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BackgroundExposure to trauma can result in various mental health disorders including anxiety, depression, and posttraumatic stress disorder (PTSD). Although psychotherapies and pharmacotherapies exist for the treatment of these disorders, many individuals fail to receive treatment and among those who do, many remain symptomatic. Therefore, it is critical to continue developing new interventions for traumatic stress that target underlying mechanisms of pathology and offer a safe and acceptable alternative to current treatments. Morning light treatment has good potential as a novel non-invasive, low risk treatment for traumatic stress. Evidence suggests that morning light may improve traumatic stress by reducing reactivity in the amygdala, a brain region implicated in the pathophysiology of PTSD and anatomically linked to circadian photoreceptors in the eye.MethodsIn this study, we aim to establish a significant dose-response relationship between duration of morning light treatment and reduction in amygdala reactivity among individuals with traumatic stress symptoms (NCT# 04117347). Using a transdiagnostic approach, sixty-six individuals with a history of a DSM-5 criterion A trauma and traumatic stress symptoms will be recruited to participate in a 5-week study. Participants will be randomized across three treatment arms based on morning light treatment duration: 15-minutes, 30-minutes, or 60-minutes of light treatment per day for four weeks. To evaluate amygdala activity, participants will undergo fMRI at pre-treatment, mid-treatment, and post-treatment. Participants will also complete clinical assessments and self-report measures of PTSD, depression, and anxiety at pre-treatment, mid-treatment, and post-treatment.DiscussionMorning light therapy may be an acceptable, feasible, and effective treatment for individuals suffering from traumatic stress. Identifying mechanistically relevant targets, and the doses needed to impact them, are critical steps in developing this new treatment approach for the sequelae of traumatic stress.

BackgroundThe reopening of college and university campuses was seen as presenting a high risk for transmission of COVID-19. Thus, these institutions faced with a new public health challenge never heretofore faced on this scale. To magnify the problem, they needed to rapidly develop and implement re-opening plans in an environment filled with uncertainty and for a population that was significantly less likely to observe COVID-19 mitigation behaviors. In response, within three weeks of opening, as part of its COVID-19 public health strategy, a West Coast university created and trained a public health workforce comprised of 282 undergraduates tasked with encouraging compliance with COVID-19 mitigating healthy behaviors.Main objectivesThis paper describes the use and outcomes of a practicum framework to quickly create a university-based public health workforce. It addresses two questions: (1) Using a practicum framework, what are important considerations in designing and building a public health workforce for a university campus? and (2) What are the benefits to the workforce in terms of public health education and professional growth?MethodsProgram administrative data were used to describe the workforce and their learning outcomes.ResultsThe majority of students indicated that through the practicum, they learned new skills/developed new attitudes (71.7%) and became aware of their own strengths and opportunities for professional growth (73.7%). The types of new skills and attitudes learned included communication (49.2%), conflict management (20.4%), time management (7.5%), and open-mindedness/less judgmental attitude (14.6%). In terms of public health, they gained an understanding of infectious disease prevention (40.9%) that is multi-disciplinary (20.5%), and involves a community effort (36.8%).ConclusionsThese findings demonstrate an effective way of rapidly addressing public health concerns that allowed for on the job training and opportunities for young adults to learn and grow. The practicum framework allowed the expeditious development of a public health workforce that ensured a fit between student interests and the role. This led to high retention with the majority of students continuing into the winter quarter. Only 5% of students reported not being satisfied with their position. None of the students contracted job-related COVID-19. The role gave students a sense of purpose during the pandemic's uncertain times that helped to protect them from the negative effects of stress. The practicum structure and support fostered a safe environment in which students were able to feel part of the larger community while gaining valuable work experience and skills and serve their community.

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.

BackgroundWhile HIV infection is associated with increased cardiovascular risk, benefit from statin is not well established in HIV-infected adults. We assessed whether statins are associated with a decrease in carotid artery intima-media thickness (cIMT) progression and all-cause mortality in HIV-infected adults who are at elevated ASCVD risk and recommended for statins.MethodsCarotid IMT was measured at baseline and follow-up in 127 HIV-infected adults who meet ACC/AHA criteria to be on statins. Inverse probability of treatment weighting (IPTW) was used to address selection bias. Multivariable models were used to control for baseline characteristics.Results28 subjects (22%) were on statins and 99 subjects (78%) were not. Mean cIMT at baseline was 1.2 mm (SD = 0.34) in statin users and 1.1 mm (SD = 0.34) in non-users, and the multivariable adjusted difference was 0.05mm (95%CI -0.11, 0.21 p = 0.53). After 3.2 years of follow-up, average cIMT progression was similar in statin users and non-users (0.062mm/yr vs. 0.058 mm/yr) and the multivariable adjusted difference over the study period was 0.004 mm/yr (95% CI -0.018, 0.025, p = 0.74). All-cause mortality appeared higher in non-statin users compared with statin users, but the difference was not significant (adjusted HR = 0.74, 95%CI 0.17-3.29, p = 0.70).ConclusionIn a HIV cohort who had elevated ASCVD risk and meet ACC/AHA criteria for statins, treatment with statins was not associated with a reduction in carotid atherosclerosis progression or total mortality. Future studies are needed to further explore the impact of statins on cardiovascular risk in the HIV-infected population.

BACKGROUND:The enteric viruses shed by different populations can be influenced by multiple factors including access to clean drinking water. We describe here the eukaryotic viral genomes in the feces of Ethiopian children participating in a clean water intervention trial. METHODOLOGY/PRINCIPAL FINDINGS:Fecal samples from 269 children with a mean age of 2.7 years were collected from 14 villages in the Amhara region of Ethiopia, half of which received a new hand-dug water well. Feces from these villages were then analyzed in 29 sample pools using viral metagenomics. A total of 127 different viruses belonging to 3 RNA and 3 DNA viral families were detected. Picornaviridae family sequence reads were the most commonly found, originating from 14 enterovirus and 6 parechovirus genotypes plus multiple members of four other picornavirus genera (cosaviruses, saliviruses, kobuviruses, and hepatoviruses). Picornaviruses with nearly identical capsid VP1 were detected in different pools reflecting recent spread of these viral strains. Next in read frequencies and positive pools were sequences from the Caliciviridae family including noroviruses GI and GII and sapoviruses. DNA viruses from multiple genera of the Parvoviridae family were detected (bocaviruses 1-4, bufavirus 3, and dependoparvoviruses), together with four species of adenoviruses and common anelloviruses shedding. RNA in the order Picornavirales and CRESS-DNA viral genomes, possibly originating from intestinal parasites or dietary sources, were also characterized. No significant difference was observed between the number of mammalian viruses shed from children from villages with and without a new water well. CONCLUSIONS:We describe an approach to estimate the efficacy of potentially virus transmission-reducing interventions and the first complete (DNA and RNA viruses) description of the enteric viromes of East African children. A wide diversity of human enteric viruses was found in both intervention and control groups. Mammalian enteric virome diversity was not reduced in children from villages with a new water well. This population-based sampling also provides a baseline of the enteric viruses present in Northern Ethiopia against which to compare future viromes.

RNA interference (RNAi) is widely used to determine the function of genes. We chose this approach to assess the collective function of the highly related reproductive homeobox 3 (Rhox3) gene paralogs. Using a Rhox3 short hairpin (sh) RNA with 100% complementarity to all 8 Rhox3 paralogs, expressed from a CRE-regulated transgene, we successfully knocked down Rhox3 expression in male germ cells in vivo. These Rhox3-shRNA transgenic mice had dramatic defects in spermatogenesis, primarily in spermatocytes and round spermatids. To determine whether this phenotype was caused by reduced Rhox3 expression, we generated mice expressing the Rhox3-shRNA but lacking the intended target of the shRNA-Rhox3. These double-mutant mice had a phenotype indistinguishable from Rhox3-shRNA-expressing mice that was different from mice lacking the Rhox3 paralogs, indicating that the Rhox3 shRNA disrupts spermatogenesis independently of Rhox3. Rhox3-shRNA transgenic mice displayed few alterations in the expression of protein-coding genes, but instead exhibited reduced levels of all endogenous siRNAs we tested. This supported a model in which the Rhox3 shRNA causes spermatogenic defects by sequestering one or more components of the endogenous small RNA biogenesis machinery. Our study serves as a warning for those using shRNA approaches to investigate gene functions in vivo.

