Lifespan Trajectories of White Matter Changes in Rhesus Monkeys

Abstract

Progress in neurodevelopmental brain research has been achieved through the use of animal models. Such models not only help understanding biological changes that govern brain development, maturation and aging, but are also essential for identifying possible mechanisms of neurodevelopmental and age-related chronic disorders, and to evaluate possible interventions with potential relevance to human disease. Genetic relationship of rhesus monkeys to humans makes those animals a great candidate for such models. With the typical lifespan of 25 years, they undergo cognitive maturation and aging that is similar to this observed in humans. Quantitative structural neuroimaging has been proposed as one of the candidate in vivo biomarkers for tracking white matter brain maturation and aging. While lifespan trajectories of white matter changes have been mapped in humans, such knowledge is not available for nonhuman primates. Here, we analyze and model lifespan trajectories of white matter microstructure using in vivo diffusion imaging in a sample of 44 rhesus monkeys. We report quantitative parameters (including slopes and peaks) of lifespan trajectories for 8 individual white matter tracts. We show different trajectories for cellular and extracellular microstructural imaging components that are associated with white matter maturation and aging, and discuss similarities and differences between those in humans and rhesus monkeys, the importance of our findings, and future directions for the field.Significance Statement: Quantitative structural neuroimaging has been proposed as one of the candidate in vivo biomarkers for tracking brain maturation and aging. While lifespan trajectories of structural white matter changes have been mapped in humans, such knowledge is not available for rhesus monkeys. We present here results of the analysis and modeling of the lifespan trajectories of white matter microstructure using in vivo diffusion imaging in a sample of 44 rhesus monkeys (age 4–27). We report and anatomically map lifespan changes related to cellular and extracellular microstructural components that are associated with white matter maturation and aging.

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Barriers to Completion of Research Projects Among Orthopaedic Trainees

Publication date: Available online 24 April 2018
Source:Journal of Surgical Education
Author(s): Sean Carter, Susan Liew, Graeme Brown, Afshin Kamali Moaveni
Introduction & AimIt is a requirement of the Australian Orthopaedic Association (AOA) training program that surgical education training (SET) trainees demonstrate competency in clinical or basic science research as part of their teaching curriculum. The aim of this study is to identify barriers in completing research by the Victorian and Tasmanian Region AOA SET trainees.MethodsWe designed a short qualitative survey which was distributed to all Victorian and Tasmanian orthopaedic trainees through the AOA. The survey consisted of 18 questions most of which were based on a 5-point Likert scale with options to add comments based on individual experience.ResultsThirty-two (61%) orthopaedic trainees responded to the survey. Two did not give consent for their data to be used. Trainees were more likely to abandon their research projects if they had insufficient time to complete a project (p = 0.01), had fewer opportunities to take part in research (p = 0.011), were unable to complete a research project within their hospital rotation (p = 0.024), and did not have access to funding (p = 0.025).ConclusionA large amount of research is abandoned by trainees. The barriers to research completion are similar to those found in the literature, however, not all barriers identified in the literature were found to be barriers to the Victorian and Tasmanian Orthopaedic trainees. By identifying barriers to research completion within training programs, we hope to assist efficiency and help improve the likelihood of project completion as well as assist mentors in their guidance of trainees while conducting research.



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A Video-Based Coaching Intervention to Improve Surgical Skill in Fourth-Year Medical Students

Publication date: Available online 24 April 2018
Source:Journal of Surgical Education
Author(s): Mitchell B. Alameddine, Michael J. Englesbe, Seth A. Waits
ObjectiveFor senior medical students pursuing careers in surgery, specific technical feedback is critical for developing foundational skills in preparation for residency. This pilot study seeks to assess the feasibility of a video-based coaching intervention to improve the suturing skills of fourth-year medical students.DesignFourth-year medical students pursuing careers in surgery were randomized to intervention vs. control groups and completed 2 video recorded suture tasks. Students in the intervention group received a structured coaching session between consecutive suturing tasks, whereas students in the control group did not. Each coaching session consisted of a video review of the students' first suture task with a faculty member that provided directed feedback regarding technique. Following each suturing task, students were asked to self-assess their performance and provide feedback regarding the utility of the coaching session. All videos were deidentified and graded by independent faculty members for evaluation of suture technique.SettingThe University of Michigan Medical School in Ann Arbor, Michigan.ParticipantsAll fourth-year medical students pursuing careers in surgical specialties were contacted via e-mail for voluntary participation. In all, 16 students completed both baseline and follow up suture tasks.ResultsAll students who completed the coaching session would definitely recommend the session for other students. A total of 94% of the students strongly agreed that the exercise was a beneficial experience, and 75% strongly agreed that it improved their technical skills. Based on faculty grading, students in the intervention group demonstrated greater average improvements in bimanual dexterity compared to students in the control group; whereas students in the control group demonstrated greater average improvements in domains of efficiency and tissue handling compared to the intervention group. Based on student self-assessments, those in the intervention group had greater subjective improvements in all scored domains of bimanual dexterity, efficiency, tissue handling, and consistency compared to the control group. Subjective, free-response comments centered on themes of becoming more aware of hand movements when viewing their suturing from a new perspective, and the usefulness of the coaching advice.ConclusionsThis pilot study demonstrates the feasibility of a video-based coaching intervention for senior medical students. Students who participated in the coaching arm of the intervention noticed improvements in all domains of technical skill and noted that the experience was overwhelmingly positive. In summary, video-based review shows promise as an educational tool in medical education as a means to provide specific technical feedback.



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Is There an Influence of Surgeon’s Experience on the Clinical Course in Patients With a Proximal Femoral Fracture?

Publication date: Available online 24 April 2018
Source:Journal of Surgical Education
Author(s): Claudio Canal, Alexander Kaserer, Bernhard Ciritsis, Hans-Peter Simmen, Valentin Neuhaus, Hans-Christoph Pape
ObjectivesTeaching of surgical procedures is of paramount importance. However, it can affect patients outcome. The aim of this study was to evaluate if teaching of hip fracture surgery is an independent predictor for negative in-hospital outcome.Design and SettingRetrospectively, we analyzed all hip fracture patients between 2008 and 2013 recorded in a national quality measurement database (AQC). Inclusion criteria were proximal femoral fracture (ICD-10 diagnostic codes S72.00-S72.11), surgical care of those fracture and a documented teaching status of the intervention. Variables were sought in bivariate and multivariate analyses. Teaching status was entered in multiple regression analysis models for in-hospital death, complications and length of stay while controlling for confounders.ParticipantsIn the 6-year study period, a total of 4397 patients at a mean age of 80 years met the inclusion criteria. Totally, 48% (n = 2107) of the procedures were conducted as teaching interventions. The rest of our examined cases (n = 2290) were conducted as nonteaching procedures.ResultsThere was no association between teaching and mortality, but complications (odds ratio = 1.3; 95% CI: 1.04–1.5; p = 0.018) and prolonged hospitalization (standardized beta = 0.045, p = 0.002) were more likely to occur in the teaching group while controlling for confounders.ConclusionsThere appears to be no effect of the educational status on the in-hospital death in patients with a proximal femoral fracture. However, teaching was an independent predictor of complications and longer length of stay. Although the differences were significant, the clinical outcome was comparable in both groups, thus justifying the benefits of resident teaching.



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Understanding Surgical Resident and Fellow Perspectives on Their Operative Performance Feedback Needs: A Qualitative Study

Publication date: Available online 22 April 2018
Source:Journal of Surgical Education
Author(s): Ricardo J. Bello, Samuel Sarmiento, Meredith L. Meyer, Gedge D. Rosson, Damon S. Cooney, Scott D. Lifchez, Carisa M. Cooney
ObjectiveOperative performance feedback is essential for surgical training. We aimed to understand surgical trainees′ views on their operative performance feedback needs and to characterize feedback to elucidate factors affecting its value from the resident perspective.DesignUsing a qualitative research approach, 2 research fellows conducted semistructured, one-on-one interviews with surgical trainees. We analyzed recurring themes generated during interviews related to feedback characteristics, as well as the extent to which performance rating tools can help meet trainees′ operative feedback needs.SettingDepartments or divisions of general or plastic surgery at 9 US academic institutions.ParticipantsSurgical residents and clinical fellows in general or plastic surgery.ResultsWe conducted 30 interviews with 9 junior residents, 14 senior residents, and 7 clinical fellows. Eighteen (60%) participants were in plastic and 12 (40%) were in general surgery. Twenty-four participants (80%) reported feedback as very or extremely important during surgical training. All trainees stated that verbal, face-to-face feedback is the most valuable, especially if occurring during (92%) or immediately after (65%) cases. Of those trainees using performance rating tools (74%), most (57%) expressed positive views about them but wanted the tools to complement and not replace verbal feedback in surgical education. Trainees value feedback more if received within 1 week or the case.ConclusionsVerbal, face-to-face feedback is very or extremely important to surgical trainees. Residents and fellows prefer to receive feedback during or immediately after a case and continue to value feedback if received within 1 week of the event. Performance rating tools can be useful for providing formative feedback and documentation but should not replace verbal, face-to-face feedback. Considering trainee views on feedback may help reduce perceived gaps in feedback demand-versus-supply in surgical training, which may be essential to overcoming current challenges in surgical education.



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Validation of a Low-Cost Do-It-Yourself Model for Neonatal Thoracoscopic Congenital Diaphragmatic Hernia Repair

Publication date: Available online 20 April 2018
Source:Journal of Surgical Education
Author(s): Pedro Reino-Pires, Manuel Lopez
ObjectiveWe aimed to develop and validate a low cost, do-it-yourself model for neonatal thoracoscopic congenital diaphragmatic hernia (CDH).DesignVolunteers with varying skills in neonatal minimally invasive surgery tested and evaluated the model simulating a neonatal thoracoscopic CDH repair. The model was built from ordinary materials purchased in a dime store: a small food container, a neoprene band simulating a diaphragm, an inflated balloon simulating a spleen, a tissue chord simulating intestine, and a body wash sponge simulating a collapsed lung. The evaluation comprised 3 sets of 5-point grading scale concerning appearance, necessary maneuvers, and ability to generate skills. Bowel reduction and suture efficacy was verified for each test.SettingMinimally invasive surgery simulation room at Pediatric Surgery Department of Hospital Universitario de Vall d'Hebron, Barcelona, Spain.ParticipantsVolunteer residents and specialists of pediatric surgery.ResultsBowel reduction was possible in every test, with 1 spleen rupture, 1 bowel entrapment, and 2 inappropriate sutures due to tension. Most volunteers considered the general endoscopic vision (63.2%), external and internal dimensions (both 89.5%) to be highly similar; bowel reduction (68.4%) and diaphragm's manipulation and suture (57.9%) to be highly or very highly similar. Regarding its ability to generate skills, most considered it to be very or extremely useful concerning: camera handling (52.6%), working in small spaces and suture (both 100%), and tissue handling (63.2%). The least liked features were the colors and the diaphragm's tension. The size, portability, and the reproducibility were the most liked features.ConclusionsWe consider this low cost and easily reproducible model to be realistic enough for CDH repair training, having the potential to be adapted for other simulations.



