Parental vaccine hesitancy in Italy – Results from a national survey

Publication date: Available online 8 January 2018
Source:Vaccine
Author(s): Cristina Giambi, Massimo Fabiani, Fortunato D'Ancona, Lorenza Ferrara, Daniel Fiacchini, Tolinda Gallo, Domenico Martinelli, Maria Grazia Pascucci, Rosa Prato, Antonietta Filia, Antonino Bella, Martina Del Manso, Caterina Rizzo, Maria Cristina Rota
In Italy, in 2016, we conducted a cross-sectional survey to estimate vaccine hesitancy and investigate its determinants among parents of children aged 16–36 months.Data on parental attitudes and beliefs about vaccinations were collected through a questionnaire administered online or self-administered at pediatricians' offices and nurseries. Parents were classified as pro-vaccine, vaccine-hesitant or anti-vaccine, according to self-reported tetanus and measles vaccination status of their child. Multivariable logistic regression was used to investigate factors associated with hesitancy.A total of 3130 questionnaires were analysed: 83.7% of parents were pro-vaccine, 15.6% vaccine-hesitant and 0.7% anti-vaccine. Safety concerns are the main reported reason for refusing (38.1%) or interrupting (42.4%) vaccination. Anti-vaccine and hesitant parents are significantly more afraid than pro-vaccine parents of short-term (85.7 and 79.7% vs 60.4%) and long-term (95.2 and 72.3% vs 43.7%) vaccine adverse reactions. Most pro-vaccine and hesitant parents agree about the benefits of vaccinations. Family pediatricians are considered a reliable source of information by most pro-vaccine and hesitant parents (96.9 and 83.3% respectively), against 45% of anti-vaccine parents. The main factors associated with hesitancy were found to be: not having received from a paediatrician a recommendation to fully vaccinate their child [adjusted odds ratio (AOR): 3.21, 95% CI: 2.14–4.79], having received discordant opinions on vaccinations (AOR: 1.64, 95% CI: 1.11–2.43), having met parents of children who experienced serious adverse reactions (AOR: 1.49, 95% CI: 1.03–2.15), and mainly using non-traditional medical treatments (AOR: 2.05, 95% CI: 1.31–3.19).Vaccine safety is perceived as a concern by all parents, although more so by hesitant and anti-vaccine parents. Similarly to pro-vaccine parents, hesitant parents consider vaccination an important prevention tool and trust their family pediatricians, suggesting that they could benefit from appropriate communication interventions. Training health professionals and providing homogenous information about vaccinations, in line with national recommendations, are crucial for responding to their concerns.



http://ift.tt/2CWOBgM

An assessment of shedding with the oral rabies virus vaccine strain SPBN GASGAS in target and non-target species

Publication date: Available online 8 January 2018
Source:Vaccine
Author(s): Ad Vos, Conrad Freuling, Steffen Ortmann, Antje Kretzschmar, Dietmar Mayer, Annette Schliephake, Thomas Müller
A safety requirement for live vaccines is investigating possible shedding in recipients since the presence of replication competent vaccine in secretions could result in direct and indirect horizontal transmission. This is especially relevant for oral rabies vaccine baits that are deliberately distributed into the environment. In the current study, survival of an oral rabies virus vaccine, SPBN GASGAS, was examined in excretions from different target and non-target species; red fox, raccoon dog, small Indian mongoose, raccoon, striped skunk, domestic dog, domestic cat and domestic pig. Saliva – and (pooled) fecal samples collected at different time points after oral administration of the vaccine strain were examined for the presence of viral RNA (rt-PCR). All PCR-positive and a subset of PCR-negative samples were subsequently investigated for the presence of infectious virus by isolation in cell culture (RTCIT). Up to 7 days post vaccine administration viral RNA could be detected in 50 of 758 fecal samples but no infectious virus was detected in any of the examined PCR-positive fecal samples. In contrast, RNA-fragments were detected in 248 of 1053 saliva swabs for an extended period (up to 10 days) after vaccine administration, but viable virus was only present during the first hours post vaccine administration in 38 samples. No infectious vaccine virus was isolated in saliva swabs taken 24 h or more after vaccine administration. Hence, no active shedding of the vaccine virus SPBN GASGAS after oral administration occurred and the virus isolated during the initial hours was material originally administered and not a result of virus replication within the host. Thus, potential horizontal transmission of this vaccine virus is limited to a short period directly after vaccine bait uptake. It can be concluded that the environmental risks associated with shedding after distributing vaccine baits containing SPBN GASGAS are negligible.



http://ift.tt/2AJDodF

DNA vaccine encoding myristoylated membrane protein (MMP) of rock bream iridovirus (RBIV) induces protective immunity in rock bream (Oplegnathus fasciatus)

Publication date: Available online 8 January 2018
Source:Vaccine
Author(s): Myung-Hwa Jung, Chamilani Nikapitiya, Sung-Ju Jung
Rock bream iridovirus (RBIV) causes severe mass mortalities in rock bream (Oplegnathus fasciatus) in Korea. In this study, we investigated the potential of viral membrane protein to induce antiviral status protecting rock bream against RBIV infection. We found that fish administered with ORF008L (myristoylated membrane protein, MMP) vaccine exhibited significantly higher levels of survival compared to ORF007L (major capsid protein, MCP). Moreover, ORF008L-based DNA vaccinated fish showed significant protection at 4 and 8 weeks post vaccination (wpv) than non-vaccinated fish after infected with RBIV (6.7 × 10⁵) at 23 °C, with relative percent survival (RPS) of 73.36% and 46.72%, respectively. All of the survivors from the first RBIV infection were strongly protected (100% RPS) from re-infected with RBIV (1.1 × 10⁷) at 100 dpi. In addition, the MMP (ORF008L)-based DNA vaccine significantly induced the gene expression of TLR3 (14.2-fold), MyD88 (11.6-fold), Mx (84.7-fold), ISG15 (8.7-fold), PKR (25.6-fold), MHC class I (13.3-fold), Fas (6.7-fold), Fas ligand (6.7-fold), caspase9 (17.0-fold) and caspase3 (15.3-fold) at 7 days post vaccination in the muscle (vaccine injection site). Our results showed the induction of immune responses and suggest the possibility of developing preventive measures against RBIV using myristoylated membrane protein-based DNA vaccine.



http://ift.tt/2CWxWKp

Tender Subcutaneous Fluctuant Forehead Nodule: An Unexpected Foray Into the Cranium

No abstract available

http://ift.tt/2mjtWsL

The Use of Silicone Microdroplet Injections for Correction of Depressed Scars

No abstract available

http://ift.tt/2qKyj54

Conjunctival Concretions Found in Mohs Micrographic Surgery

No abstract available

http://ift.tt/2miW8Mp

Nonmelanoma Skin Cancer Risk in Patients With Inflammatory Bowel Disease Undergoing Thiopurine Therapy: A Systematic Review of the Literature

BACKGROUND Azathioprine and 6-mercaptopurine (thiopurines) are common adjunct treatments for inflammatory bowel disease (IBD). Although thiopurine therapy in organ transplant recipients is known to increase nonmelanoma skin cancers (NMSCs), dermatologic literature yields less data regarding NMSC risk of thiopurine use in IBD. OBJECTIVE The aim of this study was to systematically review current literature on NMSC risk in patients with IBD using thiopurine therapy. METHODS Systematic review of PubMed was performed with keywords "inflammatory bowel disease," "ulcerative colitis," "Crohn's disease," "thiopurine," "azathioprine," "6-mercaptopurine," "skin cancer," "non-melanoma," "squamous cell carcinoma," and "basal cell carcinoma." All available publication years were included. Publications were evaluated using PRISMA guidelines. RESULTS The systematic review yielded 67 articles; 18 met final inclusion criteria. LIMITATIONS Heterogeneity of study designs limited direct comparisons of thiopurine exposure and NMSC risk. CONCLUSION Patients with IBD using thiopurines seem to have a moderately increased risk of NMSC that is proportional to therapy duration. Risk of NMSC seems to decrease or return to baseline after discontinuing therapy, although additional data are needed to support this trend. Younger patients with IBD using thiopurines seem to be at greater risk of NMSC. Appreciating NMSC risk in patients with IBD undergoing thiopurine therapy should help direct skin cancer screening recommendations and sun protective measures. Address correspondence and reprint requests to: Joshua W. Hagen, MD, PhD, Department of Dermatology, University of Pittsburgh Medical Center, 11 Vassar Avenue, Pittsburgh, PA 15229, or e-mail: josh.w.hagen@gmail.com Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the full text and PDF versions of this article on the journal's Web site (http://ift.tt/2bw6lgr). The primary author (J.W.H.) was funded through an ACGME-approved training program. The authors have indicated no significant interest with commercial supporters. © 2018 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2miVJJT

Examining the Relevance to Patients of Complications in the American College of Mohs Surgery Registry: Results of a Delphi Consensus Process

BACKGROUND Surgical registries are valuable tools for tracking outcomes. Incorporating patient input allows registries to address the interests of this important stakeholder group. OBJECTIVE The aim of this study was to identify a list of "patient-selected complications" and to explore the relevance to patients of previously published physician-identified complications. METHODS Delphi process with 2 rounds using patients to identify complications that are highly relevant for tracking by the proposed American College of Mohs Surgery (ACMS) National Registry. RESULTS Complications that physicians identified as highly relevant (death from any cause, hospitalization related to the procedure, functional loss attributable to surgery, bleeding requiring a second procedure, and surgical site infection) were each rated as highly relevant by patients. Patients also identified scarring, recurrence, and wound dehiscence as highly relevant outcomes for registry tracking. CONCLUSION Incorporating patient input into the ACMS registry design process identified 2 additional complication outcomes to be considered for inclusion within the registry—wound dehiscence and scarring. Patient input also corroborated the relevance of complications previously identified by ACMS physicians for inclusion in the registry. Furthermore, the importance of tracking local recurrence was confirmed from a patient-centered perspective. Address correspondence and reprint requests to: Jeremy R. Etzkorn, MD, Mohs and Reconstructive Surgery, Division of Dermatologic Surgery, University of Pennsylvania Health System, 3400 Civic Center Boulevard, Philadelphia, PA 19104, or e-mail: Jeremy.etzkorn@uphs.upenn.edu J.R. Etzkorn is supported by a Dermatology Foundation Clinical Career Development Award in Dermatologic Surgery. The authors have indicated no significant interest with commercial supporters. This study was approved by the institutional review board of St. Louis University. © 2018 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2qI09yJ

Cohesive Polydensified Matrix Hyaluronic Acid for the Treatment of Etched-In Fine Facial Lines: A 6-Month, Open-Label Clinical Trial

