Metformin and insulin impact on clinical outcome in patients with advanced hepatocellular carcinoma receiving sorafenib: Validation study and biological rationale

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): Andrea Casadei Gardini, Luca Faloppi, Serena De Matteis, Francesco Giuseppe Foschi, Nicola Silvestris, Francesco Tovoli, Vincenzo Palmieri, Giorgia Marisi, Oronzo Brunetti, Umberto Vespasiani-Gentilucci, Giuseppe Perrone, Martina Valgiusti, Anna Maria Granato, Giorgio Ercolani, Giulia Negrini, Emiliano Tamburini, Giuseppe Aprile, Alessandro Passardi, Daniele Santini, Stefano Cascinu, Giovanni Luca Frassineti, Mario Scartozzi
PurposeIn 2015, we published a study on a small series of patients with hepatocellular carcinoma (HCC) treated chronically with metformin for type II diabetes mellitus (DM2) who showed a poorer response to sorafenib. The aim of the present study was to validate the prognostic significance of metformin in HCC patients treated with sorafenib, providing a biological rationale for the mechanism of resistance to sorafenib in patients on chronic metformin therapy, and to clarify the role of sirtuin-3 (SIRT-3), a protein involved in metabolic diseases and acknowledged as a tumour suppressor in HCC, in this resistance.Patients and methodsWe analysed 279 patients consecutively treated with sorafenib for the clinical analysis. Of the 86 (30%) patients with DM2, 52 (19%) were on chronic treatment with metformin and 34 (12%) with insulin. We included 43 patients with HCC for the biological study: 19 (44.1%) were diabetic and 14 (73.7%) of these received metformin for DM2. SIRT-3 expression was investigated by immunohistochemistry (IHC) in formalin-fixed and paraffin-embedded (FFPE) samples.ResultsIn HCC patients undergoing chronic treatment with metformin, the use of sorafenib was associated with poor progression-free survival (PFS) and overall survival (OS) (1.9 and 6.6 months, respectively) compared to 3.7 months and 10.8 months, respectively, for patients without DM2 and 8.4 months and 16.6 months, respectively, for patients on insulin (P < .0001). We also observed that SIRT-3 protein expression was significantly higher in patients treated with metformin than in those not taking this medication (65% versus 25%, respectively) (P = .013).ConclusionsOur findings could be attributed to increased tumour aggressiveness and resistance to sorafenib caused by chronic treatment with metformin.



http://ift.tt/2xT9qnC

‘Corrigendum to “Severe hepatitis under combined immunotherapy: Resolution under corticosteroids plus anti-thymocyte immunoglobulins” [Eur J Cancer 81 (August 2017) 203–205]’

Publication date: Available online 3 October 2017
Source:European Journal of Cancer
Author(s): Iris Spänkuch, Maximilian Gassenmaier, Ioanna Tampouri, Seema Noor, Andrea Forschner, Claus Garbe, Teresa Amaral




http://ift.tt/2wvUOZG

The quest for exceptional drug solubilization in diluted surfactant solutions and consideration of residual solid state

Publication date: 1 January 2018
Source:European Journal of Pharmaceutical Sciences, Volume 111
Author(s): Wiebke Saal, Nicole Wyttenbach, Jochem Alsenz, Martin Kuentz
Solubility screening in different surfactant solutions is an important part of pharmaceutical profiling. A particular interest is in low surfactant concentrations that mimic the dilution of an oral dosage form. Despite of intensive previous research on solubilization in micelles, there is only limited data available at low surfactant concentrations and generally missing is a physical state analysis of the residual solid. The present work therefore studied 13 model drugs in 6 different oral surfactant solutions (0.5%, w/w) by concomitant X-ray diffraction (XRPD) analysis to consider effects on solvent-mediated phase transformations. A particular aspect was potential occurrence of exceptionally high drug solubilization. As a result, general solubilization correlations were observed especially between surfactants that share chemical similarity. Exceptional solubility enhancement of several hundred-fold was evidenced in case of sodium dodecyl sulfate solutions with dipyridamole and progesterone. Furthermore, carbamazepine and testosterone showed surfactant-type dependent hydrate formation. The present results are of practical relevance for an optimization of surfactant screenings in preformulation and early development and provide a basis for mechanistic modeling of surfactant effects on solubilization and solid state modifications.

Graphical abstract

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Preparation and characterization of intravaginal vardenafil suppositories targeting a complementary treatment to boost in vitro fertilization process

Publication date: 1 January 2018
Source:European Journal of Pharmaceutical Sciences, Volume 111
Author(s): Eman Gomaa, Amr S. Abu Lila, Azza A. Hasan, Fakhr-eldin S. Ghazy
Vaginal route has been recently considered as a potential route for systemic delivery of drugs with poor oral bioavailability. Vardenafil (VDF) is a relatively new phosphodiesterase-5 inhibitor that exhibits a limited oral bioavailability (≈15%) due to extensive first-pass metabolism. In this study, we attempted to enhance the systemic bioavailability of VDF via its formulation within vaginal suppositories. Witepsol H15 and Suppocire NA50 were adopted as lipophilic suppository bases while polyethylene glycol 4000/400 and glycerogelatin were used as hydrophilic suppository bases. The effect of different base types and/or the incorporation of bioadhesive polymer on in vitro release of VDF were evaluated. The in vivo fate and organ biodistribution of VDF following intravaginal (IVG) administration were also investigated. VDF release from water-soluble bases was higher than that from lipophilic bases. The incorporation of bioadhesive polymers, such as Na alginate, remarkably sustained drug release from suppository base. The organ biodistribution study showed a higher Cmax (32 times) and AUC0–4h (20 times) of VDF in uterus following IVG administration of conventional suppositories, compared to oral administration of VDF suspension. In addition, cyclic guanosine monophosphate (cGMP) serum levels, used as an indicator of the in vivo activity of VDF, in animals were higher following IVG administration rather than oral administration. This study suggests that IVG administration of VDF might represent a potential alternative to oral route with superior therapeutic benefits especially when targeting the uterus.

Graphical abstract

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Evaluation of critical parameters for in vitro skin permeation and penetration studies using animal skin models

Publication date: 1 January 2018
Source:European Journal of Pharmaceutical Sciences, Volume 111
Author(s): Fabíola Silva Garcia Praça, Wanessa Silva Garcia Medina, Josimar O. Eloy, Raquel Petrilli, Patrícia Mazureki Campos, Andreia Ascenso, Maria Vitória L.B. Bentley
In vitro skin permeation/penetration studies may be affected by many sources of variation. Herein, we aimed to investigate the major critical procedures of in vitro skin delivery studies. These experiments were performed with model drugs according to official guidelines. The influence of skin source on penetration studies was studied as well as the use of a cryopreservation agent on skin freezing evaluated by transepidermal water loss, electrical resistance, permeation/penetration profiles and histological changes of the skin. The best condition for tape stripping procedure was validated through the evaluation of the distribution of corneocytes, mass of stratum corneum (SC) removed and amount of protein removed using finger pressure, a 2kg weight and a roller. The interchangeability of the tape stripping procedures followed by the epidermis and dermis homogenate and the micrometric horizontal cryostat skin sectioning methods were also investigated, besides the effect of different formulations. Noteworthy, different skin sources were able to ensure reliable interchangeability for in vitro permeation studies. Furthermore, an increased penetration was obtained for stored frozen skin compared to fresh skin, even with the addition of a cryoprotectant agent. The best method for tape stripping was the finger pressure followed by the addition of a propylene glycol solvent leading to better SC removal. Finally, no significant difference was found in skin penetration studies performed by different methods suggesting their possible interchangeability.

Graphical abstract

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Nanocapsules improve indole-3-carbinol photostability and prolong its antinociceptive action in acute pain animal models

Publication date: 1 January 2018
Source:European Journal of Pharmaceutical Sciences, Volume 111
Author(s): Mailine Gehrcke, Marcel Henrique Marcondes Sari, Luana Mota Ferreira, Allanna Valentini Barbieri, Laura Minussi Giuliani, Vinicius Costa Prado, Jessica Mendes Nadal, Paulo Vitor Farago, Cristina Wayne Nogueira, Letícia Cruz
This study aimed the development of nanocapsules (NCs) for oral indole-3-carbinol (I3C) administration and evaluation of antinociceptive potential of this compound in its two forms, free and nanoencapsulated, using acute pain models. NCs showed adequate physicochemical characteristics and protected the I3C against UVC radiation exposure. It was observed no chemical bond between I3C and polymer by FTIR. Besides, X-ray and DSC analysis suggested that I3C was molecularly dispersed in NCs. The dialysis bag technique showed that almost 100% of the compound was released from NCs at 360min. Mathematical modeling demonstrated that this release occurred in two rates, with an initial burst effect followed by a slower release of I3C. Regarding the in vivo analysis, time-response curve showed that both forms of I3C caused an inhibition in inflammatory phase of nociception induced by formalin and increased the latency response in hot plate test. Interestingly, NCs were able to prolong the I3C effect in both tests. Furthermore, in dose-response curve, only I3C in its nanoencapsulated form presented effect on inflammatory phase of the formalin test. In conclusion, NCs to I3C incorporation presented adequate nanometric characteristics and prolonged its antinociceptive action in acute pain models tested.