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Mentorship in Orthopedics: A National Survey of Orthopedic Surgery Residents

Publication date: Available online 25 April 2018
Source:Journal of Surgical Education
Author(s): Lasun O. Oladeji, Brent A. Ponce, John R. Worley, James A. Keeney
ObjectiveMentorship is an important component of graduate medical education. It has been associated with numerous benefits including personal development, increased career satisfaction, and reduced stress and burnout. The purpose of this study was to assess orthopedic resident attitudes regarding mentorship and to determine if there were sociodemographic differences.DesignA total of 243 orthopedic surgery residents completed this 25-item mixed response questionnaire.ResultsNearly two-thirds of residents conveyed that their training program either had a formal or informal mentorship program, and 95.8% of residents indicated that they believed mentorship played an important role with respect to their development as an orthopedic resident. Minorities were more likely to have a mentor that was obtained while they were in medical school, less likely to have multiple mentors, and more likely to be dissatisfied with the quality of mentorship in residency. Females were more likely to pursue a mentor on their own. Overall, 31% of orthopedic residents were classified as experiencing burnout. There was no difference in the prevalence of mentorship in respondents experiencing burnout, but they were more likely to be unsatisfied with the quality of mentorship in residency. Finally, only two-thirds of residency programs have mentorship programs despite the fact that the vast majority of orthopedic residents believe that the mentorship plays an important role in their development as surgeons.ResultsGiven these findings, future work should focus on identifying and addressing race and sex-based mentorship disparities while simultaneously working to improve access to mentorship for all residents.



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Feasibility and Benefit of Incorporating a Multimedia Cadaver Laboratory Training Program into a Didactics Curriculum for Junior and Senior Surgical Residents

Publication date: Available online 18 April 2018
Source:Journal of Surgical Education
Author(s): Erika Simmerman, Andrew Simmerman, Randi Lassiter, Ray King, Ben Ham, Bao-Ling Adam, Colville Ferdinand, Steven Holsten
ObjectiveAs operative experience in general surgery decreases and work hour limitations increase there is less exposure of surgical residents to advanced vascular and trauma exposures. Many institutions have demonstrated benefits of cadaver laboratory courses. We have incorporated a multimedia cadaver laboratory course into our general surgery residency didactics curriculum with the objective to demonstrate a benefit of the program as well as the feasibility of incorporation.Study DesignThis is a prospective study at a tertiary care institution including general surgery residents within our residency program. A curriculum was designed, requiring residents to complete multimedia learning modules before both a trauma cadaver laboratory and vascular exposure cadaver laboratory. Outcome measures included self-efficacy/confidence (precourse and postcourse 5-point Likert surveys), knowledge (net performance on precourse and postcourse multiple choice examinations), and resident perception of the curriculum (postcourse 5-point Likert survey). Data were analyzed using ANOVA paired t-tests.ResultsFor the vascular cadaver laboratory, resident knowledge improved overall from an average of 41.2% to 50.0% of questions correct (p = 0.032) and self-efficacy/confidence improved by 0.59 from 1.52 to 2.11 out of 5 (p = 0.009). Median confidence is 1.37 out of 5 and 2.32 out of 5, before and after course, respectively. Wilcoxon nonparametric test reveals a p = 0.011. Resident's perception of the usefulness of the laboratory evaluation was 3.85 out 5. There were 85.71% agreed that the laboratory is useful and 14.29% were disagree. The Z-score is −0.1579 (means 0.1579 standard deviations a score of 3.85 below the benchmark). The percentile rank is 56.27%. The coefficient of variation is 24.68%.For the trauma cadaver laboratory, resident knowledge improved overall from an average of 55.89% to 66.17% of questions correct (p = 0.001) and self-efficacy/confidence improved by 0.75 from 1.68 out of 5 to 2.43 out of 5 (p = 0.011). Median confidence level is 1.41 out of 5 before the training course and 2.64 out of 5 after the training course. Wilcoxon signed rank test gives a p value of 0.008. Resident's perception of the usefulness of the laboratory evaluation was 3.94 out 5. There were 72.22% agreed that the laboratory is useful and 27.78% were neutral. The Z-score is −0.098 (means 0.098 standard deviations a score of 3.94 below the benchmark). The percentile rank is 53.90%. The coefficient of variation is 15.48%.ConclusionsIncorporating a multimedia cadaver laboratory into a residency education didactics curriculum was both feasible and beneficial for resident education. We demonstrate an improvement in knowledge and self efficacy/confidence following both cadaver laboratory courses.



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The Effects of Feedback Fatigue and Sex Disparities in Medical Student Feedback Assessed Using a Minute Feedback System

Publication date: Available online 17 April 2018
Source:Journal of Surgical Education
Author(s): Meredith Barrett, Patrick Georgoff, Niki Matusko, Lisa Leininger, Rishindra M. Reddy, Gurjit Sandhu, David T. Hughes
ObjectiveFeedback is critical to the development of medical students. To enhance feedback, we created a web application, the Minute Feedback System (MFS). This app allows students to request precise, timely, written feedback from residents and staff without the burden of vague, end-of-rotation surveys. In this study, we investigate variations in response rates and feedback fatigue based on sex and rank (resident/fellow vs. faculty).DesignData were collected from May 2015-October 2016. The MFS stores student requests for feedback along with faculty responses allowing for analysis of feedback response rate as well as sex and rank identification. Variation in response rate was analyzed using Chi-square and log-rank testing. Feedback fatigue was assessed using Cox regression modeling.SettingUniversity Affiliated, Tertiary Care Center.ParticipantsMedical Students, Residents and Faculty.ResultsAbout 98.6% of students (138 women, 140 men) used the MFS on their surgery clerkship. They requested feedback from 159 trainees (residents or fellows) and 114 surgical faculty. Feedback was requested more from faculty (26.3 requests per individual) compared to trainees (16.4 requests per individual).The overall evaluator response rate was 60%. Male students were 13% less likely to receive feedback than female students. There was a higher prevalence of feedback fatigue among female faculty (11% less likely to respond) and residents (23% less likely to respond). Regression analysis showed that the overall hazard of nonresponse over time was 1.05, indicative of overall feedback fatigue among all respondents.ConclusionsThe MFS is a novel tool for feedback used by nearly all M3 students during their surgery clerkship at our institution. Evaluation of response rates demonstrated feedback fatigue, especially among women faculty and residents. Feedback fatigue was more likely to affect male students, although the reason for this is unclear. Further analysis is necessary to understand this sex-associated response disparity and its effect on student feedback in the learning environment.



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Mixed-Method Evaluation of a Cadaver Dissection Course for General Surgery Interns: An Innovative Approach for Filling the Gap Between Gross Anatomy and the Operating Room

Publication date: Available online 16 April 2018
Source:Journal of Surgical Education
Author(s): Yen-Yi Juo, Christina Hanna, Quach Chi, Grace Chang, Warwick J. Peacock, Areti Tillou, Catherine E. Lewis
ObjectiveTo evaluate an innovative whole cadaver dissection curriculum designed to focus on teaching procedure-relevant anatomy and surgical skills to surgery interns.DesignA mixed methods explanatory sequential design incorporating both quantitative and qualitative evaluations was used to evaluate the cadaver dissection course. Quantitative data were prospectively collected and retrospectively reviewed in order to compare anatomy knowledge and operative skills before and after the course. In the qualitative phase, open-ended telephone interviews were conducted in order to explore the major strengths and weaknesses of the course and gain a more in-depth understanding of resident perceptions and attitudes toward the course.SettingAll UCLA categorical surgery interns who have undergone the cadaver dissection curriculum between the years 2010 to 2016 were recruited for evaluation and interview.ParticipantsFrom 2010 to 2016, 6 to 7 categorical surgery interns were enrolled in the cadaver dissection course each year.ResultsAnatomy practical examination scores increased following implementation of the course from 50.5% to 83.5% (p < 0.01). Faculty ratings of operative skills improved as well (average Likert scale rating for technical skills improved from 4.1 ± 0.4 to 4.4 ± 0.3, p = 0.06). Almost all interviewees (96%) reported that the course improved their knowledge of anatomy, and 78% of respondents believed the course was conducive to improving technical skills.ConclusionsWe believe that cadaver dissection courses offer a superior educational model for teaching clinically relevant anatomy as well as surgical skills. We found improvements in anatomy knowledge and technical skills, and trainees expressed strongly favorable views of the program.



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The Economics of Private Practice versus Academia in Surgery

Publication date: Available online 16 April 2018
Source:Journal of Surgical Education
Author(s): Maria Baimas-George, Brian Fleischer, James R. Korndorffer, Douglas Slakey, Christopher DuCoin
ObjectiveResidents often make career decisions regarding future practice without adequate knowledge to the realities of professional life. Currently there is a paucity of data regarding economic differences between practice models. This study seeks to illuminate the financial differences of surgical subspecialties between academic and private practice.DesignData were collected from the Association of American Medical College (AAMC) and the Medical Group Management Association's (MGMA) 2015 reports of average annual salaries. Salaries were analyzed for general surgery and 7 subspecialties. Fixed time of practice was set at 30 years. Assumptions included 5 years as assistant professor, 10 years as associate professor, and 15 years as full professor. Formula used: (average yearly salary) × [years of practice (30 yrs − fellowship/research yrs)] + ($50,000 × yrs of fellowship/research) = total adjusted lifetime revenue.ResultsAs a full professor, academic surgeons in all subspecialties make significantly less than their private practice counterparts. The largest discrepancy is in vascular and cardiothoracic surgery, with full professors earning 16% and 14% less than private practitioners. Plastic surgery and general surgery are the only 2 disciplines that have similar lifetime revenues to private practitioners, earning 2% and 6% less than their counterparts′ lifetime revenue.ConclusionsAcademic surgeons in all surgical subspecialties examined earn less lifetime revenue compared to those in private practice. This difference in earnings decreases but remains substantial as an academic surgeon advances. With limited exposure to the diversity of professional arenas, residents must be aware of this discrepancy.



