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  • A potent risk model for predicting new-onset acute coronary syndrome in patients with type 2 diabetes mellitus in Northwest China

    Lyu, J.; Li, Z.; Gong, D.-W. (Springer, 2020)
    AIMS: Type 2 diabetes mellitus (T2DM) is now very prevalent in China. Due to the lower rate of controlled diabetes in China compared to that in developed countries, there is a higher incidence of serious cardiovascular complications, especially acute coronary syndrome (ACS). The aim of this study was to establish a potent risk predictive model in the economically disadvantaged northwest region of China, which could predict the probability of new-onset ACS in patients with T2DM. METHODS: Of 456 patients with T2DM admitted to the First Affiliated Hospital of Xi'an Jiaotong University from January 2018 to January 2019 and included in this study, 270 had no ACS, while 186 had newly diagnosed ACS. Overall, 32 demographic characteristics and serum biomarkers of the study patients were analysed. The least absolute shrinkage and selection operator regression was used to select variables, while the multivariate logistic regression was used to establish the predictive model that was presented using a nomogram. The area under the receiver operating characteristics curve (AUC) was used to evaluate the discriminatory capacity of the model. A calibration plot and Hosmer-Lemeshow test were used for the calibration of the predictive model, while the decision curve analysis (DCA) was used to evaluate its clinical validity. RESULTS: After random sampling, 319 and 137 T2DM patients were included in the training and validation sets, respectively. The predictive model included age, body mass index, diabetes duration, systolic blood pressure (SBP), diastolic blood pressure (DBP), low-density lipoprotein cholesterol, serum uric acid, lipoprotein(a), hypertension history and alcohol drinking status as predictors. The AUC of the predictive model and that of the internal validation set was 0.830 [95% confidence interval (CI) 0.786-0.874] and 0.827 (95% CI 0.756-0.899), respectively. The predictive model showed very good fitting degree, and DCA demonstrated a clinically effective predictive model. CONCLUSIONS: A potent risk predictive model was established, which is of great value for the secondary prevention of diabetes. Weight loss, lowering of SBP and blood uric acid levels and appropriate control for DBP may significantly reduce the risk of new-onset ACS in T2DM patients in Northwest China. Copyright 2020, The Author(s).
  • A Mixed-Methods Study on Acceptability, Tolerability, and Substitution of Brown Rice for White Rice to Lower Blood Glucose Levels among Nigerian Adults

    Adebamowo, S.N.; Adebamowo, C.A.; The Global Nutrition Epidemiologic Transition Initiative (Frontiers Media S.A., 2017)
    Background: Whole-grain products such as brown rice have been associated with lower risk of metabolic disorders including diabetes. We examined the acceptability and tolerability of substituting brown rice for white rice and the feasibility of introducing brown rice into the diet through a long-term trial to lower the risk of type 2 diabetes. Methods: Fifty-one adults residing in Abuja, Nigeria, participated in this study. Using purposeful sampling for focus group discussions (FGDs), participants were enrolled based on their age (19–25 vs. 40–60 years) and body mass index (BMI) (normal weight vs. overweight/obese). Participants tasted four meals with different constitution of brown and white rice (25:75%, 50:50%, 75:25%, and 100% brown rice). Twelve FGDs were conducted, six before and six after the food tasting. Two-hour postprandial blood glucose was measured after consumption of each rice meal. Results: The mean age of the participants was 39 (±14) years, their mean BMI was 25.6 (±5.2) and about half of them were male. Most of the participants (61%) reported that rice was their main source of carbohydrate and 67% consumed rice at least five times/week. Before the food tasting, participants considered white polished rice superior to brown rice with regard to quality, taste, and nutritional value. After the food tasting, most of the participants (49%) indicated a preference for the 100% brown rice, 19% preferred the 25% brown rice, 18% preferred the 50% brown rice, and 7% preferred the 75% brown rice meals. Factors that may affect the acceptability of brown rice include its appearance, longer cooking time, cost, limited availability, and poor appreciation of its nutritional value. In general, 2-h postprandial glucose levels were lower, after consumption of meals with higher proportion of brown rice. Conclusion: This study provides valuable insight into the acceptability of brown rice as a substitute for white rice in Nigeria. If confirmed in larger studies, these results highlight the importance of increasing awareness on the nutritional value of brown rice and support the rationale for conducting a large-scale intervention trial to examine the effect of brown rice consumption on blood sugar levels among Nigerians. Copyright The Authors.
  • Real-world experience with ceftazidime-avibactam for multidrug-resistant gram-negative bacterial infections

