• Estimating the incidence of influenza at the state level - Utah, 2016-17 and 2017-18 influenza seasons

      Hughes, M.M.; Carmack, A.E.; McCaffrey, K. (Department of Health and Human Services, 2019)
      What is already known about this topic? Influenza activity can vary widely based on geographic location, and national data on the numbers of persons affected by influenza do not reflect this potential variation. What is added by this report? Application of national methods to estimate the burden of influenza at the state level found that influenza affected 9% and 11% of Utah residents during the 2016-17 and 2017-18 influenza seasons, respectively. What are the implications for public health practice? Local estimation of influenza disease burden can help public health officials, policymakers, and clinicians tailor influenza messaging, planning, and responses for their jurisdictions. State and county health departments might consider adapting these methods to their jurisdictions in future influenza seasons.
    • Targeting HIV/SIV infection of CD4+ T follicular helper (Tfh) Cells: BCL6 inhibition represses HIV infection CD4+ T cells and reduces germinal center hyperplasia in rhesus macaque

      Cai, Y.; Abdel-Mohsen, M.; Watkins, M.; Xue, F.; Ai, Y.; Cheng, H.; Midkiff, C.; Tomescu, C.; Wang, X.; Alvarez, X.; et al. (Mediscript Ltd, 2019-07-01)
    • Treatment with One Dose of Reltecimod is Superior to Two Doses in Mouse Models of Lethal Infection

      Edgar, Rotem; Tarrio, Margarite L.; Maislin, Greg; Chiguang, Feng; Kaempfer, Raymond; Cross, Alan; Opal, Steven M.; Shirvan, Anat (Springer Science and Business Media LLC, 2019-11-12)
      Soft-tissue bacterial infection can progress to severe sepsis and septic shock as a result of a disproportionate infammatory response, characterized by an excessive release of cytokines and infux of immune cells. Reltecimod (previously known as AB103 or p2TA), a peptide derived from the T-cell receptor CD28, modulates the host immune response by targeting the co-stimulatory pathway, which is essential for the induction of multiple pro-infammatory cytokines. Consequently, reltecimod has demonstrated benefcial efects against diferent bacterial infections, their exotoxins and endotoxins, and ionizing radiation. The dosing regimen of reltecimod was evaluated in three mouse models of infection. The efect of the number of reltecimod doses with respect to survival, cytokine/chemokine levels, and blood leukocyte profles was assessed. Overall, mice treated with a single intravenous dose of reltecimod (5 mg/kg) at 1–2 h after infection showed signifcantly greater survival as compared with saline-treated controls. Mice treated with a second doses demonstrated improved survival compared with saline-treated controls. However, in all models of infection, administration of a single therapeutic dose of reltecimod was superior to two or multiple doses. Further examination showed that the single therapeutic dose of reltecimod was associated with an early (within 24 h) decrease in cytokine/chemokine levels and most circulating leukocyte subpopulations. A second dose of reltecimod did not improve these early positive efects and appeared to attenuate further changes. These results provided insight into the mechanism of action of reltecimod and established a basis for the dosing regimen utilized in clinical trials, where reltecimod is administered as a single dose.
    • The Envelope Residues E152/156/158 of Zika Virus Influence the Early Stages of Virus Infection in Human Cells