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Resident-Specific Morbidity Reduced Following ACS NSQIP Data-Driven Quality Program

Publication date: Available online 16 April 2018
Source:Journal of Surgical Education
Author(s): Florence E. Turrentine, John B. Hanks, Megan C. Tracci, R. Scott Jones, Bruce D. Schirmer, Philip W. Smith
BackgroundThe Accreditation Council for Graduate Medical Education Milestone Project for general surgery provided a more robust method for developing and tracking residents' competence. This framework enhanced systematic and progressive development of residents' competencies in surgical quality improvement.Study DesignA 22-month interactive, educational program based on resident-specific surgical outcomes data culminated in a quality improvement project for postgraduate year 4 surgery residents. Self- assessment, quality knowledge test, and resident-specific American College of Surgeons National Surgical Quality Improvement Program Quality In-Training Initiative morbidity were compared before and after the intervention.ResultsQuality in-training initiative morbidity decreased from 25% (82/325) to 18% (93/517), p = 0.015 despite residents performing more complex cases. All participants achieved level 4 competency (4/4) within the general surgery milestones improvement of care, practice-based learning and improvement competency. Institutional American College of Surgeons National Surgical Quality Improvement Program general surgery morbidity improved from the ninth to the sixth decile. Quality assessment and improvement self-assessment postintervention scores (M = 23.80, SD = 4.97) were not significantly higher than preintervention scores (M = 19.20, SD = 5.26), p = 0.061. Quality Improvement Knowledge Application Tool postintervention test scores (M = 17.4, SD = 4.88), were not significantly higher than pretest scores (M = 13.2, SD = 1.92), p = 0.12.ConclusionSharing validated resident-specific clinical data with participants was associated with improved surgical outcomes. Participating fourth year surgical residents achieved the highest score, a level 4, in the practice based learning and improvement competency of the improvement of care practice domain and observed significantly reduced surgical morbidity for cases in which they participated.



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Treatment choice, satisfaction and quality of life in patients with Graves’ disease

Clinical Endocrinology, EarlyView.


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Effects of the two types of anorexia nervosa (binge eating/purging and restrictive) on bone metabolism in female patients

Clinical Endocrinology, EarlyView.


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Sarcomatoid pilomatrix carcinoma

Journal of Cutaneous Pathology, EarlyView.


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Target-enriched sequencing of chromosome 17q21.31 in sporadic tauopathies reveals no candidate variants

Publication date: June 2018
Source:Neurobiology of Aging, Volume 66
Author(s): Cristina Razquin, Sara Ortega-Cubero, Estefania Rojo-Bustamante, Monica Diez-Fairen, Elena Lorenzo, Elena Alonso, Mario Ezquerra, Owen A. Ross, Maria Carcel, Oswaldo Lorenzo-Betancor, Alexandra I. Soto, Jeremy D. Burgess, Nilüfer Ertekin-Taner, Dennis W. Dickson, Maria A. Pastor, Eduard Tolosa, Pau Pastor
The main genetic risk factors for progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are located at chromosome 17q21.31. The identification of risk H1 subhaplotypes suggests that disease-specific variants can be identified by resequencing the 17q21.31 region (1.4 Mb) in carriers of risk H1 subhaplotypes. We hypothesized that PSP/CBD H1 subhaplotype carriers could have undergone a mutational event absent among unaffected carriers leading to the disease risk. We performed this strategy in definite PSP subjects, definite CBD subjects, and healthy controls and tried to replicate the findings in a larger PSP/CBD case-control series. In the resequencing process, 40 candidate variants were identified, but an association between PSP and rs76970862 was replicated only using an unadjusted model. Gene expression association analysis of this variant suggested no potential functional effect. Although our results failed to identify disease-associated variants, it is still possible that the risk of PSP/CBD at chromosome 17 is driven by rare variants, even in PSP/CBD H1 cases or variants located outside the capture regions.



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Cerebrospinal fluid β-amyloid42 and neurofilament light relate to white matter hyperintensities

Publication date: August 2018
Source:Neurobiology of Aging, Volume 68
Author(s): Katie E. Osborn, Dandan Liu, Lauren R. Samuels, Elizabeth E. Moore, Francis E. Cambronero, Lealani Mae Y. Acosta, Susan P. Bell, Michelle A. Babicz, Elizabeth A. Gordon, Kimberly R. Pechman, L. Taylor Davis, Katherine A. Gifford, Timothy J. Hohman, Kaj Blennow, Henrik Zetterberg, Angela L. Jefferson
White matter hyperintensities (WMHs) are associated with poorer brain health, but their pathophysiological substrates remain elusive. To better understand the mechanistic underpinnings of WMHs among older adults, this study examined in vivo cerebrospinal fluid biomarkers of β-amyloid42 deposition (Aβ42), hyperphosphorylated tau pathology, neurodegeneration (total tau), and axonal injury (neurofilament light [NFL]) in relation to log-transformed WMHs volume. Participants free of clinical stroke and dementia were drawn from the Vanderbilt Memory & Aging Project (n = 148, 72 ± 6 years). Linear regression models adjusted for age, sex, race/ethnicity, education, intracranial volume, modified Framingham Stroke Risk Profile (excluding points assigned for age), cognitive diagnosis, and APOE-ε4 carrier status. Aβ42 (β = −0.001, p = 0.007) and NFL (β = 0.0003, p = 0.01) concentrations related to WMHs but neither hyperphosphorylated tau nor total tau associations with WMHs reached statistical significance (p-values > 0.21). In a combined model, NFL accounted for 3.2% of unique variance in WMHs and Aβ42 accounted for an additional 4.3% beyond NFL, providing novel evidence of the co-occurrence of at least 2 distinct pathways for WMHs among older adults, including amyloid deposition and axonal injury.



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Cover 2: Editorial Advisory Board

Publication date: June 2018
Source:Neurobiology of Aging, Volume 66





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The association of mid-to late-life systemic inflammation with white matter structure in older adults: The Atherosclerosis Risk in Communities Study

Publication date: August 2018
Source:Neurobiology of Aging, Volume 68
Author(s): Keenan A. Walker, B. Gwen Windham, Melinda C. Power, Ron C. Hoogeveen, Aaron R. Folsom, Christie M. Ballantyne, David S. Knopman, Elizabeth Selvin, Clifford R. Jack, Rebecca F. Gottesman
We examined whether the pattern of middle- to late-life systemic inflammation was associated with white matter (WM) structural abnormalities in older adults. A total of 1532 participants (age = 76.5; standard deviations = 5.4) underwent 3T brain magnetic resonance imaging to quantify white matter hyperintensity volume and whole-brain WM microstructural integrity (fractional anisotropy, mean diffusivity). High-sensitivity C-reactive protein (CRP), a marker of systemic inflammation, was measured at 3 visits (21 and 14 years before, and concurrent with, neuroimaging). Participants were categorized into 1 of 6 groups based on their 21-year pattern of low (<3 mg/L) versus elevated (≥3 mg/L) CRP. Compared to the group with low CRP at all 3 visits, the group that transitioned from low to elevated CRP during midlife demonstrated greatest white matter hyperintensity volume and poorest WM microstructural integrity, after adjusting for demographic variables and cardiovascular risk factors. Participants with high CRP at all visits also demonstrated greater WM structural abnormalities, but only after accounting for differential attrition. These results suggest that increasing and persistent inflammation in the decades spanning middle-to late-life may promote WM disease in older adults.



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Preferential consolidation of emotionally salient information during a nap is preserved in middle age

Publication date: August 2018
Source:Neurobiology of Aging, Volume 68
Author(s): Sara E. Alger, Elizabeth A. Kensinger, Jessica D. Payne
Sleep preferentially preserves aspects of memory that are most salient and valuable to remember at the expense of memory for less relevant details. Daytime naps and nocturnal sleep enhance this emotional memory trade-off effect, with memory for emotional components correlated with slow-wave sleep during the day and rapid eye movement sleep overnight. However, these studies have primarily sampled from young adult populations. Sleep and memory are altered by middle age, and the aim of the present study was to examine how age affects sleep-based mechanisms of emotional memory prioritization, using a daytime nap protocol to compare young to middle-aged adults. In both age groups, a nap soon after encoding scenes that contained a negative or neutral object on a neutral background led to superior retention of emotional object memory at the expense of memory for the related backgrounds. Sleep spindle activity during slow-wave sleep was related to memory for this emotionally salient information across the age range.



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Shades of white: diffusion properties of T1- and FLAIR-defined white matter signal abnormalities differ in stages from cognitively normal to dementia

Publication date: August 2018
Source:Neurobiology of Aging, Volume 68
Author(s): Joost M. Riphagen, Ed HBM. Gronenschild, David H. Salat, Whitney M. Freeze, Dimo Ivanov, Lies Clerx, Frans R.J. Verhey, Pauline Aalten, Heidi I.L. Jacobs
The underlying pathology of white matter signal abnormalities (WMSAs) is heterogeneous and may vary dependent on the magnetic resonance imaging contrast used to define them. We investigated differences in white matter diffusivity as an indicator for white matter integrity underlying WMSA based on T1-weighted and fluid-attenuated inversion recovery (FLAIR) imaging contrast. In addition, we investigated which white matter region of interest (ROI) could predict clinical diagnosis best using diffusion metrics. One hundred three older individuals with varying cognitive impairment levels were included and underwent neuroimaging. Diffusion metrics were extracted from WMSA areas based on T1 and FLAIR contrast and from their overlapping areas, the border surrounding the WMSA and the normal-appearing white matter (NAWM). Regional diffusivity differences were calculated with linear mixed effects models. Multinomial logistic regression determined which ROI diffusion values classified individuals best into clinically defined diagnostic groups. T1-based WMSA showed lower white matter integrity compared to FLAIR WMSA-defined regions. Diffusion values of NAWM predicted diagnostic group best compared to other ROI's. To conclude, T1- or FLAIR-defined WMSA provides distinct information on the underlying white matter integrity associated with cognitive decline. Importantly, not the "diseased" but the NAWM is a potentially sensitive indicator for cognitive brain health status.



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The effect of rare variants in TREM2 and PLD3 on longitudinal cognitive function in the Wisconsin Registry for Alzheimer's Prevention

Publication date: June 2018
Source:Neurobiology of Aging, Volume 66
Author(s): Corinne D. Engelman, Burcu F. Darst, Murat Bilgel, Eva Vasiljevic, Rebecca L. Koscik, Bruno M. Jedynak, Sterling C. Johnson
Recent studies have found an association between functional variants in TREM2 and PLD3 and Alzheimer's disease (AD), but their effect on cognitive function is unknown. We examined the effect of these variants on cognitive function in 1449 participants from the Wisconsin Registry for Alzheimer's Prevention, a longitudinal study of initially asymptomatic adults, aged 36–73 years at baseline, enriched for a parental history of AD. A comprehensive cognitive test battery was performed at up to 5 visits. A factor analysis resulted in 6 cognitive factors that were standardized into z scores (∼N [0, 1]); the mean of these z scores was also calculated. In linear mixed models adjusted for age, gender, practice effects, and self-reported race/ethnicity, PLD3 V232M carriers had significantly lower mean z scores (p = 0.02) and lower z scores for story recall (p = 0.04), visual learning and memory (p = 0.049), and speed and flexibility (p = 0.02) than noncarriers. TREM2 R47H carriers had marginally lower z scores for speed and flexibility (p = 0.06). In conclusion, a functional variant in PLD3 was associated with significantly lower cognitive function in individuals carrying the variant than in noncarriers.



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Individual Differences in Working Memory Capacity and Filtering.

