British Dental Journal 223, 397 (2017). doi:10.1038/sj.bdj.2017.800
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Παρασκευή 22 Σεπτεμβρίου 2017
Oral health: Couvade syndrome and toothache
British Dental Journal 223, 389 (2017). doi:10.1038/sj.bdj.2017.787
Author: B. Steel
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NHS dentistry: Improving our public standing
British Dental Journal 223, 389 (2017). doi:10.1038/sj.bdj.2017.789
Author: E. C. MacKessack-Leitch
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A dentist's life: 'My job really has the best of both worlds'
British Dental Journal 223, 395 (2017). doi:10.1038/sj.bdj.2017.795
Natalie Waylen, 30, qualified as a dentist in 2014 and is now a civilian dental practitioner within the Ministry of Defence.
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Alternative sugars: Dates
British Dental Journal 223, 393 (2017). doi:10.1038/sj.bdj.2017.792
Elaine Gardner, British Dietetic Association (BDA) Spokesperson, discusses the sugar content in dates and other dried fruits, and related oral health advice.
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Book Review: On the toss of a coin
British Dental Journal 223, 394 (2017). doi:10.1038/sj.bdj.2017.803
Author: C. Porter
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Methods for regionalization of impacts of non-toxic air pollutants in life-cycle assessments often tell a consistent story
Source:Atmospheric Environment, Volume 169
Author(s): S. Njakou Djomo, M.T. Knudsen, M.S. Andersen, J.E. Hermansen
There is an ongoing debate regarding the influence of the source location of pollution on the fate of pollutants and their subsequent impacts. Several methods have been developed to derive site-dependent characterization factors (CFs) for use in life-cycle assessment (LCA). Consistent, precise, and accurate estimates of CFs are crucial for establishing long-term, sustainable air pollution abatement policies. We reviewed currently available studies on the regionalization of non-toxic air pollutants in LCA. We also extracted and converted data into indices for analysis. We showed that CFs can distinguish between emissions occurring in different locations, and that the different methods used to derive CFs map locations consistently from very sensitive to less sensitive. Seasonal variations are less important for the computation of CFs for acidification and eutrophication, but they are relevant for the calculation of CFs for tropospheric ozone formation. Large intra-country differences in estimated CFs suggest that an abatement policy relying on quantitative estimates based upon a single method may have undesirable outcomes. Within country differences in estimates of CFs for acidification and eutrophication are the results of the models used, category definitions, soil sensitivity factors, background emission concentration, critical loads database, and input data. Striking features in these studies were the lack of CFs for countries outside Europe, the USA, Japan, and Canada, the lack of quantification of uncertainties. Parameter and input data uncertainties are well quantified, but the uncertainty associated with the choice of category indicator is rarely quantified and this can be significant. Although CFs are scientifically robust, further refinements are needed before they can be integrated in LCA. Future research should include uncertainty analyses, and should develop a consensus model for CFs. CFs for countries outside Europe, Japan, Canada and the USA are urgently needed.
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Evaluation of emission factors for light-duty gasoline vehicles based on chassis dynamometer and tunnel studies in Shanghai, China
Publication date: November 2017
Source:Atmospheric Environment, Volume 169
Author(s): Cheng Huang, Shikang Tao, Shengrong Lou, Qingyao Hu, Hongli Wang, Qian Wang, Li Li, Hongyu Wang, Jian'gang Liu, Yifeng Quan, Lanlan Zhou
CO, THC, NOx, and PM emission factors of 51 light-duty gasoline vehicles (LDGVs) spanning the emission standards from Euro 2 to Euro 5 were measured by a chassis dynamometer. High frequencies of high-emitting vehicles were observed in Euro 2 and Euro 3 LDGV fleet. 56% and 33% of high-emitting vehicles contributed 81%–92% and 82%–85% of the emissions in Euro 2 and Euro 3 test fleet, respectively. Malfunctions of catalytic convertors after high strength use are the main cause of the high emissions. Continuous monitoring of a gasoline vehicle dominated tunnel in Shanghai, China was conducted to evaluate the average emission factors of vehicles in real-world. The results indicated that the emission factors of LDGVs were considerably underestimated in EI guidebook in China. The overlook of high-emitting vehicles in older vehicle fleet is the main reason for this underestimation. Enhancing the supervision of high emission vehicles and strengthening the compliance tests of in-use vehicles are essential measures to control the emissions of in-use gasoline vehicles at the present stage in China.
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Evaluation of a multi-scale WRF-CAM5 simulation during the 2010 East Asian Summer Monsoon
Source:Atmospheric Environment, Volume 169
Author(s): Patrick Campbell, Yang Zhang, Kai Wang, Ruby Leung, Jiwen Fan, Bo Zheng, Qiang Zhang, Kebin He
The Weather Research and Forecasting model with Chemistry (WRF-Chem) with the physics package of the Community Atmosphere Model Version 5 (CAM5) has been applied at multiple scales over Eastern China (EC) and the Yangtze River Delta (YRD) to evaluate how increased horizontal resolution with physics designed for a coarser resolution climate model impacts aerosols and clouds, and the resulting precipitation characteristics and performance during the 2010 East Asian Summer Monsoon (EASM). Despite large underpredictions in surface aerosol concentrations and aerosol optical depth, there is good spatial agreement with surface observations of chemical predictions, and increasing spatial resolution tends to improve performance. Model bias and normalized root mean square values for precipitation predictions are relatively small, but there are significant differences when comparing modeled and observed probability density functions for precipitation in EC and YRD. Increasing model horizontal resolution tends to reduce model bias and error for precipitation predictions. The surface and column aerosol loading is maximized between about 32°N and 42°N in early to mid-May during the 2010 EASM, and then shifts north while decreasing in magnitude during July and August. Changing model resolution moderately changes the spatiotemporal relationships between aerosols, cloud properties, and precipitation during the EASM, thus demonstrating the importance of model grid resolution in simulating EASM circulation and rainfall patterns over EC and the YRD. Results from this work demonstrate the capability and limitations in the aerosol, cloud, and precipitation representation of WRF-CAM5 for regional-scale applications down to relatively fine horizontal resolutions. Further WRF-CAM5 model development and application in this area is needed.
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PM2.5 emissions and source profiles from open burning of crop residues
Publication date: November 2017
Source:Atmospheric Environment, Volume 169
Author(s): Haiyan Ni, Jie Tian, Xiaoliang Wang, Qiyuan Wang, Yongming Han, Junji Cao, Xin Long, L.-W. Antony Chen, Judith C. Chow, John G. Watson, Ru-Jin Huang, Ulrike Dusek
Wheat straw, rice straw, and corn stalks, the major agricultural crop residues in China, were collected from six major crop producing regions, and burned in a laboratory combustion chamber to determine PM2.5 source profiles and speciated emission factors (EFs). Organic carbon (OC) and water-soluble ions (the sum of NH4+, Na+, K+, Mg2+, Ca2+, Cl−, NO3− and SO42−) are major constituents, accounting for 43.1 ± 8.3% and 27.4 ± 14.6% of PM2.5, respectively. Chloride (Cl−) and water-soluble potassium (K+) are the dominant ionic species, with an average abundance of 14.5 ± 8.2% and 6.4 ± 4.4% in PM2.5, respectively. The average K+/Cl− ratio is ∼0.4, lower than 2.8–5.4 for wood combustion. Similarity measures (i.e., Student's t-test, coefficient of divergence, correlations, and residual to uncertainty ratios) show the crop profiles are too similar for the species measured to be resolved from one another by receptor modeling. The largest difference was found between rice straw and corn stalk emissions, with higher OC and lower Cl− and K+ abundances (50%, 8%, and 3% of PM2.5, respectively) for corn stalks; lower OC, and higher Cl− and K+ abundances (38%, 21%, and 10% of PM2.5, respectively) for rice straw. Average EFs were 4.8 ± 3.1 g kg−1 for OC, 1.3 ± 0.8 g kg−1 for Cl− and 0.59 ± 0.56 g kg−1 for K+. Flaming and smoldering combustions resulted in an average modified combustion efficiency (MCE) of 0.92 ± 0.03, and low elemental carbon (EC) EFs (0.24 ± 0.12 g kg−1). OC/EC ratios from individual source profiles ranged from 12.9 ± 4.3 for rice straw to 24.1 ± 13.5 for wheat straw. The average K+/EC ratio was 2.4 ± 1.5, an order of magnitude higher than those from residential wood combustion (0.2–0.76). Elevated emission rates were found for OC (387 Gg yr−1) and Cl− (122 Gg yr−1), accounting for 44% and 14% of 2008 PM2.5 emissions in China.