BACKGROUND Available hyaluronic acid dermal fillers have unique biophysical properties that influence their clinical utility, longevity, and aesthetic outcomes. OBJECTIVE To evaluate the effectiveness and durability of a cohesive polydensified matrix hyaluronic acid dermal filler (CPM-HA) for the treatment of etched-in fine facial lines. MATERIALS AND METHODS Subjects with etched-in fine lines of the forehead, cutaneous lip, melolabial folds, nasolabial folds, and/or radial cheek received treatment with CPM-HA mixed with lidocaine and epinephrine, with an optional touch-up treatment at Week 2, if deemed necessary. Response to treatment (as measured by the Merz Aesthetics Scales, Lemperle Facial Wrinkle Scales, and subject self-assessment) and safety/tolerability were monitored over the course of 26 weeks. RESULTS Thirty-one subjects received treatment with CPM-HA to 1 or more facial areas. All 5 treatment areas showed clinically meaningful and statistically significant improvements in average clinician rating scale scores at all study visits (p

http://ift.tt/2mgB75i

Predictive Techniques for Neurotoxin Outcomes

BACKGROUND Botulinum-derived neurotoxins have become a substantial tool in dermatologists' armamentarium for facial/neck rejuvenation. Current literature discusses anatomical "danger zones" to avoid during neurotoxin injection to prevent brow ptosis, blepharoptosis, and lower facial ptosis. OBJECTIVE The aim of this study was to determine whether lidocaine 1% local anesthetic can be used to predict botulinum toxin treatment outcomes and prevent adverse effects of unwanted paralysis. MATERIALS AND METHODS One percent lidocaine was drawn up using BD ultra-fine 31 G (5/16″), 0.5-mL insulin syringes in the same quantity that would be drawn up for neurotoxin placement. The patient's face was cleansed and mapped; 0.1 mL of 1% lidocaine was injected × 5 sites in the glabella; and 3 sites were injected with 0.05 mL in the frontalis. The patient was assessed after 10 minutes. RESULTS Improvement in frontalis and glabellar rhytides was appreciated, with noted "spocking" of the lateral brows. This technique allowed the authors to visualize the need for placement of toxin more laterally with eventual successful predictive placement for neurotoxin. CONCLUSION This technique of using local 1% lidocaine allows the practitioner to devise a neurotoxin distribution map tailored for each patient to limit unwanted paralysis from improper neurotoxin placement. Address correspondence and reprint requests to: Liza Brown, DO, Dermatology and Cutaneous Surgery, Larkin Community Hospital, Miami, FL 33143, or e-mail: Dermachurm@gmail.com The authors have indicated no significant interest with commercial supporters. © 2018 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2qGIwza

Calorie Labels on the Restaurant Menu: Is the Use of Weight-Control Behaviors Related to Ordering Decisions?

Publication date: Available online 8 January 2018
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Nicole Larson, Ann F. Haynos, Christina A. Roberto, Katie A. Loth, Dianne Neumark-Sztainer
BackgroundThere is emerging evidence that calorie information on restaurant menus does not similarly influence the ordering decisions of all population groups and may have unintended consequences for individuals who struggle with disordered eating or other weight-related concerns.ObjectiveThis study describes demographic patterns in the use of calorie information on restaurant menus and investigates relationships between using this information to limit calorie intake and measures of restaurant visit frequency and weight-related concerns and behavior.Design/participantsThere were 788 men and 1042 women (mean age=31.0±1.6 years) who participated in the fourth wave of the Project EAT study. Participants were initially recruited from Minneapolis-St Paul, MN, schools and completed EAT-IV surveys online or by mail from 2015 to 2016.Main outcome measuresParticipants self-reported weight-related concerns, restaurant eating, intuitive eating, dieting, healthy (eg, exercise) and unhealthy (eg, use of laxatives) weight-control behaviors, and binge eating.Statistical analyses performedDescriptive statistics and linear and logistic regression models accounting for demographics and weight status.ResultsApproximately half of participants (52.7%) reported they had noticed calorie information while purchasing a meal or snack in a restaurant within the previous month. Among individuals who noticed calorie information, 38.2% reported they did not use it in deciding what to order. The most common use of calorie information was to avoid high-calorie menu items (50.1%) or to decide on a smaller portion (20.2%). Using menu labels to limit calories was related to binge eating among women and was associated with more weight-related concerns, dieting, and unhealthy weight-control behaviors among both women and men.ConclusionsNutrition educators and other health care professionals should talk with clients who struggle with disordered eating or weight-related concerns to learn about their use of calorie information at restaurants, address any potential unintended consequences, and promote healthy uses of calorie information.



http://ift.tt/2mii22w

Fresh Fruit and Vegetable Program and Requests for Fruits and Vegetables Outside School Settings

Publication date: Available online 8 January 2018
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Punam Ohri-Vachaspati, Elizabeth Dachenhaus, Jessie Gruner, Kristina Mollner, Eric B. Hekler, Michael Todd
BackgroundConsumption of fruits and vegetables (F/V) among elementary school-aged children remains inadequate, especially among low-income children. The US Department of Agriculture's Fresh Fruit and Vegetable Program (FFVP) provides F/V as snacks to children during the school day, outside of school meals. School-based initiatives are successful in changing behaviors in school settings; however, their influence on behaviors outside of schools needs investigation.ObjectiveTo examine whether FFVP participation is associated with F/V requests at stores, self-efficacy to ask for and choose F/V at home, and F/V consumption.DesignCross-sectional study.Participant/settingFourth graders in six classrooms (n=296) from three urban, low-income school districts in Phoenix, AZ, were surveyed during 2015; one FFVP and one non-FFVP school from each district that were similar in school size, percent free/reduced-price meal eligibility, and race/ethnicity of enrolled students were selected.Main outcome measuresChildren's self-reported F/V requests during shopping, their self-efficacy to ask for and choose F/V at home, and F/V consumption on the previous day (non-FFVP school day) were measured using questions adapted from validated surveys.Statistical analysisMultivariable mixed-effect regression models, adjusting for clustering of students within classes and classes within schools were explored.ResultsIn models adjusting for individual-level factors (ie, age and sex) only, several significant positive associations were observed between school FFVP participation and healthier F/V outcomes. After additionally adjusting for school-level factors (ie, total enrollment and % Hispanic/Latino students) significant associations were observed between school FFVP participation and more requests for vegetables during shopping (P<0.001), higher scores on self-efficacy to choose vegetables at home (P=0.004), stronger preferences for vegetables (P<0.001), and more frequent consumption of fruit (P=0.006).ConclusionsSchool FFVP participation was associated with more requests for vegetables during shopping and higher self-efficacy to make healthy choices at home, suggesting the influence of the FFVP may extend beyond the school day.



http://ift.tt/2qNGSMt

Added Sugar Intake among Pregnant Women in the United States: National Health and Nutrition Examination Survey 2003-2012

Publication date: Available online 9 January 2018
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Catherine E. Cioffi, Janet Figueroa, Jean A. Welsh
BackgroundDespite associations of dietary added sugar with excess weight gain and chronic disease risk, intake among most Americans exceeds the recommended limits (<10% total energy). Maternal diet plays an important role in pregnancy-related outcomes, but little is known about the extent of added sugar intake during pregnancy.ObjectiveTo assess intake and identify the top sources of added sugars in the diets of pregnant vs nonpregnant women in the United States.DesignCross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES), 2003-2004 to 2011-2012.ParticipantsFour thousand one hundred seventy-nine pregnant and nonpregnant women (aged 20 to 39 years) who completed a dietary recall.Statistical analyses performedSurvey-weighted analyses were used to estimate means (95% CIs) in total grams and as percentage of total energy for added sugar intake by pregnancy status and by demographic subgroup and to identify leading sources of added sugar.ResultsAdded sugar intake trended toward being higher in pregnant compared with nonpregnant women in absolute grams, 85.1 g (95% CI: 77.4 to 92.7) vs 76.7 g (95% CI: 73.6 to 79.9), respectively (P=0.06), but was lower among pregnant women when total energy intake was accounted for, 14.8% (95% CI: 13.8 to 15.7) vs 15.9% (95% CI: 15.2 to 16.6) of total energy, respectively (P=0.03). Among pregnant women, added sugar intake was similar among demographic subgroups. However, in multivariable regression, pregnancy status significantly modified the associations of education and income with added sugar intake, whereby less educated and lower-income women who were pregnant had lower added sugar intakes compared with those who were not pregnant, but more educated or higher-income women did not exhibit this pattern. The top five sources of added sugar for all women were sugar-sweetened beverages; cakes, cookies, and pastries; sugars and sweets; juice drinks and smoothies; and milk-based desserts.ConclusionsAlthough pregnant women had higher energy intakes, this was not attributed to higher intakes of added sugar. Although education and income affected consumption during pregnancy, intake of added sugar among all women, regardless of pregnancy status, exceeded recommendations.



http://ift.tt/2mibwc6

Bendamustine plus Rituximab Versus R‐CHOP as First‐Line Treatment for Patients with Follicular Lymphoma Grade 3A: Evidence from a Multicenter, Retrospective Study

AbstractBackground.Rituximab plus bendamustine (R‐B) has been demonstrated to improve outcomes and reduce toxicity compared with rituximab, cyclophosphamide, doxorubicin, and prednisone (R‐CHOP) in follicular lymphoma (FL). Nevertheless, in clinical practice, many centers still prefer R‐CHOP to R‐B in patients with FL grade 3A (FL3A). Therefore, we retrospectively assessed patients with FL3A treated with either R‐CHOP or R‐B in five European cancer centers and compared their outcomes.Materials and Methods.We retrospectively assessed 132 patients affected by FL grade 3A treated with either R‐B or R‐CHOP in the first line and evaluated outcome and toxicity according to the type of treatment. This study included 101 patients who were a subgroup of a previously published cohort.Results.R‐B was less toxic and achieved a similar percentage of complete remissions compared with R‐CHOP (97% vs. 96%, p = .3). During follow‐up, 10 (16%) patients relapsed after R‐B and 29 (41%) after R‐CHOP (p = .001), leading to a median progression‐free survival (PFS) of 15 versus 11.7 years, respectively (p = .03). Furthermore, R‐B overcame the negative prognostic impact of BCL2 expression (15 vs. 4.8 years; p = .001). However, median overall survival was similar between both groups (not reached for both; p = .8).Conclusion.R‐B as a first‐line treatment of FL3A is better tolerated than R‐CHOP and seems to induce more profound responses, leading to a significantly lower relapse rate and prolonged PFS. Therefore, R‐B is a valid treatment option for FL grade 3A.Implications for Practice.Rituximab plus bendamustine (R‐B) has shown to be less toxic and more effective than rituximab, cyclophosphamide, doxorubicin, and prednisone (R‐CHOP) in follicular lymphoma grade 3A. Although both regimens can induce a complete remission in >95% of patients, relapses occur more frequently after R‐CHOP than R‐B, leading to a significantly longer progression‐free survival in the latter. R‐B is also able to overcome the impact of negative prognosticators, such as BCL2 expression. However, because of the indolent course of this disease and efficient salvage treatments, overall survival was similar in both treatment groups. Therefore, R‐B is a valid treatment option in this patient setting.