Author: Robison, Matthew K.; Miller, Ashley L.; Unsworth, Nash

DOI: 10.1037/xhp0000513

Publication Date: POST AUTHOR CORRECTIONS, 23 April 2018

https://ift.tt/2HRyId7

Redundancy Gain in the Simon Task: Does Increasing Relevant Activation Reduce the Effect of Irrelevant Activation?.

Author: Mittelstadt, Victor; Miller, Jeff

DOI: 10.1037/xhp0000523

Publication Date: POST AUTHOR CORRECTIONS, 23 April 2018

https://ift.tt/2FhetQV

A facile synthesis and assembly of ultrasmall Pt nanoparticles on reduced graphene oxide‑carbon black hybrid for enhanced performance in PEMFC

Publication date: 5 August 2018
Source:Materials & Design, Volume 151
Author(s): Melike Sevim Yılmaz, Begüm Yarar Kaplan, Önder Metin, Selmiye Alkan Gürsel
A new and straightforward approach for the synthesis of ultrasmall and monodisperse Pt nanoparticles (NPs) and their controlled assembly on graphene based supports including reduced graphene oxide (rGO), commercial carbon black (VC) and rGO-VC hybrid were reported. These supported NPs were utilized as the electrocatalysts for polymer electrolyte membrane fuel cells (PEMFC). Surfactant-assisted reduction of platinum(II) acetylacetonate in hot organic solution yielded 1.2 nm Pt NPs. These ultrasmall Pt NPs were decorated on rGO, VC and the rGO-VC hybrid by using a simple liquid-phase self-assembly method. In the previous studies on Pt/rGO-VC hybrids, on one hand, Pt NPs were synthesized in situ on support, on the other hand, VC was added to synthesized Pt/rGO, and their fuel cell performance have been rarely shown. In our study, rGO and VC were directly mixed and prepared Pt NPs were assembled on rGO-VC hybrid support. Pt/rGO-VC hybrid electrocatalyst possessed substantially better electrocatalytic activity owing to better utilization of Pt compared to Pt/rGO and Pt/VC. Membrane electrode assemblies based on resultant catalysts were characterized in-situ in PEMFC. A superior PEMFC performance of 857 mW cm⁻² (maximum power density) was achieved with the hybrid catalyst as compared to Pt NPs supported on rGO or VC.

Graphical abstract

https://ift.tt/2HvLkmQ

Bipolar resistive switching and memristive properties of hydrothermally synthesized TiO2 nanorod array: Effect of growth temperature

Publication date: 5 August 2018
Source:Materials & Design, Volume 151
Author(s): A.C. Khot, N.D. Desai, K.V. Khot, M.M. Salunkhe, M.A. Chougule, T.M. Bhave, R.K. Kamat, K.P. Musselman, T.D. Dongale
In the present work, the hydrothermal approach is employed to develop 1D-TiO2 nanorod array memristive devices and the effect of hydrothermal growth temperature on TiO2 memristive devices is studied. X-ray diffraction (XRD) analysis suggested that the rutile phase is dominant in the developed TiO2 nanorod array. Field emission scanning electron microscopy (FESEM) images show well adherent and pinhole free one dimensional (1D) TiO2 nanorods. The presence of titanium and oxygen in all the samples was confirmed by energy dispersive X-ray spectroscopy (EDS). Furthermore, growth of the 1D TiO2 nanorods depends on the growth temperature and uniform growth is observed at the higher growth temperatures. The well-known memristive hysteresis loop is observed in the TiO2 nanorod thin films. Furthermore, resistive switching voltages, the shape of I-V loops and (non)rectifying behavior changed as the growth temperature varied from 140 °C to 170 °C. The biological synapse properties such as paired-pulse facilitation and short-term depression are observed in some devices. The detailed electrical characterizations suggested that the developed devices show doubled valued charge-magnetic flux characteristic and charge transportation is due to the Ohmic and space charge limited current.

Graphical abstract

https://ift.tt/2r0bNTv

Uranyl fluorescence lifetime in nanoporous silica gel: The influence of pore size, pH, and water

Publication date: 5 August 2018
Source:Materials & Design, Volume 151
Author(s): Brandon M. Dodd, Gary C. Tepper
The fluorescence lifetime of uranyl adsorbed within nanoporous silica gel was measured as a function of pore size at two different pH values and both wet and dry. It was determined that for uranyl adsorbed within pores larger than 4 nm, the lifetime is relatively independent of pore size, whereas below 4 nm, the lifetime increases with decreasing pore size. A blue shift in the emission spectra was observed at the smallest pore size (2.2 nm) and is believed to be caused by quantum confinement. The lifetime was found to be longer at a neutral pH than in an acidic pH, and this is caused by the formation of a uranyl hydroxyl complex at higher pH values. The presence of water within the pores is found to increase the fluorescence lifetime at all pore sizes and pH values studied in this paper; this is caused by the formation of a uranyl silicate bond in the absence of water. An understanding of the parameters that influence the fluorescence lifetime of uranyl within silica gel is important for the development of more sensitive detection methods.

Graphical abstract

https://ift.tt/2JqJLqO

In-situ growth of highly monodisperse ITO nanoparticles regulated by mesoporous silica glasses

Publication date: 5 August 2018
Source:Materials & Design, Volume 151
Author(s): Ping Chen, Zhangru Chen, Shaodong Hou, Xiang Shen, Yingbo Chu, Yu Yang, Luyun Yang, Jinyan Li, Nengli Dai
In this work, we firstly introduce a facile method to synthesize bulk silica glass contained indium tin oxide nanoparticles (ITO NPs). Water solution with InCl3 and SnCl4 was mixed and dipped into the mesoporous silica glass (MSG) followed by an in-situ growth of ITO NPs under 1000 °C heat treatment. X-ray diffraction (XRD) and transmission electron microscopy (TEM) show that the ITO NPs are highly monodisperse and crystalline in the silica glass with size around 20–30 nm. The size and distribution of ITO NPs can be regulated by the mesopores of mesoporous silica glass (MSG) effectively. The absorption and photoluminescence (PL) spectra exhibit an optical band gap and a PL emission of the ITO NPs doped silica glass at 3.12 eV and 560 nm, respectively. Results indicate that this kind of composite material has potential applications for optical nonlinearity, plasmonic formation, and sensing in the future.

Graphical abstract

https://ift.tt/2HMNJNk

Editorial Board

Publication date: 5 July 2018
Source:Materials & Design, Volume 149





https://ift.tt/2JqJzYC

Optimal microstructural design for high thermal stability of pure FCC metals based on studying effect of twin boundaries character and network of grain boundaries

Publication date: 5 August 2018
Source:Materials & Design, Volume 151
Author(s): Hossein Alimadadi, Alice Bastos Fanta, Ryutaro Akiyoshi, Takeshi Kasama, Anthony D. Rollett, Marcel A.J. Somers, Karen Pantleon

Graphical abstract

https://ift.tt/2HOE494

Vapor-defect-solid growth mechanism for NanoNets utilizing natural defect networks in polycrystals

Publication date: 15 July 2018
Source:Materials & Design, Volume 150
Author(s): Zumin Wang, Eric J. Mittemeijer
Nanowires are major building components for nanotechnology. The growth and the assembly of nanowires are often complicated and expensive, which has impeded practical applications of such nanotechnology. This work discloses a Vapor-Defect-Solid (VDS) mechanism for growth of nanowall networks (NanoNets), by exploring a spontaneous interaction of vapor and defect networks in polycrystalline materials. A kinetic model analysis of the precondition and the characteristics of the VDS growth process is presented. The VDS growth mechanism allows straightforward, fast growth of two-dimensional NanoNets at near room temperature from vapor sources with a very high production yield, and thus holds potential as a general route for large-area production of NanoNets at a reduced cost. The VDS growth mechanism further allows exploration of fundamental knowledge of grain-boundary networks in nanocrystalline materials, and opens new avenues for grain-boundary engineering.

Graphical abstract

https://ift.tt/2Jt3MNE

Heterogeneous nanostructure array for electrochemical energy conversion and storage

Publication date: Available online 25 April 2018
Source:Nano Today
Author(s): Min Zhou, Yang Xu, Yong Lei
Rapid development of modern society raises more and more requirements for highly efficient energy conversion and storage. Electrochemical devices stand out as a most viable option for eventual substitute for fossil fuels, but suffer from problems like durability, operability, etc. Heterogeneous nanostructure arrays with distinguished superiorities have thus attracted intensive attention and yielded favorable electrochemical performance. In pursuit of deep understandings of their working modes, this review will focus on the interconnection among different constituents within each individual unit to correlate microscopic electrochemical processes with macroscopic performance. Here, the motivation of employing heterogeneous nanostructure arrays is first summarized. Then, the design principles, including three working modes, 'Function-Function', 'Function-Assistance', 'Single-unit device', are analyzed comprehensively to illuminate the interconnection among different constituents in electrochemical energy conversion and storage processes. Solar water splitting (energy conversion), alkali-ion battery and supercapacitors (energy storage) are termed collectively as typical electrochemical energy technologies to illustrate the superiorities of heterogeneous nanostructure arrays. Finally, perspectives of related fields will be concluded to broaden the future of heterogeneous nanostructure arrays.

Graphical abstract

https://ift.tt/2HsCwOE

Inventory of methane emissions from livestock in China from 1980 to 2013

Publication date: July 2018
Source:Atmospheric Environment, Volume 184
Author(s): Jiashuo Yu, Shushi Peng, Jinfeng Chang, Philippe Ciais, Patrice Dumas, Xin Lin, Shilong Piao
Livestock is the largest anthropogenic methane (CH4) source at the global scale. Previous inventories of this source for China were based on the accounting of livestock populations and constant emission factors (EFs) per head. Here, we re-evaluate how livestock CH4 emissions have changed from China over the last three decades, considering increasing population, body weight and milk production per head which cause EF to change with time, and decreasing average life span (ALS) of livestock. Our results show that annual CH4 emissions by livestock have increased from 4.5 to 11.8 Tg CH4 yr⁻¹ over the period 1980–2013. The increasing trend in emissions (0.25 Tg CH4 yr⁻²) over this period is ∼12% larger than that if using constant EFs and ALS. The increasing livestock population, production per head and decreasing ALS contributed +91%, +28% and −19% to the increase in CH4 emissions from livestock, respectively. This implies that the temporal changes in EF and ALS of livestock cannot be overlooked in inventories, especially in countries like China where livestock production systems are experiencing rapid transformations.



https://ift.tt/2r28UAH

Homologous series of n-alkanes (C19-C35), fatty acids (C12-C32) and n-alcohols (C8-C30) in atmospheric aerosols from central Alaska: Molecular distributions, seasonality and source indices