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Chronic Granulomatous Dermatitis Induced by Talimogene Laherparepvec Therapy of Melanoma Metastases
Talimogene laherparepvec is the first oncolytic viral immunotherapy approved by the FDA, for advanced melanoma consisting of genetically modified herpes simplex type 1 virus which selectively replicates causing tumor lysis, expressing GM-CSF and activating dendritic cells. Intratumoral injection of TVEC produces objective response in 41% of stage IIB-IV M1a melanoma. However, clinical response assessments can be problematic due to immune-related inflammation at established tumor sites. Herein, we report 5 cases of granulomatous dermatitis developing at sites of TVEC injection associated with pathologic complete response in 4 of 5 patients. Over 5 months TVEC injections were administrated in 20 tumors for 9 doses prior to biopsy of persistent, indurated nodules.
Granulomatous dermatitis with melanophages and melanin pigment incontinence was observed in all samples without evidence of melanoma cells in 4 patients. The 5th patient was rendered melanoma-free by resection of the 1 nodule out of 4 with persistent tumor. Repetitive administration of TVEC or other oncolytic viral immunotherapies mimicking unresolved infection can produce granulomatous inflammation confounding the degree of tumor response and additional TVEC therapy. Tumor biopsies are encouraged after 4-6 months of TVEC administration to differentiate melanoma from granulomatous inflammation. Patients with confirmed granulomatous dermatitis continued in remission after treatment discontinuation. Inflammatory nodules typically regress spontaneously.
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Editorial Board
Source:Microbiological Research, Volume 205
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Why narcissists are at risk for developing Facebook addiction: The need to be admired and the need to belong
Source:Addictive Behaviors, Volume 76
Author(s): Silvia Casale, Giulia Fioravanti
Building upon previous research establishing a positive association between grandiose and vulnerable narcissism and problematic social networking use, the present study tests a model that explains how grandiose and vulnerable narcissists might develop Facebook (Fb) addiction symptoms through the need for admiration and the need to belong. A sample of 535 undergraduates (50.08% F; mean age 22.70±2.76years) completed measures of grandiose narcissism, vulnerable narcissism, Fb addiction symptoms, and two brief scales measuring the need for admiration and the need to belong. Results from structural equation modelling show that the association between grandiose narcissism and Fb addiction levels was completely mediated by the need for admiration and the need to belong. On the other hand, vulnerable narcissism was not found to be associated either directly or indirectly with Fb addiction levels. The variables in the model accounted for 30% of the variance in Fb addiction levels. The present study represents a step toward a better understanding of the psychological mechanisms underlying the link between grandiose narcissism and problematic Fb use.
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How acceptable are intoxicated behaviors? Discrepancy between personal versus perceived approval
Source:Addictive Behaviors, Volume 76
Author(s): Ashley D. Lowery, Jennifer E. Merrill, Kate B. Carey
IntroductionCollege students report high rates of binge drinking yet they reliably endorse elevated perceptions of drinking by their peers. However, the drinking norms literature offers little insight into how college students think about behaviors exhibited while intoxicated. This study aims to determine (a) if the predicted self-other differences (SODs) are seen among college students with respect to approval of intoxicated behaviors and (b) whether gender and race/ethnicity moderate these differences. We hypothesized that students would perceive others as more approving of intoxicated behaviors than they were themselves, resulting in significant SODs. We also predicted that women would have larger SODs relative to their male counterparts, and minority students would have larger SODs relative to their white counterparts.MethodsParticipants (N=233, 63% female) were recruited from an introductory psychology course at a large public northeastern university. They completed online surveys that assessed demographics, and responded to a list of intoxicated behaviors with ratings of personal approval and perceived peer approval.ResultsPerceived others' approval ratings exceeded personal approval ratings for 42 of the 44 different intoxicated behaviors. Women had significantly higher SODs relative to men and differed on personal approval. Non-white students had significantly higher SODs relative to white students, and differed both on personal approval and perceptions of others' approval of intoxicated behaviors.ConclusionsConsistent SODs were observed in the approval of intoxicated behaviors. These findings may help to inform normative feedback interventions by revealing the potential for normative pressure, especially for non-white students.
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Editorial Board
Source:Addictive Behaviors, Volume 76
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Solitary drinking is associated with specific alcohol problems in emerging adults
Source:Addictive Behaviors, Volume 76
Author(s): Matthew T. Keough, Roisin M. O'Connor, Sherry H. Stewart
Hazardous drinking in emerging adulthood is associated with multiple domains of alcohol problems, which range in type and severity. Alcohol problems at the severe end of the spectrum (e.g., impaired control) may be early warning signs of alcohol use disorders (AUDs) among emerging adults. However, given the emphasis in the literature on predictors of overall problem risk, we still know very little about predictors of these specific (and severe) domains of alcohol problems in emerging adults. Many emerging adults drink at social events (e.g., parties), but an estimated 15% engage in solitary drinking. Solitary drinking – a developmentally atypical behavior in emerging adulthood – may be especially risky. Data suggests that frequent solitary drinking may reflect a loss of control over drinking, leading to hazardous use and subsequent problems. Accordingly, we expected that frequent solitary drinking among emerging adults would predict severe alcohol problems that map onto diagnostic criteria for AUDs and these effects would be mediated by hazardous alcohol use. Undergraduates (N=118) completed self-report measures as a part of a larger study on motivation and alcohol use. As predicted, path analysis showed that solitary drinking positively predicted hazardous alcohol use, and this in turn predicted severe alcohol problems associated with diagnostic criteria for AUDs, particularly risky behaviors and blackout drinking. Solitary drinking also positively predicted less severe problems of diminished self-perception and poor self-care through hazardous use. Though comparatively smaller, some indirect effects were observed from social drinking (at parties, but not at bars) to alcohol problems, via hazardous alcohol use. Overall, our results suggest that solitary drinking is particularly harmful in emerging adulthood.
