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Selective chemical inhibitors are critical for reaction phenotyping to identify drug-metabolizing enzymes that are involved in the elimination of drug candidates. Although relatively selective inhibitors are available for the major cytochrome P450 enzymes (CYP), they are quite limited for the less common CYPs and non-CYPs. To address this gap, we developed a multiplexed high throughput screening (HTS) assay using 20 substrate reactions of multiple enzymes to simultaneously monitor the inhibition of enzymes in a 384-well format. Four 384-well assay plates can be run at the same time to maximize throughput. This is the first multiplexed HTS assay for drug-metabolizing enzymes reported. The HTS assay is technologically enabled with state-of-the-art robotic systems and highly sensitive modern LC-MS/MS instrumentation. Virtual screening is utilized to identify inhibitors for HTS based on known inhibitors and enzyme structures. Screening of ~4600 compounds generated many hits for many drug-metabolizing enzymes including the two time-dependent and selective aldehyde oxidase inhibitors, erlotinib and dibenzothiophene. The hit rate is much higher than that for the traditional HTS for biological targets due to the promiscuous nature of the drug-metabolizing enzymes and the biased compound selection process. Future efforts will focus on using this method to identify selective inhibitors for enzymes that do not currently have quality hits and thoroughly characterizing the newly identified selective inhibitors from our screen. We encourage colleagues from other organizations to explore their proprietary libraries using a similar approach to identify better inhibitors that can be used across the industry.
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Ensayos Analíticos de Alto Rendimiento , Espectrometría de Masas en Tándem , Humanos , Cromatografía Liquida , Sistema Enzimático del Citocromo P-450 , Hepatocitos , Inhibidores Enzimáticos/farmacologíaRESUMEN
Daprodustat is the first oral hypoxia-inducible factor prolyl hydroxylase inhibitor approved recently for the treatment of anemia caused by chronic kidney disease (CKD) in adults receiving dialysis. We evaluated the role of organic anion transporting polypeptide (OATP)1B-mediated hepatic uptake transport in the pharmacokinetics (PKs) of daprodustat using in vitro and in vivo studies, and physiologically-based PK (PBPK) modeling of its drug-drug interactions (DDIs) with inhibitor drugs. In vitro, daprodustat showed specific transport by OATP1B1/1B3 in the transfected cell systems and primary human and monkey hepatocytes. A single-dose oral rifampin (OATP1B inhibitor) reduced daprodustat intravenous clearance by a notable 9.9 ± 1.2-fold (P < 0.05) in cynomolgus monkeys. Correspondingly, volume of distribution at steady-state was also reduced by 5.0 ± 1.1-fold, whereas the half-life change was minimal (1.5-fold), corroborating daprodustat hepatic uptake inhibition by rifampin. A PBPK model accounting for OATP1B-CYP2C8 interplay was developed, which well described daprodustat PK and DDIs with gemfibrozil (CYP2C8 and OATP1B inhibitor) and trimethoprim (weak CYP2C8 inhibitor) within 25% error of the observed data in healthy subjects. About 18-fold increase in daprodustat area under the curve (AUC) following gemfibrozil treatment was found to be associated with strong CYP2C8 inhibition and moderate OATP1B inhibition. Moreover, PK modulation in hepatic dysfunction and subjects with CKD, in comparison to healthy control, was well-captured by the model. CYP2C8 and/or OATP1B inhibitor drugs (e.g., gemfibrozil, clopidogrel, rifampin, and cyclosporine) were predicted to perpetrate moderate-to-strong DDIs in healthy subjects, as well as, in target CKD population. Daprodustat can be used as a sensitive CYP2C8 index substrate in the absence of OATP1B modulation.