Publication date: July 2018
Source:Atmospheric Environment, Volume 184
Author(s): Suresh K.R. Boreddy, Md. Mozammel Haque, Kimitaka Kawamura, Pingqing Fu, Yongwon Kim
To better understand the molecular distributions, seasonality and source indices of organic aerosols in central Alaska, we measured homologous series of n-alkanes (C19-C35), fatty acids (C12-C32) and n-alcohols (C8-C30) in total suspended aerosols collected during June 2008 to 2009 using a gas chromatography/mass spectrometry (GC-MS). The whole sampling period was divided as warm (early May to late September; summer) and cold (late September to early May; winter) periods. Molecular distribution was characterized in both periods by the predominance of C25 for n-alkanes and C24:0 for fatty acids. However, we noticed a difference in molecular distribution of n-alcohols between warm and cold periods, which was characterized by the predominance of C22 in warm season while C26 in cold period. Except for fatty acids, n-alkanes and n-alcohols showed higher concentrations in warm period than in cold period. We found significantly higher ratios of C18:1/C18:0 in warm period than those in cold period, suggesting the fresh biogenic and aged anthropogenic aerosols in warm and cold periods, respectively. This inference was consistent with significantly higher ratios of WSOC/OC, a proxy for photochemical aging, in cold period. Based on the carbon preference index (CPI), average chain length (ACL), low-to-high molecular weight (LMW/HMW) ratios, wax n-alkanes (%WNA) and estimated fossil fuel concentrations, we demonstrate that higher plant waxes, biomass burning from wildfires are two important sources in warm period while combustion derived anthropogenic emissions are major sources in cold period in central Alaska. This finding was further supported by higher ratios of nss-K⁺/elemental carbon (EC) and methanesulfonate (MSA⁻)/EC ratios in warm period.



https://ift.tt/2HtkYWM

A cool-temperate young larch plantation as a net methane source - A 4-year continuous hyperbolic relaxed eddy accumulation and chamber measurements

Publication date: July 2018
Source:Atmospheric Environment, Volume 184
Author(s): Masahito Ueyama, Kota Yoshikawa, Kentaro Takagi
Upland forests are thought to be methane (CH4) sinks due to oxidation by methanotrophs in aerobic soils. However, CH4 budget for upland forests are not well quantified at the ecosystem scale, when possible CH4 sources, such as small wet areas, exists in the ecosystem. Here, we quantified CH4 fluxes in a cool-temperate larch plantation based on four-year continuous measurements using the hyperbolic relaxed eddy accumulation (HREA) method and dynamic closed chambers with a laser-based analyzer. After filling data gaps for half-hourly data using machine-learning-based regressions, we found that the forest acted as a net CH4 source at the canopy scale: 30 ± 11 mg CH4 m⁻² yr⁻¹ in 2014, 56 ± 8 mg CH4 m⁻² yr⁻¹ in 2015, 154 ± 5 mg CH4 m⁻² yr⁻¹ in 2016, and 132 ± 6 mg CH4 m⁻² yr⁻¹ in 2017. Hotspot emissions from the edge of the pond could strongly contribute to the canopy-scale emissions. The magnitude of the hotspot emissions was 10–100 times greater than the order of the canopy-scale and chamber-based CH4 fluxes at the dry soils. The high temperatures with wet conditions stimulated the hotspot emissions, and thus induced canopy-scale CH4 emissions in the summer. Understanding and modeling the dynamics of hotspot emissions are important for quantifying CH4 budgets of upland forests. Micrometeorological measurements at various forests are required for revisiting CH4 budget of upland forests.



https://ift.tt/2r1nQyL

Real world vehicle fleet emission factors: Seasonal and diurnal variations in traffic related air pollutants

Publication date: July 2018
Source:Atmospheric Environment, Volume 184
Author(s): Jonathan M. Wang, Cheol-Heon Jeong, Naomi Zimmerman, Robert M. Healy, Greg J. Evans
Temporal variations of vehicle emissions are affected by various compounding factors in the real world. The focus of this study is to determine the effects of ambient conditions and post-tailpipe changes on traffic emissions measured in the near-road region. Emission factors allowed for the isolation of the traffic signal and accounted for effects of local meteorology and dilution. Five month-long measurement campaigns were conducted at an urban near-road site that exhibited a broad range of ambient conditions with temperatures ranging between −18 and +30 °C. Particle number emission factors were 2.0× higher in the winter relative to the summer, which was attributed to changes in particles post-tailpipe. Conversely, toluene emissions were 2.5× higher in the summer relative to the winter, attributed to changes in fuel composition. Diurnal trends of emission factors showed substantial increases in emissions during the morning rush hour for black carbon (1.9×), particle number (2.4×), and particle-bound polycyclic aromatic hydrocarbons (3.0×), affected by fleet make-up. In contrast, particle number emission factors were highest midday with mean values 3.7× higher than at night. This midday increase was attributed to particle formation or growth from local traffic emissions and showed different wind direction dependence than regional events.



https://ift.tt/2HrjBrE

Small-scale variations in ozone concentration in low mountains

Publication date: July 2018
Source:Atmospheric Environment, Volume 184
Author(s): Isao Kanda, Shinji Wakamatsu
In a relatively low mountain area adjacent to Matsuyama city in Japan, ozone concentration variations were studied at spatial scales of O(10)∼O(103) m. Walking mobile measurements were complemented by vertical profiling, wind measurements, and passive sampling. The broad-scale distribution at O(102)∼O(103) m was found to depend on time of day, atmospheric stability, and geography in ways consistent with previous studies. Well-defined areas of low ozone concentrations O(10) m in width were found at several locations. No distinctive features of these locations were immediately discernible, but detailed examination of the temporal variations coupled with the wind field suggested that the distribution of the low-ozone areas was determined by subtle differences in the terrain topography.



https://ift.tt/2r28MBd

Composite Faces are not (Necessarily) Processed Coactively: A Test Using Systems Factorial Technology and Logical-Rule Models.

Author: Cheng, Xue Jun; McCarthy, Callum J.; Wang, Tony S. L.; Palmeri, Thomas J.; Little, Daniel R.

DOI: 10.1037/xlm0000479

Publication Date: POST AUTHOR CORRECTIONS, 23 April 2018

https://ift.tt/2r12sdg

Associations or Repetitions? Testing the Basis of the Perruchet Effect in Voluntary Response Speed.

Author: Lee Cheong Lem, V. Annabelle; Moul, Caroline; Harris, Justin A.; Livesey, Evan J.

DOI: 10.1037/xlm0000556

Publication Date: POST AUTHOR CORRECTIONS, 23 April 2018

https://ift.tt/2HvDc9V

Ambiguity Effects of Rhyme and Meter.

Author: Wallot, Sebastian; Menninghaus, Winfried

DOI: 10.1037/xlm0000557

Publication Date: POST AUTHOR CORRECTIONS, 23 April 2018

https://ift.tt/2r12nX0

A Further Examination of Word Frequency and Age-of-Acquisition Effects in English Lexical Decision Task Performance: The Role of Frequency Trajectory.

Author: Juhasz, Barbara J.; Yap, Melvin J.; Raoul, Akila; Kaye, Micaela

DOI: 10.1037/xlm0000564

Publication Date: POST AUTHOR CORRECTIONS, 23 April 2018

https://ift.tt/2r5KmqD

The Motor Locus of No-Go Backward Crosstalk.

Author: Durst, Moritz; Janczyk, Markus

DOI: 10.1037/xlm0000565

Publication Date: POST AUTHOR CORRECTIONS, 23 April 2018

https://ift.tt/2HsTmAO

The Resilience of Verbal Sequence Learning: Evidence From the Hebb Repetition Effect.

Author: St-Louis, Marie-Eve; Hughes, Robert W.; Saint-Aubin, Jean; Tremblay, Sebastien

DOI: 10.1037/xlm0000566

Publication Date: POST AUTHOR CORRECTIONS, 23 April 2018

https://ift.tt/2r5Kgzh

Traffic-emitted metal status and uptake by Carex meyeriana Kunth and Thelypteris palustris var . pubescens Fernald growing in roadside turfy swamp in the Changbai Mountain area, China

Abstract

Six traffic-emitted metals (Cr, Zn, Cu, Cd, Pb, and Ni) were determined in soil and plants for below- and aboveground parts along different distances from highway to evaluate their behavior and uptake by Carex meyeriana Kunth and Thelypteris palustris var. pubescens Fernald growing in turfy swamps. The results indicated that the different plant tissues showed significantly different levels of metal content. Nonlinear regression analysis indicated that metal contents leveled off at constant values before they decreased as the distance from the roadside increased. The high R² values of the regression model indicated good fit of the exponential function applied to depict the distribution pattern of the metal elements. It was deduced that Cr, Cu, and Cd in Thelypteris palustris var. pubescens Fernald were mainly derived from the soil; Carex meyeriana Kunth and Thelypteris palustris var. pubescens Fernald absorbed Pb mainly through the stomata from atmospheric depositions; Cr, Cu, and Cd in Carex meyeriana Kunth and Zn in Thelypteris palustris var. pubescens Fernald were mainly affected by soil and atmospheric depositions. After excluding the effects of traffic, only the bioaccumulation factor of Cd (1.34) in Carex meyeriana Kunth and the translocation factor of Zn (1.13) in Thelypteris palustris var. pubescens Fernald were greater than 1, suggesting that Carex meyeriana Kunth could be a good candidate for assimilating Cd from soils and Thelypteris palustris var. pubescens Fernald could be suitable for the phytoextraction of Zn.

https://ift.tt/2Ke65oY

What's what in auditory cortices?