http://ift.tt/2mbWGmz

Safety Profile of Biosimilar Filgrastim (Zarzio/Zarxio): A Combined Analysis of Phase III Studies

AbstractBackground.Evaluation of adverse events (AEs) in pivotal registration trials and ongoing postmarketing surveillance is important for all biologics, including biosimilars. A combined analysis of two pivotal registration studies was performed to strengthen evidence on safety for biosimilar filgrastim EP2006 in patients with breast cancer receiving myelosuppressive chemotherapy, a sensitive clinical setting to confirm biosimilarity of filgrastim.Materials and Methods.Data were combined from two phase III studies of biosimilar filgrastim EP2006. The U.S. registration study was a randomized, double‐blind comparison of biosimilar and reference filgrastim in women aged ≥18 years with breast cancer, receiving (neo)adjuvant treatment with TAC (docetaxel + doxorubicin + cyclophosphamide). The European Union registration study was a single‐arm, open‐label study of biosimilar filgrastim in women aged ≥18 years with breast cancer receiving doxorubicin + docetaxel. Patients received filgrastim as a subcutaneous injection on day 2 of each cycle for <14 days or until the absolute neutrophil count reached 10 × 109/L after the expected nadir. Results were combined for cycles 1–4.Results.A total of 277 patients received biosimilar filgrastim EP2006. Patients had a mean (± standard deviation) age of 51.1 (± 10.8) years, and 78.7% of patients had stage II or III breast cancer. A total of 46 (20.6%) patients receiving biosimilar filgrastim had AEs considered filgrastim‐related. The most frequently reported filgrastim‐related AEs were musculoskeletal or connective tissue disorders (15.2%), including bone pain (7.2%). One death (due to pulmonary embolism) occurred of a patient receiving biosimilar filgrastim (not considered filgrastim‐related). No patient developed antidrug antibodies during the study.Conclusion.Biosimilar filgrastim has a safety profile consistent with previous filgrastim studies and is effective in preventing febrile neutropenia in patients with breast cancer.Implications for Practice.The biosimilar filgrastim EP2006 (Zarzio, Zarxio, biosimilar filgrastim‐sndz) has been approved in Europe since 2009 and in the U.S. since 2015. This combined analysis of two phase III studies provides additional clinical evidence that the biosimilar filgrastim EP2006 has a safety profile consistent with previous studies of reference filgrastim and supports large postmarketing studies of EP2006 in Europe. Strengthening the evidence for biosimilar filgrastim can help improve acceptance of biosimilars and increase patient access to biologics.

http://ift.tt/2CUs6bn

Validation and Refinement of the Age, Comorbidities, and Albumin Index in Elderly Patients with Diffuse Large B‐Cell Lymphoma: An Effective Tool for Comprehensive Geriatric Assessment

AbstractBackground.We aimed to validate and refine the Age, Comorbidities, and Albumin (ACA) index in elderly Chinese patients with diffuse large B‐cell lymphoma (DLBCL) and propose a more effective method for comprehensive geriatric assessment (CGA).Materials and Methods.Patients ≥65 years of age who had been diagnosed with de novo DLBCL in the Institute of Hematology, Beijing Hospital, were screened for eligibility (n = 99).Results.Based on the ACA index, 39, 31, 26, and 3 patients were categorized into the "excellent," "good," "moderate," and "poor" groups, respectively. The 2‐year treatment‐related mortality rate was significantly higher and the survival rates poorer in the ACA "moderate to poor" group compared with those of the ACA "good" and "excellent" groups. Multivariable model analysis identified two independent predictors of overall survival: the instrumental activities of daily living (IADL) scale and the ACA index. IADL scores of 6 to 7 and the ACA "good" group were assigned 1 point; IADL scores ≤5 and the ACA "moderate to poor" group were assigned 2 points. Based on these data, we created a three‐category system (IADL ACA index [IACA index]): low risk, score 0; intermediate risk, score 1 to 2; and high risk, score 3 to 4. The IACA index could effectively discriminate the response rates, overall survival, and progression‐free survival rates in elderly patients with DLBCL.Conclusion.We observed that the ACA index could partially predict the clinical outcomes of elderly DLBCL patients in China. Based on this index, we proposed the IACA index as an effective tool for CGA in DLBCL.Implications for Practice.Diffuse large B‐cell lymphoma (DLBCL) is one of the most frequent types of malignant lymphoma in elderly people, and identifying patients suitable for curative therapy is critical in the improvement of clinical outcomes. Recently, some authors proposed the Age, Comorbidities, and Albumin (ACA) index. Combining the use of the instrumental activities of daily living (IADL) scale and the ACA index, this article describes the IADL ACA index (IACA index), which is an effective tool for comprehensive geriatric assessment in DLBCL.

http://ift.tt/2mfw4RQ

Characteristics of Real‐World Metastatic Non‐Small Cell Lung Cancer Patients Treated with Nivolumab and Pembrolizumab During the Year Following Approval

AbstractBackground.Evidence from cancer clinical trials can be difficult to generalize to real‐world patient populations, but can be complemented by real‐world evidence to optimize personalization of care. Further, real‐world usage patterns of programmed cell death protein 1 (PD‐1) inhibitors following approval can inform future studies of subpopulations underrepresented in clinical trials.Materials and Methods.We performed a multicenter analysis using electronic health record data collected during routine care of patients treated in community cancer care clinics in the Flatiron Health network. Real‐world metastatic non‐small cell lung cancer (NSCLC) patients who received nivolumab or pembrolizumab in the metastatic setting (n = 1,344) were selected from a starting random sample of 55,969 NSCLC patients with two or more documented visits from January 1, 2011, through March 31, 2016. The primary study outcome measurement was demographic and treatment characteristics of the cohort.Results.Median age at PD‐1 inhibitor initiation was 69 years (interquartile range 61–75). Patients were 56% male, 88% smokers, 65% nonsquamous histology, and 64% diagnosed at stage IV. Of 1,344 patients, 112 (8%) were tested for programmed death‐ligand 1 expression. Overall, 50% received nivolumab or pembrolizumab in the second line, with a substantial proportion of third and later line use that began to decline in Q4 2015.Conclusion.During the year following U.S. regulatory approval of PD‐1 inhibitors for treatment of NSCLC, real‐world patients receiving nivolumab or pembrolizumab were older at treatment initiation and more had smoking history relative to clinical trial cohorts. Studies of outcomes in underrepresented subgroups are needed to inform real‐world treatment decisions.Implications for Practice.Evidence gathered in conventional clinical trials used to assess safety and efficacy of new therapies is not necessarily generalizable to real‐world patients receiving these drugs following regulatory approval. Real‐world evidence derived from electronic health record data can yield complementary evidence to enable optimal clinical decisions. Examined here is a cohort of programmed cell death protein 1 inhibitor‐treated metastatic non‐small cell lung cancer patients in the first year following regulatory approval of these therapies in this indication. The analysis revealed how the real‐world cohort differed from the clinical trial cohorts, which will inform which patients are underrepresented and warrant additional studies.

http://ift.tt/2CXGNuu

Fertility‐Sparing Treatment of Endometrial Cancer with Initial Infiltration of Myometrium by Resectoscopic Surgery: A Pilot Study

AbstractThree women with a well‐differentiated grade 1 endometrioid adenocarcinoma of the endometrium with minimal myometrial infiltration were treated with hysteroscopic resection and hormone therapy. The presence of myometrial infiltration has often been mentioned as an exclusion criterion for conservative management in young patients because of worsening cancer prognosis. The subsequent 5‐year follow‐up and the pregnancies achieved may confirm the choice of this temporary treatment and indicate a new option for fertility‐sparing treatment in highly motivated patients.

http://ift.tt/2mfvKT8

Pattern of programmed cell death-ligand 1 expression and CD8-positive T-cell infiltration before and after chemoradiotherapy in rectal cancer

Publication date: March 2018
Source:European Journal of Cancer, Volume 91
Author(s): Atsushi Ogura, Takashi Akiyoshi, Noriko Yamamoto, Hiroshi Kawachi, Yuichi Ishikawa, Seiichi Mori, Koji Oba, Masato Nagino, Yosuke Fukunaga, Masashi Ueno
BackgroundThe synergistic effect of combining immune checkpoint inhibitors with radiotherapy was reported recently, but there are few studies on programmed cell death-ligand 1 (PD-L1) expression in rectal cancer treated by preoperative chemoradiotherapy (CRT). The aim of the present study was to investigate the PD-L1 expression status before and after CRT and its association with clinicopathological characteristics and recurrence in rectal cancer.MethodsImmunostainings of PD-L1 and CD8 were performed in 287 patients with rectal cancer treated by CRT. PD-L1 expression on the tumour cells (tPD-L1) and on the stromal immune cells (iPD-L1) was evaluated before and after CRT. CD8+ cell density in tumour area (tCD8+) before CRT and in the stromal area (sCD8+) before and after CRT was also evaluated.ResultsHigh tPD-L1 expression was observed in only three patients (1.0%). High iPD-L1 expression significantly increased from 31.7% before CRT to 49.2% after CRT (P < 0.0001). The increase in high iPD-L1 expression after CRT was only observed in patients with tumour regression grades 1 and 2. High iPD-L1 expression was associated with high tCD8+ cell density before CRT (P < 0.0001) and sCD8+ cell density after CRT (P < 0.0001). High tCD8+ cell density before CRT was associated with better disease-free survival (DFS) (P = 0.0331), but its improved effect on DFS could be observed in patients with high iPD-L1 expression (P = 0.0081), not in patients with low iPD-L1 expression (P = 0.516).ConclusionThe present study demonstrated the significant correlations between iPD-L1 expression and CD8+ cell density both before and after CRT.



http://ift.tt/2CLf1hd

Pharmacokinetics partly explains the relationship between carcinoembryonic antigen level and survival of colorectal cancer patients treated with ramucirumab

Publication date: Available online 9 January 2018
Source:European Journal of Cancer
Author(s): Sajida Ibrahim, William Raoul, Thierry Lecomte, Gilles Paintaud, David Ternant




http://ift.tt/2CUJQnO

One-step fabrication of PEGylated fluorescent nanodiamonds through the thiol-ene click reaction and their potential for biological imaging

Publication date: Available online 8 January 2018
Source:Applied Surface Science
Author(s): Hongye Huang, Meiying Liu, Xun Tuo, Junyu Chen, Liucheng Mao, Yuanqing Wen, Jianwen Tian, Naigen Zhou, Xiaoyong Zhang, Yen Wei
Over the past years, fluorescent carbon nanoparticles have got growing interest for biological imaging. Fluorescent nanodiamonds (FNDs) are novel fluorescent carbon nanoparticles with multitudinous useful properties, including remarkable fluorescence properties, extremely low toxicity and high refractive index. However, facile preparation of FNDs with designable properties and functions from non-fluorescent detonation nanodiamonds (DNDs) has demonstrated to be challengeable. In this work, we reported for the first time that preparation of Polyethylene glycol (PEG) functionalized FNDs through a one-step thiol-ene click reaction using thiol containing PEG (PEG-SH) as the coating agent. Based on the characterization results, we demonstrated that PEG-SH could be efficiently introduced on DNDs to obtain FNDs through the thiol-ene click chemistry. The resultant FND-PEG composites showed high water dispersibility, strong fluorescence and low cytotoxicity. Moreover, FND-PEG composites could be internalized by cells and displayed good cell dyeing performance. All of these features implied that FND-PEG composites are of great potential for biological imaging. Taken together, a facile one-step strategy based on the one-step thiol-ene click reaction has been developed for efficient preparation of FND-PEG composites from non-fluorescent DNDs. The strategy should be also useful for fabrication of many other functional FNDs via using different thiol containing compounds for the universality of thiol-ene click reaction.