    Jorgensen, S.C.J.; Trinh, T.D.; Claeys, K.C. (Oxford University Press, 2019)
    Background. We conducted this study to describe the clinical characteristics, microbiology, and outcomes of patients treated with ceftazidime-avibactam (CZA) for a range of multidrug-resistant Gram-negative (MDR-GN) infections. Methods. This is a multicenter, retrospective cohort study conducted at 6 medical centers in the United States between 2015 and 2019. Adult patients who received CZA (?72 hours) were eligible. The primary outcome was clinical failure defined as a composite of 30-day all-cause mortality, 30-day microbiological failure, and/or failure to resolve or improve signs or symptoms of infection on CZA. Results. In total, data from 203 patients were evaluated. Carbapenem-resistant Enterobacteriaceae (CRE) and Pseudomonas spp were isolated from 117 (57.6%) and 63 (31.0%) culture specimens, respectively. The most common infection sources were respiratory (37.4%), urinary (19.7%), and intra-abdominal (18.7%). Blood cultures were positive in 22 (10.8%) patients. Clinical failure, 30-day mortality, and 30-day recurrence occurred in 59 (29.1%), 35 (17.2%), and 12 (5.9%) patients, respectively. On therapy, CZA resistance developed in 1 of 62 patients with repeat testing. Primary bacteremia or respiratory tract infection and higher SOFA score were positively associated with clinical failure (adjusted odds ratio [aOR] = 2.270, 95% confidence interval [CI] = 1.115-4.620 and aOR = 1.234, 95% CI = 1.118–1.362, respectively). Receipt of CZA within 48 hours of infection onset was protective (aOR, 0.409; 95% CI, 0.180-0.930). Seventeen (8.4%) patients experienced a potential drug-related adverse effect (10 acute kidney injury, 3 Clostridioides difficile infection, 2 rash, and 1 each gastrointestinal intolerance and neutropenia) Conclusions. Ceftazidime-avibactam is being used to treat a range of MDR-GN infections including Pseudomonas spp as well as CRE. Copyright The Author(s) 2019.
  • Factors influencing malignant mesothelioma survival: A retrospective review of the national mesothelioma virtual bank cohort[version 3; peer review: 2 approved, 1 approved with reservations]

    Amin, W.; Linkov, F.; Friedberg, J.S. (F1000 Research Ltd, 2018)
    Background: Malignant mesothelioma (MM) is a rare but deadly malignancy with about 3,000 new cases being diagnosed each year in the US. Very few studies have been performed to analyze factors associated with mesothelioma survival, especially for peritoneal presentation. The overarching aim of this study is to examine survival of the cohort of patients with malignant mesothelioma enrolled in the National Mesothelioma Virtual Bank (NMVB). Methods: 888 cases of pleural and peritoneal mesothelioma cases were selected from the NMVB database, which houses data and associated biospecimens for over 1400 cases that were diagnosed from 1990 to 2017. Kaplan Meier’s method was performed for survival analysis. The association between prognostic factors and survival was estimated using Cox Hazard Regression method and using R software for analysis. Results: The median overall survival (OS) rate of all MM patients, including pleural and peritoneal mesothelioma cases is 15 months (14 months for pleural and 31 months for peritoneal). Significant prognostic factors associated with improved survival of malignant mesothelioma cases in this NMVB cohort were younger than 45, female gender, epithelioid histological subtype, stage I, peritoneal occurrence, and having combination treatment of surgical therapy with chemotherapy. Combined surgical and chemotherapy treatment was associated with improved survival of 23 months in comparison to single line therapies. Conclusions: There has not been improvement in the overall survival for patients with malignant mesothelioma over many years with current available treatment options. Our findings show that combined surgical and chemotherapy treatment in peritoneal mesothelioma is associated with improved survival compared to local therapy alone. Copyright 2019 Amin W et al.
  • Psychosocial Factors Associated with Healthy and Unhealthy Interpregnancy Intervals