BACKGROUND: Childhood tuberculosis causes significant morbidity and mortality in Southeast Asia, yet little is known about the epidemiology and clinical characteristics of this disease in Viet Nam. OBJECTIVES: To determine the demographics, clinical presentations, radiographic and microbiologic findings, treatment regimens, and outcomes of children admitted with tuberculosis (TB) to a national referral hospital in Viet Nam. METHODS: We conducted a retrospective case series study of children ≤ 15 years old with bacteriologically confirmed or clinically diagnosed TB admitted to a national referral hospital in Ha Noi, Viet Nam from January through December 2007. RESULTS: One hundred three children were identified: median age 5 years (IQR 2-10), 44% female, 99% Kinh ethnicity, 27% residing in Ha Noi, 88% with BCG vaccination, 27% with known TB contact, and 38% malnourished. Intrathoracic TB was present in 62%, extrathoracic in 52%, both intra and extrathoracic in 19%, and undetermined site in 5%. The most common extrathoracic manifestation was peripheral lymphadenitis, and children under 5 were more likely to have miliary TB or both intra and extrathoracic TB. Fever and failure to thrive were common presenting symptoms among all participants (65% and 56%, respectively), 66% of those with intrathoracic TB presented with cough, and 92% of those with TB meningitis presented with severe neurologic impairment. Acid-fast bacilli smears and mycobacterial cultures were positive in 18% and 21% of children tested, and histopathology was positive in 88% of those biopsied. There were no adverse drug reactions necessitating change in therapy, and no inpatient mortality. CONCLUSIONS: Extrathoracic TB was common, treatment well tolerated and clinical outcomes excellent. Culture confirmation rates were low and emphasize the need for improved diagnostics.

Cellular heterogeneity is an integral part of cancer development and progression. Progression can be associated with emergence of cells that exhibit high phenotypic plasticity (including "de-differentiation" to primitive developmental states), and aggressive behavioral properties (including high tumorigenic potentials). We observed that many biomarkers that are used to identify Cancer Stem Cells (CSC) can label cell subsets in an advanced clinical stage of lung cancer (malignant pleural effusions, or MPE). Thus, CSC-biomarkers may be useful for live sorting functionally distinct cell subsets from individual tumors, which may enable investigators to hone in on the molecular basis for functional heterogeneity. We demonstrate that the CD44(hi) (CD44-high) cancer cell subsets display higher clonal, colony forming potential than CD44(lo) cells (n=3) and are also tumorigenic (n=2/2) when transplanted in mouse xenograft model. The CD44(hi) subsets express different levels of embryonal (de-differentiation) markers or chromatin regulators. In archived lung cancer tissues, ALDH markers co-localize more with CD44 in squamous cell carcinoma (n=5/7) than Adeno Carcinoma (n=1/12). MPE cancer cells and a lung cancer cell line (NCI-H-2122) exhibit chromosomal abnormalities and 1p36 deletion (n=3/3). Since miR-34a maps to the 1p36 deletion site, low miR-34a expression levels were detected in these cells. The colony forming efficiency of CD44(hi) cells, characteristic property of CSC, can be inhibited by mir-34a replacement in these samples. In addition the highly tumorigenic CD44(hi) cells are enriched for cells in the G2 phase of cell cycle.

G protein-coupled receptors (GPCRs) are attractive targets for pharmaceutical research. With the recent determination of several GPCR X-ray structures, the applicability of structure-based computational methods for ligand identification, such as docking, has increased. Yet, as only about 1% of GPCRs have a known structure, receptor homology modeling remains necessary. In order to investigate the usability of homology models and the inherent selectivity of a particular model in relation to close homologs, we constructed multiple homology models for the A(1) adenosine receptor (A(1)AR) and docked ∼2.2 M lead-like compounds. High-ranking molecules were tested on the A(1)AR as well as the close homologs A(2A)AR and A(3)AR. While the screen yielded numerous potent and novel ligands (hit rate 21% and highest affinity of 400 nM), it delivered few selective compounds. Moreover, most compounds appeared in the top ranks of only one model. These findings have implications for future screens.

BackgroundDisaggregated data is a cornerstone of precision health. Vietnamese Americans (VietAms) are the fourth-largest Asian subgroup in the United States (US), and demonstrate a unique burden of disease and mortality. However, most prior studies have aggregated VietAms under the broader Asian American category for analytic purposes. This study examined the leading causes of death among VietAms compared to aggregated Asian Americans and non-Hispanic Whites (NHWs) during the period 2005-2020.MethodsDecedent data, including underlying cause of death, were obtained from the National Center for Health Statistics national mortality file from 2005 to 2020. Population denominator estimates were obtained from the American Community Survey one-year population estimates. Outcome measures included proportional mortality, age-adjusted mortality rates per 100,000 (AMR), and annual percent change (APC) in mortality over time. Data were stratified by sex and nativity status. Due to large differences in age structure, we report native- and foreign-born VietAms separately.FindingsWe identified 74,524 VietAm decedents over the study period (71,305 foreign-born, 3,219 native-born). Among foreign-born VietAms, the three leading causes of death were cancer (26.6%), heart disease (18.0%), and cerebrovascular disease (9.0%). Among native-born VietAms the three leading causes were accidents (19.0%), self-harm (12.0%), and cancer (10.4%). For every leading cause of death, VietAms exhibited lower mortality compared to both aggregated Asians and NHWs. Over the course of the study period, VietAms witnessed an increase in mortality in every leading cause. This effect was mostly driven by foreign-born, male VietAms.Conclusions and relevanceWhile VietAms have lower overall mortality from leading causes of death compared to aggregated Asians and NHWs, these advantages have eroded markedly between 2005 and 2020. These data emphasize the importance of racial disaggregation in the reporting of public health measures.

This study explores the effects of banking uncertainty on firms' debt financing. Employing data from 2007 to 2022 of Vietnam-a bank-based economy, we document that banking uncertainty negatively impacts corporate debt. The impact firmly holds across various debt maturities and sources, with the most predominant driver witnessed in bank debt. We also investigate the potential underlying mechanism linking banking uncertainty to debt financing, thereby validating the working of three crucial channels, including increased costs of debt, substitution of trade credit, and contractions in firm investment. Furthermore, conducting extended analysis, we find that debt financing exhibits more pronounced reactions to banking uncertainty for firms with closer ties to banks or during macroeconomic shocks, as captured by the financial crisis and the COVID-19 pandemic. Our findings survive after robustness checks by alternative measurement, static and dynamic econometric models, and endogeneity controls.

BackgroundOvarian cancer is a challenging disease to diagnose and treat effectively with five-year survival rates below 50%. Previous patient experience research in high-income countries highlighted common challenges and opportunities to improve survival and quality of life for women affected by ovarian cancer. However, no comparable data exist for low-and middle-income countries, where 70% of women with the disease live. This study aims to address this evidence gap.MethodsThis is an observational multi-country study set in low- and middle-income countries. We aim to recruit over 2000 women diagnosed with ovarian cancer across multiple hospitals in 24 countries in Asia, Africa and South America. Country sample sizes have been calculated (n = 70-96 participants /country), taking account of varying national five-year disease prevalence rates. Women within five years of their diagnosis, who are in contact with participating hospitals, are invited to take part in the study. A questionnaire has been adapted from a tool previously used in high-income countries. It comprises 57 multiple choice and two open-ended questions designed to collect information on demographics, women's knowledge of ovarian cancer, route to diagnosis, access to treatments, surgery and genetic testing, support needs, the impact of the disease on women and their families, and their priorities for action. The questionnaire has been designed in English, translated into local languages and tested according to local ethics requirements. Questionnaires will be administered by a trained member of the clinical team.ConclusionThis study will inform further research, advocacy, and action in low- and middle-income countries based on tailored approaches to the national, regional and global challenges and opportunities. In addition, participating countries can choose to repeat the study to track progress and the protocol can be adapted for other countries and other diseases.

Digital speech recognition is a challenging problem that requires the ability to learn complex signal characteristics such as frequency, pitch, intensity, timbre, and melody, which traditional methods often face issues in recognizing. This article introduces three solutions based on convolutional neural networks (CNN) to solve the problem: 1D-CNN is designed to learn directly from digital data; 2DS-CNN and 2DM-CNN have a more complex architecture, transferring raw waveform into transformed images using Fourier transform to learn essential features. Experimental results on four large data sets, containing 30,000 samples for each, show that the three proposed models achieve superior performance compared to well-known models such as GoogLeNet and AlexNet, with the best accuracy of 95.87%, 99.65%, and 99.76%, respectively. With 5-10% higher performance than other models, the proposed solution has demonstrated the ability to effectively learn features, improve recognition accuracy and speed, and open up the potential for broad applications in virtual assistants, medical recording, and voice commands.