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Citocromo P-450 CYP2C8 , Interacciones Farmacológicas , Hepatocitos , Transportador 1 de Anión Orgánico Específico del Hígado , Insuficiencia Renal Crónica , Rifampin , Miembro 1B3 de la Familia de los Transportadores de Solutos de Aniones Orgánicos , Adulto , Animales , Femenino , Humanos , Masculino , Citocromo P-450 CYP2C8/metabolismo , Inhibidores del Citocromo P-450 CYP2C8/farmacocinética , Glicina/análogos & derivados , Glicina/farmacocinética , Células HEK293 , Hepatocitos/metabolismo , Hepatocitos/efectos de los fármacos , Hepatopatías/metabolismo , Transportador 1 de Anión Orgánico Específico del Hígado/metabolismo , Transportador 1 de Anión Orgánico Específico del Hígado/antagonistas & inhibidores , Macaca fascicularis , Insuficiencia Renal Crónica/metabolismo , Rifampin/farmacología , Miembro 1B3 de la Familia de los Transportadores de Solutos de Aniones Orgánicos/metabolismo , Miembro 1B3 de la Familia de los Transportadores de Solutos de Aniones Orgánicos/antagonistas & inhibidoresRESUMEN
CYP3A is one of the most important classes of enzymes and is involved in the metabolism of over 70% drugs. While several selective CYP3A4 inhibitors have been identified, the search for a selective CYP3A5 inhibitor has turned out to be rather challenging. Recently, several selective CYP3A5 inhibitors have been identified through high-throughput screening of ~ 11,000 compounds and hit expansion using human recombinant enzymes. We set forth to characterize the three most selective CYP3A5 inhibitors in a more physiologically relevant system of human liver microsomes to understand if these inhibitors can be used for reaction phenotyping studies in drug discovery settings. Gomisin A and T-5 were used as selective substrate reactions for CYP3A4 and CYP3A5 to determine IC50 values of the two enzymes. The results showed that clobetasol propionate and loteprednol etabonate were potent and selective CYP3A5 reversible inhibitors with selectivity of 24-fold against CYP3A4 and 39-fold or more against the other major CYPs. The selectivity of difluprednate in HLM is much weaker than that in the recombinant enzymes due to hydrolysis of the acetate group in HLM. Based on the selectivity data, loteprednol etabonate can be utilized as an orthogonal approach, when experimental fraction metabolized of CYP3A5 is greater than 0.5, to understand CYP3A5 contribution to drug metabolism and its clinical significance. Future endeavors to identify even more selective CYP3A5 inhibitors are warranted to enable accurate determination of CYP3A5 contribution to metabolism versus CYP3A4.
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Inhibidores del Citocromo P-450 CYP3A , Citocromo P-450 CYP3A , Humanos , Inhibidores del Citocromo P-450 CYP3A/farmacología , Citocromo P-450 CYP3A/metabolismo , Etabonato de Loteprednol , Sistema Enzimático del Citocromo P-450/metabolismo , Microsomas Hepáticos/metabolismoRESUMEN
Organic anion transporting polypeptide (OATP1B) plays a key role in the hepatic clearance of a majority of high molecular weight (MW) acids and zwitterions. Here, we evaluated the role of OATP1B-mediated uptake in the clearance of novel hypoxia-inducible factor prolyl hydroxylase inhibitors ("Dustats"), which are typically low MW (300-400 daltons) aliphatic carboxylic acids. Five acid dustats, namely daprodustat, desidustat, enarodustat, roxadustat and vadadustat, showed specific transport by OATP1B1/1B3 in transporter-transfected HEK293 cells. Neutral compound, molidustat, was not a substrate to OATP1B1/1B3. None of the dustats showed transport by other hepatic uptake transporters, including NTCP, OAT2 and OAT7. In the primary human hepatocytes, uptake of all acids was significantly reduced by rifampin (OATP1B inhibitor); with an estimated fraction transported by OATP1B (ft ,OATP1B) of up to >80% (daprodustat). Molidustat uptake was minimally inhibited by rifampin; and low permeability acids (desidustat and enarodustat) also showed biliary efflux in sandwich culture human hepatocytes. In vivo, intravenous pharmacokinetics of all 5 acids was significantly altered by a single-dose rifampin (30 mg/kg) in Cynomolgus monkey. Hepatic clearance (non-renal) was about 4-fold (vadadustat) to >11-fod (daprodustat and roxadustat) higher in control group compared to rifampin-treated subjects. In vivo ft ,OATP1B was estimated to be ~70-90%. In the case of molidustat, rifampin had a minimal effect on overall clearance. Rifampin also considerably reduced volume of distribution of daprodustat and roxadustat. Overall, OATP1B significantly contribute to the hepatic clearance and pharmacokinetics of several dustats, which are low MW carboxylic acids. OATP1B activity should therefore by evaluated in this property space. Significance Statement Our in vitro and in vivo results suggest that OATP1B-mediated hepatic uptake play a significant role in the pharmacokinetics of low MW acidic dustats, which are being developed or approved for the treatment of anemia in chronic kidney disease. Significant active uptake mechanisms are not apparent for the neutral compound, molidustat. Characterization of uptake mechanisms is therefore important in predicting human pharmacokinetics and evaluating drug-drug interactions for low MW acids.