    Young, R.; Lane, W.G.; Stephens, S.B.; Mayden, B.W., (Mary Ann Liebert Inc., 2018)
    Purpose: To examine the influence of psychosocial factors, including anxiety, depression, social support, maternal substance abuse, and intimate partner violence (IPV) on interpregnancy intervals (IPIs). Methods: B'more for Healthy Babies-Upton/Druid Heights is part of a citywide initiative to improve the health of at-risk pregnant women and their children. Participants with at least one prior birth completed baseline, postpartum, and 3-month follow-up surveys with questions about pregnancy, medical, and psychosocial history. Associations between IPI and the independent variables were assessed using chi-square analysis and analysis of variance. Multivariable multinomial logistic regression models examined significant associations while controlling for other independent variables and potential confounders. Results: Participants with current IPV were more likely to have a short IPI (odds ratio [OR]=13.1; 95% confidence interval [CI]=1.07-158.9; p=0.04) than healthy IPI. Women with family social support were more likely to have a healthy IPI (OR=5.88, 95% CI=1.02-31.25, p=0.05) than those without family social support. Maternal anxiety and depression did not significantly influence IPI. Conclusion: IPV increased the likelihood of having an unhealthy IPI among this population and family social support increased the likelihood of having a healthy IPI. Additional efforts to address IPV and enhance family social support may lead to improved pregnancy outcomes. Copyright Ruth Young et al. 2018.
  • Infrastructure and organization of adult intensive care units in resource-limited settings

    Papali, A.; Adhikari, N.K.J.; Diaz, J.V. (Springer International Publishing, 2019)
  • Metabolomic biomarkers are associated with mortality in patients with cirrhosis caused by primary biliary cholangitis or primary sclerosing cholangitis

    Mindikoglu, A.L.; Seliger, S.L.; Raufman, J.-P. (Future Medicine Ltd., 2020)
    Aim: To assess the ability of signature metabolites alone, or in combination with the model for end-stage liver disease-Na (MELD-Na) score to predict mortality in patients with cirrhosis caused by primary biliary cholangitis or primary sclerosing cholangitis. Materials & methods: Plasma metabolites were detected using ultrahigh-performance liquid chromatography/tandem mass spectrometry in 39 patients with cirrhosis caused by primary biliary cholangitis or primary sclerosing cholangitis. Mortality was predicted using Cox proportional hazards regression and time-dependent receiver operating characteristic curve analyses. Results: The top five metabolites with significantly greater accuracy than the MELD-Na score (area under the receiver operating characteristic curve [AUROC] = 0.7591) to predict 1-year mortality were myo-inositol (AUROC = 0.9537), N-Acetylputrescine (AUROC = 0.9018), trans-Aconitate (AUROC = 0.8880), erythronate (AUROC = 0.8345) and N6-carbamoylthreonyladenosine (AUROC = 0.8055). Several combined MELD-Na-metabolite models increased the accuracy of predicted 1-year mortality substantially (AUROC increased from 0.7591 up to 0.9392). Conclusion: Plasma metabolites have the potential to enhance the accuracy of mortality predictions, minimize underestimates of mortality in patients with cirrhosis and low MELD-Na scores, and promote equitable allocation of donor livers. Copyright 2020 The authors.
  • A single dose of modified vaccinia ankara expressing lassa virus-like particles protects mice from lethal intra-cerebral virus challenge

    Salvato, M.S.; Medina-Moreno, S.; Zapata, J.C.; Hsu, H.; Guzmán-Cardozo, C. (MDPI AG, 2019)
    Lassa fever surpasses Ebola, Marburg, and all other hemorrhagic fevers except Dengue in its public health impact. Caused by Lassa virus (LASV), the disease is a scourge on populations in endemic areas of West Africa, where reported incidence is higher. Here, we report construction, characterization, and preclinical efficacy of a novel recombinant vaccine candidate GEO-LM01. Constructed in the Modified Vaccinia Ankara (MVA) vector, GEO-LM01 expresses the glycoprotein precursor (GPC) and zinc-binding matrix protein (Z) from the prototype Josiah strain lineage IV. When expressed together, GP and Z form Virus-Like Particles (VLPs) in cell culture. Immunogenicity and efficacy of GEO-LM01 was tested in a mouse challenge model. A single intramuscular dose of GEO-LM01 protected 100% of CBA/J mice challenged with a lethal dose of ML29, a Mopeia/Lassa reassortant virus, delivered directly into the brain. In contrast, all control animals died within one week. The vaccine induced low levels of antibodies but Lassa-specific CD4+ and CD8+ T cell responses. This is the first report showing that a single dose of a replication-deficient MVA vector can confer full protection against a lethal challenge with ML29 virus. Copyright 2019 by the authors.
  • Healthcare practitioners' views of social media as an educational resource