Graphical abstract

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TERT promoter mutation and its interaction with IDH mutations in glioma: Combined TERT promoter and IDH mutations stratifies lower-grade glioma into distinct survival subgroups—A meta-analysis of aggregate data

Publication date: Available online 3 October 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Huy Gia Vuong, Ahmed M.A. Altibi, Uyen N.P. Duong, Hanh T.T. Ngo, Thong Quang Pham, Aden Ka-Yin Chan, Chul-Kee Park, Kar-Ming Fung, Lewis Hassell
The clinical significance of telomerase reverse transcriptase (TERT) promoter mutation in glioma remains unclear. The aim of our meta-analysis is to investigate the prognostic impact TERT promoter mutation in glioma patients and its interaction with other molecular markers, particularly Isocitrate Dehydrogenase (IDH) mutation from aggregate level data. Relevant articles were searched in four electronic databases including PubMed, Scopus, Web of Science and Virtual Health Library. Pooled HRs were calculated using random effect model weighted by inverse variance method. From 1010 studies, we finally included 28 studies with 11519 patients for meta-analyses. TERT mutation is significantly associated with compromised overall survival (OS) (HR=1.38; 95% CI=1.15–1.67) and progression-free survival (PFS) (HR=1.31; 95% CI=1.06–1.63) in glioma patients. In studying its reaction with IDH, TERT promoter mutation was associated with reduced OS in both IDH-mutant (IDH-mut) and IDH-wild type (IDH-wt) glioblastomas but shown to have inverse effects on IDH-mut and IDH-wt grade II/III tumors. Our analysis categorized WHO grade II/III glioma patients into four distinct survival subgroups with descending survival as follow: TERT-mut/IDH-mut≫TERT-wt/IDH-mut≫TERT-wt/IDH-wt≫TERT-mut/IDH-wt. Prognostic value of TERT promoter mutations in gliomas is dependent on tumor grade and the IDH mutational status. With the same tumor grade in WHO grade II and III tumors and the same IDH mutation status, TERT-mut is a prognostic factor.



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Asthma disease as cause of admission to hospitals due to exposure to ambient oxidants in Mashhad, Iran

Abstract

Nowadays, asthma is one of the most common chronic respiratory diseases, worldwide. Many reports have emphasized the correlation between the short-term exposure to the ambient air pollutants and acute respiratory diseases, especially among children with asthmatic symptoms. The aim of this study was to evaluate the relationship between the exposure to three atmospheric antioxidants (NO₂, SO₂, and O₃) and hospital admission due to asthmatic disease (HAAD) in the city of Mashhad, Iran. The concentrations of atmospheric antioxidants were obtained from the real-time monitoring stations located in the city. The collected data were employed for developing predictive models in the AirQ software. In order to investigate the association between short-term exposure to air pollutants and HAAD, the study participants were categorized into two age groups: less than 15 and from 15 to 64 years old. The results indicated that in people less than 15 years increase in NO₂ (attributable proportion (AP) = 3.775%, 95% CI 0.897–6.883%), SO₂ (AP = 3.649%, 95% CI 1.295–5.937%), and O₃ (AP = 0.554%,95% CI 0.00–3.321) results in increase in HAAD. While for those aged between 15 and 64 years, the AP was 4.192% (95% CI 0.450–7.662%) for NO₂; 0.0% (95% CI 0.00–1.687%) for SO₂; and 0.236% (95% CI 0.00–1.216%) for O₃. The number of asthmatic cases who were less than 15 years admitted to the hospitals during the study period was higher than that of those within the age groups between 15 and 64 years as a consequence of exposure to NO₂ (101 vs. 75), SO₂ (98 vs. 0), and O₃ (15 vs. 3), respectively. To the best of our knowledge, the AirQ model has not been applied before to estimate the effect of atmospheric antioxidant exposure on hospital admission because of asthma disease. Eventually, this model is proposed to be applicable for other cities around the world.

http://ift.tt/2hLjNG4

Major and trace metals in suspended and bottom sediments of the Mandovi and Zuari estuaries, western India: distribution, source, and pollution

Abstract

Major elements and trace metals in suspended sediments along transect stations of the Mandovi and Zuari estuaries showed three types of distribution: (a) high concentrations of most metals (Al, Fe, Mn, Cr, Pb, Cu, Ni, Zn, Co, Sc, Mo, and U) in the upper estuary and their decreasing concentrations seaward in every season, (b) lower concentrations of some metals (Mg, Cr, Zr, V, Al, Th) in the upper estuary and bay and their increased concentrations in the lower estuary, and (c) higher concentrations of some metals (Cu, Ni, Zn, Pb, and Cr) in the upper estuary and bay and their decreased concentrations in the lower estuary. Mn was the most significant pollutant in both the estuaries. The Zn, Cr, Fe, and Mo in Mandovi during the monsoon and post-monsoon and, Pb, Ni, and Cr in Zuari during the post- and pre-monsoons were in the range "moderately to heavily polluted." The pollution load index of metals was high at upstream stations, with higher values in Mandovi during monsoon and Zuari during the post- and pre-monsoons. Most trace metals were correlated with Fe and Mn indicating their association primarily with Fe-Mn ore material. The principal component analysis indicated natural and anthropogenic inputs and the latter was predominantly related to ore material in both the estuaries. The distribution factor was high for Al, Mg, Zr, Th, and U in < 2-μm fraction and Cr, Cu, Ni, Zn, Co, V, Sc, and Zr in 2–4-μm size fraction sediments suggesting two sources of sediments. More than 60% concentrations of all trace metals were associated with < 2-μm fraction sediments. The distribution of trace metals along transect was affected by the physico-chemical conditions of the estuary, grain size of sediments, and anthropogenic contribution of metals.

http://ift.tt/2fPaO5U

American Thyroid Association Set to Launch 87th Annual Meeting

ATA Meets in Victoria, BC

October 3, 2017—The American Thyroid Association (ATA) is set to launch its 87^th Annual Meeting on October 18‒22, 2017, in Victoria, British Columbia. Key opinion leaders, thyroid specialists, clinical and basic researchers, and young trainees will gather for four exciting and information-filled days of symposia, scientific presentations, and discussions on the latest advances in thyroidology and clinical management of thyroid diseases. Nearly 1200 attendees have already registered for this outstanding educational and networking opportunity.  A record-setting 519 regular and late-breaking abstracts have been accepted.

Three leaders in the thyroid field, Carmelo Nucera, MD, PhD (Harvard Univ.), Gregory Brent, MD (UCLA), and Julie Ann Sosa, MD (Duke Univ.), will present the opening session on Wednesday evening, "A Year in Thyroidology," in which they will discuss the top recent papers in basic, clinical, and surgical thyroidology.

Weiping Teng, MD, PhD, of First Affiliated Hospital, China Medical University, Shenyang, will give one of two plenary lectures. His topic, "Effect of Iodine Intake on Thyroid Disorders: Learning from China," describes the results of the Chinese government's initial implementation of universal salt iodization in 1999, intended to reduce the high iodine deficiency disorders prevalent across the country (except in Shanghai), and its subsequent reduction of the concentration of salt iodine when excessive iodine intake became a serious problem in many provinces. Dr. Teng provides comparisons with CDC results from the US and some from WHO for pregnant women.

On day three of the meeting, the plenary lecture, "Understanding How Breaches in Immune Tolerance Lead to Autoimmune Thyroid Disease (AITD)," will be given by John C. Cambier, PhD, of the Department of Immunology and Microbiology, University of Colorado School of Medicine. Dr. Cambier and his research team are studying the thyroid antigen-reactive B cells in the peripheral blood of both recent-onset and long-standing AITD patients.

The ATA will reveal the recipient of the 2017 Van Meter Award the first morning of the meeting, and the winner, recognized for outstanding contributions to research on the thyroid gland or related subjects, will present the Van Meter Award Lecture. The Paul Starr Award lecturer is Quan-Yang Duh, MD, recognized for his outstanding contributions to clinical thyroidology, and Julie Ann Sosa, MD will deliver the 2017 Lewis E. Braverman Lectureship with a talk entitled "Re-Telling the Story About Thyroid Cancer – Rising Incidence, Mortality, and Maybe an Explanation."  Yuri Nikiforov, MD, PhD is this year's Sidney H. Ingbar Awardee speaking on "Genomic Evolution of Thyroid Nodules and Cancer – New Answers to Old Questions." The ATA will also present the John B. Stanbury Thyroid Pathophysiology Medal to James A. Fagin, MD, and the 2017 Distinguished Service Award to Bryan R. Haugen, MD, both of whom are past presidents of the Society.

The program highlights presentations by the seven recent ATA Research Grant recipients. This year's awardees are investigating research topics that include the genetics of advanced thyroid cancer, mouse modeling of medullary thyroid carcinoma, and the role of the renal sodium/iodide symporter in iodide metabolism and thyroid function. See the ATA website for full details www.thyroid.org.  In addition to the plenary and award lectures at the Annual Meeting, many specialized symposia, panel and small workshop educational formats will be offered.

Dr. John Morris, President of the American Thyroid Association, remarks, "ATA meeting attendees will have the opportunity to network with clinicians and investigators, colleagues and newcomers, making scientific and professional connections that will last throughout their careers. Given that we will be located in one of the most beautiful places in the world, it is a meeting not to be missed."