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Communicating accurate and complete information
Source:Addictive Behaviors, Volume 76
Author(s): David T. Levy
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The relationship between family-based adverse childhood experiences and substance use behaviors among a diverse sample of college students
Source:Addictive Behaviors, Volume 76
Author(s): Myriam Forster, Timothy J. Grigsby, Christopher J. Rogers, Stephanie M. Benjamin
IntroductionResearch suggests that college students are an especially vulnerable subset of the population for substance use and misuse. However, despite evidence of the high prevalence of adverse childhood experiences (ACE) among students and the link between family-based ACE and substance use among older adults, this relationship remains understudied in college populations. Moreover, whether ACE represents a shared risk across substance use behaviors and ethnic groups is unknown.MethodsData are student responses (n=2953) on the 2015 American College Health Association's National College Health Assessment II (ACHA-NCHA II) administered at one of the largest, most diverse public universities in California. Multivariable logistic and negative binomial regression models tested the association between individual and accumulated ACE and past 30-day alcohol, tobacco, marijuana, and illicit drug use, past 12-month prescription medication misuse and polysubstance use.ResultsBetween 50% and 75% of students involved in substance use were ACE exposed. There was a significant dose-response relationship between ACE and substance use and polysubstance use. Although accumulated ACE increased risk for substance use, there was considerable ethnic variability in these associations.ConclusionsThe graded effects of ACE for substance use underscore the link between family-based stressors and these behaviors in emergent adult college students. Our findings make a compelling case for investing in health initiatives that prioritize ACE screening and access to trauma-informed care in campus communities. Continued research with college populations is needed to replicate findings and clarify the role of ethnicity and culture in trauma response and help seeking behaviors.
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Affective dysregulation predicts incident nonmedical prescription analgesic use among college students
Source:Addictive Behaviors, Volume 76
Author(s): Christine K. Morioka, Donna E. Howard, Kimberly M. Caldeira, Min Qi Wang, Amelia M. Arria
IntroductionThis study investigated the relationship between four suspected risk factors—affective dysregulation, conduct problems, depressive symptoms, and psychological distress—and incident nonmedical prescription analgesic (NPA) use among college students.MethodsThe sample was derived from 929 college students from a large, mid-Atlantic university who completed the third annual College Life Study assessment (Y3) and were NPA use naïve at baseline (Y1). A series of logistic regression analyses were conducted to evaluate the predictors of incident NPA use by Y3. Separate models were developed to evaluate the association between the suspected risk factors and (a) NPA use relative to non-use of other drugs, including nonmedical use of other drug classes, (b) NPA use relative to other drug use, and (c) other drug use relative to non-use. All models included gender, parental education level, and race/ethnicity.ResultsAffective dysregulation was significantly associated with becoming an incident NPA user relative to both drug users without NPA use as well as non-users, after statistically controlling for demographic characteristics and other factors. Conduct problems in early childhood were positively related to both incident NPA use and other drug use without NPA use relative to non-users, after statistically controlling for demographic characteristics and other factors. Depressive symptoms were associated with NPA incidence at the bivariate level only.ConclusionsThese findings extend previous research suggesting that NPA use might be related to deficits in regulating negative emotional states, and highlight possible markers for screening and intervention to prevent NPA use.
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Change in college students' perceived parental permissibility of alcohol use and its relation to college drinking
Source:Addictive Behaviors, Volume 76
Author(s): Brian H. Calhoun, Jennifer L. Maggs, Eric Loken
College students who perceive their parents to hold permissive views about their alcohol use engage in heavier drinking. However, few studies have assessed perceived parental permissibility of alcohol use (PPP) longitudinally across the later college years, and few have assessed variation in changes in PPP and whether or not these changes differentially predict drinking. This study assessed whether PPP changed across college and used two approaches to determine whether PPP predicted binge drinking frequency and peak drinking. Data on college students' daily lives and risk behaviors were collected from 687 students (51% female) in a large university in the Northeast United States over four years. Perceived parental permissibility of alcohol use increased from the last year of high school through the third year of college with males reporting significantly higher PPP by the third year of college. From 12th grade through the third year of college, between-person differences in mean PPP were positively associated with binge drinking frequency and peak drinking, and patterns of PPP change differentially predicted both drinking outcomes through fourth year. These findings suggest that PPP is a dynamic construct that may evidence important developmental changes across college and the transition to adulthood. More broadly, the results indicate that aspects of the parent-child relationship continue to change after high school and may be important as they are linked with college student risk behaviors.
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Personality, marijuana norms, and marijuana outcomes among college students
Source:Addictive Behaviors, Volume 76
Author(s): Matthew R. Pearson, John T.P. Hustad, Clayton Neighbors, Bradley T. Conner, Adrian J. Bravo
Based on the high prevalence of marijuana use among college students, we examined distal and proximal antecedents to marijuana-related outcomes in this population. Specifically, we examined three marijuana-related perceptions (descriptive norms, injunctive norms, and internalization of college marijuana use culture) as potential mediators of the associations between four personality traits (impulsivity, sensation seeking, hopelessness, and anxiety sensitivity) and marijuana-related outcomes (marijuana use, negative marijuana-related consequences). In a large sample of college student marijuana users (n=2129), our path analysis revealed marijuana-related perceptions to significantly mediate the associations between personality and marijuana-related outcomes. Specifically, internalization of college marijuana use culture mediated the effects of both impulsivity and sensation seeking on marijuana-related outcomes. Not only do our findings suggest the importance of distinct types of marijuana-related norms in predicting marijuana involvement, but also the possibility that such normative beliefs could be targeted as part of personality-tailored interventions.
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Protective effect of oleane-12-en-3β-ol-28-oic acid 3β-D-glucopyranoside in ethanol induced gastric ulcer by enhancing the prostaglandin E2 level
Publication date: Available online 21 September 2017
Source:Journal of Ethnopharmacology
Author(s): Imran Kazmi, Tanveer Ahmad, Muhammad Afzal, Firoz Anwar
Ethnopharmacological relevanceLantana camara is a popular invasive weed utilized in the management of ulcer in different part of world. Study of specific compound present in this plant responsible for their antulcer activity is main topic of concern. Current study designed for evaluation of the antiulcer activity of oleane-12-en-3β-ol-28-oic acid 3β-D-glucopyranoside (OAG) from Lantana camara L.Materials and methodsAntiulcer activity was carried out on NSAID's (Aspirin) and ethanol induced ulcer model. The efficacy of the OAG on ulcer index, percentage protection and gastric acid secretion were evaluated.ResultsUlcer protection percentage (38.37%) was significant (P < 0.001) higher in the groups treated with the higher OAG dose (50 mg/kg), it also recover the mucosa with no redness, no inflammation, mild dilation of blood vessels. OAG significantly (P<0.01 and P<0.001) reduce acidity, free acidity and gastric acid volume. It also significantly (P<0.01) increases the pH of stomach.ConclusionOn the basis of results, it can be concluded that OAG shows significant gastroprotective activity by gastric acid secretion inhibition and afford protection against gastric mucosal damage. Further increase of prostaglandin E2 level establishes the mechanism of antiulcer activity of OAG.