Incidence of endometrial cancer (EC) is rising in the developed world. The current standard of care, hysterectomy, is often infeasible for younger patients and those with high body mass index. There are limited non-surgical treatment options and a lack of biologically relevant research models to investigate novel alternatives to surgery for EC. The aim of the present study was to develop a long-term, patient-derived explant (PDE) model of early-stage EC and demonstrate its use for investigating predictive biomarkers for a current non-surgical treatment option, the levonorgestrel intra-uterine system (LNG-IUS). Fresh tumour specimens were obtained from patients with early-stage endometrioid EC. Tumours were cut into explants, cultured on media-soaked gelatin sponges for up to 21 days and treated with LNG. Formalin-fixed, paraffin embedded (FFPE) blocks were generated for each explant after 21 days in culture. Tumour architecture and integrity were assessed by haematoxylin and eosin (H&E) and immunohistochemistry (IHC). IHC was additionally performed for the expression of five candidate biomarkers of LNG resistance. The developed ex vivo PDE model is capable of culturing explants from early-stage EC tumours long-term (21 Days). This model can complement existing models and may serve as a tool to validate results obtained in higher-throughput in vitro studies. Our study provides the foundation to validate the extent to which EC PDEs reflect patient response in future research.

The paper explores the role of business models in the link between uncertainty and bank risk. From the perspective of banks, given that future outcomes tend to be less predictable if banking uncertainty rises, we highlight a framework that a larger dispersion of bank shocks to bank-specific variables might mirror such decreased predictability as a consequence of increasing uncertainty. To compensate for the persistence of bank risk and address the endogeneity issue, we applied the system generalized method of moments (GMM) estimator as the main regressions. Analyzing a panel of commercial banks from Vietnam between 2007 and 2019, we find that higher levels of banking uncertainty may increase bank risk, as gauged by banks' credit risk (loan loss reverses and non-performing loans) and default risk (Z-score index). This detrimental influence of uncertainty appears to be most pronounced with banks relying on pure lending, and it decreases with more non-interest income. A deeper investigation after estimating the marginal effects with plots reveals an asymmetric pattern that bank risk is immune to uncertainty in banks with the highest level of income diversification. Interestingly, we also provide evidence that uncertainty may lower the default risk level when income diversification exceeds a sufficiently high level. Our findings demonstrate that diversified business models are an efficient buffer against higher bank risk in times of increased uncertainty.

Candida auris is a newly emerged multidrug-resistant fungus capable of causing invasive infections with high mortality. Despite intense efforts to understand how this pathogen rapidly emerged and spread worldwide, its environmental reservoirs are poorly understood. Here, we present a collaborative effort between the U.S. Centers for Disease Control and Prevention, the National Center for Biotechnology Information, and GridRepublic (a volunteer computing platform) to identify C. auris sequences in publicly available metagenomic datasets. We developed the MetaNISH pipeline that uses SRPRISM to align sequences to a set of reference genomes and computes a score for each reference genome. We used MetaNISH to scan ~300,000 SRA metagenomic runs from 2010 onwards and identified five datasets containing C. auris reads. Finally, GridRepublic has implemented a prospective C. auris molecular monitoring system using MetaNISH and volunteer computing.

"Faster, higher, stronger" is the motto of any professional athlete. Does that apply to brain dynamics as well? In our paper, we performed a series of EEG experiments on Visually Evoked Potentials and a series of cognitive tests-reaction time and visual search, with professional eSport players in Counter-Strike: Global Offensive (CS:GO) and novices (control group) in order to find important differences between them. EEG data were studied in a temporal domain by Event-Related Potentials (ERPs) and in a frequency domain by Variational Mode Decomposition. The EEG analysis showed that the brain reaction of eSport players is faster (P300 latency is earlier on average by 20-70 ms, p < 0.005) and stronger (P300 peak amplitude is higher on average by 7-9 mkV, p < 0.01). Professional eSport players also exhibit stronger stimulus-locked alpha-band power. Besides, the Spearman correlation analysis showed a significant correlation between hours spend in CS:GO and mean amplitude of P200 and N200 for the professional players. The comparison of cognitive test results showed the superiority of the professional players to the novices in reaction time (faster) and choice reaction time-faster reaction, but similar correctness, while a significant difference in visual search skills was not detected. Thus, significant differences in EEG signals (in spectrograms and ERPs) and cognitive test results (reaction time) were detected between the professional players and the control group. Cognitive tests could be used to separate skilled players from novices, while EEG testing can help to understand the skilled player's level. The results can contribute to understanding the impact of eSport on a player's cognitive state and associating eSport with a real sport. Moreover, the presented results can be useful for evaluating eSport team members and making training plans.

Cannabis flower odour is an important aspect of product quality as it impacts the sensory experience when administered, which can affect therapeutic outcomes in paediatric patient populations who may reject unpalatable products. However, the cannabis industry has a reputation for having products with inconsistent odour descriptions and misattributed strain names due to the costly and laborious nature of sensory testing. Herein, we evaluate the potential of using odour vector modelling for predicting the odour intensity of cannabis products. Odour vector modelling is proposed as a process for transforming routinely produced volatile profiles into odour intensity (OI) profiles which are hypothesised to be more informative to the overall product odour (sensory descriptor; SD). However, the calculation of OI requires compound odour detection thresholds (ODT), which are not available for many of the compounds present in natural volatile profiles. Accordingly, to apply the odour vector modelling process to cannabis, a QSPR statistical model was first produced to predict ODT from physicochemical properties. The model presented herein was produced by polynomial regression with 10-fold cross-validation from 1,274 median ODT values to produce a model with R2 = 0.6892 and a 10-fold R2 = 0.6484. This model was then applied to terpenes which lacked experimentally determined ODT values to facilitate vector modelling of cannabis OI profiles. Logistic regression and k-means unsupervised cluster analysis was applied to both the raw terpene data and the transformed OI profiles to predict the SD of 265 cannabis samples and the accuracy of the predictions across the two datasets was compared. Out of the 13 SD categories modelled, OI profiles performed equally well or better than the volatile profiles for 11 of the SD, and across all SD the OI data was on average 21.9% more accurate (p = 0.031). The work herein is the first example of the application of odour vector modelling to complex volatile profiles of natural products and demonstrates the utility of OI profiles for the prediction of cannabis odour. These findings advance both the understanding of the odour modelling process which has previously only been applied to simple mixtures, and the cannabis industry which can utilise this process for more accurate prediction of cannabis odour and thereby reduce unpleasant patient experiences.

Background This study aimed to determine the association between parental absence during childhood and metabolic syndrome (MetS) in adulthood among middle-aged adults in rural Khanh Hoa province, Vietnam. Given that broader literature on adverse childhood experiences (ACEs) suggests a strong positive association between ACEs and cardiometabolic risk or diseases, we hypothesized that parental absence during childhood, which is a major component of ACEs, is more likely to cause MetS in adulthood. Methods Data were obtained from the baseline survey of the Khanh Hoa Cardiovascular Study, in which 3000 residents aged between 40 to 60 years participated. MetS was assessed using the modified Adult Treatment Panel III (ATP III) criteria. It was considered parental absence if the participants had experienced parental absence due to death, divorce, or out-migration before three or between three to 15 years. We used multiple logistic regression analyses to examine the association between parental absence during childhood and metabolic syndrome during adulthood. Results There was no significant association between parental absence and MetS; adjusted odds ratio [AOR] was 0.97 (95% confidence interval [CI] = 0.76–1.22) for those who experienced parental absence between three to 15 years and the corresponding figure for those who experienced it before three years was 0.93 (95% CI = 0.72–1.20). No significant associations were observed when these were examined for the causes of parental absence. Conclusion This study did not support our hypothesis of an association between parental absence during childhood and metabolic syndrome during adulthood. Parental absence may not be a predictor of MetS among Vietnamese people in rural communities.