    Pizzuti, A.G.; Patel, K.H.; Heil, E. (Public Library of Science, 2020)
    Social media is increasingly utilized as a resource in healthcare. We sought to identify perceptions of using social media as an educational tool among healthcare practitioners. An electronic survey was distributed to healthcare administrators, nurses, nurse practitioners, pharmacists, physicians, and physician assistants f hospital systems and affiliated health science schools in Georgia, Maryland, South Carolina, and Wisconsin. Survey questions evaluated respondents' use and views of social media for educational purposes and workplace accessibility using a Likert scale (1 = strongly disagree, 5 = strongly agree). Nurses (75%), pharmacists (11%), and administrators (7%) were the most frequent respondents. Facebook® (27%), Pinterest® (17%), and Instagram® (17%) were the most frequently accessed social media platforms. Nearly 85% agreed or strongly agreed that social media can be an effective tool for educational purposes. Among those who had social media platforms, 43.0% use them for educational purposes. Pinterest® (30%), Facebook® (22%), LinkedIn® (16%), and Twitter® (14%) were most frequently used for education. About 50% of respondents had limited or no access to social media at work. Administrators, those with unlimited and limited work access, and respondents aged 20-29 and 30-39 years were more likely to agree that social media is an educational tool (OR: 3.41 (95% CI 1.31 to 8.84), 4.18 (95% CI 2.30 to 7.60), 1.66 (95% CI 1.22 to 2.25), 4.40 (95% CI 2.80 to 6.92), 2.14 (95% CI 1.53 to 3.01) respectively). Residents, physicians, and those with unlimited access were less likely to agree with allowing social media access at work for educational purposes only. Healthcare practitioners frequently utilize social media, and many believe it can be an effective educational tool in healthcare. Copyright: 2020 Pizzuti et al.
  • Current challenges in the management of sepsis in icus in resource-poor settings and suggestions for the future

    Schultz, M.J.; Papali, A.; Dünser, M.W. (Springer International Publishing, 2019)
  • International ResearchKit App for Women with Menstrual Pain (Development, Access, and Engagement): Pragmatic Randomized Control Trial

    Wang, J.; D'Adamo, C.R.; Witt, C.M. (JMIR Publications, 2020)
    BACKGROUND: Primary dysmenorrhea is a common condition in women of reproductive age. A previous app-based study undertaken by our group demonstrated that a smartphone app supporting self-acupressure introduced by a health care professional can reduce menstrual pain. OBJECTIVE: This study aims to evaluate whether a specific smartphone app is effective in reducing menstrual pain in 18- to 34-year-old women with primary dysmenorrhea in a self-care setting. One group of women has access to the full-featured study app and will be compared with 2 control groups who have access to fewer app features. Here, we report the trial design, app development, user access, and engagement. METHODS: On the basis of the practical implications of the previous app-based study, we revised and reengineered the study app and included the ResearchKit (Apple Inc) framework. Behavior change techniques (BCTs) were implemented in the app and validated by expert ratings. User access was estimated by assessing recruitment progress over time. User evolution and baseline survey respondent rate were assessed to evaluate user engagement. RESULTS: The development of the study app for a 3-armed randomized controlled trial required a multidisciplinary team. The app is accessible for the target population free of charge via the Apple App Store. In Germany, within 9 months, the app was downloaded 1458 times and 328 study participants were recruited using it without external advertising. A total of 98.27% (5157/5248) of the app-based baseline questions were answered. The correct classification of BCTs used in the app required psychological expertise. CONCLUSIONS: Conducting an innovative app study requires multidisciplinary effort. Easy access and engagement with such an app can be achieved by recruitment via the App Store. Future research is needed to investigate the determinants of user engagement, optimal BCT application, and potential clinical and self-care scenarios for app use. TRIAL REGISTRATION: NCT03432611; (Archived by WebCite at Copyright The Authors.
  • Setting priorities to inform assessment of care homes' readiness to participate in healthcare innovation: A systematic mapping review and consensus process