      Bos, Sandra; Viranaicken, Wildriss; Frumence, Etienne; Li, Ge; Desprès, Philippe; Zhao, Richard Y.; Gadea, Gilles (MDPI AG, 2019-11-15)
      Emerging infections of mosquito-borne Zika virus (ZIKV) pose an increasing threat to human health, as documented over the recent years in South Pacific islands and the Americas in recent years. To better understand molecular mechanisms underlying the increase in human cases with severe pathologies, we recently demonstrated the functional roles of structural proteins capsid (C), pre-membrane (prM), and envelop (E) of ZIKV epidemic strains with the initiation of viral infection in human cells. Specifically, we found that the C-prM region contributes to permissiveness of human host cells to ZIKV infection and ZIKV-induced cytopathic effects, whereas the E protein is associated with viral attachment and early infection. In the present study, we further characterize ZIKV E proteins by investigating the roles of residues isoleucine 152 (Ile152), threonine 156 (Thr156), and histidine 158 (His158) (i.e., the E-152/156/158 residues), which surround a unique N-glycosylation site (E-154), in permissiveness of human host cells to epidemic ZIKV infection. For comparison purpose, we generated mutant molecular clones of epidemic BeH819015 (BR15) and historical MR766-NIID (MR766) strains that carry each other's E-152/156/158 residues, respectively. We observed that the BR15 mutant containing the E-152/156/158 residues from MR766 was less infectious in A549-Dual™ cells than parental virus. In contrast, the MR766 mutant containing E-152/156/158 residues from BR15 displayed increased infectivity. The observed differences in infectivity were, however, not correlated with changes in viral binding onto host-cells or cellular responses to viral infection. Instead, the E-152/156/158 residues from BR15 were associated with an increased efficiency of viral membrane fusion inside infected cells due to conformational changes of E protein that enhance exposure of the fusion loop. Our data highlight an important contribution of E-152/156/158 residues to the early steps of ZIKV infection in human cells.
    • ZSCAN4 facilitates chromatin remodeling and promotes the cancer stem cell phenotype

      Portney, B.A.; Arad, M.; Gupta, A.; Brown, R.A.; Khatri, R.; Lin, P.N.; Hebert, A.M.; Angster, K.H.; Silipino, L.E.; Meltzer, W.A.; et al. (Springer Nature, 2020)
      Cancer stem cells (CSCs) are cells within tumors that maintain the ability to self-renew, drive tumor growth, and contribute to therapeutic resistance and cancer recurrence. In this study, we investigate the role of Zinc finger and SCAN domain containing 4 (ZSCAN4) in human head and neck squamous cell carcinoma (HNSCC). The murine Zscan4 is involved in telomere maintenance and genomic stability of mouse embryonic stem cells. Our data indicate that the human ZSCAN4 is enriched for, marks and is co-expressed with CSC markers in HNSCC. We show that transient ZSCAN4 induction for just 2 days increases CSC frequency both in vitro and in vivo and leads to upregulation of pluripotency and CSC factors. Importantly, we define for the first time the role of ZSCAN4 in altering the epigenetic profile and regulating the chromatin state. Our data show that ZSCAN4 leads to a functional histone 3 hyperacetylation at the promoters of OCT3/4 and NANOG, leading to an upregulation of CSC factors. Consistently, ZSCAN4 depletion leads to downregulation of CSC markers, decreased ability to form tumorspheres and severely affects tumor growth. Our study suggests that ZSCAN4 plays an important role in the maintenance of the CSC phenotype, indicating it is a potential therapeutic target in HNSCC. Copyright 2020, The Author(s).
    • Histone demethylase JMJD1A promotes expression of DNA repair factors and radio-resistance of prostate cancer cells

      Fan, L.; Xu, S.; Zhang, F.; Cui, X.; Clark, D.J.; Yang, A.; Hussain, A.; Rassool, F.; Qi, J. (Springer Nature, 2020)
      The DNA damage response (DDR) pathway is a promising target for anticancer therapies. The androgen receptor and myeloblastosis transcription factors have been reported to regulate expression of an overlapping set of DDR genes in prostate cancer cells. Here, we found that histone demethylase JMJD1A regulates expression of a different set of DDR genes largely through c-Myc. Inhibition of JMJD1A delayed the resolution of γ-H2AX foci, reduced the formation of foci containing ubiquitin, 53BP1, BRCA1 or Rad51, and inhibited the reporter activity of double-strand break (DSB) repair. Mechanistically, JMJD1A regulated expression of DDR genes by increasing not only the level but also the chromatin recruitment of c-Myc through H3K9 demethylation. Further, we found that ubiquitin ligase HUWE1 induced the K27-/K29-linked noncanonical ubiquitination of JMJD1A at lysine-918. Ablation of the JMJD1A noncanonical ubiquitination lowered DDR gene expression, impaired DSB repair, and sensitized response of prostate cells to irradiation, topoisomerase inhibitors or PARP inhibitors. Thus, development of agents that target JMJD1A or its noncanonical ubiquitination may sensitize the response of prostate cancer to radiotherapy and possibly also genotoxic therapy. Copyright 2020, The Author(s).
    • Re-annotation of the Theileria parva genome refines 53% of the proteome and uncovers essential components of N-glycosylation, a conserved pathway in many organisms