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Tumor binding is an important parameter to derive unbound tumor concentration to explore pharmacokinetics (PK) and pharmacodynamics (PD) relationships for oncology disease targets. Tumor binding was evaluated using eleven matrices, including various commonly used ex vivo human and mouse xenograft and syngeneic tumors, tumor cell lines and liver as a surrogate tissue. The results showed that tumor binding is highly correlated among the different tumors and tumor cell lines except for the mouse melanoma (B16F10) tumor type. Liver fraction unbound (fu) has a good correlation with B16F10 tumor binding. Liver also demonstrates a two-fold equivalency, on average, with binding of other tumor types when a scaling factor is applied. Predictive models were developed for tumor binding, with correlations established with LogD (acids), predicted muscle fu (neutrals) and measured plasma protein binding (bases) to estimate tumor fu when experimental data are not available. Many approaches can be applied to obtain and estimate tumor binding values. One strategy proposed is to use a surrogate tumor tissue, such as mouse xenograft ovarian cancer (OVCAR3) tumor, as a surrogate for tumor binding (except for B16F10) to provide an early assessment of unbound tumor concentrations for development of PK/PD relationships.
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Apoptosis , Neoplasias Ováricas , Humanos , Ratones , Animales , Femenino , Línea Celular Tumoral , Proteínas Sanguíneas/metabolismo , Unión Proteica , Descubrimiento de DrogasRESUMEN
Although human capital resources (HCR) can be important for organizational performance, researchers have defined and measured HCR in various ways. Consequently, it is unclear whether existing measures provide valid inferences about HCR or their relations with other constructs. We conducted this three-study research to address these issues. In Study 1, we reviewed HCR definitions (k = 84) and found that most definitions focus on collective knowledge, skills, and abilities. Recent definitions also tend to include other characteristics (e.g., personality). In Study 2, a content analysis of HCR measures (k = 127) revealed that only 23.6% of the measures focused solely on HCR and they tended to assess only one or two dimensions of the construct (i.e., were deficient). Many measures (46.5%) assessed both HCR and other constructs (i.e., were partially contaminated), and other measures (29.9%) assessed only non-HCR constructs (i.e., were fully contaminated). In Study 3 (k = 94), we found that HCR measures that were less deficient demonstrated stronger criterion-related validity for predicting unit and firm performance. Interestingly, partially contaminated measures were somewhat more predictive than uncontaminated measures (ρ = .35 vs. .25, respectively), mainly because they assessed both HCR and other constructs that are related to performance. Both types of measures demonstrated stronger validity than fully contaminated measures. Overall, findings suggest that extant HCR measures often are deficient and/or contaminated. We discuss implications, as well as offer guidance for measuring HCR in future research. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Eficiencia Organizacional , Recursos Humanos , Humanos , PersonalidadRESUMEN
OBJECTIVES: In this study, we aimed to explore the oral and emotional health challenges experienced by a sample of refugees in Massachusetts across different stages of resettlement using a mixed methods approach. METHODS: We collaborated with two Federally Qualified Health Centers to identify and recruit participants for either surveys (n = 69) or semi-structured interviews (n = 12). Data collection was conducted in 2018. We performed descriptive statistics using STATA 14, and analyzed the interviews using qualitative methods. RESULTS: Overall, cost and lack of structure were the largest barriers identified for accessing dental care in participants' home and host countries. In the US, participants reported receiving state-provided public health insurance, but still experienced disrupted access to dental care due to coverage limitations. We identified several mental health risk factors that may affect participants' oral health, including trauma, depression, and sleeping problems. Despite these challenges, participants also identified areas of resilience and adaptability in both attitude and actions. CONCLUSIONS: The themes identified in our study suggest that refugees have attitudes, beliefs, and experiences that contribute to their perspectives on oral health care. While some of the reported barriers to access dental care were attitudinal, others were structural. Access to dental care in the US was reported to be structured and available, but with limited coverage issues. This paper underscores the oral and emotional health aspects of refugees for future considerations and planning of appropriate, affordable and cost-effective policies in the global health care systems.