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 The American Thyroid Association (ATA) is the leading worldwide organization dedicated to the advancement, understanding, prevention, diagnosis, and treatment of thyroid disorders and thyroid cancer. ATA is an international membership medical society with over 1,700 members from 43 countries around the world. Celebrating its 94^th anniversary, the ATA continues to deliver its mission of being devoted to thyroid biology and to the prevention and treatment of thyroid disease through excellence in research, clinical care, education, and public health.  These efforts are carried out via several key endeavors:

• The publication of the highly regarded professional journals Thyroid, Clinical Thyroidology, and VideoEndocrinology
• Annual scientific meetings
• Biennial clinical and research symposia
• Research grant programs for young investigators
• Support of online professional, public, and patient educational programs
• Development of guidelines for clinical management of thyroid disease and thyroid cancer

 The ATA promotes thyroid awareness and information online through Clinical Thyroidology for the Public and extensive, authoritative explanations of thyroid disease and thyroid cancer in both English and Spanish. The ATA website serves as the clinical resource for patients and the public who look for reliable information on the Internet. Every fifth year, the American Thyroid Association joins with the Latin American Thyroid Society, the European Thyroid Association, and the Asia and Oceania Thyroid Association to cosponsor the International Thyroid Congress (ITC).

The post American Thyroid Association Set to Launch 87th Annual Meeting appeared first on American Thyroid Association.

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American Thyroid Association Symposia Highlight Novel Thyroid Research

87^th Annual Meeting of the ATA – Victoria, BC

October 2, 2017—The 87^th Annual Meeting of the American Thyroid Association (ATA), taking place October 18‒22, 2017, in Victoria, British Columbia, will offer informative symposia presented by pioneering investigators and key opinion leaders.

New exciting formats this year include an interactive Grand Rounds symposium, moderated by Mary Samuels, MD, focusing on the diagnosis and management of thyroid dysfunction, plus a session featuring recent publications from VideoEndocrinology, one of the flagship journals of the ATA. Andrew Bauer, MD, will lead a special half-day pediatric endocrinology forum in which several experts will discuss the latest research in pediatric endocrinology and clinical disease management.

Opportunity for lively discussions in clinical symposia will focus on advances in the understanding of thyroid cancer. Bryan Haugen, MD, will chair a session entitled "New Directions in Thyroid Nodules and Thyroid Cancer," featuring discussions on the updated Bethesda classification system for reporting thyroid cytopathology, the 8^th edition of the thyroid cancer staging system written by the American Joint Committee on Cancer (AJCC), and the art of balancing necessary thyroid surgeries while reducing risks in a cost-conscious manner.

John Lazarus, MD, will moderate a symposium covering the engaging topic of thyroid disease and pregnancy. The experts in this session will review the controversies surrounding subclinical hypothyroidism during pregnancy, the potential relationships between pregnancy and thyroid cancer, and the newly published "ATA Guidelines for the Diagnosis and Management of Thyroid Disease During Pregnancy and Postpartum."

Basic research symposia will feature:

• Peter Kopp, MD, moderating a discussion of "Thyroid Hormone Transporters," featuring presentations on the role of thyroid hormone receptors in the brain and novel clinical translational approaches
• Antonio Di Cristofano, PhD, chairing presentations in the session "Modulation of TSH Receptors in Thyroid Disease"
• Electron Kebebew, MD, facilitating the symposium "MicroRNAs in Thyroid Cancer"
• Young Kee Shong, MD, PhD, leading a stimulating session on "Novel Molecular Mechanisms in Thyroid Cancer," with an international presentation team on the topics of nuclear receptor signaling and novel genetic mechanisms in benign and malignant thyroid tumors

The annual meeting will focus on recent advances regarding mechanisms, screening, diagnosis, and management of thyroid disorders with attention to translating the latest research findings and clinical management guidelines into practice to enhance patient care.

###

 The American Thyroid Association (ATA) is the leading worldwide organization dedicated to the advancement, understanding, prevention, diagnosis, and treatment of thyroid disorders and thyroid cancer. ATA is an international membership medical society with over 1,700 members from 43 countries around the world. Celebrating its 94^th anniversary, the ATA continues to deliver its mission of being devoted to thyroid biology and to the prevention and treatment of thyroid disease through excellence in research, clinical care, education, and public health.  These efforts are carried out via several key endeavors:

• The publication of the highly regarded professional journals Thyroid, Clinical Thyroidology, and VideoEndocrinology
• Annual scientific meetings
• Biennial clinical and research symposia
• Research grant programs for young investigators
• Support of online professional, public, and patient educational programs
• Development of guidelines for clinical management of thyroid disease and thyroid cancer

The ATA promotes thyroid awareness and information online through Clinical Thyroidology for the Public and extensive, authoritative explanations of thyroid disease and thyroid cancer in both English and Spanish. The ATA website serves as the clinical resource for patients and the public who look for reliable information on the Internet. Every fifth year, the American Thyroid Association joins with the Latin American Thyroid Society, the European Thyroid Association, and the Asia and Oceania Thyroid Association to cosponsor the International Thyroid Congress (ITC).

The post American Thyroid Association Symposia Highlight Novel Thyroid Research appeared first on American Thyroid Association.

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“The importance of surgical maneuvers during treatment of frontal migraines (site I): a prospective, randomized cohort study evaluating foraminotomy/fasciotomy, myectomy, and arterectomy”

The current prospective, blinded, randomized cohort study aims to delineate the relative contribution of different surgical treatments for frontal migraines.

http://ift.tt/2g7xIT1

Preoperative fasting in children

1A012A033J03

http://ift.tt/2yHpLuy

Paediatric airway infections

1C022D013D00

http://ift.tt/2xSgLDG

Error and Root Cause Analysis

1I032A063I00

http://ift.tt/2yGpTup

Burnout and resilience in anaesthesia and intensive care medicine

1H022H013J02

http://ift.tt/2xRkHof

Decision Making and Psychological Outcomes in Low-Risk Papillary Thyroid Cancer

Condition:   Thyroid Cancer
Intervention:   Behavioral: Questionnaires
Sponsor:   Memorial Sloan Kettering Cancer Center
Recruiting

http://ift.tt/2xOIFmz

Trail Evaluating Apatinib With IMRT for Inoperable or Iodine Refractory Thyroid Cancer

Condition:   Thyroid Cancer
Interventions:   Drug: Apatinib;   Radiation: Intensity modulated radiation therapy
Sponsor:   Xiayun He, MD
Recruiting

http://ift.tt/2g9kJjL

Genetic damage in Rhinella marina populations in habitats affected by agriculture in the middle region of the Sinú River, Colombia

Abstract

Contamination with pesticide residues affects the environmental health of agroecosystems, especially the amphibian fauna that lives in these environments. The objective of the present study was to determine pesticides concentrations in sediments of agroecosystems and to evaluate genetic damage in Rhinella marina populations living in these zones. A total of 91 individuals were collected, 51 in the group exposed in different areas of the middle region of the Sinú River (Irrigation District of Mocari 16, Irrigation District of Aguas Negras 21, Irrigation District of Cerete 14) and 40 in a control group; at the same time, 36 subsamples of sediments were taken at each sampled station to determine pesticides organochlorine by means of chromatography coupled with ISQ Thermo Scientific mass spectrometer. The micronucleus test was applied in erythrocytes of the individuals collected. Results showed the presence of persistent organochlorine pesticides (POPs) in the sediment samples (p,p′-DDT, p,p′-DDE, and p,p′-DDD) of agricultural soils. Two individuals were registered with abnormalities in their limbs at the Mocari station, representing 12.5% of the morphological malformations to this sector. Micronucleus analysis revealed statistically significant genetic damage in exposed individuals (Mocari 9.87 ± 5.1, Cerete 7.7 ± 1.7, Aguas Negras 5.6 ± 3.6) with respect to the control group (2.4 ± 1.9) (p < 0.05). Spearman correlation analysis revealed a positive association between genetic damage and POP concentrations (p < 0.05). In addition, cellular alterations such as nuclear buds, and pyknosis (cell death), were statistically significant in the exposed group compared to the control group (p < 0.05). This study suggests that there is evidence for morphological and genotoxic effects in R. marina populations inhabiting areas influenced by agriculture, possibly associated with the presence of p,p′-DDT, p,p′-DDD, and p,p′-DDE.

http://ift.tt/2fHxXDT

Large-scale Meta-analysis Suggests Low Regional Modularity in Lateral Frontal Cortex

Abstract

Extensive fMRI study of human lateral frontal cortex (LFC) has yet to yield a consensus mapping between discrete anatomy and psychological states, partly due to the difficulty of inferring mental states from brain activity. Despite this, there have been few large-scale efforts to map the full range of psychological states across the entirety of LFC. Here, we used a data-driven approach to generate a comprehensive functional-anatomical mapping of LFC from 11 406 neuroimaging studies. We identified putatively separable LFC regions on the basis of whole-brain co-activation, revealing 14 clusters organized into 3 whole-brain networks. Next, we generated functional preference profiles by using multivariate classification to identify the psychological states that best predicted activity within each cluster. We observed large functional differences between networks, suggesting brain networks support distinct modes of processing. Within each network, however, we observed relatively low functional specificity, suggesting discrete psychological states are not strongly localized to individual regions; instead, our results are consistent with the view that individual LFC regions work as part of distributed networks to give rise to flexible behavior. Collectively, our results provide a comprehensive synthesis of a diverse neuroimaging literature using relatively unbiased data-driven methods.

http://ift.tt/2hJzAF6

The late effect of Kinesio Taping® on handgrip strength

Publication date: Available online 3 October 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Rodrigo Sousa Nilo de Araújo Aguiar, Silvia Regina Matos da Silva Boschi, Leandro Lazzareschi, Alessandro Pereira da Silva, Terigi Augusto Scardovelli, Eduardo Filoni, Ana Lúcia Manrique, Annie France Frère
The Kinesio Taping^® elastic tape is increasingly used in physiotherapy treatment. However, there is a lack of scientific research regarding the late effects of its use. This study quantified the late effects of applying the Kinesio Taping^® elastic tape by measuring changes in handgrip muscle strength after 24, 48 and 72 h of application. The Kinesio Taping^® elastic tape was applied on the dominant and non-dominant limbs of 36 volunteers randomly assigned to three groups: muscle facilitation, muscle inhibition and control group. The statistical test showed there was a statistically significant difference among all groups of dominant limb and non-dominant limb. However, the analysis on intragroup relationship to periods of application (Initial, 24, 48 and 72 h) and the interaction among repeated measures showed there was no statistically significant difference. This result may contribute to the investigation of the late effects of the Kinesio Taping^® elastic tape on the physical rehabilitation.



http://ift.tt/2xREc06

Transabdominal ultrasound: Can it be used to detect and quantify adhesions/reported pain, following Caesarean section?