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Ethnopharmacological approaches to kidney disease-prospecting an indigenous species from Brazilian Pantanal
Publication date: Available online 21 September 2017
Source:Journal of Ethnopharmacology
Author(s): Cleide Adriane Signor Tirloni, Rhanany Alan Calloi Palozi, Thainá de Almeida Tomazetto, Paulo César de Paula Vasconcelos, Roosevelt Isaias Carvalho Souza, Ariany Carvalho dos Santos, Valter Paes de Almeida, Jane Manfron Budel, Lauro Mera de Souza, Arquimedes Gasparotto Junior
Ethnopharmacological relevanceAlthough Luehea divaricata Mart. (Malvaceae) is popularly used by the population of the Brazilian Pantanal for the treatment of different types of kidney diseases, no study has been carried out to prove this ethnobotanical indication.AimTo investigate the possible cardiorenal effects of an herbal preparation obtained from L. divaricata leaves.Materials and MethodsFirst, to provide quality control standards, a detailed morphological and microchemical characterization of L. divaricata leaves was performed. Then, the purified aqueous extract was obtained from the leaves of this species (ESLD) and a thorough phytochemical characterization was performed. Subsequently, acute oral toxicity test was performed after single administration of different doses (5, 50, 300, 2000 mg/kg) in male and female Wistar rats. Finally, the diuretic, hypotensive and antioxidant properties of ESLD (30, 100, 300mg/kg) were evaluated after acute and prolonged treatment and the role of angiotensin converting enzyme, aldosterone, vasopressin, and nitric oxide in these effects was investigated.ResultsAnalyses performed by liquid chromatography–mass spectrometry showed that the main secondary metabolites present in ESLD were flavonol O-glycosides and flavone C-glycosides. Acute and prolonged treatment with ESLD was able to expressively increase urinary volume and electrolyte excretion. Mean blood pressure and systolic blood pressure were also significantly reduced after acute treatment. Moreover, treatment with ESLD was able to reduce thiobarbituric acid reactive species and increase serum nitrate levels.ConclusionThe data obtained showed that ESLD has an important diuretic and hypotensive effect, which is probably dependent on the reduction of oxidative stress and increased bioavailability of nitric oxide.
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Evaluation of genotoxicity and subchronic toxicity of the standardized leaves infusion extract of Copaifera malmei Harms in experimental models
Publication date: Available online 21 September 2017
Source:Journal of Ethnopharmacology
Author(s): Eduarda Pavan, Amilcar Sabino Damazo, Larissa Maria Scalon Lemos, Bulus Adzu, Sikiru Olaitan Balogun, Karuppusamy Arunachalam, Domingos Tabajara de Oliveira Martins
Ethnopharmacological relevanceCopaifera malmei Harms (Fabaceae), known mainly as óleo-mirim, is a native and endemic plant found in the states of Mato Grosso and Goiás of Brazil. The plant's leaves infusion is popularly used by riverine communities of the northern Araguaia microregion, Mato Grosso, Brazil, for the treatment of gastric ulcers and inflammatory diseases of the respiratory tract. The gastric antiulcer activity of the standardized leaves infusion extract of Copaifera malmei (SIECm) in rodents has been reported. The objective of this study was to advance the investigatation of the safety profile of SIECm by evaluating the genotoxicity and subchronic toxicity using in vitro and in vivo experimental models.Materials and methodsSIECm was prepared by infusion, by incubating the powdered dried leaves material in boiled water for 15min. In vitro genotoxicity of SIECm (10, 30 or 100μg/mL) was assessed by micronucleus and comet tests using Chinese hamster ovary (CHO-k1) epithelial cells. The evaluation of subchronic toxicity profile was performed by daily oral administration of SIECm (100, 400 or 1000mg/kg) to Wistar rats for 30 days. Clinical observations of toxicological related parameters were done every 6 days. After the treatment period, blood was collected for hematological and biochemical analyzes, and some organs were removed for macroscopic and histopathological analysis.ResultsIn the micronucleus assay, SIECm demonstrated anti-mutagenic activity. In the comet assay, SIECm presented anti-genotoxic effect preventing DNA damage at all the three concentrations tested with pre-treatment, while the same effect was only observed in the co-treatment at the lowest concentration. Post-treatment with SIECm increased the genetic damage induced by hydrogen peroxide (H2O2) at the highest concentration. In the subchronic toxicity test, few changes were observed, such as increase in feed consumption in the group of animals treated with 100mg/kg of the SIECm, which reversed after 6 days. There were no macroscopic, histological and relative weights changes in the organs of animals treated with SIECm. No toxicologically relevant changes were observed in the hematological analysis. Subchronic administration of SIECm reduced levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in animals treated with 100mg/kg and serum triglyceride levels at 400 and 1000mg/kg. However, the hematological and biochemical changes observed are within the physiological ranges for this animal species.ConclusionThe results demonstrate that SIECm is not genotoxic, and does not present toxicity when used orally for up to 30 days. In addition, it showed protection to the genetic damage induced by H2O2. The SIECm therefore has a high safety margin for therapeutic use.
Graphical abstract
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Traditional wound-healing plants used in the Balkan region (Southeast Europe)
Publication date: Available online 21 September 2017
Source:Journal of Ethnopharmacology
Author(s): Snežana Jarić, Olga Kostić, Zorana Mataruga, Dragana Pavlović, Marija Pavlović, Miroslava Mitrović, Pavle Pavlović
Ethnopharmacological relevanceThe geographical and ecological specificity of the Balkan Peninsula has resulted in the development of a distinct diversity of medicinal plants. In the traditional culture of the Balkan peoples, plants have medicinal, economic and anthropological/cultural importance, which is reflected in the sound knowledge of their diversity and use. This study analyses the traditional use of medicinal plants in the treatment of wounds and the pharmacological characteristics of the most frequently used species.Materials and methodsA detailed analysis of the literature related to ethnobhe uses of medicinal plants in the Balkan region was carried out. Twenty-five studies were analysed and those plants used for the treatment of wounds were singled out.ResultAn ethnobotanical analysis showed that 128 plant species (105 wild, 22 cultivated and 1 wild/cultivated) are used in the treatment of wounds. Their application is external, in the form of infusions, decoctions, tinctures, syrups, oils, ointments, and balms, or direct to the skin. Among those plants recorded, the most commonly used are Plantago major, Hypericum perforatum, Plantago lanceolata, Achillea millefolium, Calendula officinalis, Sambucus nigra, Tussilago farfara and Prunus domestica. The study showed that the traditional use of plants in wound healing is confirmed by in vitro and/or in vivo studies for P. major and P. lanceolata (3 laboratory studies for P. major and 2 for P. lanceolata), H. perforatum (5 laboratory studies and 3 clinical trials), A. millefolium (3 laboratory studies and one clinical trial), C. officinalis (6 laboratory studies and 1 clinical trial), S. nigra (3 laboratory studies) and T. farfara (one laboratory study).ConclusionThe beneficial effects of using medicinal plants from the Balkan region to heal wounds according to traditional practices have been proven in many scientific studies. However, information on the quantitative benefits to human health of using herbal medicines to heal wounds is still scarce or fragmented, hindering a proper evaluation. Therefore, further studies should be aimed at isolating and identifying specific active substances from plant extracts, which could also reveal compounds with more valuable therapeutic properties. Furthermore, additional reliable clinical trials are needed to confirm those experiences encountered when using traditional medicines. A combination of traditional and modern knowledge could result in new wound-healing drugs with a significant reduction in unwanted side effects.
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Scholar : These new articles for Spanish Journal of Finance and Accounting / Revista Española de Financiación y Contabilidad are available online
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Cell wall: A versatile fountain of drug targets in Mycobacterium tuberculosis
Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Zubair Shanib Bhat, Muzafar Ahmad Rather, Mubashir Maqbool, Hafiz UL Lah, Syed Khalid Yousuf, Zahoor Ahmad
Tuberculosis is the leading infectious disease responsible for an estimated one and a half million human deaths each year around the globe. HIV-TB coinfection and rapid increase in the emergence of drug resistant forms of TB is a dangerous scenario. This underlines the urgent need for new drugs with novel mechanism of action. A plethora of literature exist that highlight the importance of enzymes involved in the biosynthesis of mycobacterial cell wall responsible for its survival, growth, permeability, virulence and resistance to antibiotics. Therefore, assembly of cell wall components is an attractive target for the development of chemotherapeutics against Mycobacterium tuberculosis. The aim of this review is to highlight novel sets of enzyme inhibitors that disrupt its cell wall biosynthetic pathway. These include the currently approved first and second line drugs, candidates in clinical trials and current structure activity guided endeavors of scientific community to identify new potent inhibitors with least cytotoxicity and better efficacy against emergence of drug resistance till date.