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Salud Mental , Refugiados , Humanos , Accesibilidad a los Servicios de Salud , Refugiados/psicología , Massachusetts , Encuestas y CuestionariosRESUMEN
Despite the legalization of same-sex marriage in the United States (U.S.) and an increasing number of out gay and lesbian business leaders, we have little knowledge of the role played by leaders' same-sex sexual orientation in the leadership process. To fill this important research void, we drew from a recent theoretical model on leaders' sexual orientation and conducted four experimental studies designed to test and retest whether leaders' same-sex sexual orientation affects followers' leadership perceptions and conformity to influence attempts, and how the intersectionality of leaders' same-sex sexual orientation with leaders' gender orientation and follower characteristics may modify the influences of leaders' same-sex sexual orientation on the follower outcomes. Based on over 2,100 working adults in the U.S., the results of the four studies, where leaders were depicted as charismatic, indicate that leaders' same-sex sexual orientation could have negative impacts on the follower outcomes. However, same-sex sexual orientation leaders did not suffer double stigma penalization by having additional marginalized identities (e.g., also being women). Female followers were more supportive of same-sex sexual orientation leaders than male followers. Our research advances knowledge of and responds to calls for more research attention to leader sexual orientation in the leadership process. Research and practical implications and directions for future research are discussed.
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PURPOSE: In response to COVID-19, dental educators have been tasked with maintaining the quality of education while reducing cost, increasing efficiency, and leveraging technology. METHODS: This collaborative, multisite virtual health policy course used the Staged Self-Directed Learning Model (SSDL) to lead a diverse group of students studying health policy. Twelve Core sessions were offered with three additional sessions in August or December for a total of 15 total synchronous Zoom sessions that covered policy issues on supply, demand, and need for dental care. RESULTS: Twenty-eight students, seven lead instructors, and two course directors from six schools reported positive feedback on the course format, use of technology and the SSDL model, and breadth of topics presented. Participation by universities in four states with differing health policies stimulated virtual classroom discussions. CONCLUSION: In conclusion, collaborative interinstitutional virtual teaching and learning is cost effective, efficient, and engaging for students. This model has the potential to continue even when institutions are no longer affected by COVID-19.
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COVID-19 , Universidades , Curriculum , Atención Odontológica , Política de Salud , Humanos , SARS-CoV-2 , EnseñanzaRESUMEN
Alcohol dehydrogenases (ADHs) are most known for their roles in oxidation and elimination of ethanol. Although less known, ADHs also play a critical role in the metabolism of a number of drugs and metabolites that contain alcohol functional groups, such as abacavir (HIV/AIDS), hydroxyzine (antihistamine), and ethambutol (antituberculosis). ADHs consist of 7 gene family numbers and several genetic polymorphic forms. ADHs are cytosolic enzymes that are most abundantly found in the liver, although also present in other tissues including gastrointestinal tract and adipose. Marked species differences exist for ADHs including genes, proteins, enzymatic activity, and tissue distribution. The active site of ADHs is relatively small and cylindrical in shape. This results in somewhat narrow substrate specificity. Secondary alcohols are generally poor substrates for ADHs. In vitro-in vivo correlations for ADHs have not been established, partly due to insufficient clinical data. Fomepizole (4-methylpyrazole) is a nonspecific ADH inhibitor currently being used as an antidote for the treatment of methanol and ethylene glycol poisoning. Fomepizole also has the potential to treat intoxication of other substances of abuse by inhibiting ADHs to prevent formation of toxic metabolites. ADHs are inducible through farnesoid X receptor (FXR) and other transcription factors. Drug-drug interactions have been observed in the clinic for ADHs between ethanol and therapeutic drugs, and between fomepizole and ADH substrates. Future research in this area will provide additional insights about this class of complex, yet fascinating enzymes.