Publication date: 1 August 2018
Source:NeuroImage, Volume 176
Author(s): Chrysa Retsa, Pawel J. Matusz, Jan W.H. Schnupp, Micah M. Murray
Distinct anatomical and functional pathways are postulated for analysing a sound's object-related ('what') and space-related ('where') information. It remains unresolved to which extent distinct or overlapping neural resources subserve specific object-related dimensions (i.e. who is speaking and what is being said can both be derived from the same acoustic input). To address this issue, we recorded high-density auditory evoked potentials (AEPs) while participants selectively attended and discriminated sounds according to their pitch, speaker identity, uttered syllable ('what' dimensions) or their location ('where'). Sound acoustics were held constant across blocks; the only manipulation involved the sound dimension that participants had to attend to. The task-relevant dimension was varied across blocks. AEPs from healthy participants were analysed within an electrical neuroimaging framework to differentiate modulations in response strength from modulations in response topography; the latter of which forcibly follow from changes in the configuration of underlying sources. There were no behavioural differences in discrimination of sounds across the 4 feature dimensions. As early as 90ms post-stimulus onset, AEP topographies differed across 'what' conditions, supporting a functional sub-segregation within the auditory 'what' pathway. This study characterises the spatio-temporal dynamics of segregated, yet parallel, processing of multiple sound object-related feature dimensions when selective attention is directed to them.



https://ift.tt/2vJJPAc

Age-dependent effects of brain stimulation on network centrality

Publication date: 1 August 2018
Source:NeuroImage, Volume 176
Author(s): Daria Antonenko, Till Nierhaus, Marcus Meinzer, Kristin Prehn, Axel Thielscher, Bernd Ittermann, Agnes Flöel
Functional magnetic resonance imaging (fMRI) studies have suggested that advanced age may mediate the effects of transcranial direct current stimulation (tDCS) on brain function. However, studies directly comparing neural tDCS effects between young and older adults are scarce and limited to task-related imaging paradigms. Resting-state (rs-) fMRI, that is independent of age-related differences in performance, is well suited to investigate age-associated differential neural tDCS effects. Three "online" tDCS conditions (anodal, cathodal, sham) were compared in a cross-over, within-subject design, in 30 young and 30 older adults. Active stimulation targeted the left sensorimotor network (active electrode over left sensorimotor cortex with right supraorbital reference electrode). A graph-based rs-fMRI data analysis approach (eigenvector centrality mapping) and complementary seed-based analyses characterized neural tDCS effects. An interaction between anodal tDCS and age group was observed. Specifically, centrality in bilateral paracentral and posterior regions (precuneus, superior parietal cortex) was increased in young, but decreased in older adults. Seed-based analyses revealed that these opposing patterns of tDCS-induced centrality modulation originated from differential effects of tDCS on functional coupling of the stimulated left paracentral lobule. Cathodal tDCS did not show significant effects. Our study provides first evidence for differential tDCS effects on neural network organization in young and older adults. Anodal stimulation mainly affected coupling of sensorimotor with ventromedial prefrontal areas in young and decoupling with posteromedial areas in older adults.



https://ift.tt/2HQ7Ud9

Warnings and caveats in brain controllability

Publication date: 1 August 2018
Source:NeuroImage, Volume 176
Author(s): Chengyi Tu, Rodrigo P. Rocha, Maurizio Corbetta, Sandro Zampieri, Marco Zorzi, S. Suweis
A recent article by Gu et al. (Nat. Commun. 6, 2015) proposed to characterize brain networks, quantified using anatomical diffusion imaging, in terms of their "controllability", drawing on concepts and methods of control theory. They reported that brain activity is controllable from a single node, and that the topology of brain networks provides an explanation for the types of control roles that different regions play in the brain. In this work, we first briefly review the framework of control theory applied to complex networks. We then show contrasting results on brain controllability through the analysis of five different datasets and numerical simulations. We find that brain networks are not controllable (in a statistical significant way) by one single region. Additionally, we show that random null models, with no biological resemblance to brain network architecture, produce the same type of relationship observed by Gu et al. between the average/modal controllability and weighted degree. Finally, we find that resting state networks defined with fMRI cannot be attributed specific control roles. In summary, our study highlights some warning and caveats in the brain controllability framework.



https://ift.tt/2vMpcmL

Network specialization during adolescence: Hippocampal effective connectivity in boys and girls

Publication date: 15 July 2018
Source:NeuroImage, Volume 175
Author(s): Jeffrey D. Riley, E. Elinor Chen, Jessica Winsell, Elysia Poggi Davis, Laura M. Glynn, Tallie Z. Baram, Curt A. Sandman, Steven L. Small, Ana Solodkin
Adolescence is a complex period of concurrent mental and physical development that facilitates adult functioning at multiple levels. Despite the growing number of neuroimaging studies of cognitive development in adolescence focusing on regional activation patterns, there remains a paucity of information about the functional interactions across these participating regions that are critical for cognitive functioning, including memory. The current study used structural equation modeling (SEM) to determine how interactions among brain regions critical for memory change over the course of adolescence. We obtained functional MRI in 77 individuals aged 8–16 years old, divided into younger (ages 8–10) and older (ages > 11) cohorts, using an incidental encoding memory task to activate hippocampus formation and associated brain networks, as well as behavioral data on memory function. SEM was performed on the imaging data for four groups (younger girls, younger boys, older girls, and older boys) that were subsequently compared using a stacked model approach. Significant differences were seen between the models for these groups. Younger boys had a predominantly posterior distribution of connections originating in primary visual regions and terminating on multi-modal processing regions. In older boys, there was a relatively greater anterior connection distribution, with increased effective connectivity within association and multi-modal processing regions. Connection patterns in younger girls were similar to those of older boys, with a generally anterior-posterior distributed network among sensory, multi-modal, and limbic regions. In contrast, connections in older girls were widely distributed but relatively weaker. Memory performance increased with age, without a significant difference between the sexes. These findings suggest a progressive reorganization among brain regions, with a commensurate increase in efficiency of cognitive functioning, from younger to older individuals in both girls and boys, providing insight into the age- and gender-specific processes at play during this critical transition period.



https://ift.tt/2HO2RtN

The left inferior frontal gyrus: A neural crossroads between abstract and concrete knowledge

Publication date: 15 July 2018
Source:NeuroImage, Volume 175
Author(s): Pasquale Anthony Della Rosa, Eleonora Catricalà, Matteo Canini, Gabriella Vigliocco, Stefano F. Cappa
Evidence from both neuropsychology and neuroimaging suggests that different types of information are necessary for representing and processing concrete and abstract word meanings. Both abstract and concrete concepts, however, conjointly rely on perceptual, verbal and contextual knowledge, with abstract concepts characterized by low values of imageability (IMG) (low sensory-motor grounding) and low context availability (CA) (more difficult to contextualize). Imaging studies supporting differences between abstract and concrete concepts show a greater recruitment of the left inferior frontal gyrus (LIFG) for abstract concepts, which has been attributed either to the representation of abstract-specific semantic knowledge or to the request for more executive control than in the case of concrete concepts. We conducted an fMRI study on 27 participants, using a lexical decision task involving both abstract and concrete words, whose IMG and CA values were explicitly modelled in separate parametric analyses. The LIFG was significantly more activated for abstract than for concrete words, and a conjunction analysis showed a common activation for words with low IMG or low CA only in the LIFG, in the same area reported for abstract words. A regional template map of brain activations was then traced for words with low IMG or low CA, and BOLD regional time-series were extracted and correlated with the specific LIFG neural activity elicited for abstract words. The regions associated to low IMG, which were functionally correlated with LIFG, were mainly in the left hemisphere, while those associated with low CA were in the right hemisphere. Finally, in order to reveal which LIFG-related network increased its connectivity with decreases of IMG or CA, we conducted generalized psychophysiological interaction analyses. The connectivity strength values extracted from each region connected with the LIFG were correlated with specific LIFG neural activity for abstract words, and a regression analysis was conducted to highlight which areas recruited by low IMG or low CA predicted the greater activation of the IFG for abstract concepts. Only the left middle temporal gyrus/angular gyrus, known to be involved in semantic processing, was a significant predictor of LIFG activity differentiating abstract from concrete words.The results show that the abstract conceptual processing requires the interplay of multiple brain regions, necessary for both the intrinsic and extrinsic properties of abstract knowledge. The LIFG can be thus identified as the neural crossroads between different types of information equally necessary for representing processing and differentiating abstract concepts from concrete ones.



https://ift.tt/2vVWVuj

Hydrogel chitosan sorbent application for nutrient removal from soilless plant cultivation wastewater

Abstract

In this study, we determined the effectiveness of removal of nutrients (nitrates and orthophosphates) from greenhouse wastewaters (GW) using non-cross-linked chitosan (CHs) and chitosan cross-linked with epichlorohydrin (CHs-ECH) in the form of hydrogel beads. GW used in the study had the following parameters: N-NO₃ 621.1 mg/L, P-PO₄ 60.8 mg/L, SO₄²⁻ 605.0 mg/L, Cl⁻ 0.9 mg/L, Ca²⁺ 545.0 mg/L, Mg²⁺ 178.0 mg/L, K⁺ 482.0 mg/L, hardness 113° dH, and pH 6.2. The scope of the study included determination of the effect of pH on wastewater composition and effectiveness of nutrient sorption, analyses of nutrient sorption kinetics, and analyses of the effect of sorbent dose on percentage removal of nutrients from GW. CHs-ECH was able to sorb 79.4% of P-PO₄ and 76.7% of N-NO₃ from GW, whereas CHs to remove 92.8% of P-PO₄ and 53.2% of N-NO₃.

https://ift.tt/2I3nNLe

Assessment of pectin-coated magnetite nanoparticles in low-energy water desalination applications

Abstract

Novel magnetite nanoparticles (NPs) modified with pectin coating were fabricated, characterized, and evaluated as potential draw solute in a forward osmosis (FO) process for water desalination applications. The prepared NPs had a spherical shape with an average diameter of 200 nm and saturation magnetization of 23.13 emu/g. Thermogravimetric analysis (TGA) and FTIR spectra elucidated the successful pectin coating on magnetite surface. The potential use of the fabricated NPs in water desalination was conducted via a newly developed lab-scale FO system. Deionized water, saline water (0.2, 0.5, and 1 g% NaCl solution), and real well water (TDS = 0.9 g%) were used as feed solutions. In all experiments, the water flux gradually decreased along with the extension of experimental time and NaCl rejection rate by the FO membrane was measured to be higher than 95%. Moreover, it was found that the pectin-coated magnetite NPs demonstrated to be able to draw clean water across the FO membrane from well water with a remarkable salt rejection of 97%. Thus, it is believed that the proposed FO system using pectin-coated magnetite NPs as draw solute can be a promising technique for desalination of well waters in an environmental-friendly and energy-saving manner.

https://ift.tt/2FfaT9H

A facile method to prepare translucent anatase thin films in monolithic structures for gas stream purification

Abstract

In the present work, a facile method to prepare translucent anatase thin films on cellulose acetate monolithic (CAM) structures was developed. A simple sol–gel method was applied to synthesize photoactive TiO₂ anatase nanoparticles using tetra-n-butyl titanium as precursor. The immobilization of the photocatalyst on CAM structures was performed by a simple dip-coating method. The translucent anatase thin films allow the UV light penetration through the CAM internal walls. The photocatalytic activity was tested on the degradation of n-decane (model volatile organic compound—VOC) in gas phase, using a tubular lab-scale (irradiated by simulated solar light) and pilot-scale (irradiated by natural solar light or UVA light) reactors packed with TiO₂-CAM structures, both equipped with compound parabolic collectors (CPCs). The efficiency of the photocatalytic oxidation (PCO) process in the degradation of n-decane molecules was studied at different operating conditions at lab-scale, such as catalytic bed size (40–160 cm), TiO₂ film thickness (0.435–0.869 μm), feed flow rate (75–300 cm³ min⁻¹), n-decane feed concentration (44–194 ppm), humidity (3 and 40%), oxygen concentration (0 and 21%), and incident UV irradiance (18.9, 29.1, and 38.4 W_UV m⁻²). The decontamination of a bioaerosol stream was also evaluated by the PCO process, using Pseudomonas aeruginosa (Gram-negative) and Staphylococcus aureus (Gram-positive) as model bacteria. A pilot-scale unit was operated day and night, using natural sunlight and artificial UV light, to show its performance in the mineralization of n-decane air streams under real outdoor conditions.