Publication date: Available online 3 October 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Katharine Spens, Lance Bird, Philip Bright
BackgroundCaesarean section is common in the UK with post–procedural adhesions causing life-long clinical symptoms and impacting future pregnancies. This study's aim was to explore associations between these surgical adhesions, via transabdominal ultrasound findings, and perceived symptoms.MethodFemales demonstrating 1–3 transverse, lower-segment Caesareans were included. Visceral slide transabdominal ultrasound elicited positive adhesions (<1 cm movement) and negative adhesions (>1 cm movement). Scar tissue quality was assessed by the Patient and Observer Scar Assessment Scale (POSAS) and Numerical rating scales (NRS) described pain symptoms. The relationship between adhesions was explored using Fisher's exact test and multiple regression analysis.ResultsTwenty-two subjects (mean-age 35) were recruited; twenty participants (91%) had undergone 1 Caesarean, one each of the remainder had undergone 2 and 3 Caesareans respectively. Increased Visceral slide (>1 cm) was seen as predictive of increased scar pain (R² = 0.76 (95% CI 0.12–0.28), P < 0.001).ConclusionCaesarean adhesion scans showed significant associations with pain symptomology. Comprehensive adhesion assessment needs to be developed to improve long term outcomes of adhesions. Transabdominal Ultrasound can be considered a useful, quick and non-deleterious alternative diagnostic tool to Laparoscopy, therefore preventing further adhesion formation.



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Leg press exercise can reduce functional hamstring/quadriceps ratio in the elderly

Publication date: Available online 3 October 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Lucas Bet da Rosa Orssatto, Bruno Monteiro de Moura, Raphael Luiz Sakugawa, Regis Radaelli, Fernando Diefenthaeler
The aim of this study was to investigate whether 12 weeks of leg press strength training exercise could affect the conventional and functional hamstring/quadriceps ratios in elderly. Twelve elderly participants were submitted to a 12 week progressive training protocol (two sessions/week) using a 45° leg press exercise. A significant increase in the one repetition maximum was observed after 4, 8, and 12 weeks (p = 0.001, p < 0.001, and p < 0.001, respectively) compared to week 0 and after 8 (p = 0.011) and 12 weeks (p = 0.001) compared to week 4. The concentric knee extensor peak torque was significantly higher at weeks 8 (p = 0.001) and 12 (p = 0.024) compared to week 0. There was no change in the concentric and eccentric knee flexor peak torques (p = 0.629 and 0.274, respectively) and conventional ratio (p > 0.314) after 12 weeks of training. The functional ratio (eccentric knee flexor peak torque:concentric knee extensor peak torque) reduced significantly after 8 (p = 0.034) and 12 (p = 0.036) weeks of strength training. Although the 45° leg press exercise requires knee extensor and flexor, hip extensor, and plantar flexor muscle strength, our findings suggest that the isolated use of the 45° leg press exercise reduces the knee functional ratio after 8 weeks of training. Therefore, 45° leg press exercise alone, without a hamstring exercise, should not be recommended for elderly individuals.



http://ift.tt/2hKebfi

Correction to: The 3.5-year survival rates of primary molars treated according to three treatment protocols: a controlled clinical trial

Abstract

Mw. M. Mijan will defend her PhD thesis on 15th September 2017. Whilst reviewing her work in preparation to the event, we discovered a few irregularities that prompted a recheck of the database and ditto analyses. These activities have lead to a few textual changes in the publication.

http://ift.tt/2khN4ZC

Does endogenous GLP-1 affect resting energy expenditure and fuel selection in overweight and obese adults?

Abstract

Purpose

To investigate the association between fasting glucagon-like peptide 1 (GLP-1) levels and resting energy expenditure (REE), and respiratory quotient (RQ) in overweight and obese adults.

Method

Study participants were enrolled at the Dietetic and Metabolic Unit, University of Pavia, Italy. Inclusion criteria were age ≥ 25 and ≤ 45 years, and body mass index (BMI) ≥ 25 and ≤ 35 kg/m². Diabetic subjects were excluded. Body composition was measured by dual-energy X-ray absorptiometry. REE was evaluated using indirect calorimetry, and RQ was calculated from respiratory gas exchanges. Fasting GLP-1, glucose, insulin and free fatty acid (FFA) levels, and 24-h norepinephrine urinary excretion were measured. Homeostasis model assessments of insulin resistance (HOMA-IR) and beta-cell function (HOMA-β) were calculated.

Results

Thirty-seven participants were included (age 43.4 ± 1.6 years; BMI 30.6 ± 0.5 kg/m²). REE was not associated with fasting GLP-1 levels (p = 0.98) after adjustment for age, sex, fat-free mass (FFM), and fat mass (FM). Similarly, no association was observed between RQ and GLP-1 levels (p = 0.95), after adjustment for age, sex, and body fat.

Conclusion

In adults subjects with increased adiposity fasting, GLP-1 levels do not seem to play a role in the regulation of energy metabolism and in fuel selection.

http://ift.tt/2wwrLW2

Cadmium uptake and partitioning in potato ( Solanum tuberosum L.) cultivars with different tuber-Cd concentration

Abstract

Potatoes grown in soil with high Cd concentrations can accumulate high levels of Cd in the tubers. Although there is significant environmental variation involved in the trait of crop uptake of Cd, there are also distinctive cultivar differences. In order to understand this differential Cd accumulation mechanism, two potato cultivars were chosen that accumulate high and low levels of Cd in tubers. The patterns of Cd concentration, Cd content and dry weight accumulation of the two cultivars were examined at different stages of plant growth. The data suggest that differences in total Cd uptake and in Cd partitioning among organs are the mechanisms governing differential Cd-tuber accumulation in the two cultivars. The low tuber-Cd accumulator exhibited lower root-to-shoot and shoot-to-tuber translocation driven by higher root and shoot biomass that retained more Cd in roots and shoots, respectively, reducing its movement to the tubers. Higher remobilization and more efficient tuber loading was observed in the high tuber-Cd accumulator, indicating that remobilization of Cd from leaves to tubers was a major factor, not only in tuber-Cd loading, but also in the establishment of differential tuber-Cd levels. Regardless of cultivar differences, the concentration of Cd in the tuber was very low compared to that in other organs suggesting that, despite its high phloem mobility, Cd tends to be sequestered in the shoots.

http://ift.tt/2fO744H

The conformation-independent QSPR approach for predicting the oxidation rate constant of water micropollutants

Abstract

In advanced water treatment processes, the degradation efficiency of contaminants depends on the reactivity of the hydroxyl radical toward a target micropollutant. The present study predicts the hydroxyl radical rate constant in water (k _OH) for 118 emerging micropollutants, by means of quantitative structure-property relationships (QSPR). The conformation-independent QSPR approach is employed, together with a large number of 15,251 molecular descriptors derived with the PaDEL, Epi Suite, and Mold2 freewares. The best multivariable linear regression (MLR) models are found with the replacement method variable subset selection technique. The proposed five-descriptor model has the following statistics for the training set: \( {R}_{\mathrm{train}}^2=0.88 \) , RMS _train = 0.21, while for the test set is \( {R}_{\mathrm{test}}^2=0.87 \) , RMS _test = 0.11. This QSPR serves as a rational guide for predicting oxidation processes of micropollutants.

http://ift.tt/2xPWfpY

Concentrations and chemical forms of heavy metals in the bulk atmospheric deposition of Beijing, China

Abstract

This study aimed to investigate concentrations and mobility of selected metals (As, Cd, Cr, Co, Cu, Mn, Ni, Pb and Zn) contained in the bulk atmospheric deposition of Beijing, China, between March 2007 and February 2008, and to evaluate the metal deposition fluxes. Beijing endured heavy atmospheric deposited metal pollution with a deposition flux of 149.28 kg km⁻² year⁻¹ from nine metals studied, and a significant increasing trend was noted from metals studied during the past 23 years. High enrichment factors (EFs) of As, Zn, Pb, Cd, and Cu manifested their major anthropogenic sources. Among which, Cd and Pb require a consistent monitoring and to be strictly controlled regarding their high mobility and ecotoxicity. Furthermore, a declined metal concentration was observed in the bulk atmospheric deposition during spring, and long-transported crustal particles sourced from East Asian dust emission belt can reasonably account for this phenomenon.

http://ift.tt/2kk8m92

The ecogenotoxic plant biomonitoring of a long-term polluted area in central Slovakia