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Alcohol Deshidrogenasa/metabolismo , Fármacos Anti-VIH/farmacocinética , Antituberculosos/farmacocinética , Etanol/metabolismo , Antagonistas de los Receptores Histamínicos H1/farmacocinética , Alcohol Deshidrogenasa/antagonistas & inhibidores , Alcohol Deshidrogenasa/genética , Animales , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/química , Antituberculosos/administración & dosificación , Antituberculosos/química , Didesoxinucleósidos/administración & dosificación , Didesoxinucleósidos/química , Didesoxinucleósidos/farmacocinética , Interacciones Farmacológicas , Etambutol/administración & dosificación , Etambutol/química , Etambutol/farmacocinética , Etanol/química , Fomepizol/farmacología , Antagonistas de los Receptores Histamínicos H1/administración & dosificación , Antagonistas de los Receptores Histamínicos H1/química , Humanos , Hidroxizina/administración & dosificación , Hidroxizina/química , Hidroxizina/farmacocinética , Isoenzimas/antagonistas & inhibidores , Isoenzimas/genética , Isoenzimas/metabolismo , Oxidación-Reducción/efectos de los fármacos , Receptores Citoplasmáticos y Nucleares/metabolismo , Especificidad de la Especie , Especificidad por SustratoRESUMEN
Volume of distribution at steady state (Vss) is an important pharmacokinetic parameter of a drug candidate. In this study, Vss prediction accuracy was evaluated by using: (1) seven methods for rat with 56 compounds, (2) four methods for human with 1276 compounds, and (3) four in vivo methods and three Kp (partition coefficient) scalar methods from scaling of three preclinical species with 125 compounds. The results showed that the global QSAR models outperformed the PBPK methods. Tissue fraction unbound (fu,t) method with adipose and muscle also provided high Vss prediction accuracy. Overall, the high performing methods for human Vss prediction are the global QSAR models, Øie-Tozer and equivalency methods from scaling of preclinical species, as well as PBPK methods with Kp scalar from preclinical species. Certain input parameter ranges rendered PBPK models inaccurate due to mass balance issues. These were addressed using appropriate theoretical limit checks. Prediction accuracy of tissue Kp were also examined. The fu,t method predicted Kp values more accurately than the PBPK methods for adipose, heart and muscle. All the methods overpredicted brain Kp and underpredicted liver Kp due to transporter effects. Successful Vss prediction involves strategic integration of in silico, in vitro and in vivo approaches.
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Modelos Biológicos , Relación Estructura-Actividad Cuantitativa , Animales , Humanos , Farmacocinética , Fenómenos Físicos , RatasRESUMEN
Human liver microsomes (HLM) and human hepatocytes (HHEP) are two common in vitro systems used in metabolic stability and inhibition studies. The comparison between the assays using the two systems can provide mechanistic insights on the interplay of metabolism, passive permeability and transporters. This study investigated the critical factors impacting the unbound intrinsic clearance (CLint,u) and IC50 of CYP3A inhibition between HLM and HHEP. The HLM/HHEP CLint,u ratio and HHEP/HLM IC50 ratio are inversely correlated to passive permeability, but have no correlation with P-gp efflux ratio. Cofactor-supplemented permeabilized HHEP (MetMax™) collapses the IC50 differences between HHEP and HLM. P-gp inhibitor, encequidar, shows minimal impact on CLint,u and IC50 in HHEP. This is the first study that is able to separately investigate the effects of passive permeability and efflux transport. These data collectively show that passive permeability plays a critical role in metabolism and enzyme inhibition in HHEP, while P-gp efflux has a minor role. This may be due to low functional P-gp activity in suspension HHEP under the assay conditions. Low passive permeability may limit metabolism and enzyme inhibition in HHEP, leading to lower CLint,u and higher IC50 in HHEP compared to HLM. When liver microsomes give higher CLint,u than hepatocytes, microsomes are more predictive of in vivo clearance than hepatocytes.
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Hepatocitos , Microsomas Hepáticos , Transporte Biológico , Humanos , Cinética , Hígado/metabolismo , Tasa de Depuración Metabólica , Microsomas Hepáticos/metabolismoRESUMEN
Fraction unbound (fu) values obtained from liver or hepatocyte homogenate with equilibrium dialysis (fu,homo) or the hepatocyte partition coefficient method at 4°C (fu,c) are both frequently used to estimate unbound drug concentrations (Cu) and unbound partition coefficient (Kpuu) of the liver. Literature data are somewhat controversial on this topic: some reported that the two methods gave comparable fu values, while others showed that they had no correlation. To better understand the two approaches, 44 structurally diverse compounds with wide ranges of fu values were used for the comparison study. The results indicate that fu values from the two methods are comparable with an average fold error of 2.9-fold and a bias of 1.0. Although some outliers were observed, the reasons are not entirely clear and further investigations are needed. As the fu data from both methods are correlated, fu,homo measurement using tissue homogenate is recommended over cells at 4°C (fu,c) in early drug discovery. This is because fu,homo method is more reliable, has good in vivo predictability, and feasibility for any tissue types where representative cells may not be readily available. The approach can be used to estimate Cu and Kpuu of tissues in order to develop pharmacokinetic/pharmacodynamic relationships, and to estimate therapeutic indices, as well as to predict drug-drug interactions.