    Bunn, F.; Goodman, C.; Corazzini, K. (MDPI AG, 2020)
    Organisational context is known to impact on the successful implementation of healthcare initiatives in care homes. We undertook a systematic mapping review to examine whether researchers have considered organisational context when planning, conducting, and reporting the implementation of healthcare innovations in care homes. Review data were mapped against the Alberta Context Tool, which was designed to assess organizational context in care homes. The review included 56 papers. No studies involved a systematic assessment of organisational context prior to implementation, but many provided post hoc explanations of how organisational context affected the success or otherwise of the innovation. Factors identified to explain a lack of success included poor senior staff engagement, non-alignment with care home culture, limited staff capacity to engage, and low levels of participation from health professionals such as general practitioners (GPs). Thirty-five stakeholders participated in workshops to discuss findings and develop questions for assessing care home readiness to participate in innovations. Ten questions were developed to initiate conversations between innovators and care home staff to support research and implementation. This framework can help researchers initiate discussions about health-related innovation. This will begin to address the gap between implementation theory and practice. Copyright 2020 by the authors.
  • Novel Insights Into Immune Systems of Bats

    Banerjee, A.; Baker, M.L.; Kulcsar, K. (Frontiers Media S.A., 2020)
    In recent years, viruses similar to those that cause serious disease in humans and other mammals have been detected in apparently healthy bats. These include filoviruses, paramyxoviruses, and coronaviruses that cause severe diseases such as Ebola virus disease, Marburg haemorrhagic fever and severe acute respiratory syndrome (SARS) in humans. The evolution of flight in bats seem to have selected for a unique set of antiviral immune responses that control virus propagation, while limiting self-damaging inflammatory responses. Here, we summarize our current understanding of antiviral immune responses in bats and discuss their ability to co-exist with emerging viruses that cause serious disease in other mammals. We highlight how this knowledge may help us to predict viral spillovers into new hosts and discuss future directions for the field. Copyright 2020 The Authors.
  • Antimicrobial usage at a large teaching hospital in Lusaka, Zambia

    Callahan, P.; Herbert, A.; Hachaambwa, L. (Public Library of Science, 2020)
    Antimicrobial resistance is a growing global health concern. Antimicrobial stewardship (AMS) curbs resistance rates by encouraging rational antimicrobial use. However, data on antimicrobial stewardship in developing countries is scarce. The objective of this study was to characterize antimicrobial use at the University Teaching Hospital (UTH) in Lusaka, Zambia as a guiding step in the development of an AMS program. This was a cross-sectional, observational study evaluating antimicrobial appropriateness and consumption in non-critically ill adult medicine patients admitted to UTH. Appropriateness was defined as a composite measure based upon daily chart review. Sixty percent (88/146) of all adult patients admitted to the general wards had at least one antimicrobial ordered and were included in this study. The most commonly treated infectious diseases were tuberculosis, pneumonia, and septicemia. Treatment of drug sensitive tuberculosis is standardized in a four-drug combination pill of rifampicin, isoniazid, pyrazinamide and ethambutol, therefore appropriateness of therapy was not further evaluated. The most common antimicrobials ordered were cefotaxime (n = 45), ceftriaxone (n = 28), and metronidazole (n = 14). Overall, 67% of antimicrobial orders were inappropriately prescribed to some extent, largely driven by incorrect dose or frequency in patients with renal dysfunction. Antimicrobial prescribing among hospitalized patients at UTH is common and there is room for optimization of a majority of antimicrobial orders. Availability of certain antimicrobials must be taken into consideration during AMS program development.
  • Cognitive impairment and depression symptoms are independently associated with suicidal ideation in US Veterans