Abstract

The aim of the study was to analyze, update, and complete the results of research in the field of in situ phytoindication of environmental genotoxicity near the aluminum plant in Žiar nad Hronom in central Slovakia. The authors focused on two methodologies: pollen abortivity assay of native flora and Trad-MCN assay. Comparison of changes in responses of living systems to changes in precipitation was conducted, and it suggests that there is an existence of an impact from a dilution effect to the plants. Also, the gradual increase of pollen abortivity in the 1990s and its decrease from 2009 were observed in a majority of species of wild flora. On an annual basis, abortivity has declined, although it has risen up slightly within each season. Despite a gradual decrease in the micronucleus frequency, the study area is still influenced by the ecogenotoxic factors. Pollen analysis of native flora and introduced Tradescantia plants indicates the long-time presence of ecogenotoxicity in this region due to the presence of aluminum plant.

http://ift.tt/2xQsSE5

RE: “SELECTIVE CUTOFF REPORTING IN STUDIES OF DIAGNOSTIC TEST ACCURACY: A COMPARISON OF CONVENTIONAL AND INDIVIDUAL-PATIENT-DATA META-ANALYSES OF THE PATIENT HEALTH QUESTIONNAIRE–9 DEPRESSION SCREENING TOOL”

http://ift.tt/2xe2bJI

THREE AUTHORS REPLY

http://ift.tt/2fIaZMQ

RE: “THE HIDDEN EPIDEMIC OF FIREARM INJURY: INCREASING FIREARM INJURY RATES DURING 2001–2013”

http://ift.tt/2xcVBmN

THREE AUTHORS REPLY

http://ift.tt/2fHAI82

Incorporation of Biological Knowledge Into the Study of Gene-Environment Interactions

Abstract

A growing knowledge base of genetic and environmental information has greatly enabled the study of disease risk factors. However, the computational complexity and statistical burden of testing all variants by all environments has required novel study designs and hypothesis-driven approaches. We discuss how incorporating biological knowledge from model organisms, functional genomics, and integrative approaches can empower the discovery of novel gene-environment interactions and discuss specific methodological considerations with each approach. We consider specific examples where the application of these approaches has uncovered effects of gene-environment interactions relevant to drug response and immunity, and we highlight how such improvements enable a greater understanding of the pathogenesis of disease and the realization of precision medicine.

http://ift.tt/2xdNir1

Current Challenges and New Opportunities for Gene-Environment Interaction Studies of Complex Diseases

Abstract

Recently, many new approaches, study designs, and statistical and analytical methods have emerged for studying gene-environment interactions (G×Es) in large-scale studies of human populations. There are opportunities in this field, particularly with respect to the incorporation of -omics and next-generation sequencing data and continual improvement in measures of environmental exposures implicated in complex disease outcomes. In a workshop called "Current Challenges and New Opportunities for Gene-Environment Interaction Studies of Complex Diseases," held October 17–18, 2014, by the National Institute of Environmental Health Sciences and the National Cancer Institute in conjunction with the annual American Society of Human Genetics meeting, participants explored new approaches and tools that have been developed in recent years for G×E discovery. This paper highlights current and critical issues and themes in G×E research that need additional consideration, including the improved data analytical methods, environmental exposure assessment, and incorporation of functional data and annotations.

http://ift.tt/2fHeQtD

Update on the State of the Science for Analytical Methods for Gene-Environment Interactions

Abstract

The analysis of gene-environment interaction (G×E) may hold the key for further understanding the etiology of many complex traits. The current availability of high-volume genetic data, the wide range in types of environmental data that can be measured, and the formation of consortiums of multiple studies provide new opportunities to identify G×E but also new analytical challenges. In this article, we summarize several statistical approaches that can be used to test for G×E in a genome-wide association study. These include traditional models of G×E in a case-control or quantitative trait study as well as alternative approaches that can provide substantially greater power. The latest methods for analyzing G×E with gene sets and with data in a consortium setting are summarized, as are issues that arise due to the complexity of environmental data. We provide some speculation on why detecting G×E in a genome-wide association study has thus far been difficult. We conclude with a description of software programs that can be used to implement most of the methods described in the paper.

http://ift.tt/2xdHRIy

Editorial: Emergence of Gene-Environment Interaction Analysis in Epidemiologic Research

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Lessons Learned From Past Gene-Environment Interaction Successes

Abstract

Genetic and environmental factors are both known to contribute to susceptibility to complex diseases. Therefore, the study of gene-environment interaction (G×E) has been a focus of research for several years. In this article, select examples of G×E from the literature are described to highlight different approaches and underlying principles related to the success of these studies. These examples can be broadly categorized as studies of single metabolism genes, genes in complex metabolism pathways, ranges of exposure levels, functional approaches and model systems, and pharmacogenomics. Some studies illustrated the success of studying exposure metabolism for which candidate genes can be identified. Moreover, some G×E successes depended on the availability of high-quality exposure assessment and longitudinal measures, study populations with a wide range of exposure levels, and the inclusion of ethnically and geographically diverse populations. In several examples, large population sizes were required to detect G×Es. Other examples illustrated the impact of accurately defining scale of the interactions (i.e., additive or multiplicative). Last, model systems and functional approaches provided insights into G×E in several examples. Future studies may benefit from these lessons learned.

http://ift.tt/2xe8L36

Residential Proximity to Major Roadways, Fine Particulate Matter, and Hepatic Steatosis The Framingham Heart Study

Abstract

We examined associations between ambient air pollution and hepatic steatosis among 2,513 participants from the Framingham (Massachusetts) Offspring Study and Third Generation Cohort who underwent a computed tomography scan (2002–2005), after excluding men who reported >21 drinks/week and women who reported >14 drinks/week. We calculated each participant's residential-based distance to a major roadway and used a spatiotemporal model to estimate the annual mean concentrations of fine particulate matter. Liver attenuation was measured by computed tomography, and liver-to-phantom ratio (LPR) was calculated. Lower values of LPR represent more liver fat. We estimated differences in continuous LPR using linear regression models and prevalence ratios for presence of hepatic steatosis (LPR ≤ 0.33) using generalized linear models, adjusting for demographics, individual and area-level measures of socioeconomic position, and clinical and lifestyle factors. Participants who lived 58 m (25th percentile) from major roadways had lower LPR (β = −0.003, 95% confidence interval: −0.006, −0.001) and higher prevalence of hepatic steatosis (prevalence ratio = 1.16, 95% confidence interval: 1.05, 1.28) than those who lived 416 m (75th percentile) away. The 2003 annual average fine particulate matter concentration was not associated with liver-fat measurements. Our findings suggest that living closer to major roadways was associated with more liver fat.

http://ift.tt/2fIHURu

Contribution of Socioeconomic Status at 3 Life-Course Periods to Late-Life Memory Function and Decline: Early and Late Predictors of Dementia Risk

Abstract

Both early life and adult socioeconomic status (SES) predict late-life level of memory; however, evidence is mixed on the relationship between SES and rate of memory decline. Further, the relative importance of different life-course periods for rate of late-life memory decline has not been evaluated. We examined associations between life-course SES and late-life memory function and decline. Health and Retirement Study participants (n = 10,781) were interviewed biennially from 1998–2012 (United States). SES measurements for childhood (composite score including parents' educational attainment), early adulthood (high-school or college completion), and older adulthood (income, mean age 66 years) were all dichotomized. Word-list memory was modeled via inverse-probability weighted longitudinal models accounting for differential attrition, survival, and time-varying confounding, with nonrespondents retained via proxy assessments. Compared to low SES at all 3 points (referent), stable, high SES predicted the best memory function and slowest decline. High-school completion had the largest estimated effect on memory (β = 0.19; 95% confidence interval: 0.15, 0.22), but high late-life income had the largest estimated benefit for slowing declines (for 10-year memory change, β = 0.35; 95% confidence interval: 0.24, 0.46). Both early and late-life interventions are potentially relevant for reducing dementia risk by improving memory function or slowing decline.

http://ift.tt/2xdNhTZ

Meat, Dietary Heme Iron, and Risk of Type 2 Diabetes Mellitus The Singapore Chinese Health Study

Abstract

We evaluated the relationships of red meat, poultry, fish, and shellfish intakes, as well as heme iron intake, with the risk of type 2 diabetes mellitus (T2D).The Singapore Chinese Health Study is a population-based cohort study that recruited 63,257 Chinese adults aged 45–74 years from 1993 to 1998. Usual diet was evaluated using a validated 165-item semiquantitative food frequency questionnaire at recruitment. Physician-diagnosed T2D was self-reported during 2 follow-up interviews in 1999–2004 and 2006–2010. During a mean follow-up of 10.9 years, 5,207 incident cases of T2D were reported. When comparing persons in the highest intake quartiles with those in the lowest, the multivariate-adjusted hazard ratio for T2D was 1.23 (95% confidence interval (CI): 1.14, 1.33) for red meat intake (P for trend < 0.001), 1.15 (95% CI: 1.06, 1.24) for poultry intake (P for trend = 0.004), and 1.07 (95% CI: 0.99, 1.16) for fish/shellfish intake (P for trend = 0.12). After additional adjustment for heme iron, only red meat intake remained significantly associated with T2D risk (multivariate-adjusted hazard ratio = 1.13, 95% CI: 1.01, 1.25; P for trend = 0.02). Heme iron was associated with a higher risk of T2D even after additional adjustment for red meat intake (multivariate-adjusted hazard ratio = 1.14, 95% CI: 1.02, 1.28; P for trend = 0.03). In conclusion, red meat and poultry intakes were associated with a higher risk of T2D. These associations were mediated completely for poultry and partially for red meat by heme iron intake.

http://ift.tt/2fHeKSN

Parental Age and Risk of Pediatric Cancer in the Offspring: A Population-Based Record-Linkage Study in California