Graphical abstract

http://ift.tt/2Fg8Pzv

Ovulation is associated with the LH-dependent induction of pla2g4aa in zebrafish

Publication date: Available online 8 January 2018
Source:Molecular and Cellular Endocrinology
Author(s): Haipei Tang, Le Wang, Yu Chen, Jianan He, Ling Qu, Yin Guo, Yun Liu, Xiaochun Liu, Haoran Lin
The effects of the preovulatory luteinizing hormone (LH) surge on the ovulatory process are mediated by prostaglandins (PGs), the synthesis of which involves prostaglandin synthetase and cytosolic phospholipase A2 (cPLA2). In our previous study, we systematically investigated the function of prostaglandin endoperoxide synthase (ptgs) genes on ovulation in zebrafish. However, the role of cPLA2 in ovulation was not determined in zebrafish. In this study, we investigated the function of cpla2α in PGs production and ovulation in periovulatory follicles. Our data showed that the expression of pla2g4aa increased during zebrafish folliculogenesis and the follicular layer was the primary region with expression of pla2g4aa. In addition, the expression of pla2g4aa was regulated by LH in vitro and in vivo. Furthermore, injection of AACOCF3, a specific inhibitor of cPLA2, significantly reduced ovarian PGs level and blocked hCG-induced ovulation. Collectively, these findings suggest that pla2g4aa is related to the ovulation process in zebrafish.



http://ift.tt/2CLeJHv

Gene Therapy and Genome Editing

Publication date: Available online 9 January 2018
Source:Hematology/Oncology Clinics of North America
Author(s): Farid Boulad, Jorge Mansilla-Soto, Annalisa Cabriolu, Isabelle Rivière, Michel Sadelain

Teaser

The β-thalassemias are inherited blood disorders that result from insufficient production of the β-chain of hemoglobin. More than 200 different mutations have been identified. β-Thalassemia major requires life-long transfusions. The only cure for severe β-thalassemia is to provide patients with hematopoietic stem cells. Globin gene therapy promises a curative autologous stem cell transplantation without the immunologic complications of allogeneic transplantation. The future directions of gene therapy include enhancement of lentiviral vector-based approaches, fine tuning of the conditioning regimen, and the design of safer vectors. Progress in genetic engineering bodes well for finding a cure for severe globin disorders.


http://ift.tt/2CLevQF

The exposure to water with cigarette residue changes the anti-predator response in female Swiss albino mice

Abstract

Recent studies have shown that cigarette consumption affects much more than human health. Smoked cigarette butt (SCB) disposal into the environment can bring little-known negative biological consequences to mammals, since it contains many organic and inorganic toxic chemical constituents. Thus, we aim at assessing whether the ingestion of water with leached SCB for 60 days by female Swiss mice changes their defensive behavioral response to potential predators (cats and snakes). We worked with the following groups of animals: control (pollutant-free water), water with environmental concentration of SCB (1.9 μg/L of nicotine), and concentration 1000 times higher (EC1000×). Our data show that the treatments did not cause locomotor, visual, auditory, and olfactory deficit in the animals. However, we observed that the animals exposed to the pollutants did not present behavioral differences in the test session with or without the snake. On the other hand, animals in all groups showed defensive behavior when the test was conducted with the cat in the apparatus. However, female mice presented weaker response than the control. Thus, our data point towards the potential neurotoxic damage caused to mice who have ingested water with SCB residues, even at low concentrations.

http://ift.tt/2CIVWwc

Acquired idiopathic generalized anhidriosis: Successful treatment with cyclosporine in two cases

http://ift.tt/2DarrAv

Group schema therapy for eating disorders: study protocol

Abstract

Background

The treatment of eating disorders is a difficult endeavor, with only a relatively small proportion of clients responding to and completing standard cognitive behavioural therapy (CBT). Given the prevalence of co-morbidity and complex personality traits in this population, Schema Therapy has been identified as a potentially viable treatment option. A case series of Group Schema Therapy for Eating Disorders (ST-E-g) yielded positive findings and the study protocol outlined in this article aims to extend upon these preliminary findings to evaluate group Schema Therapy for eating disorders in a larger sample (n = 40).

Methods/design

Participants undergo a two-hour assessment where they complete a number of standard questionnaires and their diagnostic status is ascertained using the Eating Disorder Examination. Participants then commence treatment, which consists of 25 weekly group sessions lasting for 1.5 h and four individual sessions. Each group consists of five to eight participants and is facilitated by two therapists, at least one of who is a registered psychologist trained on schema therapy. The primary outcome in this study is eating disorder symptom severity. Secondary outcomes include: cognitive schemas, self-objectification, general quality of life, self-compassion, schema mode presentations, and Personality Disorder features. Participants complete psychological measures and questionnaires at pre, post, six-month and 1-year follow-up.

Discussion

This study will expand upon preliminary research into the efficacy of group Schema Therapy for individuals with eating disorders. If group Schema Therapy is shown to reduce eating disorder symptoms, it will hold considerable promise as an intervention option for a group of disorders that is typically difficult to treat.

Trial registration

ACTRN12615001323516. Registered: 2/12/2015 (retrospectively registered, still recruiting).

http://ift.tt/2FicPzz

Skin Infections due to Bacteria in Solid Organ Transplant Recipients: A Review

Though there is an abundance of information on cutaneous malignancies in transplant recipients, cutaneous infections in solid organ transplant recipients (SOTRs) are underrepresented in the dermatological literature. Our paper provides a comprehensive review of bacterial cutaneous infections within the solid organ transplant population. Cutaneous bacterial infections may lead to significant morbidity and even mortality in this immunosuppressed population. Thus, it is to the benefit of both dermatologists and other transplant care providers to better understand and recognize the features of cutaneous bacterial infections in SOTRs. This paper can aid providers in promptly identifying, diagnosing, and treating bacterial skin infections. This review discusses the diagnosis and treatment of the following bacterial species: Staphylococcus, Streptococcus, Pseudomonas aeruginosa, Escherichia coli, Nocardia, Mycobacteria, and Bartonella henselae.
Dermatology

http://ift.tt/2CKHSCp

Analytic tractography: A closed-form solution for estimating local white matter connectivity with diffusion MRI

Publication date: 1 April 2018
Source:NeuroImage, Volume 169
Author(s): Matthew Cieslak, Tegan Brennan, Wendy Meiring, Lukas J. Volz, Clint Greene, Alexander Asturias, Subhash Suri, Scott T. Grafton
White matter structures composed of myelinated axons in the living human brain are primarily studied by diffusion-weighted MRI (dMRI). These long-range projections are typically characterized in a two-step process: dMRI signal is used to estimate the orientation of axon segments within each voxel, then these local orientations are linked together to estimate the spatial extent of putative white matter bundles. Tractography, the process of tracing bundles across voxels, either requires computationally expensive (probabilistic) simulations to model uncertainty in fiber orientation or ignores it completely (deterministic). Furthermore, simulation necessarily generates a finite number of trajectories, introducing "simulation error" to trajectory estimates. Here we introduce a method to analytically (via a closed-form solution) take an orientation distribution function (ODF) from each voxel and calculate the probabilities that a trajectory projects from a voxel into each directly adjacent voxels. We validate our method by demonstrating experimentally that probabilistic simulations converge to our analytically computed transition probabilities at the voxel level as the number of simulated seeds increases. We then show that our method accurately calculates the ground-truth transition probabilities from a publicly available phantom dataset. As a demonstration, we incorporate our analytic method for voxel transition probabilities into the Voxel Graph framework, creating a quantitative framework for assessing white matter structure, which we call "analytic tractography". The long-range connectivity problem is reduced to finding paths in a graph whose adjacency structure reflects voxel-to-voxel analytic transition probabilities. We demonstrate that this approach performs comparably to the current most widely-used probabilistic and deterministic approaches at a fraction of the computational cost. We also demonstrate that analytic tractography works on multiple diffusion sampling schemes, reconstruction method or parameters used to define paths. Open source software compatible with popular dMRI reconstruction software is provided.



http://ift.tt/2CU5ms1

False positive rates in surface-based anatomical analysis

Publication date: 1 May 2018
Source:NeuroImage, Volume 171
Author(s): Douglas N. Greve, Bruce Fischl
The false positive rates (FPR) for surface-based group analysis of cortical thickness, surface area, and volume were evaluated for parametric and non-parametric clusterwise correction for multiple comparisons for a range of smoothing levels and cluster-forming thresholds (CFT) using real data under group assignments that should not yield significant results. For whole cortical surface analysis, thickness showed modest inflation in parametric FPRs above the nominal level (10% versus 5%). Surface area and volume FPRs were much higher (20–30%). In the analysis of interhemispheric thickness asymmetries, FPRs were well controlled by parametric correction, but FPRs for surface area and volume asymmetries were still inflated. In all cases, non-parametric permutation adequately controlled the FPRs. It was found that inflated parametric FPRs were caused by violations in the parametric assumptions, namely a heavier-than-Gaussian spatial correlation. The non-Gaussian spatial correlation originates from anatomical features unique to individuals (e.g., a patch of cortex slightly thicker or thinner than average) and is not a by-product of scanning or processing. Thickness performed better than surface area and volume because thickness does not require a Jacobian correction.



http://ift.tt/2mfgJ3I

Musical genre-dependent behavioural and EEG signatures of action planning. A comparison between classical and jazz pianists