Guidelines for the management of elderly patients with early breast cancer are scarce. Additional adjuvant systemic treatment to surgery for early breast cancer in elderly populations is challenged by increasing comorbidities with age. In non-metastatic settings, treatment decisions are often made under considerable uncertainty; this commonly leads to undertreatment and, consequently, poorer outcomes. This study aimed to develop a decision support tool that can help to identify candidate adjuvant post-surgery treatment schemes for elderly breast cancer patients based on tumor and patient characteristics. Our approach was to generate predictions of patient outcomes for different courses of action; these predictions can, in turn, be used to inform clinical decisions for new patients. We used a cohort of elderly patients (≥ 70 years) who underwent surgery with curative intent for early breast cancer to train the models. We tested seven classification algorithms using 5-fold cross-validation, with 80% of the data being randomly selected for training and the remaining 20% for testing. We assessed model performance using accuracy, precision, recall, F1-score, and AUC score. We used an autoencoder to perform dimensionality reduction prior to classification. We observed consistently better performance using logistic regression and linear discriminant analysis models when compared to the other models we tested. Classification performance generally improved when an autoencoder was used, except for when we predicted the need for adjuvant treatment. We obtained overall best results using a logistic regression model without autoencoding to predict the need for adjuvant treatment (F1-score = 0.869).

The study of optimal best practice, coinciding with a person's 'motivational mindset', is an interesting research inquiry for development. Optimal best practice, in brief, relates to the maximization of a person's state of functioning (e.g., cognitive functioning). Moreover, the nature of optimal best practice is positive and motivational, helping individuals to flourish in different courses of action (e.g., academic performance at school). Several research undertakings, non-experimental in design, have provided clear and consistent evidence to substantiate the existing viewpoints and perspectives of optimal best practice. Our proposed investigation, which involved physical education pre-service teacher students from Spain (N = 681), explored one notable focus of inquiry-namely, the formation of optimal best practice and its predictive and explanatory account on future adaptive outcomes. As such, using Likert-scale measures and path analysis techniques, we were able to identify two associative patterns: achievement of optimal best practice is positively accounted for by academic self-concept, optimism, and current best practice and, in contrast, negatively accounted for by pessimism; and that optimal best practice could act as a determinant of academic engagement for effective learning. Such associations are significant, providing relevant information for different teaching and research purposes.

BackgroundPost-stroke pneumonia is a frequent complication of stroke and is associated with high mortality. Investigators have described its associations with beta-blocker. However, there has been no evaluation of the role of recombinant tissue plasminogen activator (RTPA). We postulate that RTPA may modify the effect of stroke on pneumonia by reducing stroke disability. We explore this using data from neuroprotection trials in Virtual International Stroke Trials Archive (VISTA)-Acute.MethodWe evaluated the impact of RTPA and other medications in random forest model. Random forest is a type of supervised ensemble tree-based machine learning method. We used the standard approach for performing random forest and partitioned the data into training (70%) and validation (30%) sets. This action enabled to the model developed on training data to be evaluated in the validation data. We borrowed idea from Coalition Game Theory on fair distribution of marginal profit (Shapley value) to determine proportional contribution of a covariate to the model. Consistent with other analysis using the VISTA-Acute data, the diagnosis of post-stroke pneumonia was based on reports of serious adverse events.ResultsThe overall frequency of pneumonia was 10.9% (614/5652). It was present in 11.5% of the RTPA (270/2358) and 10.4% (344/3295) of the no RTPA groups. There was significant (pConclusionIn this cohort pneumonia was strongly associated with stroke severity and age whereas RTPA had a much lower effect. An intriguing finding is a possible association between benzodiazepine and pneumonia but this requires further evaluation.

IntroductionIncreasing access to viral load (VL) monitoring is essential to fight HIV epidemics. In remote settings in Vietnam, using dried blood spot (DBS) sampling for specimen collection could improve the situation. Here, people who inject drugs (PWID) represent many newly antiretroviral therapy (ART)-initiated patients. The goals of this evaluation were to evaluate if access to VL monitoring and the rate of virological failure differed between PWID and non-PWID.MethodsProspective cohort study of patients newly initiated on ART in remote settings in Vietnam. DBS coverage at 6, 12 and 24 months of ART was investigated. Factors associated with DBS coverage were identified through logistic regression, as were factors associated with virological failure (VL ≥1,000 copies/mL) at 6, 12 and 24 months of ART.ResultsOverall 578 patients were enrolled in the cohort, of whom 261 (45%) were PWID. DBS coverage improved from 74.7% to 82.9% between 6 and 24 months of ART (p = 0.001). PWID status was not associated with DBS coverage (p = 0.74), but DBS coverage was lower in patients who were late to clinical visits and in those in WHO stage 4 (p = 0.023 and p = 0.001, respectively). The virological failure rate decreased from 15.8% to 6.6% between 6 and 24 months of ART (pConclusionsDespite training and simple procedures, DBS coverage was not perfect. DBS coverage was not associated with PWID status. Close management is required for effective routine HIV VL monitoring. PWID were more at risk of failure, as were patients who were not fully adherent and patients who were late to clinical visits. Specific interventions targeting these patients are needed to improve their outcomes. Overall, efforts in coordination and communication are essential to improve global HIV care.Trial registrationClinical Trial Number: NCT03249493.

One of the main factors in controlling infectious diseases such as COVID-19 is to prevent touching preoral and prenasal regions. Face touching is a habitual behaviour that occurs frequently. Studies showed that people touch their faces 23 times per hour on average. A contaminated hand could transmit the infection to the body by a facial touch. Since controlling this spontaneous habit is not easy, this study aimed to develop and validate a technology to detect and monitor face touch using dynamic time warping (DTW) and KNN (k-nearest neighbours) based on a wrist-mounted inertial measurement unit (IMU) in a controlled environment and natural environment trials. For this purpose, eleven volunteers were recruited and their hand motions were recorded in controlled and natural environment trials using a wrist-mounted IMU. Then the sensitivity, precision, and accuracy of our developed technology in detecting the face touch were evaluated. It was observed that the sensitivity, precision, and accuracy of the DTW-KNN classifier were 91%, 97%, and 85% in controlled environment trials and 79%, 92%, and 79% in natural environment trials (daily life). In conclusion, a wrist-mounted IMU, widely available in smartwatches, could detect the face touch with high sensitivity, precision, and accuracy and can be used as an ambulatory system to detect and monitor face touching as a high-risk habit in daily life.

BackgroundThe success of early dexamethasone therapy for hospitalised COVID-19 cases in treatment of Sars-CoV-2 infection may predominantly reflect its anti-inflammatory action against a hyperinflammation (HI) response. It is likely that there is substantial heterogeneity in HI responses in COVID-19.MethodsBlood CRP, ferritin, neutrophil, lymphocyte and platelet counts were scored to assess HI (HI5) and combined with a validated measure of generalised medical deterioration (NEWS2) before day 2. Our primary outcome was 28 day mortality from early treatment with dexamethasone stratified by HI5-NEWS2 status.FindingsOf 1265 patients, high risk of HI (high HI5-NEWS2) (n = 367, 29.0%) conferred a strikingly increased mortality (36.0% vs 7.8%; Age adjusted hazard ratio (aHR) 5.9; 95% CI 3.6-9.8, pInterpretationHigher HI5-NEWS2 scores measured at COVID-19 diagnosis, strongly associate with increased mortality at 28 days. Significant reduction in mortality with early dexamethasone treatment was only observed in the high risk group. Therefore, the HI5-NEWS2 score could be utilised to stratify randomised clinical trials to test whether intensified anti-inflammatory therapy would further benefit high risk patients and whether alternative approaches would benefit low risk groups. Considering its recognised morbidity, we suggest that early dexamethasone should not be routinely prescribed for HI5-NEWS2 low risk individuals with COVID-19 and clinicians should cautiously assess the risk benefit of this intervention in all cases.

BackgroundSARS-CoV-2 Delta variant caused a large number of COVID-19 cases in many countries, including Vietnam. Understanding mortality risk factors is crucial for the clinical management of severe COVID-19.MethodsWe conducted a retrospective study at an intensive care center in Ho Chi Minh City that urgently built by Bach Mai Hospital during the COVID-19 outbreak in Vietnam, when the Delta variant predominated. Participants were laboratory-confirmed patients with SARS-CoV-2 infection, admitted in August 2021. Data on patients' demographic and clinical characteristics, radiographic and laboratory findings, treatment, and clinical time course were compared between survivors and non-survivors. Risk factors to mortality were assessed using logistic regression.ResultsAmong 504 eligible COVID-19 patients, case fatality was 52.2%. Unvaccinated patients accounted for 61.2% of non-survivors and 43.6% of survivors (p < 0.001). The time from onset to hospital admission was 8 days in non-survivors and 7 days in survivors (p = 0.004). Among non-survivors, 90.2% developed acute respiratory distress syndrome (ARDS). Oxygen therapy was administered for all patients, but antiviral agent was given to 51.7% of non-survivors. 54.2% of non-survivors tested positive for the bacterial infection using blood culture. The risk factors for mortality were diabetes mellitus, respiration rate, oxygen saturation, vaccination status, time from onset to admission, and older age.ConclusionsCritical patients with COVID-19 owing to the Delta variant in Vietnam had delayed hospital admission, leading to ARDS and death. Early availability of vaccines and preventing bacterial infections are crucial for reducing mortality of COVID-19, especially in low- and middle-income countries.