Graphical abstract

Normally graphics abstract are not presented with captions/legend. The diagram is a collection of images that resume the work

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Chronic Nerve Compression Accelerates the Progression of Diabetic Peripheral Neuropathy in a Rat Model: A Study of Gene Expression Profiling

J reconstr Microsurg
DOI: 10.1055/s-0038-1642023

Objective This article investigates the role of chronic nerve compression in the progression of diabetic peripheral neuropathy (DPN) by gene expression profiling. Methods Chronic nerve compression was created in streptozotocin (STZ)-induced diabetic rats by wrapping a silicone tube around the sciatic nerve (SCN). Neurological deficits were evaluated using pain threshold test, motor nerve conduction velocity (MNCV), and histopathologic examination. Differentially expressed genes (DGEs) and metabolic processes associated with chronic nerve compression were analyzed. Results Significant changes in withdrawal threshold and MNCV were observed in diabetic rats 6 weeks after diabetes induction, and in DPN rats 4 weeks after diabetes induction. Histopathologic examination of the SCN in DPN rats presented typical changes of myelin degeneration in DPN. Function analyses of DEGs demonstrated that biological processes related to inflammatory response, extracellular matrix component, and synaptic transmission were upregulated after diabetes induction, and chronic nerve compression further enhanced those changes. While processes related to lipid and glucose metabolism, response to insulin, and apoptosis regulation were inhibited after diabetes induction, chronic nerve compression further enhanced these inhibitions. Conclusion Our study suggests that additional silicone tube wrapping on the SCN of rat with diabetes closely mimics the course and pathologic findings of human DPN. Further studies are needed to verify the effectiveness of this rat model of DPN and elucidate the roles of the individual genes in the progression of DPN.
[...]

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Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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The role of circulating tumour cells and nucleic acids in blood for the detection of bladder cancer: A systematic review

Publication date: May 2018
Source:Cancer Treatment Reviews, Volume 66
Author(s): Pramit Khetrapal, Matthew Wei Liang Lee, Wei Shen Tan, Liqin Dong, Patricia de Winter, Andrew Feber, John D. Kelly
BackgroundBlood-based biomarkers are a neglected resource in bladder cancer, where the mainstay of focus has been on urinary biomarkers. However, blood-based biomarkers are gaining popularity in other solid cancers, particularly circulating tumour cells (CTCs) and circulating nucleic acids. In this systematic review, we identify and discuss the diagnostic value of CTC, cell-free DNA and RNA based biomarkers in bladder cancer.MethodsA MEDLINE/Pubmed systematic search was performed using the following keywords: (bladder cancer) AND (blood OR plasma OR serum) AND biomarker AND (DNA OR RNA OR cfDNA OR cell-free DNA OR RNA OR CTC). All studies including blood-based biomarkers based on DNA, RNA and CTCs were reviewed. Of the included studies, studies reporting sensitivity, specificity and/or AUC/ROC values were further described.ResultsSystematic searched yielded 47 studies that were eligible, of which 21, 19 and 3 studies reported DNA, RNA and CTC biomarkers respectively. 15 of these studies included sensitivity, specificity and/or AUC/ROC values. Biomarkers sensitivity and specificity ranged widely at 2.4–97.6% and 43.3–100% respectively. Median number of patients recruited in the studies was 56 (IQR 41–90). Only 3 studies included an independent validation cohort. The highest sensitivity and specificity pairing achieved in the validation cohort was 80.0% and 89.1% respectively.ConclusionsThis systematic review provides a comprehensive overview of the blood-based CTC and nucleic acid biomarkers that have been investigated. An overlap in interest of targets between studies suggests that these could be promising biomarkers, but few biomarkers achieve high sensitivity and specificity, and fewer still have been validated independently.



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BRAF in non-small cell lung cancer (NSCLC): pickaxing another brick in the wall

Publication date: Available online 24 April 2018
Source:Cancer Treatment Reviews
Author(s): Alessandro Leonetti, Francesco Facchinetti, Giulio Rossi, Roberta Minari, Antonia Conti, Luc Friboulet, Marcello Tiseo, David Planchard
Molecular characterization of non-small cell lung cancer (NSCLC) marked an historical turning point for the treatment of lung tumors harboring kinase alterations suitable of specific targeted drugs inhibition, translating into major clinical improvements. Besides EGFR, ALK and ROS1, BRAF represents a novel therapeutic target for the treatment of advanced NSCLC. BRAF mutations, found in 1.5-3.5% of NSCLC, are responsible of the constitutive activation of mitogen activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway. Clinical trials evaluating the efficacy of the BRAF inhibitor dabrafenib in combination with the downstream MEK inhibitor trametinib in metastatic BRAF^V600E-mutated NSCLC guaranteed FDA and EMA rapid approval of the combination regimen in this clinical setting. In line with the striking results observed in metastatic melanoma harboring the same molecular alteration, BRAF and MEK inhibition should be considered a new standard of care in this molecular subtype of NSCLC. In the present review, we propose an overview of the available evidence about BRAF in NSCLC mutations (V600E and non-V600E), from biological significance to emerging clinical implications of BRAF mutations detection. Focusing on the current strategies to act against the mutated kinase, we moreover approach additional strategies to overcome treatment resistance.



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Molecular analyses in the diagnosis and prediction of prognosis in non-GIST soft tissue sarcomas: a systematic review and meta-analysis

Publication date: Available online 22 April 2018
Source:Cancer Treatment Reviews
Author(s): Rita A. Kandel, Xiaomei Yao, Brendan C. Dickson, Michelle Ghert, Snezana Popovic, Bibianna M. Purgina, Shailendra Verma, Joel Werier
BackgroundThe molecular pathogenesis of many forms of soft tissue sarcomas (STS) have been rigorously characterized in the medical literature, which may be particularly important for the diagnosis and prediction of prognosis in STS.MethodsElectronic databases (2005 to October 2016) were searched. Gastrointestinal stromal tumor and pediatric sarcomas were excluded. The eligible individual study's risk of bias and the quality of aggregate evidence were assessed. Meta-analyses were performed.ResultsOf 6674 identified articles, 70 were eligible and analyzed, covering 13 types of STS. Meta-analyses showed that the test of detecting MDM2 amplification by fluorescence in situ hybridization was accurate in differentiating atypical lipomatous tumor/well-differentiated liposarcoma/dedifferentiated liposarcoma from benign tumors (N = 971; sensitivity = 95%, 95% confidence interval [CI] 89–98; specificity = 100%, CI 89-100) or from other STS (N = 347; sensitivity = 99%, CI 72–100; specificity = 90%, CI 78–95); that the test of detecting SS18-SSX fusion by reverse transcription polymerase chain reaction (PCR) was accurate in differentiating synovial sarcoma from other STS (N = 532; sensitivity = 93%, CI 85–96; specificity = 99%, CI 96–100). The presence of a CTNNB1 S45F mutation detected by PCR was a risk factor for decreased recurrence-free survival in desmoid tumors (N = 418; hazard ratio from 3.50 [CI 1.51–8.14] to 6.20 [CI 2.24–17.15]).ConclusionsSarcomas are rare cancers whose molecular pathogenesis is becoming increasingly understood. The current evidence demonstrates that molecular analyses are useful in the diagnosis and prediction of prognosis in some STS.



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Evolution of checkpoint inhibitors for the treatment of metastatic gastric cancers: current status and future perspectives

Publication date: Available online 22 April 2018
Source:Cancer Treatment Reviews
Author(s): Julien Taieb, Markus Moehler, Narikazu Boku, Jaffer A. Ajani, Eduardo Yañez Ruiz, Min-Hee Ryu, Silke Guenther, Vikram Chand, Yung-Jue Bang
BackgroundStandard treatment options for patients with advanced gastric or gastroesophageal junction cancer (GC/GEJC) are associated with limited efficacy and some toxicity. Recently, immunotherapy with antibodies that inhibit the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) interaction has emerged as a new treatment option. This manuscript reviews early-phase and late-phase trials of immunotherapy in advanced GC/GEJC.MethodsSearches for studies of immunotherapy in GC/GEJC were performed using PubMed, ClinicalTrials.gov, and abstract databases for select annual congresses. Findings were interpreted based on expert opinion.ResultsMonotherapy with anti–PD-1/PD-L1 antibodies, including pembrolizumab, nivolumab, avelumab, durvalumab, and atezolizumab, has shown interesting objective response rates (ORRs; 7–26%) across varying GC/GEJC populations, with ORRs potentially higher in PD-L1+ vs PD-L1− tumors. Safety profiles compare favorably with chemotherapy, with grade ≥3 treatment-related adverse events occurring in 5–17%. Based on a large phase 2 study, pembrolizumab was approved in the United States for third-line treatment of patients with PD-L1+ GC/GEJC. In a phase 3 trial, third-line or later nivolumab increased overall survival vs placebo in an Asian population, leading to regulatory approval in Japan, although other completed phase 3 trials did not show superiority for pembrolizumab or avelumab monotherapy vs chemotherapy. Other trials in advanced GC/GEJC are assessing various anti–PD-1/PD-L1–based strategies, including administration in first-line and later-line settings and as combination (with chemotherapy or agents targeting other immune checkpoint proteins, eg, CTLA-4, LAG-3, and IDO) or switch-maintenance regimens.ConclusionsAnti–PD-1/PD-L1 antibodies have shown encouraging clinical activity in advanced GC/GEJC. Results from ongoing phase 3 trials are needed to further evaluate the potential roles of these agents within the continuum of care.



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Management of Treatment-Related Toxicities in Advanced Medullary Thyroid Cancer

Publication date: Available online 22 April 2018
Source:Cancer Treatment Reviews
Author(s): Marcia S. Brose, Keith C. Bible, Laura QM Chow, Jill Gilbert, Carolyn Grande, Francis Worden, Robert Haddad
Progress in the treatment of advanced medullary thyroid cancer (MTC) has resulted from the approval of 2 drugs within the past 5 years, vandetanib and cabozantinib. These multikinase inhibitors (MKIs) possess overlapping specificities for multiple kinase targets implicated in the progression of MTC. Both drugs are associated with toxicities, including hypertension, hemorrhage/perforation, diarrhea and other gastrointestinal events, several dermatologic events, and hypothyroidism. In addition, vandetanib is uniquely associated with QTc prolongation through interaction with myocardial potassium channels, and cabozantinib is uniquely associated with hand-foot skin reaction. Treatment-related toxicities occur frequently and can be severe or life-threatening, and patients undergoing long-term treatment will likely experience adverse events (AEs). Here we offer specific practical recommendations for managing AEs commonly occurring with vandetanib and cabozantinib. The recommended approach relies on early recognition and palliation of symptoms, dose interruption, and dose reduction as necessary in order for the patient to maintain the highest tolerable dose for as long as possible and optimal quality of life. Treatment guidelines do not specify a recommended sequence for treating with vandetanib and cabozantinib; however, most patients will receive both drugs during their lifetime. The choice for first-line therapy is individualized after a risk-benefit assessment and depends on physician preference and patient-related factors, such as comorbid conditions. Because most generalist practices may not be familiar with the intricacies of agents such as vandetanib and cabozantinib, we commend that patients with advanced MTC be managed and treated by a thyroid cancer specialist with coordination of care within a multidisciplinary team.