      Tretina, K.; Pelle, R.; Silva, J.C. (Springer Nature, 2020)
      BACKGROUND: The apicomplexan parasite Theileria parva causes a livestock disease called East coast fever (ECF), with millions of animals at risk in sub-Saharan East and Southern Africa, the geographic distribution of T. parva. Over a million bovines die each year of ECF, with a tremendous economic burden to pastoralists in endemic countries. Comprehensive, accurate parasite genome annotation can facilitate the discovery of novel chemotherapeutic targets for disease treatment, as well as elucidate the biology of the parasite. However, genome annotation remains a significant challenge because of limitations in the quality and quantity of the data being used to inform the location and function of protein-coding genes and, when RNA data are used, the underlying biological complexity of the processes involved in gene expression. Here, we apply our recently published RNAseq dataset derived from the schizont life-cycle stage of T. parva to update structural and functional gene annotations across the entire nuclear genome. RESULTS: The re-annotation effort lead to evidence-supported updates in over half of all protein-coding sequence (CDS) predictions, including exon changes, gene merges and gene splitting, an increase in average CDS length of approximately 50 base pairs, and the identification of 128 new genes. Among the new genes identified were those involved in N-glycosylation, a process previously thought not to exist in this organism and a potentially new chemotherapeutic target pathway for treating ECF. Alternatively-spliced genes were identified, and antisense and multi-gene family transcription were extensively characterized. CONCLUSIONS: The process of re-annotation led to novel insights into the organization and expression profiles of protein-coding sequences in this parasite, and uncovered a minimal N-glycosylation pathway that changes our current understanding of the evolution of this post-translational modification in apicomplexan parasites.
    • Attitudes and Perceptions Toward Authorized Deception: A Pilot Comparison of Healthy Controls and Fibromyalgia Patients

      Goo, S.J.; Frangos, E.; Colloca, L. (Oxford University Press, 2020)
      Objective: Little is known about the perceptions and attitudes of participants who volunteer in studies involving authorized deception. Thus, this cross-sectional pilot study measured, for the first time, the perceptions about participation in an authorized-deception placebo analgesia study in chronic pain patients with fibromyalgia and assessed whether their perceptions differed from healthy controls. Methods: An anonymous survey with questions about trust in research and willingness to participate in future research involving deception was mailed to participants in both groups after completion of the parent study. Statistical analyses were performed using the Mann-Whitney U and chi-square tests (31 controls and 16 fibromyalgia patients were included in the analyses). Results: The majority of participants expressed little or no concern about the deception, still trusted the scientific process, and found the debriefing procedure helpful and worthwhile. Group differences were found in willingness to 1) participate in the parent study had the deceptive element been disclosed in advance (controls = definitely, fibromyalgia patients = probably, U = 341.5, P = 0.01) and 2) participate in future studies (controls = definitely, fibromyalgia patients = probably, U = 373, P < 0.001). Conclusions: Despite slightly less favorable responses of fibromyalgia patients and the relatively small size of the study, these findings suggest that attitudes and perceptions about participating in an authorized placebo study remain positive in both healthy and chronic pain populations.
    • Review of Emerging Pharmacotherapy for the Treatment of Coronavirus Disease 2019