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Hepatocitos/metabolismo , Hígado/metabolismo , Preparaciones Farmacéuticas/metabolismo , Criopreservación/métodos , Humanos , Hígado/citología , Preparaciones Farmacéuticas/análisis , Unión Proteica/fisiologíaRESUMEN
Many organizational representatives review social media (SM) information (e.g., Facebook, Twitter) when recruiting and assessing job applicants. Despite this, very little empirical data exist concerning the SM information available to organizations or whether assessments of such information are a valid predictor of work outcomes. This multistudy investigation examines several critical issues in this emerging area. In Study 1, we conducted a content analysis of job seekers' Facebook sites (n = 266) and found that these sites often provide demographic variables that U.S. employment laws typically prohibit organizations from using when making personnel decisions (e.g., age, ethnicity, and religion), as well as other personal information that is not work-related (e.g., sexual orientation, marital status). In Study 2 (n = 140), we examined whether job seekers' SM information is related to recruiter evaluations. Results revealed that various types of SM information correlated with recruiter judgments of hireability, including demographic variables (e.g., gender, marital status), variables organizations routinely assess (e.g., education, training, and skills), and variables that may be a concern to organizations (e.g., profanity, sexual behavior). In Study 3 (n = 81), we examined whether structuring SM assessments (e.g., via rater training) affects criterion-related validity. Results showed that structuring SM assessments did not appear to improve the prediction of future job performance or withdrawal intentions. Overall, the present findings suggest that organizations should be cautious about assessing SM information during the staffing process. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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Medios de Comunicación Sociales , Empleo , Femenino , Humanos , Intención , Juicio , Masculino , Lugar de TrabajoRESUMEN
Antimicrobial resistance (AMR) is a global healthcare problem and therefore raising awareness within young learners is imperative. An AMR roadshow was designed to take key stage 4 students' learning 'out of the classroom', assess pre-existing knowledge of AMR and determine the impact of the roadshow on knowledge retention. Knowledge and subsequent retention were measured pre- and post-event through a standardised questionnaire. The roadshow significantly improved knowledge and understanding of AMR, which was retained for a minimum of twelve weeks. Engaging and interactive strategies addressing key health issues provide a positive learning experience which contributes to retained knowledge in young learners.
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OBJECTIVE: Twenty percent of the elderly US population is diagnosed with diabetes. The elderly are at a higher risk of developing serious complications from diabetes. Regular professional dental care may help control blood glucose levels and thereby diabetes complications. Since such potential benefits could play a clinically significant role in diabetes management, our aim was to identify and review relevant evidence among the older population. MATERIALS AND METHODS: Electronic databases were searched for periodontal intervention studies using modified search terms from previous systematic reviews. The final search date was October 31, 2016. RESULTS: Twenty-five publications (22 studies) were included in our final review. They varied in study design, duration, therapeutic interventions, and systemic outcomes measured. No study restricted its participants to seniors, and therefore, a mean age of 55 years or more was used. Fourteen studies showed significant reductions in serum glycated hemoglobin levels, but 8 studies showed nonsignificant changes. CONCLUSION: The evidence suggests a beneficial effect of receiving periodontal care on serum glycated hemoglobin and systemic biomarker levels in older persons with T2DM. Such care would be considered a novel, safe, and acceptable adjunct to current medical management of T2DM in older individuals. The dearth of studies restricted to the elderly represents a gap in knowledge that needs to be addressed in the United States.
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Raspado Dental , Diabetes Mellitus Tipo 2 , Anciano , Anciano de 80 o más Años , Hemoglobina Glucada , Humanos , Persona de Mediana EdadRESUMEN
This research addresses the challenges of assessing receptive language abilities in minimally verbal children with autism spectrum disorder by comparing several adapted measurement tools: a standardized direct assessment of receptive vocabulary (i.e. Peabody Picture Vocabulary Test-4); caregiver report measures including scores on the Vineland-II Communication domain and a vocabulary questionnaire consisting of a list of words ranging from simple, developmentally early, to more advanced words expected to be understood by at least some older children and adolescents; an eye-tracking test of word comprehension, using a word-image pair matching paradigm similar to that often used in studies of infant language acquisition; and a computerized assessment using a touch screen for directly measuring word comprehension with the same stimuli used in the eye-tracking experiment. Results of this multiple-method approach revealed significant heterogeneity in receptive language abilities across participants and across assessment methods. Our findings underscore the need to find individualized approaches for capturing the potential for language comprehension of minimally verbal children with autism spectrum disorder who remain otherwise untestable, using several types of assessment that may include methods based on eye-tracking or touch-screen responding.