Graphical abstract

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Editorial Board

Publication date: April 2018
Source:Cancer Treatment Reviews, Volume 65





https://ift.tt/2vMGeRB

Physical properties of a novel small‐particle hyaluronic acid filler: In vitro, in vivo, and clinical studies

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2qXLJZ2

Intralesional bleomycin injection vs microneedling‐assisted topical bleomycin spraying in treatment of plantar warts

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2vMhokY

Early intervention in scar management and cutaneous burns with autologous platelet‐rich plasma

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2vMh7ys

Comparative study of the efficacy of Platelet‐rich plasma combined with carboxytherapy vs its use with fractional carbon dioxide laser in atrophic acne scars

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2HO1trc

Prenatal exposure to benzophenone-3 (BP-3) induces apoptosis, disrupts estrogen receptor expression and alters the epigenetic status of mouse neurons

Publication date: Available online 25 April 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Agnieszka Wnuk, Joanna Rzemieniec, Ewa Litwa, Władysław Lasoń, Małgorzata Kajta
Current evidence indicates that benzophenone-3 (BP-3) can pass through the placental and blood–brain barriers and thus can likely affect infant neurodevelopment. Despite widespread exposure, data showing the effects of BP-3 on the developing nervous system are scarce. This study revealed for the first time that prenatal exposure to BP-3 led to apoptosis and neurotoxicity, altered the levels of estrogen receptors (ERs) and changed the epigenetic status of mouse neurons. In the present study, multiple subcutaneous injections of pregnant mice with BP-3 at 50 mg/kg, which is an environmentally relevant dose, evoked activation of caspase-3 and lactate dehydrogenase (LDH) release as well as substantial loss of mitochondrial membrane potential in neocortical cells of their embryonic offspring. Apoptosis-focused microarray analysis of neocortical cells revealed up-regulation of 22 genes involved in apoptotic cell death. This effect was supported by increased BAX and CASP3 mRNA and protein levels, as evidenced by qPCR, ELISAs and western blots. BP-3-induced apoptosis and neurotoxicity were accompanied by decreases in the mRNA and protein expression levels of ESR1 and ESR2 (also known as ERα and ERβ), with a simultaneous increase in GPER1 (also known as GPR30) expression. In addition to the demonstration that treatment of pregnant mice with BP-3 induced apoptosis, caused neurotoxicity and altered ERs expression levels in neocortical cells of their embryonic offspring, we showed that prenatal administration of BP-3 inhibited global DNA methylation as well as reduced DNMTs activity. BP-3 also caused specific hypomethylation of the genes Gper1 and Bax, an effect that was accompanied by increased mRNA and protein expression levels. In addition, BP-3 caused hypermethylation of the genes Esr1, Esr2 and Bcl2, which could explain the reduced mRNA and protein levels of the receptors. This study demonstrated for the first time that prenatal exposure to BP-3 caused severe neuronal apoptosis that was accompanied by impaired ESR1/ESR2 expression, enhanced GPER1 expression, global DNA hypomethylation and altered methylation statuses of apoptosis-related and ERs genes. We suggest that the effects of BP-3 in embryonic neurons may be the fetal basis of the adult onset of nervous system disease.

Graphical abstract

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A Sorafenib-Sparing Effect in the Treatment of Thyroid Carcinoma Cells Attained by Co-treatment with a Novel Isoflavone Derivative and 1,25 Dihydroxyvitamin D3

Publication date: Available online 24 April 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Elena Izkhakov, Orli Sharon, Esther Knoll, Asaf Aizic, Dan M. Fliss, Fortune Kohen, Naftali Stern, Dalia Somjen
BackgroundSorafenib improves progression-free survival in patients with progressive radioactive iodine-refractory differentiated thyroid carcinoma, but causes severe side effects. Estrogens may accelerate thyroid carcinoma cell growth. Our group recently reported that isoflavone derivative 7-(O)-carboxymethyl daidzein conjugated to N-t-boc-hexylenediamine (cD-tboc), a novel anti-estrogenic compound, retards the growth of both thyroid carcinoma cell lines and cultured human carcinoma cells. Vitamin D receptor (VDR) is expressed in malignant cells and responds to 1,25 dihydroxyvitamin D3 (1.25D) by decreased proliferative activity in vitro. The purpose of this study was to examine the effects of vitamin D metabolites (VDM) on the expression of estrogen receptors (ERs), VDR, and 1OHase mRNA, and to evaluate the inhibitory effect of low doses of sorafenib in combination with cDtboc and VDM on cell proliferation in cultured human papillary thyroid carcinoma (PTC).MethodsIn 19 cultured PTC specimens and 19 normal thyroid specimens, harvested during thyroidectomies from the same patients, expression levels of ERα, ERβ, VDR, and 1 alpha-hydroxylase (1OHase) mRNA (by quantitative real-time PCR) were determined at baseline and after treatment with VMD. Cell proliferation was determined by measurement of ³[H] thymidine incorporation after treatment with sorafenib alone, sorafenib with added 1.25D or cD-tboc, and sorafenib with both 1.25D and cD-tboc added.Results1,25D increased mRNA expression of all tested genes in the malignant and normal thyroid cells, while the ERα mRNA of the normal cells was unaffected. 1.25D dose-dependently inhibited cell proliferation in the malignant cells. The inhibitory effect of sorafenib on cell proliferation in the malignant cells was amplified after the addition of cDtboc and 1.25D, such that the maximal inhibition was not only greater, but also had been attained at a 10-fold lower concentration of sorafenib (20 µg/ml). This inhibition was similar to that of the generally used concentration of sorafenib (200 μg/ml) alone.ConclusionsThe demonstration that low concentrations of cDtboc and 1.25D markedly amplify the inhibitory effect of sorafenib on the growth of human PTC supports the use of a 10-fold lower concentration of sorafenib. The findings may promote a new combination treatment for progressive radioactive iodine-refractory PTC.



https://ift.tt/2Hss0qp

Signaling pathways involved in the rapid biphasic effect of aldosterone on Na+/H+ exchanger in rat proximal tubule cells

Publication date: Available online 24 April 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Deise C.A. Leite-Dellova, Shirley J. Szriber, Giovana K.F. Merighe, Juliano Z. Polidoro, Nancy A. Rebouças, Maria Oliveira-Souza, Margarida de Mello-Aires
The receptors and signaling pathways for nongenomic effects of aldosterone (Aldo) on the proximal Na⁺/H⁺ exchanger are still unknown; therefore, the aim of this study was to investigate the mineralocorticoid receptor (MR) and/or glucocorticoid receptor (GR) participation in rapid Aldo effects on NHE1 (basolateral Na⁺/H⁺ exchanger isoform) and cytosolic calcium concentration ([Ca²⁺]i). In addition, phospholipase C (PLC), protein kinase C (PKC), and mitogen-activated protein kinase kinase (MEK) involvement in signaling pathways of such effects was evaluated, using immortalized proximal tubule cells of rat (IRPTC) as an experimental model. MR and GR expression was investigated using reverse transcription polymerase chain reaction and immunoblotting. The intracellular pH recovery rate (after acid loading) and [Ca²⁺]i were determined by the probes BCECF-AM and FURA 2-AM, respectively. Aldo (10^-12 M) promoted a moderate increase in [Ca²⁺]i and stimulation of NHE1, whereas Aldo (10^-6 M) greatly increased the [Ca²⁺]i, but inhibited the NHE1. BAPTA-AM (a calcium chelator), GR antagonism and inhibition of PLC, PKC and MEK pathway abolished the biphasic and dose-dependent effect of Aldo on NHE1 and decreased the [Ca²⁺]i; whereas MR do not appear to participate in this rapid signaling in IRPTC cells. The reduction of GR content, by gene silencing, abolished the Aldo effect on NHE1, in low concentration, confirming the importance of this receptor in the rapid modulation of proximal sodium and hydrogen transports.

Graphical abstract

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Management of adrenal emergencies in educated patients with adrenal insufficiency—A prospective study

Clinical Endocrinology, EarlyView.


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Impact of cross‐sex hormone therapy on bone mineral density and body composition in transwomen

Clinical Endocrinology, EarlyView.


https://ift.tt/2Ju2At5

Effects of bimagrumab, an activin receptor type II inhibitor, on pituitary neurohormonal axes

Clinical Endocrinology, EarlyView.


https://ift.tt/2HOZF17

Mortality data from the European Adrenal Insufficiency Registry—Patient characterization and associations

Clinical Endocrinology, EarlyView.


https://ift.tt/2Hu52iG

Dermoscopy and reflectance confocal microscopy for monitoring the treatment of actinic cheilitis with ingenol mebutate gel: Report of three cases

Dermatologic Therapy, EarlyView.


https://ift.tt/2FkfCY0

Unlocking the mystery of persistent skin ulcers in a young man and successful treatment with a simple regimen

Dermatologic Therapy, EarlyView.


https://ift.tt/2KdGvQR

Long‐term remission induced by secukinumab in a 13‐year‐old boy having recalcitrant chronic erythrodermic psoriasis

Dermatologic Therapy, EarlyView.


https://ift.tt/2Fgdhgw

Efficacy of long‐term intralesional triamcinolone in Morbihan's disease and its possible association with mast cell infiltration

Dermatologic Therapy, EarlyView.


https://ift.tt/2KdhncY

Dermatologic toxicity from immune checkpoint blockade therapy with an interstitial granulomatous pattern

Journal of Cutaneous Pathology, EarlyView.


https://ift.tt/2FhtulB

Recalcitrant psoriasiform dermatosis of the face: Is it related to pityriasis rubra pilaris?

Journal of Cutaneous Pathology, EarlyView.


https://ift.tt/2HZP94P

Kaposiform haemangioendothelioma: clinical features, complications and risk factors for Kasabach–Merritt phenomenon

British Journal of Dermatology, EarlyView.


https://ift.tt/2Ka6ZTr

Fit-for-Purpose Immunohistochemical Biomarkers

Abstract

There are two aspects of immunohistochemistry (IHC) that are relevant to practicing pathologist: (1) understanding of IHC biomarker panels that are suitable for diagnostic, prognostic and predictive testing, and (2) understanding of IHC quality assurance (QA), which makes sure that the tests in these panels work as they should. The two aspects are closely linked together and call for collaborative approach between pathologists and IHC laboratory technologists as both need to be involved in developing and maintaining IHC biomarkers that are "fit-for-purpose". This article reviews the most current IHC QA concepts that are imminently material to practicing pathologists with emphasis on challenges that are specific to endocrine pathology.

https://ift.tt/2Hx0zfv