BackgroundThe COVID-19 pandemic and governments' response lead to dramatical change in quality of life worldwide. However, the extent of this change in Vietnamese medical and nursing students has not been documented.ObjectivesThe study aims to describe the quality of life and changes in quality of life of medical and nursing students during the COVID-19 pandemic and examine the association of quality of life and changes in quality of life with fear of COVID-19 and other socio-economic and demographic factors.MethodsThe study was a cross-sectional study on all students of Hanoi Medical University from 3 majors: General Medicine, Preventive Medicine, Nursing (3672 invited students); from 7th to 29th of April 2020; using an online questionnaire that included demographic and academic information, the Vietnamese version of the SF-36 Quality of Life questionnaire and the Fear of COVID-19 Scale (FCV-19S). Linear and modified Poisson regression was used to examine the association between quality of life, changes in quality of life and other factors.ResultsThe number of participants was 1583 (response rate 43%). Among 8 dimensions of the SF-36 (ranged 0-100), Vitality had the lowest score with a median score of 46. The median physical composite score (PCS) of the sample was 40.6 (IQR:20.8-53.2), 33.5% of the sample had an above-population average PCS score. The median mental composite score (MCS) of the sample was 20.3 (IQR:3.8-31.7), and 98.2% had an MCS score below average. 9.9% (95%CI:8.5%-11.4%) of the population reported a significant negative change in the quality of life. Fear of COVID-19 was not associated with significant changes in quality of life, nor MCS while having some association with PCS (Coef:-5.39;95%CI:-3to-7.8). Perceived reduction in quality of life was also associated with: being on clinical rotation COVID-19 (PR:1.5;95%CI:1.05-2.2), difficulties affording health services (PR:1.4;95%CI:1.02-1.95), obesity (PR:2.38;95%CI:1.08-5.25) and chronic disease (PR:1.92;95%CI:1.23-3), typical symptoms (PR:1.85; 95%CI:1.23-2.78) and atypical symptoms of COVID-19 (PR:2.32;95%CI:1.41-3.81).ConclusionThe majority of medical and nursing students had below average quality of life, with lower vitality and mental composite health score in the settings of COVID-19. Perceived decrease in quality of life was associated with clinical rotation, difficulties affording healthcare services and was not associated with Fear of COVID-19.

BackgroundThe reopening of college and university campuses was seen as presenting a high risk for transmission of COVID-19. Thus, these institutions faced with a new public health challenge never heretofore faced on this scale. To magnify the problem, they needed to rapidly develop and implement re-opening plans in an environment filled with uncertainty and for a population that was significantly less likely to observe COVID-19 mitigation behaviors. In response, within three weeks of opening, as part of its COVID-19 public health strategy, a West Coast university created and trained a public health workforce comprised of 282 undergraduates tasked with encouraging compliance with COVID-19 mitigating healthy behaviors.Main objectivesThis paper describes the use and outcomes of a practicum framework to quickly create a university-based public health workforce. It addresses two questions: (1) Using a practicum framework, what are important considerations in designing and building a public health workforce for a university campus? and (2) What are the benefits to the workforce in terms of public health education and professional growth?MethodsProgram administrative data were used to describe the workforce and their learning outcomes.ResultsThe majority of students indicated that through the practicum, they learned new skills/developed new attitudes (71.7%) and became aware of their own strengths and opportunities for professional growth (73.7%). The types of new skills and attitudes learned included communication (49.2%), conflict management (20.4%), time management (7.5%), and open-mindedness/less judgmental attitude (14.6%). In terms of public health, they gained an understanding of infectious disease prevention (40.9%) that is multi-disciplinary (20.5%), and involves a community effort (36.8%).ConclusionsThese findings demonstrate an effective way of rapidly addressing public health concerns that allowed for on the job training and opportunities for young adults to learn and grow. The practicum framework allowed the expeditious development of a public health workforce that ensured a fit between student interests and the role. This led to high retention with the majority of students continuing into the winter quarter. Only 5% of students reported not being satisfied with their position. None of the students contracted job-related COVID-19. The role gave students a sense of purpose during the pandemic's uncertain times that helped to protect them from the negative effects of stress. The practicum structure and support fostered a safe environment in which students were able to feel part of the larger community while gaining valuable work experience and skills and serve their community.

ObjectiveWe used SARS-CoV-2 whole-genome sequencing (WGS) and electronic health record (EHR) data to investigate the associations between viral genomes and clinical characteristics and severe outcomes among hospitalized COVID-19 patients.MethodsWe conducted a case-control study of severe COVID-19 infection among patients hospitalized at a large academic referral hospital between March 2020 and May 2021. SARS-CoV-2 WGS was performed, and demographic and clinical characteristics were obtained from the EHR. Severe COVID-19 (case patients) was defined as having one or more of the following: requirement for supplemental oxygen, mechanical ventilation, or death during hospital admission. Controls were hospitalized patients diagnosed with COVID-19 who did not meet the criteria for severe infection. We constructed predictive models incorporating clinical and demographic variables as well as WGS data including lineage, clade, and SARS-CoV-2 SNP/GWAS data for severe COVID-19 using multiple logistic regression.ResultsOf 1,802 hospitalized SARS-CoV-2-positive patients, we performed WGS on samples collected from 590 patients, of whom 396 were case patients and 194 were controls. Age (p = 0.001), BMI (p = 0.032), test positive time period (p = 0.001), Charlson comorbidity index (p = 0.001), history of chronic heart failure (p = 0.003), atrial fibrillation (p = 0.002), or diabetes (p = 0.007) were significantly associated with case-control status. SARS-CoV-2 WGS data did not appreciably change the results of the above risk factor analysis, though infection with clade 20A was associated with a higher risk of severe disease, after adjusting for confounder variables (p = 0.024, OR = 3.25; 95%CI: 1.31-8.06).ConclusionsAmong people hospitalized with COVID-19, older age, higher BMI, earlier test positive period, history of chronic heart failure, atrial fibrillation, or diabetes, and infection with clade 20A SARS-CoV-2 strains can predict severe COVID-19.

Central to cognitive load theory is the concept of element interactivity, which reflects the complexity of material. The complexity of linear equations depends on the number of operational and relational lines and the nature of the operation (balance versus inverse) in the solution procedure. A relational line refers to the quantitative relation whereby the right-hand side of the equation equals to its left-hand side. An operational line refers to the application of an operation and such a procedural step preserves the equality of the linear equation. The balance method and inverse method differ in the operational line (e.g., + 3 on both sides vs.– 3 becomes + 3) where the inverse operation imposes half the level of element interactivity as the balance method. Seventy-five students randomly assigned to either the balance group or inverse group to complete (i) one-step equations (Experiment 1), (ii) two-step equations (Experiment 2), and (iii) one-step and two-step equations with a focus on equations with negative pronumerals (Experiment 3). Performance favoured the inverse group when the gap between the low and high element interactivity equations was substantial enough. Both groups performed better and invested lower mental effort on the inverse operation than the balance operation.