Publication date: 1 April 2018
Source:NeuroImage, Volume 169
Author(s): R. Bianco, G. Novembre, P.E. Keller, A. Villringer, D. Sammler
It is well established that musical training induces sensorimotor plasticity. However, there are remarkable differences in how musicians train for proficient stage performance. The present EEG study outlines for the first time clear-cut neurobiological differences between classical and jazz musicians at high and low levels of action planning, revealing genre-specific cognitive strategies adopted in production. Pianists imitated chord progressions without sound that were manipulated in terms of harmony and context length to assess high-level planning of sequence-structure, and in terms of the manner of playing to assess low-level parameter specification of single acts. Jazz pianists revised incongruent harmonies faster as revealed by an earlier reprogramming negativity and beta power decrease, hence neutralising response costs, albeit at the expense of a higher number of manner errors. Classical pianists in turn experienced more conflict during incongruent harmony, as shown by theta power increase, but were more ready to implement the required manner of playing, as indicated by higher accuracy and beta power decrease. These findings demonstrate that specific demands and action focus of training lead to differential weighting of hierarchical action planning. This suggests different enduring markers impressed in the brain when a musician practices one or the other style.



http://ift.tt/2CSagWH

Altered reward learning and hippocampal connectivity following psychosocial stress

Publication date: 1 May 2018
Source:NeuroImage, Volume 171
Author(s): Onno Kruse, Isabell Tapia León, Tobias Stalder, Rudolf Stark, Tim Klucken
Acute stress has a profound influence on learning, as has been demonstrated in verbal learning or fear conditioning. However, its effect on appetitive conditioning is still unclear. Fear conditioning research suggests the possibility of overgeneralization of conditioning to the CS- under acute stress due to its effect on prefrontal and hippocampal processing.In this study, participants (N = 56 males) were subjected to the Trier Social Stress Test or a placebo version. After that, all participants underwent an appetitive conditioning paradigm in the fMRI, in which one neutral cue (CS+) was repeatedly paired with reward, while another (CS-) was not. Importantly, the stress-group revealed overgeneralization of conditioning to the CS- on the behavioral level. On the neural level, stressed participants showed increased connectivity between the hippocampus and amygdala, vACC, and OFC, which maintain specificity of conditioning and also showed reduced differential activation. The results indicate overgeneralization of appetitive conditioning promoted by maladaptive balancing of pattern separation and pattern completion in the hippocampus under acute stress and are discussed with respect to clinical implications.



http://ift.tt/2mdMgTk

Human in-vivo brain magnetic resonance current density imaging (MRCDI)

Publication date: 1 May 2018
Source:NeuroImage, Volume 171
Author(s): Cihan Göksu, Lars G. Hanson, Hartwig R. Siebner, Philipp Ehses, Klaus Scheffler, Axel Thielscher
Magnetic resonance current density imaging (MRCDI) and MR electrical impedance tomography (MREIT) are two emerging modalities, which combine weak time-varying currents injected via surface electrodes with magnetic resonance imaging (MRI) to acquire information about the current flow and ohmic conductivity distribution at high spatial resolution. The injected current flow creates a magnetic field in the head, and the component of the induced magnetic field ΔBz,c parallel to the main scanner field causes small shifts in the precession frequency of the magnetization. The measured MRI signal is modulated by these shifts, allowing to determine ΔBz,c for the reconstruction of the current flow and ohmic conductivity.Here, we demonstrate reliable ΔBz,c measurements in-vivo in the human brain based on multi-echo spin echo (MESE) and steady-state free precession free induction decay (SSFP-FID) sequences. In a series of experiments, we optimize their robustness for in-vivo measurements while maintaining a good sensitivity to the current-induced fields. We validate both methods by assessing the linearity of the measured ΔBz,c with respect to the current strength. For the more efficient SSFP-FID measurements, we demonstrate a strong influence of magnetic stray fields on the ΔBz,c images, caused by non-ideal paths of the electrode cables, and validate a correction method. Finally, we perform measurements with two different current injection profiles in five subjects. We demonstrate reliable recordings of ΔBz,c fields as weak as 1 nT, caused by currents of 1 mA strength. Comparison of the ΔBz,c measurements with simulated ΔBz,c images based on FEM calculations and individualized head models reveals significant linear correlations in all subjects, but only for the stray field-corrected data. As final step, we reconstruct current density distributions from the measured and simulated ΔBz,c data. Reconstructions from non-corrected ΔBz,c measurements systematically overestimate the current densities. Comparing the current densities reconstructed from corrected ΔBz,c measurements and from simulated ΔBz,c images reveals an average coefficient of determination R² of 71%. In addition, it shows that the simulations underestimated the current strength on average by 24%.Our results open up the possibility of using MRI to systematically validate and optimize numerical field simulations that play an important role in several neuroscience applications, such as transcranial brain stimulation, and electro- and magnetoencephalography.



http://ift.tt/2CT5IPT

Artificial scotoma estimation based on population receptive field mapping

Publication date: 1 April 2018
Source:NeuroImage, Volume 169
Author(s): A. Hummer, M. Ritter, M. Woletz, A.A. Ledolter, M. Tik, S.O. Dumoulin, G.E. Holder, U. Schmidt-Erfurth, C. Windischberger
Population receptive field (pRF) mapping based on functional magnetic resonance imaging (fMRI) is an ideal method for obtaining detailed retinotopic information. One particularly promising application of pRF mapping is the estimation and quantification of visual field effects, for example scotomata in patients suffering from macular dysfunction or degeneration (MD) or hemianopic defects in patients with intracranial dysfunction. However, pRF mapping performance is influenced by a number of factors including spatial and temporal resolution, distribution of dural venous sinuses and patient performance. This study addresses the ability of current pRF methodology to assess the size of simulated scotomata in healthy individuals. The data demonstrate that central scotomata down to a radius of 2.35° (4.7° diameter) visual angle can be reliably estimated in single subjects using high spatial resolution protocols and multi-channel receive array coils.



http://ift.tt/2mcUwTB

Metric learning with spectral graph convolutions on brain connectivity networks

Publication date: 1 April 2018
Source:NeuroImage, Volume 169
Author(s): Sofia Ira Ktena, Sarah Parisot, Enzo Ferrante, Martin Rajchl, Matthew Lee, Ben Glocker, Daniel Rueckert
Graph representations are often used to model structured data at an individual or population level and have numerous applications in pattern recognition problems. In the field of neuroscience, where such representations are commonly used to model structural or functional connectivity between a set of brain regions, graphs have proven to be of great importance. This is mainly due to the capability of revealing patterns related to brain development and disease, which were previously unknown. Evaluating similarity between these brain connectivity networks in a manner that accounts for the graph structure and is tailored for a particular application is, however, non-trivial. Most existing methods fail to accommodate the graph structure, discarding information that could be beneficial for further classification or regression analyses based on these similarities. We propose to learn a graph similarity metric using a siamese graph convolutional neural network (s-GCN) in a supervised setting. The proposed framework takes into consideration the graph structure for the evaluation of similarity between a pair of graphs, by employing spectral graph convolutions that allow the generalisation of traditional convolutions to irregular graphs and operates in the graph spectral domain. We apply the proposed model on two datasets: the challenging ABIDE database, which comprises functional MRI data of 403 patients with autism spectrum disorder (ASD) and 468 healthy controls aggregated from multiple acquisition sites, and a set of 2500 subjects from UK Biobank. We demonstrate the performance of the method for the tasks of classification between matching and non-matching graphs, as well as individual subject classification and manifold learning, showing that it leads to significantly improved results compared to traditional methods.



http://ift.tt/2CXPSU3

Probing the association between serotonin-1A autoreceptor binding and amygdala reactivity in healthy volunteers

Publication date: 1 May 2018
Source:NeuroImage, Volume 171
Author(s): Georg S. Kranz, Andreas Hahn, Christoph Kraus, Marie Spies, Verena Pichler, Johannes Jungwirth, Markus Mitterhauser, Wolfgang Wadsak, Christian Windischberger, Siegfried Kasper, Rupert Lanzenberger
IntroductionThe serotonergic system modulates affect and is a target in the treatment of mood disorders. 5-HT1A autoreceptors in the raphe control serotonin release by means of negative feedback inhibition. Hence, 5-HT1A autoreceptor function should influence the serotonergic regulation of emotional reactivity in limbic regions. Previous findings suggest an inverse relationship between 5-HT1A autoreceptor binding and amygdala reactivity to facial emotional expressions. The aim of the current multimodal neuroimaging study was to replicate the previous finding in a larger cohort.Methods31 healthy participants underwent fMRI as well as PET using the radioligand [carbonyl-¹¹C]WAY-100635 to quantify 5-HT1A autoreceptor binding in the dorsal raphe. The binding potential (BPND) was quantified using the multilinear reference tissue model (MRTM2) and cerebellar white matter as reference tissue. Functional MRI was done at 3T using a well-established facial emotion discrimination task (EDT). Here, participants had to match the emotional valence of facial expressions, while in a control condition they had to match geometric shapes. Effects of 5-HT1A autoreceptor binding on amygdala reactivity were investigated using linear regression analysis with SPM8.ResultsRegression analysis between 5-HT1A autoreceptor binding and mean amygdala reactivity revealed no statistically significant associations. Investigating amygdala reactivity in a voxel-wise approach revealed a positive association in the right amygdala (peak-T = 3.64, p < .05 FWE corrected for the amygdala volume) which was however conditional on the omission of age and sex as covariates in the model.ConclusionDespite highly significant amygdala reactivity to facial emotional expressions, we were unable to replicate the inverse relationship between 5-HT1A autoreceptor binding in the DRN and amygdala reactivity. Our results oppose previous multimodal imaging studies but seem to be in line with recent animal research. Deviation in results may be explained by methodological differences between our and previous multimodal studies.



http://ift.tt/2mfguWm

Chronic nicotine exposure impairs uncertainty modulation on reinforcement learning in anterior cingulate cortex and serotonin system

Publication date: 1 April 2018
Source:NeuroImage, Volume 169
Author(s): Zhengde Wei, Long Han, Xiuying Zhong, Ying Liu, Rujing Zha, Ying Wang, Li-Zhuang Yang, Junjie Bu, Hongwen Song, Wenjuan Wang, Yifeng Zhou, Ping Gao, Xiaochu Zhang
Deficits in the computational processes of reinforcement learning have been suggested to underlie addiction. Additionally, environmental uncertainty, which is encoded in the anterior cingulate cortex (ACC), modulates reward prediction errors (RPEs) during reinforcement learning and exacerbates addiction. The present study tested whether and how the ACC would have an essential role in drug addiction by failing to use uncertainty to modulate the RPEs during reinforcement learning. In Experiment I, we found that the ACC/medial prefrontal cortex (MPFC) did not modulate RPE learning according to uncertainty in smokers. The effect of uncertainty × RPE in the ACC/MPFC was correlated with the learning rate of RPEs and the duration of nicotine use. Experiment II demonstrated that serotonin, but not dopamine, receptor mRNA expression significantly decreased in the ACC of the nicotine exposed compared to the control rats. Furthermore, there was a positive correlation between learning rate and serotonin receptor mRNA expression in the ACC. Therefore, all present results suggest that impairments in uncertainty modulation in the ACC disrupt reinforcement learning processes in chronic nicotine users and contribute to maladaptive decision-making. These findings support interventions for pathological decision-making in drug addiction that strongly focus on the serotonin system in ACC.