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Mapping orbitofrontal-limbic maturation in non-human primates: A longitudinal magnetic resonance imaging study
Publication date: December 2017
Source:NeuroImage, Volume 163
Author(s): Akiko Uematsu, Junichi Hata, Yuji Komaki, Fumiko Seki, Chihoko Yamada, Norio Okahara, Yoko Kurotaki, Erika Sasaki, Hideyuki Okano
Brain development involves spatiotemporally complex microstructural changes. A number of neuropsychiatric disorders are linked to the neural processes of development and aging. Thus, it is important to understanding the typical developmental patterns of various brain structures, which will help to define critical periods of vulnerability for neural maturation, as well as anatomical mechanisms of brain structure-related neuropathology. In this study, we used magnetic resonance imaging to assess development of the orbitofrontal cortex, cingulate cortex, amygdala, and hippocampus in a non-human primate species, the common marmoset (Callithrix jacchus). We collected a total of 114 T2-weighted and 91 diffusion-weighted scans from 23 animals from infancy to early adulthood. Quantitative and qualitative evaluation of age-related brain growth patterns showed non-linear structural developmental changes in all measured brain regions, consistent with reported human data. Overall, robust volumetric growth was observed from 1 to 3 months of age (from infancy to the early juvenile period). This rapid brain growth was associated with the largest decrease in mean, axial, and radial diffusivities of diffusion tensor imaging in all brain regions, suggesting an increase in the number and size of cells, dendrites, and spines during this period. After this developmental period, the volume of various brain regions steadily increased until adolescence (7–13 months of age, depending on the region). Further, structural connectivity derived from tractography data in various brain regions continuously changed from infancy to adolescence, suggesting that the increase in brain volume was related to continued axonal myelination during adolescence. Thereafter, the volume of the cortical regions decreased considerably, while there was no change in subcortical regions. Familial factors, rather than sex, contributed the development of the front-limbic brain regions. Overall, this study provides further data on the factors and timing important for normal brain development, and suggest that the common marmoset is a useful animal model for human neural development.
http://ift.tt/2xt8BmN
How to target inter-regional phase synchronization with dual-site Transcranial Alternating Current Stimulation
Source:NeuroImage, Volume 163
Author(s): Guilherme Bicalho Saturnino, Kristoffer Hougaard Madsen, Hartwig Roman Siebner, Axel Thielscher
Large-scale synchronization of neural oscillations is a key mechanism for functional information exchange among brain areas. Dual-site Transcranial Alternating Current Stimulation (ds-TACS) has been recently introduced as non-invasive technique to manipulate the temporal phase relationship of local oscillations in two connected cortical areas. While the frequency of ds-TACS is matched, the phase of stimulation is either identical (in-phase stimulation) or opposite (anti-phase stimulation) in the two cortical target areas. In-phase stimulation is thought to synchronize the endogenous oscillations and hereby to improve behavioral performance. Conversely, anti-phase stimulation is thought to desynchronize neural oscillations in the two areas, which is expected to decrease performance. Critically, in- and anti-phase ds-TACS should only differ with respect to temporal phase, while all other stimulation parameters such as focality and stimulation intensity should be matched to enable an unambiguous interpretation of the behavioral effects. Using electric field simulations based on a realistic head geometry, we tested how well this goal has been met in studies, which have employed ds-TACS up to now. Separating the induced electrical fields in their spatial and temporal components, we investigated how the chosen electrode montages determined the spatial field distribution and the generation of phase variations in the injected electric fields. Considering the basic physical mechanisms, we derived recommendations for an optimized stimulation montage. The latter allows for a principled design of in- and anti-phase ds-TACS conditions with matched spatial distributions of the electric field. This knowledge will help cognitive neuroscientists to design optimal ds-TACS configurations, which are suited to probe unambiguously the causal contribution of phase coupling to specific cognitive processes in the human brain.
http://ift.tt/2yuRa3P
Neural oscillations reflect latent learning states underlying dual-context sensorimotor adaptation
Source:NeuroImage, Volume 163
Author(s): Justin M. Fine, Dalton Moore, Marco Santello
Recent studies have suggested that individuals can form multiple motor memories when simultaneously adapting to multiple, but oppositely-oriented perturbations. These findings predict that individuals detect the change in learning context, allowing the selective initialization and update of motor memories. However, previous electrophysiological studies of sensorimotor adaptation have not identified a neural mechanism supporting the detection of a context switch and adaptation to separate contexts. Here, we tested the hypothesis that such a mechanism is identifiable through neural oscillations measured through EEG. Human participants learned to manipulate an object in two opposite contexts (mass distribution). This task was designed based on previous work showing that people can adapt to both contexts. We found that sensorimotor α and β, and medial frontal θ frequency bands all exhibited different response patterns with respect to the error in each context. To determine whether any frequency's responses to error were distinctly related to a switch in context, we predicted single-trial EEG data from a computational learning model that can adapt to multiple contexts simultaneously based on a switching mechanism. This analysis revealed that only medial frontal θ was predicted by a component of the model state that adapts to errors based on a context switch. In contrast, α and β were predicted by a model state that was updated from performance errors independent of the context. These findings provide novel evidence showing that sensorimotor and medial frontal oscillations are predicted by different adaptation processes, and that changes in medial frontal activity may indicate the formation of motor memories by responding to changes in learning context.
http://ift.tt/2xsUz4x
Performance of five research-domain automated WM lesion segmentation methods in a multi-center MS study
Source:NeuroImage, Volume 163
Author(s): Alexandra de Sitter, Martijn D. Steenwijk, Aurélie Ruet, Adriaan Versteeg, Yaou Liu, Ronald A. van Schijndel, Petra J.W. Pouwels, Iris D. Kilsdonk, Keith S. Cover, Bob W. van Dijk, Stefan Ropele, Maria A. Rocca, Marios Yiannakas, Mike P. Wattjes, Soheil Damangir, Giovanni B. Frisoni, Jaume Sastre-Garriga, Alex Rovira, Christian Enzinger, Massimo Filippi, Jette Frederiksen, Olga Ciccarelli, Ludwig Kappos, Frederik Barkhof, Hugo Vrenken
Background and PurposeIn vivoidentification of white matter lesions plays a key-role in evaluation of patients with multiple sclerosis (MS). Automated lesion segmentation methods have been developed to substitute manual outlining, but evidence of their performance in multi-center investigations is lacking. In this work, five research-domain automated segmentation methods were evaluated using a multi-center MS dataset.Methods70 MS patients (median EDSS of 2.0 [range 0.0–6.5]) were included from a six-center dataset of the MAGNIMS Study Group (www.magnims.eu) which included 2D FLAIR and 3D T1 images with manual lesion segmentation as a reference. Automated lesion segmentations were produced using five algorithms: Cascade; Lesion Segmentation Toolbox (LST) with both the Lesion growth algorithm (LGA) and the Lesion prediction algorithm (LPA); Lesion-Topology preserving Anatomical Segmentation (Lesion-TOADS); and k-Nearest Neighbor with Tissue Type Priors (kNN-TTP). Main software parameters were optimized using a training set (N = 18), and formal testing was performed on the remaining patients (N = 52). To evaluate volumetric agreement with the reference segmentations, intraclass correlation coefficient (ICC) as well as mean difference in lesion volumes between the automated and reference segmentations were calculated. The Similarity Index (SI), False Positive (FP) volumes and False Negative (FN) volumes were used to examine spatial agreement. All analyses were repeated using a leave-one-center-out design to exclude the center of interest from the training phase to evaluate the performance of the method on 'unseen' center.ResultsCompared to the reference mean lesion volume (4.85 ± 7.29 mL), the methods displayed a mean difference of 1.60 ± 4.83 (Cascade), 2.31 ± 7.66 (LGA), 0.44 ± 4.68 (LPA), 1.76 ± 4.17 (Lesion-TOADS) and −1.39 ± 4.10 mL (kNN-TTP). The ICCs were 0.755, 0.713, 0.851, 0.806 and 0.723, respectively. Spatial agreement with reference segmentations was higher for LPA (SI = 0.37 ± 0.23), Lesion-TOADS (SI = 0.35 ± 0.18) and kNN-TTP (SI = 0.44 ± 0.14) than for Cascade (SI = 0.26 ± 0.17) or LGA (SI = 0.31 ± 0.23). All methods showed highly similar results when used on data from a center not used in software parameter optimization.ConclusionThe performance of the methods in this multi-center MS dataset was moderate, but appeared to be robust even with new datasets from centers not included in training the automated methods.