Background Exposure to trauma can result in various mental health disorders including anxiety, depression, and posttraumatic stress disorder (PTSD). Although psychotherapies and pharmacotherapies exist for the treatment of these disorders, many individuals fail to receive treatment and among those who do, many remain symptomatic. Therefore, it is critical to continue developing new interventions for traumatic stress that target underlying mechanisms of pathology and offer a safe and acceptable alternative to current treatments. Morning light treatment has good potential as a novel non-invasive, low risk treatment for traumatic stress. Evidence suggests that morning light may improve traumatic stress by reducing reactivity in the amygdala, a brain region implicated in the pathophysiology of PTSD and anatomically linked to circadian photoreceptors in the eye. Methods In this study, we aim to establish a significant dose-response relationship between duration of morning light treatment and reduction in amygdala reactivity among individuals with traumatic stress symptoms (NCT# 04117347). Using a transdiagnostic approach, sixty-six individuals with a history of a DSM-5 criterion A trauma and traumatic stress symptoms will be recruited to participate in a 5-week study. Participants will be randomized across three treatment arms based on morning light treatment duration: 15-minutes, 30-minutes, or 60-minutes of light treatment per day for four weeks. To evaluate amygdala activity, participants will undergo fMRI at pre-treatment, mid-treatment, and post-treatment. Participants will also complete clinical assessments and self-report measures of PTSD, depression, and anxiety at pre-treatment, mid-treatment, and post-treatment. Discussion Morning light therapy may be an acceptable, feasible, and effective treatment for individuals suffering from traumatic stress. Identifying mechanistically relevant targets, and the doses needed to impact them, are critical steps in developing this new treatment approach for the sequelae of traumatic stress.

PurposesThis cross-sectional study assessed the quality of life and related factors of Vietnamese women during perimenopause in terms of vasomotor, psychosocial, physical, and sexual aspects.Materials and methodsA cross-sectional study on 400 middle-aged women was conducted in Hung Yen, a delta province in Vietnam. Data about socioeconomic characteristics, daily activity patterns, quality of life in terms of vasomotor, psychosocial, physical, and sexual aspects, and level of social support were collected. Tobit multivariate regression model was used to identify factors related to the quality of life among participants.ResultsThe symptoms of perimenopause appeared to worsen with the increase of age and the existence of such health issues as migraine and diabetes. Meanwhile, exercises, recreational activities, and social support appeared to alleviate the negative impact of perimenopausal symptoms on women.ConclusionsIt is important to address the care needs of women during perimenopausal age, especially their sexual well-being, and development of specific healthcare services and programs focusing on sport, entertainment, and support for women in perimenopause should be facilitated.

There are on-going debates about what is and is not 'mindfulness'. These debates are stifling rigorous academic research as scientific precision is a precursor to shared meaning. While mindfulness is a growing field of research, these divergent and conflated meanings are limiting deeper interdisciplinary research. Interventions designed in one practice context may not be useful in other contexts because meaning is not transferred between settings. This review clarifies the various research domains that study mindfulness and the conceptual and operational definitions in each domain. This two-stage study comprises a scoping review of mindfulness classifications and a comparative content mapping of mindfulness studies from 2015 to 2021. The initial comprehensive search strategy followed the preferred reporting items for scoping reviews and meta-analysis (PRISMA) method. The comparative analysis was conducted using Leximancer. Findings illustrate a complex growing research corpus on mindfulness that is somewhat confused. The results from the scoping review show three shared domains in mindfulness classifications: short-term effects of mindfulness, long-term effects of mindfulness, and mindfulness practices. The results from the content mapping show four domains of mindfulness research: mental health, behavioural change, cognitive neuroscience, and ethical mindfulness. Operational definitions of mindfulness are not articulated clearly in these domains. Conceptual and operational definitions in the 'ethical mindfulness' domain are not yet developed. To enhance scientific progress in mindfulness research, further investigations of mindfulness classifications need to be developed. Content mapping and semantic typology is a potential candidate for future classification. More attention should be paid to developing operational definitions according to specific research domains. Scholars in the ethical mindfulness domain will need solid conceptual and operational definitions to support their research efforts.

BackgroundMedical students are known to have higher levels of these issues than the general population but in Vietnam the effects of the pandemic on medical student mental health was not documented.ObjectivesTo estimate the prevalence and identify factors associated with self-reported anxiety disorder, depression, and perception of worsening mental health among Vietnamese medical students during the COVID-19 pandemic.MethodA cross-sectional study was conducted from April 7th to 29th, 2020. All students in Doctor of General Medicine, Doctor of Preventive Medicine, and Bachelor of Nursing tracks at Hanoi Medical University (3672 students) were invited to participate. Data were collected using an online questionnaire including demographic characteristics, Generalized Anxiety Disorder 7 items, Patient Health Questionnaire 9 items, Fear of COVID-19 scale, and question about worsening mental health status. Robust Poisson regression was used to assess the association between mental health status and associated factors.ResultsAmong 1583 students (43.1% response rate), the prevalence of students screened positive for anxiety disorder was 7.3%(95%C.I.:6.0-8.7), depression was 14.5%(95%C.I.:12.8-16.3), and perceiving worsening mental health was 6.9%(95%C.I.:5.7-8.3). In multivariable regression models, significant factors associated with self-reported anxiety disorder included being male (PR = 1.99,95%C.I.:1.35-2.92), difficulty in paying for healthcare services (PR = 2.05,95%C.I.:1.39-3.01), and high level of fear of COVID-19 (Q3:PR = 2.36,95%C.I.:1.38-4.02 and Q4:PR = 4.75,95%C.I.:2.65-8.49). Significant factors associated with self-reported depression were difficulty in paying for healthcare services (PR = 1.78,95%C.I.:1.37-2.30), and high level of fear of COVID-19 (Q3:PR = 1.41,95%C.I.:1.02-1.95 and Q4:PR = 2.23,95%C.I.:1.51-3.29). Significant factors associated with perceived worsening mental health status included having clinical experience (PR = 1.83,95%C.I.:1.17-2.88) and having atypical symptoms of COVID-19 (PR = 1.96,95%C.I.:1.31-2.94).ConclusionThe prevalence of self-reported depression, anxiety disorder, and worsening mental health among Vietnamese students during the first wave of COVID-19 was lower than in medical students in other countries. Further investigation is needed to confirm this finding.

We performed whole genome sequencing on SARS-CoV-2 from 59 vaccinated individuals from southwest Pennsylvania who tested positive between February and September, 2021. A comparison of mutations among vaccine breakthrough cases to a time-matched control group identified potential adaptive responses of SARS-CoV-2 to vaccination.

Severe acute respiratory illness (SARI) is a major cause of death and morbidity in low- and middle-income countries, however, the etiologic agents are often undetermined due to the lack of molecular diagnostics in hospitals and clinics. To examine evidence for select viral infections among patients with SARI in northern Vietnam, we studied 348 nasopharyngeal samples from military and civilian patients admitted to 4 hospitals in the greater Hanoi area from 2017-2019. Initial screening for human respiratory viral pathogens was performed in Hanoi, Vietnam at the National Institute of Hygiene and Epidemiology (NIHE) or the Military Institute of Preventative Medicine (MIPM), and an aliquot was shipped to Duke-NUS Medical School in Singapore for validation. Patient demographics were recorded and used to epidemiologically describe the infections. Among military and civilian cases of SARI, 184 (52.9%) tested positive for one or more respiratory viruses. Influenza A virus was the most prevalent virus detected (64.7%), followed by influenza B virus (29.3%), enterovirus (3.8%), adenovirus (1.1%), and coronavirus (1.1%). Risk factor analyses demonstrated an increased risk of influenza A virus detection among military hospital patients (adjusted OR, 2.0; 95% CI, 1.2-3.2), and an increased risk of influenza B virus detection among patients enrolled in year 2017 (adjusted OR, 7.9; 95% CI, 2.7-22.9). As influenza A and B viruses were commonly associated with SARI and are treatable, SARI patients entering these hospitals would benefit if the hospitals were able to adapt onsite molecular diagnostics.

During government-implemented restrictions in the wake of the COVID-19 pandemic, people's everyday lives changed profoundly. However, there is to date little research chronicling how people perceived their changed everyday lives and which consequences this had. In a two-wave study, we examined the psychological characteristics of people's situations and their correlates during shutdown in a large German sample (NT1 = 1,353; NT2 = 446). First, we compared characteristics during government-issued restrictions with retrospective accounts from before and with a follow-up assessment 6 to 7 months later when many restrictions had been lifted. We found that mean levels were lower and variances were higher for most characteristics during the shutdown. Second, the experience of certain situation characteristics was associated in meaningful and theoretically expected ways with people's traits, appraisals of the COVID-19 crisis, and subjective well-being. Lastly, situation characteristics often substantially explained the associations of traits with appraisals and well-being. Our findings highlight the importance of considering perceived situations as these contribute to people's functioning during crises.