Abstract

Linking birth records and cancer registry data from California, we conducted a population-based study with 23,419 cases and 87,593 matched controls born during 1978–2009 to investigate the relationship of parental age to risk of pediatric cancer. Compared with children born to mothers aged 20–24 years, those born to mothers in older age groups had a 13%–36% higher risk of pediatric cancer; the odds ratio for each 5-year increase in maternal age was 1.06 (95% confidence interval (CI): 1.04, 1.09). For cancer diagnosed in children in age groups 0–14 years and 15–19 years, the odds ratios for each 5-year increase in maternal age were 1.05 (95% CI: 1.02, 1.07) and 1.14 (95% CI: 1.09, 1.19), respectively. Having an older father also conferred an increased risk, with an odds ratio for each 5-year increase of 1.03 (95% CI: 1.02, 1.05) for cancer diagnosed at ages 0–19 years and 1.03 (95% CI: 1.02, 1.05) for cancer diagnosed at ages 0–14 years. While advancing maternal age increased risk of leukemia and central nervous system tumors, older paternal age was not associated with risk of either type. Both maternal and paternal older ages were associated with risk of lymphoma. In this large, population-based record-linkage study, advancing parental age, especially advancing maternal age, was associated with higher pediatric cancer risk, with variations across types of cancer.

http://ift.tt/2xeefdZ

Probabilistic Multiple-Bias Modeling Applied to the Canadian Data From the Interphone Study of Mobile Phone Use and Risk of Glioma, Meningioma, Acoustic Neuroma, and Parotid Gland Tumors

Abstract

We undertook a re-analysis of the Canadian data from the 13-country case-control Interphone Study (2001–2004), in which researchers evaluated the associations of mobile phone use with the risks of brain, acoustic neuroma, and parotid gland tumors. In the main publication of the multinational Interphone Study, investigators concluded that biases and errors prevented a causal interpretation. We applied a probabilistic multiple-bias model to address possible biases simultaneously, using validation data from billing records and nonparticipant questionnaires as information on recall error and selective participation. In our modeling, we sought to adjust for these sources of uncertainty and to facilitate interpretation. For glioma, when comparing those in the highest quartile of use (>558 lifetime hours) to those who were not regular users, the odds ratio was 2.0 (95% confidence interval: 1.2, 3.4). After adjustment for selection and recall biases, the odds ratio was 2.2 (95% limits: 1.3, 4.1). There was little evidence of an increase in the risk of meningioma, acoustic neuroma, or parotid gland tumors in relation to mobile phone use. Adjustments for selection and recall biases did not materially affect interpretation in our results from Canadian data.

http://ift.tt/2fI12PG

Geographic Patterns of Autism Spectrum Disorder Among Children of Participants in Nurses’ Health Study II

Abstract

Data indicate that the prevalence of autism spectrum disorder (ASD) may be increasing and that it varies geographically. We investigated associations between residential location and ASD in the children of Nurses' Health Study II (United States) participants in order to generate hypotheses about social and environmental factors related to etiology or diagnosis. Analyses included data on 13,507 children born during 1989–1999 (486 with ASD). We explored relationships between ASD and residential location both at birth and at age 6 years (i.e., closer to average age at diagnosis). Generalized additive models were used to predict ASD odds across the United States. Children born in New England were 50% more likely to be diagnosed with ASD compared with children born elsewhere in the United States. Patterns were not explained by geographic variation in maternal age, birth year, child's sex, community income, or prenatal exposure to hazardous air pollutants, indicating that spatial variation is not attributable to these factors. Using the residential address at age 6 years produced similar results; however, areas of significantly decreased ASD odds were observed in the Southeast, where children were half as likely to have ASD. These results may indicate that diagnostic factors are driving spatial patterns; however, we cannot rule out the possibility that other environmental factors are influencing distributions.

http://ift.tt/2xcKavw

Primary Cardiovascular Disease Risk Factors Predicted by Poor Working Conditions in the GAZEL Cohort

Abstract

The mechanisms by which work environment might influence cardiovascular disease (CVD) risk are still a matter of debate. In particular, the involvement of the main behavioral and clinical risk factors and their relationships with working conditions are not always clear, despite an abundant body of literature. Most studies have investigated the impact of a limited number of characteristics of the work environment on the occurrence of 1 or a few risk factors. In contrast, in this study we used a global approach in which 30 objective and subjective indicators of working conditions were tested as predictors of 9 modifiable CVD risk factors in a well-characterized cohort of 20,625 middle-aged French workers who were followed from the 1990s until they retired or until December 31, 2013. The incidence of 3 CVD risk factors (obesity, sleep complaints, and depression) was predicted by a large number of indicators of working conditions in both age- and sex-adjusted and multivariate-adjusted Cox regression models, whatever the significance threshold retained. These results suggest the existence of close relationships between a poor work environment and a higher risk of developing obesity, sleep complaints, or depression. These risk factors may contribute to increased CVD risk not only when workers are exposed to poor working conditions but also after retirement, as predictors of the appearance of other risk factors.

http://ift.tt/2fIHSsQ

Social Network Clustering of Sexual Violence Experienced by Adolescent Girls

Abstract

We used data on 3,139 female social network friendship dyads from 3 waves of the National Longitudinal Study of Adolescent to Adult Health (wave I: 1994–1995; wave II: 1996; and wave IV: 2007–2008) to assess whether friends' reports of experiencing sexual violence (SV) and friends' substance use risk scores predicted whether adolescents and young adults would experience SV themselves. We also used longitudinal analyses to test the associations of combined wave-I and -II risk factors with wave-IV reports of SV and of combined wave-I and -II SV with network connectivity at wave II. After adjustment for a participant's substance use risk score, each 1-point increase in a friend's substance use risk score increased a respondent's odds of experiencing SV by 1.19 (95% confidence interval: 1.03, 1.36). Having a friend who reported SV increased a respondent's odds of reporting SV by 1.95 (95% confidence interval: 1.25, 3.07), although not after we included school-level fixed effects. Having a friend who experienced SV in adolescence did however increase the respondent's odds of reporting SV as a young adult by 1.54 (95% confidence interval: 1.00, 2.37). Respondents who reported SV by wave II had less network connectedness at wave II. Experiences of SV and substance use within adolescent girls' friendship networks are linked to risk for SV into young adulthood, which suggests that network-focused SV prevention and intervention approaches may be warranted.

http://ift.tt/2xeYuDw

New heteroleptic Zn(II) complexes of thiosemicarbazone and diimine Co-Ligands: Structural analysis and their biological impacts

Publication date: 5 February 2018
Source:Journal of Molecular Structure, Volume 1153
Author(s): Shanmugaiah Mathan Kumar, Mookkandi Palsamy Kesavan, Gujuluva Gangatharan Vinoth Kumar, Murugesan Sankarganesh, Ganesan Chakkaravarthi, Gurusamy Rajagopal, Jegathalaprathaban Rajesh
A thiosemicarbazone ligand HL appended new Zn(II) complexes [Zn(L)(bpy)] (1) and [Zn(L)(phen)] (2) (where, HL = {2-(3-bromo-5-chloro-2-hydroxybenzylidene)-N-phenylhydrazinecarbothioamide}, bpy = 2, 2′-bipyridine and phen = 1, 10-phenanthroline) have been synthesized and well characterized using conventional spectroscopic techniques viz.,¹H NMR, FTIR and UV–Vis spectra. The crystal structures of complexes 1 and 2 have been determined by single crystal X-ray diffraction studies. Both the complex 1 (τ = 0.5) and 2 (τ = 0.37) possesses square based pyramidally distorted trigonal bipyramidal geometry. The ground state electronic structures of complexes 1 and 2 were investigated by DFT/B3LYP theoretical analysis using 6-311G (d,p) and LANL2DZ basis set level. The superior DNA binding ability of complex 2 has been evaluated using absorption and fluorescence spectral titration studies. Antimicrobial evaluation reveals that complex 2 endowed better screening than HL and complex 1 against both bacterial as well as fungal species. Consequently, complex 2 possesses highest antibacterial screening against Staphylococcus aureus (MIC = 3.0 ± 0.23 mM) and antifungal screening against Candida albicans (MIC = 6.0 ± 0.11 mM). Furthermore, the anticancer activity of the ligand HL, complexes 1 and 2 have been examined against the MCF-7 cell line (Human breast cancer cell line) using MTT assay. It is remarkable that complex 2 (12 ± 0.67 μM) show highest anticancer activity than HL (25.0 ± 0.91 μM) and complex 1 (15 ± 0.88 μM) due to the presence of phen ligand moiety.

Graphical abstract

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Kinetochore Function from the Bottom Up

Publication date: Available online 3 October 2017
Source:Trends in Cell Biology
Author(s): Stephen M. Hinshaw, Stephen C. Harrison
During a single human lifetime, nearly one quintillion chromosomes separate from their sisters and transit to their destinations in daughter cells. Unlike DNA replication, chromosome segregation has no template, and, unlike transcription, errors frequently lead to a total loss of cell viability. Rapid progress in recent years has shown how kinetochores enable faithful execution of this process by connecting chromosomal DNA to microtubules. These findings have transformed our idea of kinetochores from cytological features to immense molecular machines and now allow molecular interpretation of many long-appreciated kinetochore functions. In this review we trace kinetochore protein connectivity from chromosomal DNA to microtubules, relating new findings to important points of regulation and function.