http://ift.tt/2CSaa1h

LEICA: Laplacian eigenmaps for group ICA decomposition of fMRI data

Publication date: 1 April 2018
Source:NeuroImage, Volume 169
Author(s): Chihuang Liu, Joseph JaJa, Luiz Pessoa
Independent component analysis (ICA) is a data-driven method that has been increasingly used for analyzing functional Magnetic Resonance Imaging (fMRI) data. However, generalizing ICA to multi-subject studies is non-trivial due to the high-dimensionality of the data, the complexity of the underlying neuronal processes, the presence of various noise sources, and inter-subject variability. Current group ICA based approaches typically use several forms of the Principal Component Analysis (PCA) method to extend ICA for generating group inferences. However, linear dimensionality reduction techniques have serious limitations including the fact that the underlying BOLD signal is a complex function of several nonlinear processes. In this paper, we propose an effective non-linear ICA-based model for extracting group-level spatial maps from multi-subject fMRI datasets. We use a non-linear dimensionality reduction algorithm based on Laplacian eigenmaps to identify a manifold subspace common to the group, such that this mapping preserves the correlation among voxels' time series as much as possible. These eigenmaps are modeled as linear mixtures of a set of group-level spatial features, which are then extracted using ICA. The resulting algorithm is called LEICA (Laplacian Eigenmaps for group ICA decomposition). We introduce a number of methods to evaluate LEICA using 100-subject resting state and 100-subject working memory task fMRI datasets from the Human Connectome Project (HCP). The test results show that the extracted spatial maps from LEICA are meaningful functional networks similar to those produced by some of the best known methods. Importantly, relative to state-of-the-art methods, our algorithm compares favorably in terms of the functional cohesiveness of the spatial maps generated, as well as in terms of the reproducibility of the results.



http://ift.tt/2md39gT

Quantitative assessment of structural image quality

Publication date: 1 April 2018
Source:NeuroImage, Volume 169
Author(s): Adon F.G. Rosen, David R. Roalf, Kosha Ruparel, Jason Blake, Kevin Seelaus, Lakshmi P. Villa, Rastko Ciric, Philip A. Cook, Christos Davatzikos, Mark A. Elliott, Angel Garcia de La Garza, Efstathios D. Gennatas, Megan Quarmley, J. Eric Schmitt, Russell T. Shinohara, M. Dylan Tisdall, R. Cameron Craddock, Raquel E. Gur, Ruben C. Gur, Theodore D. Satterthwaite
Data quality is increasingly recognized as one of the most important confounding factors in brain imaging research. It is particularly important for studies of brain development, where age is systematically related to in-scanner motion and data quality. Prior work has demonstrated that in-scanner head motion biases estimates of structural neuroimaging measures. However, objective measures of data quality are not available for most structural brain images. Here we sought to identify quantitative measures of data quality for T1-weighted volumes, describe how these measures relate to cortical thickness, and delineate how this in turn may bias inference regarding associations with age in youth. Three highly-trained raters provided manual ratings of 1840 raw T1-weighted volumes. These images included a training set of 1065 images from Philadelphia Neurodevelopmental Cohort (PNC), a test set of 533 images from the PNC, as well as an external test set of 242 adults acquired on a different scanner. Manual ratings were compared to automated quality measures provided by the Preprocessed Connectomes Project's Quality Assurance Protocol (QAP), as well as FreeSurfer's Euler number, which summarizes the topological complexity of the reconstructed cortical surface. Results revealed that the Euler number was consistently correlated with manual ratings across samples. Furthermore, the Euler number could be used to identify images scored "unusable" by human raters with a high degree of accuracy (AUC: 0.98–0.99), and out-performed proxy measures from functional timeseries acquired in the same scanning session. The Euler number also was significantly related to cortical thickness in a regionally heterogeneous pattern that was consistent across datasets and replicated prior results. Finally, data quality both inflated and obscured associations with age during adolescence. Taken together, these results indicate that reliable measures of data quality can be automatically derived from T1-weighted volumes, and that failing to control for data quality can systematically bias the results of studies of brain maturation.



http://ift.tt/2CTA7xk

The anterior-ventrolateral temporal lobe contributes to boosting visual working memory capacity for items carrying semantic information

Publication date: 1 April 2018
Source:NeuroImage, Volume 169
Author(s): Rocco Chiou, Matthew A. Lambon Ralph
Working memory (WM) is a buffer that temporarily maintains information, be it visual or auditory, in an active state, caching its contents for online rehearsal or manipulation. How the brain enables long-term semantic knowledge to affect the WM buffer is a theoretically significant issue awaiting further investigation. In the present study, we capitalise on the knowledge about famous individuals as a 'test-case' to study how it impinges upon WM capacity for human faces and its neural substrate. Using continuous theta-burst transcranial stimulation combined with a psychophysical task probing WM storage for varying contents, we provide compelling evidence that (1) faces (regardless of familiarity) continued to accrue in the WM buffer with longer encoding time, whereas for meaningless stimuli (colour shades) there was little increment; (2) the rate of WM accrual was significantly more efficient for famous faces, compared to unknown faces; (3) the right anterior-ventrolateral temporal lobe (ATL) causally mediated this superior WM storage for famous faces. Specifically, disrupting the ATL (a region tuned to semantic knowledge including person identity) selectively hinders WM accrual for celebrity faces while leaving the accrual for unfamiliar faces intact. Further, this 'semantically-accelerated' storage is impervious to disruption of the right middle frontal gyrus and vertex, supporting the specific and causative contribution of the right ATL. Our finding advances the understanding of the neural architecture of WM, demonstrating that it depends on interaction with long-term semantic knowledge underpinned by the ATL, which causally expands the WM buffer when visual content carries semantic information.



http://ift.tt/2maPTJM

Transformation from independent to integrative coding of multi-object arrangements in human visual cortex

Publication date: 1 April 2018
Source:NeuroImage, Volume 169
Author(s): Daniel Kaiser, Marius V. Peelen
To optimize processing, the human visual system utilizes regularities present in naturalistic visual input. One of these regularities is the relative position of objects in a scene (e.g., a sofa in front of a television), with behavioral research showing that regularly positioned objects are easier to perceive and to remember. Here we use fMRI to test how positional regularities are encoded in the visual system. Participants viewed pairs of objects that formed minimalistic two-object scenes (e.g., a "living room" consisting of a sofa and television) presented in their regularly experienced spatial arrangement or in an irregular arrangement (with interchanged positions). Additionally, single objects were presented centrally and in isolation. Multi-voxel activity patterns evoked by the object pairs were modeled as the average of the response patterns evoked by the two single objects forming the pair. In two experiments, this approximation in object-selective cortex was significantly less accurate for the regularly than the irregularly positioned pairs, indicating integration of individual object representations. More detailed analysis revealed a transition from independent to integrative coding along the posterior-anterior axis of the visual cortex, with the independent component (but not the integrative component) being almost perfectly predicted by object selectivity across the visual hierarchy. These results reveal a transitional stage between individual object and multi-object coding in visual cortex, providing a possible neural correlate of efficient processing of regularly positioned objects in natural scenes.



http://ift.tt/2CVeTPv

Macroscale variation in resting-state neuronal activity and connectivity assessed by simultaneous calcium imaging, hemodynamic imaging and electrophysiology

Publication date: 1 April 2018
Source:NeuroImage, Volume 169
Author(s): Matthew C. Murphy, Kevin C. Chan, Seong-Gi Kim, Alberto L. Vazquez
Functional imaging of spontaneous activity continues to play an important role in the field of connectomics. The most common imaging signal used for these experiments is the blood-oxygen-level-dependent (BOLD) functional MRI (fMRI) signal, but how this signal relates to spontaneous neuronal activity remains incompletely understood. Genetically encoded calcium indicators represent a promising tool to study this problem, as they can provide brain-wide measurements of neuronal activity compared to point measurements afforded by electrophysiological recordings. However, the relationship between the calcium signal and neurophysiological parameters at the mesoscopic scale requires further systematic characterization. Therefore, we collected simultaneous resting-state measurements of electrophysiology, along with calcium and hemodynamic imaging, in lightly anesthetized mice to investigate two aims. First, we examined the relationship between each imaging signal and the simultaneously recorded electrophysiological signal in a single brain region, finding that both signals are better correlated with multi-unit activity compared to local field potentials, with the calcium signal possessing greater signal-to-noise ratio and regional specificity. Second, we used the resting-state imaging data to model the relationship between the calcium and hemodynamic signals across the brain. We found that this relationship varied across brain regions in a way that is consistent across animals, with delays increasing by600 ms towards posterior cortical regions. Furthermore, while overall functional connectivity (FC) measured by the hemodynamic signal is significantly correlated with FC measured by calcium, the two estimates were found to be significantly different. We hypothesize that these differences arise at least in part from the observed regional variation in the hemodynamic response. In total, this work highlights some of the caveats needed in interpreting hemodynamic-based measurements of FC, as well as the need for improved modeling methods to reduce this potential source of bias.



http://ift.tt/2mbGSjy

Mn2+ dynamics in manganese-enhanced MRI (MEMRI): Cav1.2 channel-mediated uptake and preferential accumulation in projection terminals

Publication date: 1 April 2018
Source:NeuroImage, Volume 169
Author(s): Benedikt T. Bedenk, Suellen Almeida-Corrêa, Angela Jurik, Nina Dedic, Barbara Grünecker, Andreas J. Genewsky, Sebastian F. Kaltwasser, Caitlin J. Riebe, Jan M. Deussing, Michael Czisch, Carsten T. Wotjak
Manganese-enhanced magnetic resonance imaging (MEMRI) exploits the biophysical similarity of Ca²⁺ and Mn²⁺ to map the brain's activity in vivo. However, to what extent different Ca²⁺ channels contribute to the enhanced signal that MEMRI provides and how Mn²⁺ dynamics influence Mn²⁺ brain accumulation after systemic administration of MnCl2 are not yet fully understood. Here, we demonstrate that mice lacking the L-type Ca²⁺ channel 1.2 (Cav1.2) in the CNS show approximately 50% less increase in MEMRI contrast after repeated systemic MnCl2 injections, as compared to control mice. In contrast, genetic deletion of L-type Ca²⁺ channel 1.3 (Cav1.3) did not reduce signal. Brain structure- or cell type-specific deletion of Cav1.2 in combination with voxel-wise MEMRI analysis revealed a preferential accumulation of Mn²⁺ in projection terminals, which was confirmed by local MnCl2 administration to defined brain areas.Taken together, we provide unequivocal evidence that Cav1.2 represents an important channel for neuronal Mn²⁺ influx after systemic injections. We also show that after neuronal uptake, Mn²⁺ preferentially accumulates in projection terminals.