BackgroundCOVID-19 (COronaVIrus Disease 2019) is an infectious respiratory disease caused by the novel SARS-CoV-2 virus. Point of Care (POC) tests have been developed to detect specific antibodies, IgG and IgM, to SARS-CoV-2 virus in human whole blood. They need to be easily usable by the general population in order to alleviate the lockdown that many countries have initiated in response to the growing COVID-19 pandemic. A real-life study has been conducted in order to evaluate the performance of the COVID-PRESTO® POC test and the results were recently published. Even if this test showed very high sensitivity and specificity in a laboratory setting when used by trained professionals, it needs to be further evaluated for practicability when used by the general public in order to be approved by health authorities for in-home use.Methods143 participants were recruited between March 2020 and April 2020 among non-medical populations in central France (nuclear plant workers, individuals attending the Orleans University Hospital vaccination clinic and Orleans University Hospital non-medical staff). Instructions for use, with or without a tutorial video, were made available to the volunteers. Two separate objectives were pursued: evaluation of the capability of participants to obtain an interpretable result, and evaluation of the users' ability to read the results.Results88.4% of the test users judged the instructions for use leaflet to be clear and understandable. 99.3% of the users obtained a valid result and, according to the supervisors, 92.7% of the tests were properly performed by the users. Overall, 95% of the users gave positive feedback on the COVID PRESTO® as a potential self-test. Neither age nor education had an influence.ConclusionCOVID-PRESTO® was successfully used by an overwhelming majority of participants and its use was judged very satisfactory, therefore showing promising potential as a self-test to be used by the general population. This POC test can become an easy-to-use tool to help detect whether individuals are protected or not, particularly in the context of a second wave or a mass vaccination program.

BackgroundIn response to the spread of the coronavirus disease 2019 (COVID-19), plenty of control measures were proposed. To assess the impact of current control measures on the number of new case indices 14 countries with the highest confirmed cases, highest mortality rate, and having a close relationship with the outbreak's origin; were selected and analyzed.MethodsIn the study, we analyzed the impact of five control measures, including centralized isolation of all confirmed cases, closure of schools, closure of public areas, closure of cities, and closure of borders of the 14 targeted countries according to their timing; by comparing its absolute effect average, its absolute effect cumulative, and its relative effect average.ResultsOur analysis determined that early centralized isolation of all confirmed cases was represented as a core intervention in significantly disrupting the pandemic's spread. This strategy helped in successfully controlling the early stage of the outbreak when the total number of cases were under 100, without the requirement of the closure of cities and public areas, which would impose a negative impact on the society and its economy. However, when the number of cases increased with the apparition of new clusters, coordination between centralized isolation and non-pharmaceutical interventions facilitated control of the crisis efficiently.ConclusionEarly centralized isolation of all confirmed cases should be implemented at the time of the first detected infectious case.

BackgroundThe COVID-19 pandemic has had a profound worldwide impact. Vietnam, a lower middle-income country with limited resources, has successfully slowed this pandemic. The objectives of this report are to explore the impact of the COVID-19 pandemic on the research activities of an ongoing hypertension trial using a storytelling intervention in Vietnam.MethodsData were collected in a mixed-methods study among 86 patients and 10 health care workers participating in a clinical trial designed to improve hypertension control. Several questions related to the impact of COVID-19 on patient's daily activities and adherence to the study interventions were included in the follow-up visits. A focus group discussion was conducted among health care workers to discuss the impact of COVID-19 on research related activities.ResultsFewer patients in the intervention group reported that they faced difficulties in adhering to prescribed study interventions, wanted to receive a call from a dedicated hotline, or have a visit from a community health worker as compared with those in the comparison group. Most study patients are willing to participate in future health research studies. When asked about the potential use of mobile phones in health research studies, fewer patients in the intervention group felt comfortable using a mobile phone for the delivery of intervention and interviews compared with those in the comparison condition. Community health workers shared that they visited patient's homes more often than previously due to the pandemic and health care workers had to perform more virus containment activities without a corresponding increase in ancillary staff.ConclusionsBoth patients and health care workers in Vietnam faced difficulties in adhering to recommended trial interventions and procedures. Multiple approaches for intervention delivery and data collection are needed to overcome these difficulties during future health crises and enhance the implementation of future research studies.Trial registrationClinicalTrials.gov. Registration number: https://clinicaltrials.gov/ct2/show/NCT03590691 (registration date July 17, 2018).

Naegleria fowleri is a pathogenic, thermophilic, free-living amoeba which causes primary amebic meningoencephalitis (PAM). Penetrating the olfactory mucosa, the brain-eating amoeba travels along the olfactory nerves, burrowing through the cribriform plate to its destination: the brain's frontal lobes. The amoeba thrives in warm, freshwater environments, with peak infection rates in the summer months and has a mortality rate of approximately 97%. A major contributor to the pathogen's high mortality is the lack of sensitivity of N. fowleri to current drug therapies, even in the face of combination-drug therapy. To enable rational drug discovery and design efforts we have pursued protein production and crystallography-based structure determination efforts for likely drug targets from N. fowleri. The genes were selected if they had homology to drug targets listed in Drug Bank or were nominated by primary investigators engaged in N. fowleri research. In 2017, 178 N. fowleri protein targets were queued to the Seattle Structural Genomics Center of Infectious Disease (SSGCID) pipeline, and to date 89 soluble recombinant proteins and 19 unique target structures have been produced. Many of the new protein structures are potential drug targets and contain structural differences compared to their human homologs, which could allow for the development of pathogen-specific inhibitors. Five of the structures were analyzed in more detail, and four of five show promise that selective inhibitors of the active site could be found. The 19 solved crystal structures build a foundation for future work in combating this devastating disease by encouraging further investigation to stimulate drug discovery for this neglected pathogen.

In this paper, an extensive simulation program is conducted to find out the optimal ANN model to predict the shear strength of fiber-reinforced polymer (FRP) concrete beams containing both flexural and shear reinforcements. For acquiring this purpose, an experimental database containing 125 samples is collected from the literature and used to find the best architecture of ANN. In this database, the input variables consist of 9 inputs, such as the ratio of the beam width, the effective depth, the shear span to the effective depth, the compressive strength of concrete, the longitudinal FRP reinforcement ratio, the modulus of elasticity of longitudinal FRP reinforcement, the FRP shear reinforcement ratio, the tensile strength of FRP shear reinforcement, the modulus of elasticity of FRP shear reinforcement. Thereafter, the selection of the appropriate architecture of ANN model is performed and evaluated by common statistical measurements. The results show that the optimal ANN model is a highly efficient predictor of the shear strength of FRP concrete beams with a maximum R2 value of 0.9634 on the training part and an R2 of 0.9577 on the testing part, using the best architecture. In addition, a sensitivity analysis using the optimal ANN model over 500 Monte Carlo simulations is performed to interpret the influence of reinforcement type on the stability and accuracy of ANN model in predicting shear strength. The results of this investigation could facilitate and enhance the use of ANN model in different real-world problems in the field of civil engineering.

Electron microscopy (EM) has been employed for decades to analyze cell structure. To also analyze the positions and functions of specific proteins, one typically relies on immuno-EM or on a correlation with fluorescence microscopy, in the form of correlated light and electron microscopy (CLEM). Nevertheless, neither of these procedures is able to also address the isotopic composition of cells. To solve this, a correlation with secondary ion mass spectrometry (SIMS) would be necessary. SIMS has been correlated in the past to EM or to fluorescence microscopy in biological samples, but not to CLEM. We achieved this here, using a protocol based on transmission EM, conventional epifluorescence microscopy and nanoSIMS. The protocol is easily applied, and enables the use of all three technologies at high performance parameters. We suggest that CLEM-SIMS will provide substantial information that is currently beyond the scope of conventional correlative approaches.

BackgroundIn March 2020, an influx of admissions in COVID-19 positive patients threatened to overwhelm healthcare facilities in East Baton Rouge Parish, Louisiana. Exacerbating this problem was an overall shortage of diagnostic testing capability at that time, resulting in a delay in time-to-result return. An improvement in diagnostic testing availability and timeliness was necessary to improve the allocation of resources and ultimate throughput of patients. The management of a COVID-19 positive patient or patient under investigation requires infection control measures that can quickly consume personal protective equipment (PPE) stores and personnel available to treat these patients. Critical shortages of both PPE and personnel also negatively impact care in patients admitted with non-COVID-19 illnesses.MethodsA multisectoral partnership of healthcare providers, facilities and academicians created a molecular diagnostic lab within an academic research facility dedicated to testing inpatients and healthcare personnel for SARS-CoV-2. The purpose of the laboratory was to provide a temporary solution to the East Baton Rouge Parish healthcare community until individual facilities were self-sustaining in testing capabilities. We describe the partnership and the impacts of this endeavor by developing a model derived from a combination of data sources, including electronic health records, hospital operations, and state and local resources.FindingsOur model demonstrates two important principles: the impact of reduced turnaround times (TAT) on potential differences in inpatient population numbers for COVID-19 and savings in PPE attributed to the more rapid TAT.