      Barlow, A.; Landolf, K.M.; Yeung, S.Y.A.; Heavner, J.J.; Claassen, C.W.; Heavner, M.S. (Wiley-Blackwell, 2020)
      The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has evolved into an emergent global pandemic. Coronavirus disease 2019 (COVID‐19) can manifest on a spectrum of illness from mild disease to severe respiratory failure requiring intensive care unit (ICU) admission. As the incidence continues to rise at a rapid pace, critical care teams are faced with challenging treatment decisions. There is currently no widely accepted standard of care in the pharmacological management of patients with COVID‐19. Urgent identification of potential treatment strategies is a priority. Therapies include novel agents available in clinical trials or through compassionate use, and other drugs, repurposed antiviral and immune modulating therapies. Many have demonstrated in vitro or in vivo potential against other viruses that are similar to SARS‐CoV‐2. Critically ill patients with COVID‐19 have additional considerations related to adjustments for organ impairment and renal replacement therapies, complex lists of concurrent medications, limitations with drug administration and compatibility, and unique toxicities that should be evaluated when utilizing these therapies. The purpose of this review is to summarize practical considerations for pharmacotherapy in patients with COVID‐19, with the intent of serving as a resource for health care providers at the forefront of clinical care during this pandemic.
    • National Institutes of Health (NIH) grant awards: does past performance predict future success?

      Prasad, J.M.; Shipley, M.T.; Rogers, T.B.; Puche, A.C. (Palgrave Macmillan Ltd., 2020)
      The NIH is the major federal biomedical research funding agency within the United States, and NIH funding has become a priority in institutional decisions on faculty recruitment, salary, promotion, and tenure. The implicit assumption is that well-funded investigators will maintain their funding success; however, our analysis of NIH awardees from 2000 to 2015 suggests that regardless of how well funded an investigator is, their research portfolio exhibits "regression to the mean," matching the typical NIH funding profile within just 10-15 years. Thus, outperformance in past funding is not a strong predictor of future outperformance in funding success. This study indicates that faculty performance should not be solely judged upon grant success but should include other institutional mission priorities such as provision of clinical care, education, and service to community/profession. Copyright 2020, The Author(s).
    • Cost Analysis of Treating Pediatric Supracondylar Humerus Fractures in Community Hospitals Compared With a Tertiary Care Hospital

      Shasti, M.; Li, T.P.; Case, A.L.; Hariharan, A.R.; Jauregui, J.J.; Abzug, J.M. (Wolters Kluwer Health, 2020)
      OBJECTIVE: In the current healthcare environment, providing cost-efficient care is of paramount importance. One emerging strategy is to use community hospitals (CHs) rather than tertiary care hospitals (TCHs) for some procedures. This study assesses the costs of performing closed reduction percutaneous pinning (CRPP) of pediatric supracondylar humerus fractures (SCHFs) at a CH compared with a TCH. METHODS: A retrospective review of 133 consecutive SCHFs treated with CRPP at a CH versus a TCH over a 6-year period was performed. Total encounter and subcategorized costs were compared between the procedures done at a CH versus those done at a TCH. RESULTS: Performing CRPP for a SCHF at a CH compared with a TCH saved 44% in costs (P < 0.001). Cost reduction of 51% was attributable to operating room costs, 19% to anesthesia-related costs, 16% to imaging-related costs, and 7% to supplies. DISCUSSION: Performing CRPP for a SCHF at a CH compared with a TCH results in a 44% decrease in direct cost, driven largely by surgical, anesthesia, and radiology-related savings.
    • Detecting geospatial patterns of Plasmodium falciparum parasite migration in Cambodia using optimized estimated effective migration surfaces