    Ryan, A.T.; Phalen, P.; Wastler, H.; Bennett, M. (Elsevier Ireland Ltd, 2020)
    Depression is associated with cognitive impairment and suicidality. The independent association between cognitive impairment and suicidality is less clear. We examined the relationship between suicidal ideation and cognitive impairment in a sample of 50 veterans with depressive disorder diagnoses. Using zero-inflated Poisson regression, the severity of suicidal ideation was negatively associated with attention (incidence rate ratio [IRR] = 0.78, p < .001), memory (IRR = 0.87, p < .001), and total cognition (IRR = 0.90, p = .007) index scores as measured by the Dementia Rating Scale 2 (DRS-2). These three indices continued to significantly predict suicidal ideation severity once depression symptoms were controlled for.
  • Building the future for national trauma research

    Price, M.A.; A, Kozar, R.; Bulger, E.M. (BMJ Publishing Group, 2020)
    This paper describes the current funding, infrastructure growth and future state of trauma research. It also introduces a group of review articles generated from The Future of Trauma Research: Innovations in Research Methodology conference hosted by the American College of Surgeons Committee on Trauma in July 2019. Copyright Author(s) (or their employer(s)) 2020.
  • Development of peripheral eosinophilia in inflammatory bowel disease patients on infliximab treated at a tertiary pediatric inflammatory bowel disease center is associated with clinically active disease but does not result in loss of efficacy or adverse outcomes

    Zabrowski, D.; Abraham, D.; Rosenthal, G.; Kader, H. (John Wiley and Sons Inc., 2020)
    Introduction: Inflammatory bowel disease (IBD) consisting of Crohn's disease(CD) and ulcerative colitis (UC) are inflammatory conditions affecting the gastrointes-tinal tract. Infliximab (IFX) is a chimeric anti-tumor necrosis factor antibody used totreat moderate to severe IBD. Eosinophils are commonly found in chronicallyinflamed tissues in IBD. Peripheral eosinophilia (PE) was previously implicated as amarker of disease severity at diagnosis. The main aim of this study was to investigatewhether in IBD patients on IFX, development of PE is associated with adverse out-comes and poor IFX efficacy.Methods:A comprehensive retrospective chart review of IBD patients on IFX(January 2006 to July 2015) treated at a tertiary pediatric IBD center was performed.Data was collected at time specified points over a 24 month period and includeddemographics, atopy, disease severity, development of PE, human antichimeric anti-bodies (HACA), infusion reactions, cancer, psoriasis, and loss of clinical response.Results:One hundred twenty-one IBD patients starting IFX (67 male), mean age of12.4 years (range 4-22 years old), met inclusion criteria. Of them, 36.3% had?1PEepisode (CD: 25 male, 11 female; UC: 6 male, 2 female). Mean absolute eosinophilcount (AEC) did not change over time. PE was associated with clinically active dis-ease. Among patients who developed PE, adverse outcomes were not significantly dif-ferentversusthose who did not have PE.Conclusions:In a cohort of primarily pediatric IBD patients on IFX, PE was associ-ated with clinically active disease; however, PE was not related to increased incidenceof adverse outcomes or loss of drug efficacy. Copyright 2020 The Authors.
  • Resumptive Streptococcus mutans Persisters Induced From Dimethylaminododecyl Methacrylate Elevated the Cariogenic Virulence by Up-Regulating the Quorum-Sensing and VicRK Pathway Genes