Graphical abstract

http://ift.tt/2CXO3Gw

Neural circuitry underlying sustained attention in healthy adolescents and in ADHD symptomatology

Publication date: 1 April 2018
Source:NeuroImage, Volume 169
Author(s): Laura O'Halloran, Zhipeng Cao, Kathy Ruddy, Lee Jollans, Matthew D. Albaugh, Andrea Aleni, Alexandra S. Potter, Nigel Vahey, Tobias Banaschewski, Sarah Hohmann, Arun L.W. Bokde, Uli Bromberg, Christian Büchel, Erin Burke Quinlan, Sylvane Desrivières, Herta Flor, Vincent Frouin, Penny Gowland, Andreas Heinz, Bernd Ittermann, Frauke Nees, Dimitri Papadopoulos Orfanos, Tomáš Paus, Michael N. Smolka, Henrik Walter, Gunter Schumann, Hugh Garavan, Clare Kelly, Robert Whelan
Moment-to-moment reaction time variability on tasks of attention, often quantified by intra-individual response variability (IRV), provides a good indication of the degree to which an individual is vulnerable to lapses in sustained attention. Increased IRV is a hallmark of several disorders of attention, including Attention-Deficit/Hyperactivity Disorder (ADHD). Here, task-based fMRI was used to provide the first examination of how average brain activation and functional connectivity patterns in adolescents are related to individual differences in sustained attention as measured by IRV. We computed IRV in a large sample of adolescents (n = 758) across 'Go' trials of a Stop Signal Task (SST). A data-driven, multi-step analysis approach was used to identify networks associated with low IRV (i.e., good sustained attention) and high IRV (i.e., poorer sustained attention). Low IRV was associated with greater functional segregation (i.e., stronger negative connectivity) amongst an array of brain networks, particularly between cerebellum and motor, cerebellum and prefrontal, and occipital and motor networks. In contrast, high IRV was associated with stronger positive connectivity within the motor network bilaterally and between motor and parietal, prefrontal, and limbic networks. Consistent with these observations, a separate sample of adolescents exhibiting elevated ADHD symptoms had increased fMRI activation and stronger positive connectivity within the same motor network denoting poorer sustained attention, compared to a matched asymptomatic control sample. With respect to the functional connectivity signature of low IRV, there were no statistically significant differences in networks denoting good sustained attention between the ADHD symptom group and asymptomatic control group. We propose that sustained attentional processes are facilitated by an array of neural networks working together, and provide an empirical account of how the functional role of the cerebellum extends to cognition in adolescents. This work highlights the involvement of motor cortex in the integrity of sustained attention, and suggests that atypically strong connectivity within motor networks characterizes poor attentional capacity in both typically developing and ADHD symptomatic adolescents.



http://ift.tt/2CSa6P5

Transient synchronization of hippocampo-striato-thalamo-cortical networks during sleep spindle oscillations induces motor memory consolidation

Publication date: 1 April 2018
Source:NeuroImage, Volume 169
Author(s): Arnaud Boutin, Basile Pinsard, Arnaud Boré, Julie Carrier, Stuart M. Fogel, Julien Doyon
Sleep benefits motor memory consolidation. This mnemonic process is thought to be mediated by thalamo-cortical spindle activity during NREM-stage2 sleep episodes as well as changes in striatal and hippocampal activity. However, direct experimental evidence supporting the contribution of such sleep-dependent physiological mechanisms to motor memory consolidation in humans is lacking. In the present study, we combined EEG and fMRI sleep recordings following practice of a motor sequence learning (MSL) task to determine whether spindle oscillations support sleep-dependent motor memory consolidation by transiently synchronizing and coordinating specialized cortical and subcortical networks. To that end, we conducted EEG source reconstruction on spindle epochs in both cortical and subcortical regions using novel deep-source localization techniques. Coherence-based metrics were adopted to estimate functional connectivity between cortical and subcortical structures over specific frequency bands. Our findings not only confirm the critical and functional role of NREM-stage2 sleep spindles in motor skill consolidation, but provide first-time evidence that spindle oscillations [11–17 Hz] may be involved in sleep-dependent motor memory consolidation by locally reactivating and functionally binding specific task-relevant cortical and subcortical regions within networks including the hippocampus, putamen, thalamus and motor-related cortical regions.



http://ift.tt/2ma91Yz

Differential effects of childhood neglect and abuse during sensitive exposure periods on male and female hippocampus

Publication date: 1 April 2018
Source:NeuroImage, Volume 169
Author(s): Martin H. Teicher, Carl M. Anderson, Kyoko Ohashi, Alaptagin Khan, Cynthia E. McGreenery, Elizabeth A. Bolger, Michael L. Rohan, Gordana D. Vitaliano
The hippocampus is a highly stress susceptible structure and hippocampal abnormalities have been reported in a host of psychiatric disorders including major depression and post-traumatic stress disorder (PTSD). The hippocampus appears to be particularly susceptible to early life stress with a graded reduction in volume based on number of types (multiplicity) or severity of maltreatment. We assessed whether the most important predictors of adult hippocampal volume were multiplicity, severity or duration of exposure or timing of maltreatment during developmental sensitive periods. 3T MRIs were collected on 336 unmedicated, right-handed subjects (132M/204F, 18–25 years). Exposure to broad categories of abuse and neglect during each year of childhood were assessed using the Maltreatment and Abuse Chronology of Exposure scale and evaluated using artificial intelligence and predictive analytics. Male hippocampal volume was predicted by neglect, but not abuse, up through 7 years of age. Female hippocampal volume was predicted by abuse, but not neglect, at 10, 11, 15 and 16 years. Exposure at peak age had greater predictive importance than multiplicity, severity or duration. There were also marked gender differences in subfields and portions (head, body or tail) affected by exposure. History and symptoms of major depression, PTSD or anxiety disorders were not predictive of hippocampal volume once maltreatment was accounted for. Neglect appears to foster inadequate hippocampal development in males while abuse appears to produce a stress-related deficit in females. Studies assessing hippocampal volume in psychiatric disorders need to control for the gender-specific effects of abuse and neglect.



http://ift.tt/2CSa3Tp

Real-time decoding of covert attention in higher-order visual areas

Publication date: 1 April 2018
Source:NeuroImage, Volume 169
Author(s): Jinendra Ekanayake, Chloe Hutton, Gerard Ridgway, Frank Scharnowski, Nikolaus Weiskopf, Geraint Rees
Brain-computer-interfaces (BCI) provide a means of using human brain activations to control devices for communication. Until now this has only been demonstrated in primary motor and sensory brain regions, using surgical implants or non-invasive neuroimaging techniques. Here, we provide proof-of-principle for the use of higher-order brain regions involved in complex cognitive processes such as attention. Using realtime fMRI, we implemented an online 'winner-takes-all approach' with quadrant-specific parameter estimates, to achieve single-block classification of brain activations. These were linked to the covert allocation of attention to real-world images presented at 4-quadrant locations. Accuracies in three target regions were significantly above chance, with individual decoding accuracies reaching upto 70%. By utilising higher order mental processes, 'cognitive BCIs' access varied and therefore more versatile information, potentially providing a platform for communication in patients who are unable to speak or move due to brain injury.



http://ift.tt/2mc7iSl

Effective connectivity during working memory and resting states: A DCM study

Publication date: 1 April 2018
Source:NeuroImage, Volume 169
Author(s): Kyesam Jung, Karl J. Friston, Chongwon Pae, Hanseul H. Choi, Sungho Tak, Yoon Kyoung Choi, Bumhee Park, Chan-A Park, Chaejoon Cheong, Hae-Jeong Park
Although the relationship between resting-state functional connectivity and task-related activity has been addressed, the relationship between task and resting-state directed or effective connectivity – and its behavioral concomitants – remains elusive. We evaluated effective connectivity under an N-back working memory task in 24 participants using stochastic dynamic causal modelling (DCM) of 7 T fMRI data. We repeated the analysis using resting-state data, from the same subjects, to model connectivity among the same brain regions engaged by the N-back task. This allowed us to: (i) examine the relationship between intrinsic (task-independent) effective connectivity during resting (Arest) and task states (Atask), (ii) cluster phenotypes of task-related changes in effective connectivity (Btask) across participants, (iii) identify edges (Btask) showing high inter-individual effective connectivity differences and (iv) associate reaction times with the similarity between Btask and Arest in these edges. We found a strong correlation between Arest and Atask over subjects but a marked difference between Btask and Arest. We further observed a strong clustering of individuals in terms of Btask, which was not apparent in Arest. The task-related effective connectivity Btask varied highly in the edges from the parietal to the frontal lobes across individuals, so the three groups were clustered mainly by the effective connectivity within these networks. The similarity between Btask and Arest at the edges from the parietal to the frontal lobes was positively correlated with 2-back reaction times. This result implies that a greater change in context-sensitive coupling – from resting-state connectivity – is associated with faster reaction times. In summary, task-dependent connectivity endows resting-state connectivity with a context sensitivity, which predicts the speed of information processing during the N-back task.



http://ift.tt/2CUXKpf

Scholar : These new articles for Alcheringa: An Australasian Journal of Palaeontology are available online

The online platform for Taylor & Francis Online content New for Alcheringa: An Australasian Journal of Palaeontology and online now on Taylor & Francis Online: Note Corrigendum Pages: 1-1 | DOI: 10.1080/03115518.2017.1417479 Browse papers on image & data fusion, GIS, LiDAR & more in the International Journal of Image and Data Fusion's exclusive Editor's Choice collection. To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Cosmetics, Vol. 5, Pages 9: Significance of Ubiad1 for Epidermal Keratinocytes Involves More Than CoQ10 Synthesis: Implications for Skin Aging

Cosmetics, Vol. 5, Pages 9: Significance of Ubiad1 for Epidermal Keratinocytes Involves More Than CoQ10 Synthesis: Implications for Skin Aging

Cosmetics doi: 10.3390/cosmetics5010009

Authors: Florian Labarrade Gopinathan Menon Laura Labourasse Catherine Gondran Karine Cucumel Nouha Domloge

The significance of Coenzyme Q10 (CoQ10) as an anti-oxidant barrier of the skin, as well as a key component in anti-aging strategies for skin care products, has been firmly established. Biosynthesis of CoQ10 in the mitochondria is well known, but there is only limited information on the non-mitochondrial synthesis of CoQ10 in the skin. Recent findings in zebrafish identified that a tumor suppressor, Ubiad1, is also a key enzyme in the non-mitochondrial synthesis of CoQ10. The purpose of this study was to investigate expression of Ubiad1 in human skin, and its implication in the skin's cutaneous response to oxidative stress. We observed Ubiad1 localization in the epidermis, particularly a subcellular localization in the Golgi apparatus. Ubiad1 modulation by a pentapeptide was associated with an observed reduction in ROS/RNS stresses (−44%/−19% respectively), lipid peroxidation (−25%) and preservation of membrane fluidity under stress conditions. Electron microscopy of keratinocytes revealed a significant degree of stimulation of the Golgi complex, as well as significantly improved mitochondrial morphology. Given the importance of CoQ10 in mitigating the visible signs of skin aging, our findings identify Ubiad1 as an essential component of the defensive barriers of the epidermis.