      Shetty, A.C.; O'Connor, T.D.; Takala-Harrison, S. (BioMed Central Ltd., 2020)
      Background: Understanding the genetic structure of natural populations provides insight into the demographic and adaptive processes that have affected those populations. Such information, particularly when integrated with geospatial data, can have translational applications for a variety of fields, including public health. Estimated effective migration surfaces (EEMS) is an approach that allows visualization of the spatial patterns in genomic data to understand population structure and migration. In this study, we developed a workflow to optimize the resolution of spatial grids used to generate EEMS migration maps and applied this optimized workflow to estimate migration of Plasmodium falciparum in Cambodia and bordering regions of Thailand and Vietnam. Methods: The optimal density of EEMS grids was determined based on a new workflow created using density clustering to define genomic clusters and the spatial distance between genomic clusters. Topological skeletons were used to capture the spatial distribution for each genomic cluster and to determine the EEMS grid density; i.e., both genomic and spatial clustering were used to guide the optimization of EEMS grids. Model accuracy for migration estimates using the optimized workflow was tested and compared to grid resolutions selected without the optimized workflow. As a test case, the optimized workflow was applied to genomic data generated from P. falciparum sampled in Cambodia and bordering regions, and migration maps were compared to estimates of malaria endemicity, as well as geographic properties of the study area, as a means of validating observed migration patterns. Results: Optimized grids displayed both high model accuracy and reduced computing time compared to grid densities selected in an unguided manner. In addition, EEMS migration maps generated for P. falciparum using the optimized grid corresponded to estimates of malaria endemicity and geographic properties of the study region that might be expected to impact malaria parasite migration, supporting the validity of the observed migration patterns. Conclusions: Optimized grids reduce spatial uncertainty in the EEMS contours that can result from user-defined parameters, such as the resolution of the spatial grid used in the model. This workflow will be useful to a broad range of EEMS users as it can be applied to analyses involving other organisms of interest and geographic areas. Copyright 2020 The Author(s).
    • Nonalcoholic fatty liver disease experiences accumulation of hepatic liquid crystal associated with increasing lipophagy

      Wang, L.; Xu, M.; Bryant, J.L. (BioMed Central Ltd., 2020)
      Background: In the past 30 years, incidences of non-alcoholic fatty liver disease (NAFLD) has risen by 30%. However, there is still no clear mechanism or accurate method of anticipating liver failure. Here we reveal the phase transitions of liquid crystalline qualities in hepatic lipid droplets (HLDs) as a novel method of anticipating prognosis. Methods: NAFLD was induced by feeding C57BL/6J mice on a high-fat (HiF) diet. These NAFLD livers were then evaluated under polarized microscopy, X-ray diffraction and small-angle scattering, lipid component chromatography analysis and protein expression analysis. Optically active HLDs from mouse model and patient samples were both then confirmed to have liquid crystal characteristics. Liver MAP1LC3A expression was then evaluated to determine the role of autophagy in liquid crystal HLD (LC-HLD) formation. Results: Unlike the normal diet cohort, HiF diet mice developed NAFLD livers containing HLDs exhibiting Maltese cross birefringence, phase transition, and fluidity signature to liquid crystals. These LC-HLDs transitioned to anisotropic crystal at 0 °C and remain crystalline. Temperature increase to 42 °C causes both liquid crystal and crystal HLDs to convert to isotropic droplet form. These isotropic HLDs successfully transition to anisotropic LC with fast temperature decrease and anisotropic crystal with slow temperature decrease. These findings were duplicated in patient liver. Patient LC-HLDs with no inner optical activity were discovered, hinting at lipid saturation as the mechanism through which HLD acquire LC characteristics. Downregulation of MAP1LC3A in conjunction with increased LC-HLD also implicated autophagy in NAFLD LC-HLD formation. Conclusions: Increasing concentrations of amphiphilic lipids in HLDs favors organization into alternating hydrophilic and hydrophobic layers, which present as LC-HLDs. Thus, evaluating the extent of liquid crystallization with phase transition in HLDs of NAFLD patients may reveal disease severity and predict impending liver damage. Copyright 2020 The Author(s).
    • COVID-19 and the RAAS-a potential role for angiotensin II?