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Effects of a stand-alone web-based electronic screening and brief intervention targeting alcohol use in university students of legal drinking age: A randomized controlled trial

Publication date: February 2018
Source:Addictive Behaviors, Volume 77
Author(s): Thomas Ganz, Michael Braun, Marion Laging, Karin Schermelleh-Engel, Johannes Michalak, Thomas Heidenreich
BackgroundMany intervention efforts targeting student drinking were developed to address US college students, which usually involves underage drinking. It remains unclear, if research evidence from these interventions is generalizable to university and college students of legal drinking age, e.g., in Europe.ObjectiveTo evaluate the effectiveness of a translated and adapted version of the eCHECKUP TO GO, applied as stand-alone web-based electronic screening and brief intervention (e-SBI), in German university students at risk for hazardous drinking.MethodsA fully automated web-based two-arm parallel-group randomized controlled trial was conducted. Participants were randomized to an e-SBI or assessment-only (AO) condition. The current paper analyzed students with baseline AUDIT-C scores ≥3 for women and ≥4 for men (sample at baseline: e-SBI [n=514], AO [n=467]; 3-month follow-up: e-SBI [n=194], AO [n=231]; 6-month follow-up: e-SBI [n=146], AO [n=200]). The primary outcome was prior four weeks' alcohol consumption. Secondary outcomes were frequency of heavy drinking occasions, peak blood alcohol concentration, and number of alcohol-related problems.ResultsMixed linear model analyses revealed significant interaction effects between groups and time points on the primary outcome after 3 and 6months. Compared to students in the AO condition, students in the e-SBI condition reported consuming 4.11 fewer standard drinks during the previous four weeks after 3months, and 4.78 fewer standard drinks after 6months. Mixed results were found on secondary outcomes.ConclusionsThe results indicate that evidence on and knowledge of web-based e-SBIs based on US college student samples is transferable to German university students of legal drinking age. However, knowledge of what motivates students to complete programs under voluntary conditions, although rare, is needed.



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Characterizing thiol redox dynamics in the organogenesis stage rat embryo

Publication date: December 2017
Source:Free Radical Biology and Medicine, Volume 113
Author(s): K. Veltman, Y. Ahmad, C. Harris, O. Jolliet
Precise control of the glutathione (GSH): glutathione disulfide (GSSG) balance is vital for the developing embryo, but it is not yet well understood how GSH levels and the GSH redox state are regulated, maintained, and modulated over the course of mammalian embryonic development. In this study, we characterize and connect thiol redox dynamics, protein synthesis, volumetric growth and net cysteine fluxes over the course of early organogenesis (gestational day (GD) 10–GD11.13) in the rat embryo. Our results show that despite a significant exponential growth of conceptal volumes and protein mass, the GSH: GSSG redox balance is remarkably stable during early organogenesis, with distinct redox potentials for the visceral yolk sac (VYS) (− 218mV) and the embryo proper (EMB) (− 222mV). The yolk sac was found to play a key role in maintaining GSH levels and the GSH: GSSG redox balance in the developing embryo. Based on an overall cysteine (Cys) mass-balance, we show that until GD10.6, yolk sac supply of Cys, the rate-limiting precursor for GSH synthesis, is sufficient to sustain embryonic demands for its GSH synthesis and protein synthesis needs. After GD10.6, the EMB maintains the amino acid intake flux, resulting in a significant depletion of most thiols in the amniotic fluid and the yolk sac fluid. Cysteine, was found to be predominantly used for de novo protein synthesis in the developing embryo (approximately 90% of total Cys). Protein synthesis (rates) should thus be included in any quantitative assessment of GSH redox dynamics in the developing embryo. Our time-course dataset of thiol dynamics, developed exponential relationships for protein synthesis and volumetric growth, and yolk sac surface area-mediated protein influx, provide important quantitative insights in GSH redox dynamics during embryonic development and are a prerequisite to further develop quantitative 'systems biology' models for GSH metabolism in the developing embryo.

Graphical abstract

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From meaning to categorization: the hierarchical recruitment of brain circuits selective for action verbs

Publication date: Available online 3 October 2017
Source:Cortex
Author(s): Riccardo Dalla Volta, Pietro Avanzini, Doriana De Marco, Maurizio Gentilucci, Maddalena Fabbri-Destro
Sensorimotor and affective brain systems are known to be involved in language processing. However, to date it is still debated whether this involvement is a crucial step of semantic processing or, on the contrary, it is dependent on the specific context or strategy adopted to solve a task at hand. The present electroencephalographic (EEG) study is aimed at investigating which brain circuits are engaged when processing written verbs. By aligning event-related potentials (ERPs) both to the verb onset and to the motor response indexing the accomplishment of a semantic task of categorization, we were able to dissociate the relative stimulus-related and response-related cognitive components at play, respectively. EEG signal source reconstruction showed that while the recruitment of sensorimotor fronto-parietal circuits was time-locked with action verb onset, a left temporal-parietal circuit was time-locked to the task accomplishment. Crucially, by comparing the time course of both these bottom-up and top-down cognitive components, it appears that the frontal motor involvement precedes the task-related temporal-parietal activity. The present findings suggest that the recruitment of fronto-parietal sensorimotor circuits is independent of the specific strategy adopted to solve a semantic task and, given its temporal hierarchy, it may provide crucial information to brain circuits involved in the categorization task. Eventually, a discussion on how the present results may contribute to the clinical literature on patients affected by disorders specifically impairing the motor system is provided.



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The Asymmetrical Effect of Leftward and Rightward Prisms on Intact Visuospatial Cognition

Publication date: Available online 3 October 2017
Source:Cortex
Author(s): Selene Schintu, Ivan Patané, Michela Caldano, Romeo Salemme, Karen T. Reilly, Laure Pisella, Alessandro Farnè
Rightward prismatic adaptation (RPA) can reduce neglect symptoms in patients whereas adaptation to leftward deviating prisms (LPA) can induce neglect-like behavior in healthy subjects. One influential anatomo-functional model of PA postulates that it inhibits activity of the posterior parietal cortex (PPC) contralateral to the prismatic deviation. By hypo-activating the PPC and thus eventually acting on interhemispheric balance, both LPA and RPA could possibly affect visuospatial perception in healthy subjects, however, such behavioral modulation has seldom been reported after RPA. In the light of recent evidence showing that LPA-induced visuospatial shift need time to develop we hypothesised that RPA might induce significant changes in visuospatial cognition on a longer time scale. We thus assessed the Landmark task, as well as sensorimotor aftereffects, several times over eight hours after a single session of either LPA or RPA. In agreement with previous reports, sensorimotor effects were symmetrical and long-lasting, with both LPA and RPA inducing shifts of comparable amplitudes in the direction opposite to the deviation that lasted up to 8 hours. Visuospatial cognition assessed by Landmark performance, was also significantly modulated for up to 8 hours, but only after LPA. Interestingly, the timing and direction of this modulation differed according to participants' baseline bias. An initial leftward bias led to a rapid, but short-lasting rightward shift, whereas an initial rightward bias led to a slower-developing and longer-lasting leftward shift. These findings shed new light on a so-far relatively overlooked feature of spatial cognition that may interact with the effect of PA: the state of the visuospatial system prior to PA should be taken into account when attempting to understand and modulate visuospatial cognition in healthy and brain-damaged populations. This highlights the need for refining current models of PA's mechanisms of action.



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Beyond Time and Space: The Effect of a Lateralized Sustained Attention Task and Brain Stimulation on Spatial and Selective Attention

Publication date: Available online 3 October 2017
Source:Cortex
Author(s): Nir Shalev, Linde De Wandel, Paul Dockree, Nele Demeyere, Magdalena Chechlacz
The Theory of Visual Attention (TVA) provides a mathematical formalisation of the "biased competition" account of visual attention. Applying this model to individual performance in a free recall task allows the estimation of 5 independent attentional parameters: visual short-term memory capacity, speed of information processing, perceptual threshold of visual detection; attentional weights representing spatial distribution of attention (spatial bias), and the top-down selectivity index. While the TVA focuses on selection in space, complementary accounts of attention describe how attention is maintained over time, and how temporal processes interact with selection. A growing body of evidence indicates that different facets of attention interact and share common neural substrates. The aim of the current study was to modulate a spatial attentional bias via transfer effects, based on a mechanistic understanding of the interplay between spatial, selective and temporal aspects of attention. Specifically, we examined here: (i) whether a single administration of a lateralized sustained attention task could prime spatial orienting and lead to transferable changes in attentional weights (assigned to the left versus right hemi-field) and/or other attentional parameters assessed within the framework of TVA (Experiment 1); (ii) whether the effects of such spatial-priming on TVA parameters could be further enhanced by bi-parietal high frequency tRNS (Experiment 2). Our results demonstrate that spatial attentional bias, as assessed within the TVA framework, was primed by sustaining attention towards the right hemi-field, but this spatial-priming effect did not occur when sustaining attention towards the left. Furthermore, we show that bi-parietal high-frequency tRNS combined with the rightward spatial-priming resulted in an increased attentional selectivity. To conclude, we present a novel, theory-driven method for attentional modulation providing important insights into how the spatial and temporal processes in attention interact with attentional selection.



