerve fibre layer thickness and blood vessel diameter across 100 healthy participants were measured using two optical coherence tomography instruments. Individuals were categorised into two groups based on the presence or absence of interocular retinal nerve fibre layer thickness asymmetry beyond the 75th percentile of all participants.ResultsThe superonasal sectoral retinal nerve fibre layer thickness was significantly greater in the left eye compared to the right, across all three sectors. Mean blood vessel diameter showed a corresponding difference in thickness at one of the superonasal sectors. Linear regression showed a positive and moderate correlation between blood vessel diameter and focal retinal nerve fibre layer thickness. This trend persisted across both arteries and veins, but veins showed larger variability between left and right eye in participants with marked superonasal retinal nerve fibre layer asymmetry.ConclusionRetinal nerve fibre layer thickness and blood vessel diameter vary significantly between eyes even in healthy individuals. These asymmetries in a normal population should be taken into consideration when interpreting the retinal nerve fibre layer thickness measurements from optical coherence tomography to assist in distinguishing normal variations from disease.

The goal of this study is to characterize the genomic and immune profiles of metaplastic breast cancer (MpBC) and identify the association with survival through an analysis of archived tumor tissue. A next-generation sequencing-based mutational assay (Onco-48) was performed for 21 MpBC patients. Clinicopathologic characteristics were captured, including relapse free survival (RFS) and overall survival (OS). Immunohistochemistry (IHC) for CD3, CD4, CD8, and programmed death-ligand 1 (PD-L1) was also performed. Recurrence free survival (RFS) at 5 years was 57% (95% CI 0.34-0.75) and overall survival (OS) at 5 years was 66% (95% CI 0.41-0.82). The most commonly altered genes were TP53 (68.4%, 13/19), PIK3CA (42.1%, 8/19), and PTEN (15.8%, 3/19. For patients with PIK3CA mutations, RFS and OS were significantly worse than for those without (HR 5.6, 95% CI 1.33-23.1 and HR 8.0, 95% CI 1.53-41.7, respectively). Cox regression estimated that PD-L1 expression was associated with worse RFS and OS (HR 1.08, 95% CI 1.01-1.16 and HR 1.05, 95% CI 1.00-1.11, respectively, for an absolute increase in PD-L1 expression of 1%). In conclusion, PIK3CA mutation and PD-L1 expression confer poor prognosis in this cohort of patients with MpBC.

IntroductionTelomeres and telomerase play important role in maintaining chromosome integrity and genomic stability. Recent epidemiologic data showed inconsistent findings which suggested that both short and long leukocyte telomeres could be associated with increased risk of pancreatic cancer. We prospectively examined the association between telomere length and pancreatic cancer risk in a population-based cohort study.MethodsThe Singapore Chinese Health Study recruited 63,257 Chinese aged 45 to 74 years from 1993 to 1998 in Singapore. Relative telomere length in peripheral blood leukocytes was quantified using a validated monochrome multiplex quantitative polymerase chain reaction method in 26,540 participants, including 116 participants who later developed pancreatic cancer after an average of 13 years of follow-up. Cox proportional hazard regression method was used to calculate hazard ratio (HR) and its 95% confidence interval (CI) of pancreatic cancer risk associated with telomere length, with adjustment for confounding factors.ResultsLonger telomeres were significantly associated with higher risk of pancreatic cancer (Ptrend = 0.02). Compared with lowest quartile, subjects with highest quartile of telomere length had an HR of 2.18 (95% CI: 1.25-3.80) for developing pancreatic cancer. In stratified analysis, this association remained among pancreatic adenocarcinoma patients but not among pancreatic non-adenocarcinoma patients. In continuous scale, the HRs and 95% CIs were 3.08 (1.17-8.11) for adenocarcinoma patients and 1.47 (0.43-5.06) for non-adenocarcinoma patients. The HRs and 95% CIs of the highest quartile of telomere length, compared with the lowest quartile, for adenocarcinoma and non-adenocarcinoma were 2.50 (1.22-5.13) and 1.63 (0.66-4.03), respectively. The length of follow-up from the collection of blood for the measurement of telomere length to the diagnosis of cancer (median = 8.0, range: from 5.0 months to 16.2 years) had no significant impact on the association between telomere length and pancreatic cancer risk.ConclusionsThe present study demonstrates that longer telomeres are associated with increased risk of overall pancreatic cancer.