The paradigm of positive psychology, significant in nature, helps to explain the proactivity and motivation of human agency, such as a secondary school student’s state of autonomy, confidence, and personal resolve to strive for optimal learning and/or non-learning experiences. Our recent research development, in tandem with other scholars’ inquiries, has focused on one aspect of positive psychology–namely, a person’s achievement of ‘optimal best’, which reflects the maximization of his/her state of functioning (e.g., cognitive functioning). Capitalizing on our previous research, we develop a psychological concept that we term as a ‘perceived feeling of energy’. A perceived feeling of energy (e.g., a perceived feeling of liveliness) is proposed to act as a ‘motivational engine’, or as a central driver, which then could predict and enhance a person’s achievement of optimal best. Six hundred and twenty-seven university students (N = 438 women, 189 men) responded to a suite of self-report questionnaires. Structural equation modelling (SEM) techniques were used to test a conceptual model, where we focused on the antecedent (i.e., the direct impact of self-efficacy on a perceived feeling of energy) and consequence of a perceived feeling energy (i.e., the impact of a perceived feeling of energy on personal resolve, and the sustaining of optimal best). Analysis of results showed support for our original hypothesized model–for example: self-efficacy as an antecedent of energy and the central role of the energy as a predictor and potential mediator of future outcomes.

ObjectiveWe investigated the impact of human immunodeficiency virus (HIV) infection and anti-retroviral therapy (ART) on the gut microbiota of children.DesignThis cross-sectional study investigated the gut microbiota of children with and without HIV.MethodsWe collected fecal samples from 59 children with HIV (29 treated with ART [ART(+)] and 30 without ART [HIV(+)]) and 20 children without HIV [HIV(-)] in Vietnam. We performed quantitative RT-PCR to detect 14 representative intestinal bacteria targeting 16S/23S rRNA molecules. We also collected the blood samples for immunological analyses.ResultsIn spearman's correlation analyses, no significant correlation between the number of dominant bacteria and age was found among children in the HIV(-) group. However, the number of sub-dominant bacteria, including Streptococcus, Enterococcus, and Enterobacteriaceae, positively correlated with age in the HIV(-) group, but not in the HIV(+) group. In the HIV(+) group, Clostridium coccoides group positively associated with the CD4+ cell count and its subsets. In the ART(+) group, Staphylococcus and C. perfringens positively correlated with CD4+ cells and their subsets and negatively with activated CD8+ cells. C. coccoides group and Bacteroides fragilis group were associated with regulatory T-cell counts. In multiple linear regression analyses, ART duration was independently associated with the number of C. perfringens, and Th17 cell count with the number of Staphylococcus in the ART(+) group.ConclusionsHIV infection and ART may influence sub-dominant gut bacteria, directly or indirectly, in association with immune status in children with HIV.

ObjectiveManagement of multidrug-resistant tuberculosis (MDR-TB) is a significant challenge to the global healthcare system due to the complexity and long duration of the MDR-TB treatment. This study analyzed the safety of patients on longer injectable-based MDR-TB treatment regimens using active pharmacovigilance data.MethodWe conducted an observational, prospective study based on active pharmacovigilance within the national TB program. A total of 659 MDR-TB patients were enrolled and followed up at 9 TB- hospitals in 9 provinces of all 3 regions in Vietnam between 2014 and 2016. Patients received a treatment regimen (standardized or individualized) based on their drug susceptibility test result and their treatment history. Baseline and follow-up information was collected at the start and during treatment. Adverse events (AE) were defined and classified as serious adverse events (SAEs) or otherwise. Multivariate Cox regression following the Iterative Bayesian Model Averaging algorithm was performed to identify factors associated with AE occurrence.ResultsOut of 659 patients assessed, 71.3% experienced at least one AE, and 17.5% suffered at least one SAE. The most common AEs were gastrointestinal disorders (38.5%), arthralgia (34.7%), and psychiatric disorders (30.0%). The proportion of patients with nephrotoxicity and hearing loss or vestibular disorders were 7.4% and 15.2%, respectively. 13.1% of patients required modifications or interruption of one or more drugs. In 77.7% of patients, treatment was completed successfully, while 9.3% lost to follow-up, in 3.0% treatment failed, and 7.4% died. Some significant risk factors for nephrotoxicity included diabetes mellitus (HR = 8.46 [1.91-37.42]), renal dysfunction (HR = 8.46 [1.91-37.42]), alcoholism (HR = 13.28 [5.04-34.99]), and a higher average daily dose of injectable drugs (HR = 1.28 [1.14-1.43]).ConclusionWhile a majority of patients on the longer injectable-based regimens experienced non-serious AEs during MDR-TB treatment, one in six patients experienced at least an SAE. Active TB drug-safety monitoring is useful to understand the safety of MDR-TB treatment and explore the risk factors for toxicity. All-oral, shorter MDR-TB regimens might be able to reduce the inconvenience, discomfort, and toxicity of such regimens and increase adherence and likelihood of successful completion.

Endoplasmic reticulum (ER) stress is associated with acute kidney injury (AKI) caused by various mechanisms, including antibiotics, non-steroidal anti-inflammatory drugs, cisplatin, and radiocontrast. Tunicamycin (TM) is a nucleoside antibiotic that induces ER stress and is a commonly used model of AKI. 4-phenylbutyrate (4-PBA) is a chemical chaperone and histone deacetylase (HDAC) inhibitor and has been shown to protect the kidney from ER stress, apoptosis, and structural damage in a tunicamycin model of AKI. The renal protection provided by 4-PBA is attributed to its ability to prevent misfolded protein aggregation and inhibit ER stress; however, the HDAC inhibitor effects of 4-PBA have not been examined in the TM-induced model of AKI. As such, the main objective of this study was to determine if histone hyperacetylation provides any protective effects against TM-mediated AKI. The FDA-approved HDAC inhibitor vorinostat was used, as it has no ER stress inhibitory effects and therefore the histone hyperacetylation properties alone could be investigated. In vitro work demonstrated that vorinostat inhibited histone deacetylation in cultured proximal tubular cells but did not prevent ER stress or protein aggregation induced by TM. Vorinostat induced a significant increase in cell death, and exacerbated TM-mediated total cell death and apoptotic cell death. Wild type male mice were treated with TM (0.5 mg/kg, intraperitoneal injection), with or without vorinostat (50 mg/kg/day) or 4-PBA (1 g/kg/day). Mice treated with 4-PBA or vorinostat exhibited similar levels of histone hyperacetylation. Expression of the pro-apoptotic protein CHOP was induced with TM, and not inhibited by vorinostat. Further, vorinostat did not prevent any renal damage or decline in renal function caused by tunicamycin. These data suggest that the protective mechanisms found by 4-PBA are primarily due to its molecular chaperone properties, and the HDAC inhibitors used did not provide any protection against renal injury caused by ER stress.

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.

BackgroundEarly diagnosis, precise antimicrobial treatment and subsequent patient stratification can improve sepsis outcomes. Circulating biomarkers such as plasma microRNAs (miRNAs) have proven to be surrogates for diagnosis, severity and case management of infections. The expression of four selected miRNAs (miR-146-3p, miR-147b, miR-155 and miR-223) was validated for their prognostic and diagnostic potential in a clinically defined cohort of patients with sepsis and septic shock.MethodsThe expression of plasma miRNAs was quantified by quantitative PCR (qPCR) in patients with bacterial sepsis (n = 78), in patients with septic shock (n = 52) and in patients with dengue haemorrhagic fever (DHF; n = 69) and in healthy controls (n = 82).ResultsThe expression of studied miRNA was significantly increased in patients with bacterial sepsis and septic shock. The plasma miR-147b was able to differentiate bacterial sepsis from non-sepsis and septic shock (AUC = 0.77 and 0.8, respectively, p≤ 0.05), while the combination of plasma miR-147b and procalcitonin (PCT) predicted septic shock (AUC = 0.86, p≤ 0.05).ConclusionsThe plasma miR-147b may be an useful biomarker independently or in combination with PCT to support clinical diagnosis of sepsis and equally prognosis of patients with septic shock.