      Busse, L.W.; Chow, J.H.; McCurdy, M.T. (Springer Nature, 2020)
    • Immune status, and not HIV infection or exposure, drives the development of the oral microbiota

      Coker, M.O.; Mongodin, E.F.; Hittle, L.; Blattner, W.A.; Charurat, M.; El-Kamary, E.E.; Langenberg, P.; Enwonwu, C.. (Nature Research, 2020)
      Even with antiretroviral therapy, children born to HIV-infected (HI) mothers are at a higher risk of early-life infections and morbidities including dental disease. The increased risk of dental caries in HI children suggest immune-mediated changes in oral bacterial communities, however, the impact of perinatal HIV exposure on the oral microbiota remains unclear. We hypothesized that the oral microbiota of HI and perinatally HIV-exposed-but-uninfected (HEU) children will significantly differ from HIV-unexposed-and-uninfected (HUU) children. Saliva samples from 286 child-participants in Nigeria, aged ≤ 6 years, were analyzed using 16S rRNA gene sequencing. Perinatal HIV infection was significantly associated with community composition (HI vs. HUU-p = 0.04; HEU vs. HUU-p = 0.11) however, immune status had stronger impacts on bacterial profiles (p < 0.001). We observed age-stratified associations of perinatal HIV exposure on community composition, with HEU children differing from HUU children in early life but HEU children becoming more similar to HUU children with age. Our findings suggest that, regardless of age, HIV infection or exposure, low CD4 levels persistently alter the oral microbiota during this critical developmental period. Data also indicates that, while HIV infection clearly shapes the developing infant oral microbiome, the effect of perinatal exposure (without infection) appears transient. Copyright 2020, The Author(s).
    • Effects of larval exposure to sublethal doses of Bacillus thuringiensis var. israelensis on body size, oviposition and survival of adult Anopheles coluzzii mosquitoes

      Gowelo, S.; Chirombo, J.; McCann, R. (Springer Nature, 2020)
      BACKGROUND: Application of the larvicide Bacillus thuringiensis var. israelensis (Bti) is a viable complementary strategy for malaria control. Efficacy of Bti is dose-dependent. There is a knowledge gap on the effects of larval exposure to sublethal Bti doses on emerging adult mosquitoes. The present study examined the effect of larval exposure to sublethal doses of Bti on the survival, body size and oviposition rate in adult Anopheles coluzzii. METHODS: Third-instar An. coluzzii larvae were exposed to control and sublethal Bti concentrations at LC20, LC50 and LC70 for 48 h. Surviving larvae were reared to adults under standard colony conditions. Thirty randomly selected females from each treatment were placed in separate cages and allowed to blood feed. Twenty-five gravid females from the blood-feeding cages were randomly selected and transferred into new cages where they were provided with oviposition cups. Numbers of eggs laid in each cage and mortality of all adult mosquitoes were recorded daily. Wing lengths were measured of 570 mosquitoes as a proxy for body size. RESULTS: Exposure to LC70Bti doses for 48 h as third-instar larvae reduced longevity of adult An. coluzzii mosquitoes. Time to death was 2.58 times shorter in females exposed to LC70Bti when compared to the control females. Estimated mortality hazard rates were also higher in females exposed to the LC50 and LC20 treatments, but these differences were not statistically significant. The females exposed to LC70 concentrations had 12% longer wings than the control group (P < 0.01). No differences in oviposition rate of the gravid females were observed between the treatments. CONCLUSIONS: Exposure of An. coluzzii larvae to sublethal Bti doses reduces longevity of resultant adults and is associated with larger adult size and unclear effect on oviposition. These findings suggest that anopheline larval exposure to sublethal Bti doses, though not recommended, could reduce vectorial capacity for malaria vector populations by increasing mortality of resultant adults.
    • A bivalent vaccine confers immunogenicity and protection against Shigella flexneri and enterotoxigenic Escherichia coli infections in mice

      Medeiros, P.H.Q.S.; Bolick, D.T.; Barry, E.M. (Nature Research, 2020)
      Vaccine studies for Shigella flexneri and enterotoxigenic Escherichia coli have been impaired by the lack of optimal animal models. We used two murine models to show that a S. flexneri 2a bivalent vaccine (CVD 1208S-122) expressing enterotoxigenic Escherichia coli colonization factor antigen-I (CFA/I) and the binding subunits A2 and B of heat labile-enterotoxin (LTb) is immunogenic and protects against weight loss and diarrhea. These findings document the immunogenicity and pre-clinical efficacy effects of CVD 1208S-122 vaccine and suggest that further work can help elucidate relevant immune responses and ultimately its clinical efficacy in humans. Copyright 2020, The Author(s).
    • Editorial: Cell-based Therapies for Stroke: Promising Solution or Dead End?