    Lu, J.; Cheng, L.; Xu, H.H.K. (Frontiers Media S.A., 2020)
    Bacterial persistence has become a worldwide health problem due to its ability to cause the recalcitrance and relapse of infections. The existence of bacterial persistence and their possible mechanisms have been widely reported. However, the following regrowth of persister cells is not clear although the awakening of dormant surviving persisters is the key to reinitialize bacterial infection. In this study, we investigated the growth character and cariogenic virulence during the recovery of Streptococcus mutans drug-tolerant persister cells induced by a novel quaternary ammonium: dimethylaminododecyl methacrylate (DMADDM). A remarkable lag phase was observed in S. mutans persisters when regrew at the first 24 h compared to normal cells. During the entire recovery state, persisters are metabolically active to increase the production of both water-soluble and water-insoluble glucan. The shortage of cell number in persisters resulted in the decrease of lactic acid production, but persisters gradually recovered the normal acid production ability after 72 h. The up-regulated expression of gtf and vicR was in line with comDE circuit and consistent with the virulence change during the regrowth stage. Our findings proved that lethal dosages of DMADDM induced drug-tolerant S. mutans persisters in biofilm, which had a prolonged lag phase and elevated cariogenic virulence during regrowth. The recovery and elevated virulence of persisters were regulated by quorum-sensing and VicRK pathway. This alarmed the elevated cariogenicity of persisters and highlighted the critical requirement for the drug-tolerance evaluation when developing new oral antimicrobial agents. To the best of our knowledge, we characterized the regrowth and cariogenic virulence variation of S. mutans persisters induced by quaternary ammonium for the first time. Our findings suggest that S. mutans persisters with the elevated cariogenic virulence during their regrowth stage highlighted the need of new strategy to overcome bacterial persistence. Meanwhile, the prolonged lag phase and the involvement of quorum-sensing system in the regrowth of S. mutans persisters may provide the potential targets. Copyright The Authors.
  • Functional antibodies as immunological endpoints to evaluate protective immunity against Shigella

    Ndungo, E.; Pasetti, M.F. (Taylor & Francis, 2020)
    The development, clinical advancement and licensure of vaccines, and monitoring of vaccine effectiveness could be expedited and simplified by the ability to measure immunological endpoints that can predict a favorable clinical outcome. Antigen-specific and functional antibodies have been described in the context of naturally acquired immunity and vaccination against Shigella, and their presence in serum has been associated with reduced risk of disease in human subjects. The relevance of these antibodies as correlates of protective immunity, their mechanistic contribution to protection (e.g. target antigens, interference with pathogenesis, and participation in microbial clearance), and factors that influence their magnitude and makeup (e.g. host age, health condition, and environment) are important considerations that need to be explored. In addition to facilitating vaccine evaluation, immunological correlates of protection could be useful for identifying groups at risk and advancing immune therapies. Herein we discuss the precedent and value of functional antibodies as immunological endpoints to predict vaccine efficacy and the relevance of functional antibody activity to evaluate protective immunity against shigellosis.
  • Does respiratory syncytial virus lower respiratory illness in early life cause recurrent wheeze of early childhood and asthma? Critical review of the evidence and guidance for future studies from a World Health Organization-sponsored meeting

    Driscoll, A.J.; Arshad, S.H.; Bont, L. (Elsevier Ltd, 2020)
    Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI) and hospitalization in infants and children globally. Many observational studies have found an association between RSV LRTI in early life and subsequent respiratory morbidity, including recurrent wheeze of early childhood (RWEC) and asthma. Conversely, two randomized placebo-controlled trials of efficacious anti-RSV monoclonal antibodies (mAbs) in heterogenous infant populations found no difference in physician-diagnosed RWEC or asthma by treatment group. If a causal association exists and RSV vaccines and mAbs can prevent a substantial fraction of RWEC/asthma, the full public health value of these interventions would markedly increase. The primary alternative interpretation of the observational data is that RSV LRTI in early life is a marker of an underlying predisposition for the development of RWEC and asthma. If this is the case, RSV vaccines and mAbs would not necessarily be expected to impact these outcomes. To evaluate whether the available evidence supports a causal association between RSV LRTI and RWEC/asthma and to provide guidance for future studies, the World Health Organization convened a meeting of subject matter experts on February 12–13, 2019 in Geneva, Switzerland. After discussing relevant background information and reviewing the current epidemiologic evidence, the group determined that: (i) the evidence is inconclusive in establishing a causal association between RSV LRTI and RWEC/asthma, (ii) the evidence does not establish that RSV mAbs (and, by extension, future vaccines) will have a substantial effect on these outcomes and (iii) regardless of the association with long-term childhood respiratory morbidity, severe acute RSV disease in young children poses a substantial public health burden and should continue to be the primary consideration for policy-setting bodies deliberating on RSV vaccine and mAb recommendations. Nonetheless, the group recognized the public health importance of resolving this question and suggested good practice guidelines for future studies. Copyright 2020 Elsevier Ltd

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