http://ift.tt/2yv0ULz
Contribution of Intercellular Adhesion Molecule 1 (ICAM-1) to control Mycobacterium avium infection
Source:Microbes and Infection
Author(s): Rafaella R. de Paula, Fábio V. Marinho, Julia S. Fahel, Sergio C. Oliveira
Mycobacterium avium is a facultative intracellular opportunistic pathogen especially relevant in cases of people living with AIDS. The aim of this study was to evaluate the role of intercellular adhesion molecule 1 (ICAM-1) in the inflammatory response against M. avium infection. Mice deficient for ICAM-1 (ICAM KO) and infected with M. avium presented increased bacterial load in the spleen, liver and lungs compared to C57BL/6. Moreover, ICAM deficient mice presented reduced granuloma area in liver at 30 days post-infection with reduced numbers of lymphocytes and granulocytes. The assessment of in vitro cytokine production by ICAM KO spleen cells showed lower levels of IFN-γ compared to C57BL/6, whereas TNF-α remained unaltered. Additionally, the production of IFN-γ in liver and spleen tissues was also diminished in ICAM-1 KO mice. Interestingly, a persistent reduction in IFN-γ production was observed in CD3+NK1.1+ cells of ICAM-1 deficient mice compared to wild-type animals. Together, these results demonstrate the importance of ICAM-1 in the efficient control of M. avium infection and granuloma formation and highlights its role on CD3+NK1.1+ cell population as important for IFN-γ production during infection.
http://ift.tt/2yi4t6P
Scholar : These new articles for Voice and Speech Review are available online
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Ultrasound-guided versus landmark-guided local corticosteroid injection for carpal tunnel syndrome: A systematic review and meta-analysis of randomized controlled clinical trials
Publication date: Available online 21 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Arash Babaei-Ghazani, Peyman Roomizadeh, Bijan Forogh, Seyed-Mohammad Moeini-Taba, Amin Abedini, Mona Kadkhodaie, Fateme Jahanjoo, Bina Eftekharsadat
ObjectiveTo review the literature and assess the comparative effectiveness of ultrasound-guided versus landmark-guided local corticosteroid injections in patients with carpal tunnel syndrome (CTS).Data SourcesCochrane Central Register of Controlled Trials, MEDLINE (PubMed), EMBASE (Ovid), and Web of Science (from inception to 1 February 2017).Study SelectionRandomized controlled trials (RCTs) comparing ultrasound-guided injection to landmark-guided injection in patients with CTS were included.Data ExtractionTwo authors independently screened abstracts and full texts. The Outcomes of interest were symptom severity scale (SSS) and functional status scale (FSS) scores of Boston Carpal Tunnel Questionnaire as well as four electro-diagnostic parameters including compound muscle action potential (CMAP), sensory nerve action potential (SNAP), distal motor latency (DML), and distal sensory latency (DSL).Data SynthesisOverall, 569 abstracts were retrieved and checked for eligibility and finally 3 RCTs were included (181 injected hands). Pooled analysis showed that ultrasound-guided injection was more effective in SSS improvement (mean difference [MD] = -0.46, 95% confidence interval (CI) = -0.59 to -0.32, P<0.00001); whereas, no significant difference was observed between the two methods in terms of FSS (MD= -0.25, 95%CI= -0.56 to 0.05, P=0.10). There were also no statistically significant differences in improvements of CMAP (MD=1.54, 95%CI=0.01 to 3.07, P=0.05), SNAP (MD= -0.02, 95%CI= -6.27 to 6.23, P=1.00), DML (MD=0.05, 95% CI= -0.30 to 0.39, P=0.80) or DSL (MD=0.00, 95%CI= -0.65 to 0.65, P=1.00).ConclusionsThis review suggested that ultrasound-guided injection was more effective than landmark-guided injection in symptom severity improvement in patients with CTS; however, no significant differences were observed in functional status or electro-diagnostic improvements between the two methods.
http://ift.tt/2xWF7iS
Home Health Agency Characteristics and Quality Outcomes for Medicare Beneficiaries with Rehabilitation-Sensitive Conditions
Publication date: Available online 21 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Tracy M. Mroz, Ann Meadow, Elizabeth Colantuoni, Bruce Leff, Jennifer L. Wolff
ObjectiveTo examine associations between organizational characteristics of home health agencies (e.g., profit status, rehabilitation therapy staffing model, size, and rurality) and quality outcomes among Medicare beneficiaries with rehabilitation-sensitive conditions, conditions for which occupational, physical, and/or speech therapy have the potential to improve functioning, prevent or slow substantial decline in functioning, or increase ability to remain at home safely.Design, Setting, and ParticipantsRetrospective analysis of Medicare administrative data for 1,006,562 fee-for-service beneficiaries admitted to 9,250 Medicare-certified home health agencies in 2009.InterventionsNot applicable.Main Outcome MeasuresInstitutional admission during home health, community discharge, and institutional admission within 30 days of discharge.ResultsNonprofit (versus for-profit) home health agencies were more likely to discharge beneficiaries to the community (OR 1.23, 95%CI: 1.13-1.33) and less likely to have beneficiaries incur institutional admissions within 30 days of discharge (OR 0.93, 95%CI: 0.88-0.97). Agencies in rural (versus urban) counties were less likely to discharge patients to the community (OR 0.83 95%CI: 0.77-0.90) and more likely to have beneficiaries incur institutional admissions during home health (OR 1.24 95%CI: 1.18-1.30) and within 30 days of discharge (OR 1.15 95%CI: 1.10-1.22). Agencies with contract (versus in-house) therapy staff were less likely to discharge beneficiaries to the community (OR 0.79, 95%CI: 0.70-0.91) and more likely to have beneficiaries incur institutional admissions during home health (OR 1.09 95%CI: 1.03-1.15) and within 30 days of discharge (OR 1.17, 95%CI: 1.07-1.28).ConclusionsAs payers continue to test and implement reimbursement mechanisms that seek to reward value over volume of services, greater attention should be paid to organizational factors that facilitate better coordinated, higher quality home health care for beneficiaries who may benefit from rehabilitation.