      Boltze, J.; Abe, K.; Janowski, M. (Frontiers Media S.A., 2020)
    • Population Pharmacokinetics of Metoclopramide in Infants, Children, and Adolescents

      Ge, S.; Mendley, S.R.; Best Pharmaceuticals for Children Act - Pediatric Trials Network Steering Committee (Blackwell Publishing Ltd, 2020)
      Metoclopramide is commonly used for gastroesophageal reflux. The aims of the present study were to develop a pediatric population pharmacokinetic (PopPK) model, which was applied to simulate the metoclopramide exposure following dosing used in clinical practice. Opportunistic pharmacokinetic data were collected from pediatric patients receiving enteral or parenteral metoclopramide per standard of care and these data were simultaneously fitted using NONMEM. Allometric scaling with body weight was included a priori in the model. Using the final model, the steady-state maximum concentrations (Css,max) and the area under the metoclopramide plasma concentration-time curve at steady state from 0 to 6 hours (AUCss,0-6h) were simulated following 0.1 or 0.15 mg/kg orally every 6 hours in virtual patients, and compared with previously reported ranges associated with toxicity or the efficacy for gastroesophageal reflux in infants. A two-compartment model with first-order absorption best characterized 87 concentration measurements from 50 patients (median [range] postnatal age of 8.89 years [0.01-19.13]). There were 20 infants (≤ 2 years), 9 children (2 years to age ≤ 12 years), and 21 adolescents (&gt; 12 years). Body weight was the only covariate included in the final model. For &gt; 75% of virtual patients, simulated Css,max and AUCss,0-6h estimates were within the range associated with efficacy for gastroesophageal reflux in infants; however, slightly lower exposures were predicted in virtual patients &lt; 2 years. Our study suggests that a metoclopramide enteral dose of 0.1 mg/kg every 6 hours, which was previously recommended for pediatric patients, results in simulated exposure generally within suggested ranges for the treatment of gastroesophageal reflux. Copyright 2020 The Authors.
    • Age-related Smell and Taste Impairments and Vitamin D Associations in the U.S. Adults National Health and Nutrition Examination Survey

      Bigman, G. (Multidisciplinary Digital Publishing Institute (MDPI), 2020)
      Smell and taste decline with aging, and markedly deteriorate when nutritional deficiencies occur. This study aims to examine the associations between Vitamin D (VD) deficiency and smell and taste impairments among adults. This paper details a cross-sectional study utilizing data from the US National Health and Nutrition Examination Survey (NHANES, 2013-2014.). Smell impairment was assessed by the Pocket Smell Test and defined as failing to correctly identify six or more of the eight odors. Taste impairment was defined as failing to correctly identify quinine or sodium chloride. VD was measured as serum 25-hydroxyvitamin. Multivariable weighted logistic regressions were utilized. Adjusted odds ratio (OR) and 95% confidence interval (CI) were presented. Overall, 2216 (smell sample) and 2636 (taste sample) participants were included, aged between 40 and 80 years old. Of those, 18.3% had taste impairment, 12.2% had smell impairment, and 20% had VD deficiency (<20 ng/mL). Compared to participants with sufficient VD (>30 ng/mL), those with VD deficiency were more likely by 39% to report a higher prevalence of smell impairment (OR = 1.39, 95%CI: 1.02-1.89); and only participants aged 70-80 years with VD inadequacy (20-30 ng/mL) were more likely by 96% to report a higher prevalence of taste impairment (OR = 1.96, 95%CI: 1.35-1.85). VD may have a significant role in age-related smell impairment in adults aged 40 years or older, and in age-related taste impairment in the elderly aged 70-80 years.