http://ift.tt/2mhV7V6

IRF1 up-regulates isg15 gene expression in dsRNA stimulation or CSFV infection by targeting nucleotides −487 to −325 in the 5′ flanking region

Publication date: February 2018
Source:Molecular Immunology, Volume 94
Author(s): Xiao-Quan Li, Xiao Ning Li, Jing-Jing Liang, Xin-Bin Cai, Qian Tao, Yu-Xiao Li, Qing Qin, Su-Ping Xu, Ting Rong Luo
Interferon (IFN)-stimulated gene 15 (ISG15) encodes a ubiquitin-like protein that is heavily involved in immune response elicitation. As an important member of interferon regulatory factor (IRF) family, IRF1 can activate the expression of multiple genes, including the human optineurin gene (Sudhakar et al., 2013). In this study, a sequence in the promoter region of the optineurin gene was compared to the 5′ flanking region of the porcine isg15 gene. Porcine IRF1 also possesses antiviral activity against several swine viruses (Li et al., 2015), but the mechanism is not well understood. Herein, we report that porcine IRF1 and ISG15 were up-regulated in porcine kidney (PK-15) cells following stimulation with double-stranded RNA (dsRNA) or classical swine fever virus (CSFV) infection. We also found that siRNA-mediated knockdown of IRF1 expression resulted in lower ISG15 expression in response to polyinosinic:polycytidylic acid [poly(I:C)] or CSFV infection. The overexpression of IRF1 resulted in ISG15 up-regulation. IRF1 was shown to translocate to the nucleus in response to dsRNA stimulation. To further identify the functional domain of the isg15 gene that promotes IRF1 transcriptional activity, firefly luciferase and ISG15 reporter systems were constructed. The results of the firefly luciferase and ISG15 reporter assay suggested that IRF1 mediates the up-regulation of ISG15. Nucleotides −487 to −325, located in the 5′ flanking region of the isg15 gene, constituted the promoter region of IRF1. ChIP assay indicated that IRF1 protein was able to interact with the DNA in the 5′fr of isg15 gene in cells. As an innate immune response protein with broad-spectrum antiviral activity, the up-regulation of ISG15 mediated by IRF1 in porcine cells is reported for the first time. These results warrant further investigation into the antiviral activity of porcine IRF1 against reported swine viruses.



http://ift.tt/2qN21GB

DNA induction of MDM2 promotes proliferation of human renal mesangial cells and alters peripheral B cells subsets in pediatric systemic lupus erythematosus

Publication date: February 2018
Source:Molecular Immunology, Volume 94
Author(s): Chen-xing Zhang, Ji Chen, Li Cai, Jing Wu, Jia-yuan Wang, Lan-fang Cao, Wei Zhou, Tong-xin Chen
The study is aimed to investigate the role of MDM2 in the pathogenesis of lupus nephritis (LN) in pediatric SLE (pSLE). We confirmed that MDM2 expression was increased in peripheral blood mononuclear cells (PBMCs) as well as renal specimen of SLE compared with that of controls by western blot and immunofluorescence staining. Percentage of apoptotic and necrotic CD4⁺T, CD8⁺T and B cells were detected by flow cytometry respectively and levels of plasma cell free DNA (cfDNA) were quantified in SLE and healthy controls (HC). We also proved that elevated apoptotic and necrotic CD4⁺T cells were the main cause for increased plasma levels of cfDNA in pSLE. Additionally, upon DNA transfection MDM2 increased while P53 and P21 decreased in human renal mesangial cells (HRMC), with concomitant increase in proliferation rate and proportion of cells in S phase, as demonstrated by cell proliferation assay and cell cycle analysis. However, MDM2 inhibition reversed the trend. Furthermore, percentage of switched memory B cells decreased and proportion of double negative B cells increased upon blockage of MDM2 in PBMC. In summary, our study provided the first evidence that DNA induction of MDM2 promotes proliferation of HRMC and alters peripheral B cells subsets in pSLE. Thus our study has not only elucidated the pathogenesis of MDM2 in pediatric LN but also provided a novel target for drug development. In conclusion, our data suggested that apoptosis, cfDNA and MDM2 could form a pathological axis in SLE, especially in pSLE.



http://ift.tt/2mjrl2l

Immunization with recombinant FliD confers protection against Helicobacter pylori infection in mice

Publication date: February 2018
Source:Molecular Immunology, Volume 94
Author(s): Amir Ghasemi, Nazanin Mohammad, Josef Mautner, Mehrnaz Taghipour Karsabet, Abolfazl Ardjmand, Rezvan Moniri
Nearly half of the world's population is infected with Helicobacter pylori. Clinical manifestations of this infection range from gastritis and peptic ulcers to gastric adenocarcinoma and lymphoma. Due to the emerging of antibiotic resistant strains and poor patient compliance of the antibiotic therapy, there is increasing interest in the development of a protective vaccine against H. pylori infection. The bacterial protein FliD forms a capping structure on the end of each flagellum which is critical to prevent depolymerization and structural degradation. In this study, the potential of FliD as a prospective H. pylori subunit vaccine was assessed. For this purpose, immunogenicity and protective efficacy of recombinant FliD (rFliD) from H. pylori was evaluated in C57BL/6 mice. Purified rFliD was formulated with different adjuvants and administered via subcutaneous or oral route. Subcutaneous immunization with rFliD elicited predominantly mixed Th1 and Th17 immune responses, with high titers of specific IgG1 and IgG2a. Splenocytes of immunized mice exhibited strong antigen-specific memory responses, resulting in the secretion of high amounts of IFN-γ and IL-17, and low levels of IL-4. Immunization with rFliD caused a significant reduction in H. pylori bacterial load relative to naïve control mice (p < 0.001), demonstrating a robust protective effect. Taken together, these results suggest that subcutaneous vaccination with rFliD formulated with CpG or Addavax could be considered as a potential candidate for the development of a subunit vaccine against H. pylori infection.



http://ift.tt/2qMLYIK

The emerging role of nanomaterials in immunological sensing — a brief review

Publication date: Available online 8 January 2018
Source:Molecular Immunology
Author(s): Simon R. Corrie, Magdalena Plebanski
Nanomaterials are beginning to play an important role in the next generation of immunological assays and biosensors, with potential impacts both in research and clinical practice. In this brief review, we highlight two areas in which nanomaterials are already making new and important contributions in the past 5–10 years: firstly, in the improvement of assay and biosensor sensitivity for detection of low abundance proteins of immunological significance, and secondly, in the real-time and continuous monitoring of protein secretion from arrays of individual cells. We finish by challenging the immunology/sensing communities to work together to develop nanomaterials that can provide real-time, continuous, and sensitive molecular readouts in vivo, a lofty goal that will require significant collaborative effort.



http://ift.tt/2qMLYbI

StrataXRT vs Standard Clinical Practice for the Prevention of Acute Dermatitis in Head and Neck Cancers Patients

Conditions:   Head and Neck Cancers;   Acute Radiation Dermatitis
Intervention:   Device: StrataXRT
Sponsor:   National University Hospital, Singapore
Not yet recruiting

http://ift.tt/2EqAxsn

O-Arm-Guided Percutaneous Radiofrequency Cordotomy

Background: Pain is often one of the most debilitating symptoms in patients with advanced oncological disease. Patients with localized pain due to malignancy refractory to medical treatment can benefit from selective percutaneous cordotomy that disconnects the ascending pain fibers in the spinothalamic tract. Objectives: Over the past year, we have been performing percutaneous radiofrequency cordotomy with the use of the O-Arm intraoperative imaging system that allows both 2D fluoroscopy and 3D reconstructed computerized tomography imaging. We present our experience using this technique, focusing on technical nuances and complications. Methods: A retrospective analysis was conducted of all patients who underwent percutaneous cordotomy between March 2016 and March 2017. Results: Nineteen patients underwent percutaneous cordotomy procedures. Two patients developed intraoperative delirium and were unable to tolerate the procedure. In 16 out of 17 completed procedures, we achieved excellent immediate pain relief (94%). At 1 month after operation, 15 of the 17 (88%) patients were pain free, and at 3 months 5 out of 5 patients available for follow-up were still free of their original pain. Mirror pain developed in 6 of the 17 patients (35%), but was mild in 4 of these cases and controlled with medications. We experienced 1 serious complication (6%) of ipsilateral hemiparesis. Conclusion: Percutaneous cordotomy using the O-Arm is safe and effective in the treatment of intractable oncological pain.
Stereotact Funct Neurosurg 2017;95:409-416

http://ift.tt/2m8sdFY

Double Anterior Stereotactic Cingulotomy for Intractable Oncological Pain

Background: Stereotactic anterior cingulotomy has been used in the treatment of patients suffering from refractory oncological pain due to its effects on pain perception. However, the optimal targets as well as suitable candidates and outcome measures have not been well defined. We report our initial experience in the ablation of 2 cingulotomy targets on each side and the use of the Brief Pain Inventory (BPI) as a perioperative assessment tool. Methods: A retrospective review of all patients who underwent stereotactic anterior cingulotomy in our Department between November 2015 and February 2017 was performed. All patients had advanced metastatic cancer with limited prognosis and suffered from intractable oncological pain. Results: Thirteen patients (10 women and 3 men) underwent 14 cingulotomy procedures. Their mean age was 54 ± 14 years. All patients reported substantial pain relief immediately after the operation. Out of the 6 preoperatively bedridden patients, 3 started ambulating shortly after. At the 1-month follow-up, the mean preoperative Visual Analogue Scale score decreased from 9 ± 0.9 to 4 ± 2.7 (p = 0.003). Mean BPI pain severity and interference scores decreased from levels of 29 ± 4 and 55 ± 12 to 16 ± 12 (p = 0.028) and 37 ± 15 (p = 0.043), respectively. During the 1- and 3-month follow-up visits, 9/11 patients (82%) and 5/7 patients (71%) available for follow-up reported substantial pain relief. No patient reported worsening of pain during the study period. Neuropsychological analyses of 6 patients showed stable cognitive functions with a mild nonsignificant decline in focused attention and executive functions. Adverse events included transient confusion or mild apathy in 5 patients (38%) lasting 1-4 weeks. Conclusions: Our initial experience indicates that double stereotactic cingulotomy is safe and effective in alleviating refractory oncological pain.
Stereotact Funct Neurosurg 2017;95:400-408

http://ift.tt/2CVWpyk