http://ift.tt/2yuXkRD
Reply to the Letter to the Editor by Josef Finsterer and Sinda Zarrouk-Mahjoub
Source:Pediatric Neurology
Author(s): Nitish Chourasia, Rahmat Adejumo, Rajan Patel, Mary Kay Koenig
http://ift.tt/2yvxNaN
Antiepileptic Drugs and Liver Disease
Source:Pediatric Neurology
Author(s): Jorge Vidaurre, Satya Gedela, Shannon Yarosz
Acute, symptomatic seizures or epilepsy may complicate the course of hepatic disease.Choosing the most appropriate antiepileptic drug (AED) in this setting represents a difficult challenge, as most medications are metabolized by the liver. This article focuses on the acute and chronic treatment of seizures in patients with advanced liver disease and reviews the hepatotoxic potential of specific AEDs.Newer AEDs with no, or minimal, hepatic metabolism, such as levetiracetam, lacosamide, topiramate, gabapentin and pregabalin should be used as first line therapy. Medications undergoing extensive hepatic metabolism, such as valproic acid, phenytoin and felbamate should be used as drugs of last resort. In special circumstances, such as patients affected by acute intermittent porphyria; exposure to most AEDs could precipitate attacks. In this clinical scenario, bromides, levetiracetam, gabapentin and vigabatrin constitute safe choices. For the treatment of status epilepticus, levetiracetam and lacosamide, available in IV preparations, are good second line therapies after benzodiazepines fail to control seizures.Hepatotoxicity is also a rare and unexpected side effect of AED therapy. Some drugs, such as valproic acid, phenytoin and felbamate have a well-recognized association with liver toxicity. Other AEDs, including phenobarbital, benzodiazepines, ethosuximide and the newer generations of AEDs, have only rarely been linked to hepatotoxicity.It is therefore necessary for physicians to be mindful of the pharmacokinetic profile and hepatotoxic potential of the different AEDs available to treat patients affected by liver disease.
http://ift.tt/2wG2Hjq
The Child Neurology Trainee-as-Teacher: a Clinical Teaching Curriculum Tailored to Learners' Needs and Developmental Roles
Source:Pediatric Neurology
Author(s): Miya E. Bernson-Leung, David K. Urion
IntroductionClinical teaching skills programs for resident physicians are increasingly offered. Less attention has been devoted to the unique educational roles of specialty residents and subspecialty fellows, many of whom will become academic faculty physicians. These teaching roles, and therefore a trainee's learning needs and motivation, also change over the course of training.MethodsWe designed and implemented a two-year longitudinal teaching curriculum for child neurology and neurodevelopmental disabilities residents using adult learning theory principles: experiential learning and immediate applicability to specific roles. Core modules included teaching in clinical settings, adult learning, and giving feedback. Training-year-specific modules for second-year residents (n = 11) and final-year residents (n = 10) included teaching through consultation and promoting clinical reasoning in supervisory roles. Learners completed an 11-item self-assessment pre- and post-intervention.ResultsThe overall program significantly increased residents' self-assessed knowledge of how to assess the level of a learner (p = 0.02, Cohen's d = 0.84) and comfort and skill in giving feedback (p = 0.04, d = 0.64; p = 0.04, d = 0.71). The final-year-specific curriculum additionally increased self-assessed skill in teaching same-specialty residents (p = 0.05, d = 1.07) and in promoting clinical reasoning (p = 0.03, d = 1.14). The program was rated highly by trainees and faculty, and has been adopted as an ongoing part of our training program.ConclusionsOur experience offers a reproducible model and theoretical framework for child neurology, neurodevelopmental disabilities, and other specialty programs to develop customized trainee-as-teacher curricula with specialty- and training-year-specific content.
http://ift.tt/2yvy0L6
Monogenic Hashimoto thyroiditis associated with a variant in the thyroglobulin (TG) gene
Source:Journal of Autoimmunity
Author(s): Mindy S. Lo, Meghan Towne, Grace E. VanNoy, Catherine A. Brownstein, Andrew A. Lane, Talal A. Chatila, Pankaj B. Agrawal
BackgroundRisk of autoimmune thyroid disease (AITD) is strongly heritable. Multiple genes confer increased risk for AITD, but a monogenic origin has not yet been described. We studied a family with apparent autosomal dominant, early onset Hashimoto thyroiditis.MethodsThe family was enrolled in an IRB-approved protocol. Whole exome sequencing was used to study the proband and an affected sibling. The identified variant was studied in other family members by Sanger sequencing.ResultsWe identified a previously unreported splice site variant in the thyroglobulin gene (TG c.1076-1G > C). This variant was confirmed in all affected family members who underwent testing, and also noted in one unaffected child. The variant is associated with exon 9 skipping, resulting in a novel in-frame variant transcript of TG.ConclusionWe discovered a monogenic form of AITD associated with a splice site variant in the thyroglobulin gene. This finding raises questions about the origins of thyroid autoimmunity; possible explanations include increased immunogenicity of the mutated protein or thyroid toxicity with secondary development of anti-thyroid antibodies. Further study into the effects of this variant on thyroid function and thyroid autoimmunity are warranted.
http://ift.tt/2wLETFW
Standardized whole blood stimulation improves immunomonitoring of induced immune responses in multi-center study
Source:Clinical Immunology
Author(s): Darragh Duffy, Vincent Rouilly, Cecile Braudeau, Véronique Corbière, Raouf Djebali, Marie-Noelle Ungeheuer, Regis Josien, Sam LaBrie, Olivier Lantz, Delphine Louis, Eva Martinez-Caceres, Francoise Mascart, Jose G. Ruiz de Morales, Catherine Ottone, Lydia Redjah, Nina Salabert-Le Guen, Alain Savenay, Manfred Schmolz, Antoine Toubert, Matthew L. Albert
Functional immune responses are increasingly important for clinical studies, providing in depth biomarker information to assess immunotherapy or vaccination. Incorporating functional immune assays into routine clinical practice has remained limited due to challenges in standardizing sample preparation. We recently described the use of a whole blood syringe-based system, TruCulture®, which permits point-of-care standardized immune stimulation. Here, we report on a multi-center clinical study in seven FOCIS Centers of Excellence to directly compare TruCulture to conventional PBMC methods. Whole blood and PBMCs from healthy donors were exposed to LPS, anti-CD3 anti-CD28 antibodies, or media alone. 55 protein analytes were analyzed centrally by Luminex multi-analyte profiling in a CLIA-certified laboratory. TruCulture responses showed greater reproducibility and improved the statistical power for monitoring differential immune response activation. The use of TruCulture addresses a major unmet need through a robust and flexible method for immunomonitoring that can be reproducibly applied in multi-center clinical studies.One sentence summaryA multi-center study revealed greater reproducibility from whole blood stimulation systems as compared to PBMC stimulation for studying induced immune responses.
http://ift.tt/2wa7ZPR
Multiple sclerosis treatment effects on plasma cytokine receptor levels
Source:Clinical Immunology
Author(s): Sahl Khalid Bedri, Katharina Fink, Ali Manouchehrinia, Wangko Lundström, Ingrid Kockum, Tomas Olsson, Jan Hillert, Anna Glaser
Genetic variants within some cytokine receptor genes have been associated with MS susceptibility, including IL7RA and IL2RA. As these genes are expressed by cells targeted by immune-modulatory drugs, we explored the potential role of their gene products as biomarkers in monitoring MS treatment. We assessed the impact of natalizumab followed by fingolimod on the intra-individual changes of plasma protein levels of sIL-7Rα, sIL-2Rα and also sIL-6R and sgp130 in MS patients. During natalizumab treatment we observed a decline in sgp130 and sIL-7Rα levels, while subsequent fingolimod treatment lead to increased sgp130 and sIL-7Rα and decreased sIL-2Rα levels. In addition, during fingolimod treatment sIL-7Rα levels were increasing significantly more in patients homozygous for the MS risk genotype of rs6897932. We also observed an effect of the MS associated rs71624119 on sgp130 levels. These results may elucidate the pharmacodynamics of treatments and help identify biomarkers for MS outcomes.
http://ift.tt/2fgmD1a
Lack of Methemoglobin Elevations After Topical Applications of Benzocaine Alone or Benzocaine Plus Tetracaine to the Oral Mucosa
Source:Clinical Therapeutics
Author(s): Steven Wang, Helen Giannakopoulos, Jamie Lowstetter, Laura Kaye, Catherine Lee, Stacey Secreto, Vanessa Ho, Matthew C. Hutcheson, John T. Farrar, Ping Wang, Geraldine Doyle, Stephen A. Cooper, Elliot V. Hersh
PurposeThis study evaluated changes in methemoglobin and oxygen saturation concentrations after the administration of recommended doses of 14% benzocaine alone or 14% benzocaine combined with 2% tetracaine.MethodsAmerican Society of Anesthesiology class 1 and 2 subjects (n = 40) were enrolled in this modified crossover study. Subjects were administered 0.2 mL of 14% benzocaine alone, 0.2 mL of 14% benzocaine plus 2% tetracaine, or 0.4 mL of 14% benzocaine plus 0.2% benzocaine to their cheek mucosa. Venous blood (5 mL) was drawn from the antecubital fossa before and 60 minutes after drug application for methemoglobin analyses. Oxygen saturation was also recorded via pulse oximetry at baseline and every 10 minutes through 60 minutes after drug application.FindingsMethemoglobin and oxygen saturation levels did not change from baseline after the administration of benzocaine alone or when combined with tetracaine.ImplicationsRecommended doses of benzocaine or benzocaine combined with tetracaine when applied to the cheek mucosa do not induce even clinically insignificant elevations in methemoglobin levels. Metered dosing, such as that used in this study, can help avoid this overdose phenomena with these drugs. ClinicalTrials.gov identifier: NCT02908620.
http://ift.tt/2waHr0N
International Children’s Advisory Network: A Multifaceted Approach to Patient Engagement in Pediatric Clinical Research
Source:Clinical Therapeutics
Author(s): Meghan Gwara, Sharon Smith, Christine Woods, Elizabeth Sheeren, Hampton Woods
Pediatric youth advisory groups were created to provide insight and guidance to the clinical research community. Such efforts have become a priority and parallel the demand for patient-centered health care. While steps are being made to integrate the patient voice into research, there remains a lack of pediatric-specific engagement in the development of pharmaceuticals and in clinical research. For example, a significant number of children are still treated with medications that are not approved for use in this age group, due to a lack of clinical trials involving younger children and neonates. The American Academy of Pediatrics noted that physicians are faced with an ethical dilemma, as they must frequently either not treat children with potentially beneficial medications or treat them with medications based on adult studies or anecdotal empirical experience in children. By improving the approach to pediatric study design, indications for pediatric-specific therapies can be developed. We describe a structured organization with empowered youth and parents who are beginning to play a key role in the research process that suggests ways to improve pediatric research and for innovative medical products to be more "child friendly" and usable. We will also describe how investigators can engage the International Children's Advisory Network to obtain valuable youth perspectives on many aspects of clinical research and health care advocacy.
http://ift.tt/2ffVr2u
Forgotten No More: How Policy Guideline Changes Are Bringing Newborns, Infants, and Children to the Forefront of Drug Discovery and Testing
Source:Clinical Therapeutics
Author(s): Jill L. Maron
http://ift.tt/2waHgm9
HbA1c Outcomes in Patients Treated With Canagliflozin Versus Sitagliptin in US Health Plans
Source:Clinical Therapeutics
Author(s): Sarah Thayer, Richard Aguilar, Stephanie Korrer, Wing Chow
PurposeClinical trial evidence supports greater glycemic control with canagliflozin than with sitagliptin. The objective of this study was to provide real-world evidence comparing outcomes in routine clinical practice among patients initiating each medication.MethodsWith the use of a health care administrative database, patients initiating canagliflozin were compared with patients initiating sitagliptin (first prescription fill as index date). Baseline (6 months before index date) demographic and clinical (eg, comorbidities and diabetes-related complications) characteristics were compared, and propensity score matching was used to control for baseline differences between cohorts. Outcomes included change in glycosylated hemoglobin (HbA1c) and persistence with medication over a 9-month period after index date.FindingsBefore matching, the canagliflozin cohort (N = 3993) was younger than the sitagliptin cohort (N = 12,153) and was composed of fewer women and Medicare Advantage enrollees, with lower mean baseline comorbidity scores (all p < 0.001). Before matching, the canagliflozin cohort (valid n = 1482) had a significantly (p < 0.001) higher baseline HbA1c (8.60) than the sitagliptin cohort (valid n = 3697; HbA1c, 8.32). After matching (n = 1472 per cohort), patients were well balanced on baseline characteristics, and HbA1c values were not significantly different (p = 0.634) between the cohorts. Patients initiating canagliflozin had greater reductions in HbA1c than patients in the sitagliptin cohort (−0.93% versus −0.57%, respectively; p = 0.004), with similar mean (median) time from index date to follow-up HbA1c of 185.4 (199.0) and 184.3 (190.5) days, respectively (p = 0.802). Only 29.8% of canagliflozin patients discontinued during follow-up compared with 41.5% of sitagliptin patients (p < 0.001); the average days of persistence on index therapy was longer for canagliflozin patients (152 days) than for sitagliptin patients (139 days; p < 0.001).ImplicationsIn this observational study, patients initiating canagliflozin had greater reduction in HbA1c and longer persistence with medication than did patients who initiated sitagliptin, over a 9-month period. Better understanding of antihyperglycemic treatment, HbA1c results, and differences among patients in demographic/clinical characteristics as well as persistence with treatment will inform optimal diabetes treatment choice in routine practice.
http://ift.tt/2ffFxp2
Roles of Clinical Research Networks in Pediatric Drug Development
Source:Clinical Therapeutics
Author(s): Mark A. Turner, Sabah Attar, Saskia N. de Wildt, Gilles Vassal, Laura Mangiarini, Carlo Giaquinto
The evaluation of drugs that are used in children has been neglected historically but is now well established as an essential part of clinical drug development. The increase in pediatric activity among industry, and other sectors, has highlighted the importance of joint working. All participants in pediatric drug development need to be aware of the "big picture." An increasingly important part of this big picture in pediatrics, as in other populations, is the design and conduct of clinical trials in networks. This narrative review provides an overview of the roles of clinical research networks in pediatric drug development. Networks take many forms as specialty networks and geographic networks but work toward common principles, including sharing resources between trials, and using experience with trial conduct to improve trial design. Networks develop standardized processes for trial conduct (including performance management) that increase the speed and predictability of trial conduct while reducing burdens on sites, sponsors, and intermediaries. Networks can provide validated, real-world information about natural history, participant distribution, and standards of care to inform planning of development programs, including extrapolation and clinical trial simulation. Networks can work across geographic and jurisdictional barriers to promote global interoperability of drug development. Networks support participant centrality. Networks offer an opportunity to develop relationships with investigators, sites, and methodological experts that span pre-competitive foundations for drug development and specific products. Sustainable networks benefit all stakeholders by providing a multifunctional platform that promotes the quality and timeliness of clinical drug development.
http://ift.tt/2waC024
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Publication date: September 2017 Source: Free Radical Biology and Medicine, Volume 110 Author(s): Lucía Fernández-del-Río, Anish Nag, Elen...