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Identification of genes encoding glycosyltransferases involved in lipopolysaccharide synthesis in Porphyromonas gingivalis

Summary

Porphyromonas gingivalis can synthesize both A-LPS and O-LPS, which contain anionic O-polysaccharides and conventional O-polysaccharides, respectively. A-LPS can anchor virulence proteins to the cell surface, and elucidating the mechanism of A-LPS synthesis is therefore important for understanding the pathogenicity of this bacterium. To identify the genes involved in LPS synthesis, we focused on uncharacterized genes encoding the glycosyltransferases, PGN_0361, PGN_ 1239, PGN_1240, and PGN_1668, which were tentatively named gtfC, gtfD, gtfE, and gtfF, respectively, and characterized their mutants. We found that disruption of gtfC and gtfF resulted in A-LPS deficiency. In addition, a gtfD mutant had abnormal A-LPS synthesis, and a gtfE mutant exhibited a rough-type LPS which possesses a short oligosaccharide with lipid A-core. We then constructed a gtfC and gtfD double mutant, since their amino acid sequences are very similar, and this mutant similarly possessed a rough-type LPS. Cross-complementation analysis revealed that the GtfD protein is a functional homolog of the Escherichia coli WbbL protein, which is a rhamnosyltransferase. These results suggested that the GtfE protein is essential for the synthesis of both O-LPS and A-LPS, and that GtfC and GtfD proteins may work together to synthesize the two kinds of LPS. In addition, the GtfF protein was essential for A-LPS synthesis, although this may be achieved in a strain-specific manner.

This article is protected by copyright. All rights reserved.

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Traumatic Injury to the Portal Vein with Shock Bowel

Publication date: Available online 3 October 2017
Source:Current Problems in Diagnostic Radiology
Author(s): Nicholas C. Cleveland, Don N. Nguyen, Cassie D. Tran, Rishi K. Maheshwary, Matthew S. Hartman
A portal vein aneurysm is the dilatation of the portal vein due to a defect in the vein wall. This rare disease manifestation is difficult to predict and has the potential for severe complications. We describe the case of a 68-year-old man involved in a MVC who presented with abdominal hemorrhage found on ultrasound, hypotension, and vague abdominal pain. The patient underwent an exploratory laparotomy to control bleeding. Surgery and a subsequent abdominal CT revealed the presence of a portal vein pseudoaneurysm and shock bowel. This case highlights the importance of radiologists to consider the prospect of portal vein aneurysm in the differential diagnosis of hypotension following abdominal trauma.



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Active immunotherapy for TNF-mediated inflammation using self-assembled peptide nanofibers

Publication date: December 2017
Source:Biomaterials, Volume 149
Author(s): Carolina Mora-Solano, Yi Wen, Huifang Han, Jianjun Chen, Anita S. Chong, Michelle L. Miller, Rebecca R. Pompano, Joel H. Collier
Active immunotherapies raising antibody responses against autologous targets are receiving increasing interest as alternatives to the administration of manufactured antibodies. The challenge in such an approach is generating protective and adjustable levels of therapeutic antibodies while at the same time avoiding strong T cell responses that could lead to autoimmune reactions. Here we demonstrate the design of an active immunotherapy against TNF-mediated inflammation using short synthetic peptides that assemble into supramolecular peptide nanofibers. Immunization with these materials, without additional adjuvants, was able to break B cell tolerance and raise protective antibody responses against autologous TNF in mice. The strength of the anti-TNF antibody response could be tuned by adjusting the epitope content in the nanofibers, and the T-cell response was focused on exogenous and non-autoreactive T-cell epitopes. Immunization with unadjuvanted peptide nanofibers was therapeutic in a lethal model of acute inflammation induced by intraperitoneally delivered lipopolysaccharide, whereas formulations adjuvanted with CpG showed comparatively poorer protection that correlated with a more Th1-polarized response. Additionally, immunization with peptide nanofibers did not diminish the ability of mice to clear infections of Listeria monocytogenes. Collectively this work suggests that synthetic self-assembled peptides can be attractive platforms for active immunotherapies against autologous targets.



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Decrease of salivary cortisol levels after glucocorticoid dose reduction in patients with adrenal insufficiency: a prospective proof-of-concept study

Abstract

Background and aim

Patients with adrenal insufficiency (AI) require life-long glucocorticoid (GC) replacement therapy. Cortisol measurement in saliva is increasingly being used: we assessed salivary cortisol rhythm in outpatients with AI, in order to provide new insights regarding the management of GC treatment.

Materials and methods

19 AI outpatients collected six saliva samples from awakening (F^a, before taking the morning GC therapy), during the day (F^1.5h, F^6h before the afternoon GC dose, F^8.5h, F^12h)until bedtime (F^b).We measured daily cortisol exposure by calculating the area under the curve (AUC^FaFb).Saliva samples were collected at baseline and one year after GG dose reduction (by at least 5 mg of hydrocortisone)

Results

Hydrocortisone equivalents decreased from median 25 mg/day (baseline, interquartile range IQR 20-27.5) to 15 mg/day (IQR 15-20, p<0.01). As expected, we observed a reduction of both daily cortisol exposure (AUC^FaFb 23982 nmol·h/L, IQR 12635-45369, to 14689 nmol·h/L, IQR 7168-25378, p<0.001) and salivary cortisol levels at F^6h (24.8 nmol/l, IQR 20.1-35.7, to 21 nmol/l, IQR 8.7-29.2, p<0.05) and F^b (8.7 nmol/l, IQR 3.4-20.2, to 3.7 nmol/l, IQR 3.0-5.8, p<0.05). None of the patients developed signs or symptoms consistent with AI after GC reduction. Median diastolic blood pressure (DPB) values fell from baseline to the end of follow-up (87.5 mmHg, IQR 80-90, to 80 mmHg, IQR 80-85, p<0.05). The AUC^FaFb of patients at baseline was above the reference value (90^th percentile of controls) in 12 patients (60%); after the dosage reduction, 30% of patients normalized their daily cortisol exposure (AUC^FaFb).

Conclusions

The reduction of GC treatment in patients with AI resulted in better control of daily cortisol rhythm, measured with salivary cortisol, and in an improvement of DPB. Further studies are needed to ascertain if salivary cortisol could be used as a biomarker to manage GC replacement therapy.

This article is protected by copyright. All rights reserved.

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Prognostic Indicators of Outcomes in Patients with Lung Metastases from Differentiated Thyroid Carcinoma during Long-term Follow-up

Abstract

Background

Distant metastases, although uncommon, represent maximum disease-related mortality in differentiated thyroid carcinoma (DTC). Lungs are the most frequent sites of metastases. We aimed to evaluate long-term outcomes and identify prognostic factors in metastatic DTC limited to the lungs.

Methods

This retrospective study included 89 patients with DTC and metastases limited to the lungs, who were treated between 1996 and 2012 at Samsung Medical Center. Progression free survival (PFS) and cancer specific survival (CSS) rates were evaluated according to clinicopathologic factors. Cox regression analysis was used to identify independent factors associated with structural progressive disease (PD) and cancer specific death.

Results

With a median follow-up of 84 months, the 5- and 10-year CSS rates were 78% and 73%, respectively. Older age at diagnosis (≥ 55 years), radioactive iodine (RAI) non-avidity, pre-operative or late diagnosis of metastasis, and macro-nodular metastasis (≥1 cm) were predictive of decreased PFS and CSS. Multivariate analysis identified older age (p = 0.002), RAI non-avidity (p = 0.045), and pre-operative (p = 0.030) or late diagnosis (p = 0.026) as independent predictors of structural PD. RAI avidity was also independent predictor of cancer specific death (p = 0.025).

Conclusion

Patients with DTC and metastatic disease limited to the lungs had favorable long-term outcomes. Age, RAI avidity, and timing of metastasis were found to be major factors for predicting prognosis.

This article is protected by copyright. All rights reserved.

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Paraprotein deposits in the skin

Publication date: Available online 3 October 2017
Source:Journal of the American Academy of Dermatology
Author(s): Victoria Alegría-Landa, Lorenzo Cerroni, Heinz Kutzner, Luis Requena
Cutaneous manifestations secondary to paraprotein deposits in the skin include a group of different disorders that although rare, may be the first clinical manifestation of the underlying hematologic dyscrasia. In this article we review the clinical manifestations and histopathologic findings of the processes that result from specific deposition of the paraprotein in different structures of the skin. Paraneoplastic processes frequently associated with hematologic malignancies will not be covered in this review. Some of the disorders included here result from deposition of the intact paraprotein in the skin, whereas in other cases the lesions are due to deposition of modified paraproteins in the form of amyloid substance, cryoglobulins, or crystalglobulins. Cutaneous amyloidoma refers to nodular dermal deposits of amyloid derived from immunoglobulin light chains produced by local plasma cells in the absence of systemic amyloidosis. Dermatologists and dermatopathologists should be aware of the clinical and histopathologic features of these rare disorders because sometimes the cutaneous lesions are the first sign of an underlying silent hematologic malignancy with paraproteinemia.



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Psychiatric adverse events during treatment with brodalumab: Analysis of psoriasis clinical trials

Publication date: Available online 3 October 2017
Source:Journal of the American Academy of Dermatology
Author(s): Mark G. Lebwohl, Kim A. Papp, Lauren B. Marangell, John Koo, Andrew Blauvelt, Melinda Gooderham, Jashin J. Wu, Shipra Rastogi, Susan Harris, Radhakrishnan Pillai, Robert J. Israel
BackgroundIndividuals with psoriasis are at increased risk for psychiatric comorbidities, including suicidal ideation and behavior (SIB).ObjectiveTo distinguish between the underlying risk and potential for treatment-induced psychiatric adverse events in patients with psoriasis being treated with brodalumab, a fully human anti–interleukin 17 receptor A monoclonal antibody.MethodsData were evaluated from a placebo-controlled, phase 2 clinical trial; the open-label, long-term extension of the phase 2 clinical trial; and three phase 3, randomized, double-blind, controlled clinical trials (AMAGINE-1, AMAGINE-2, and AMAGINE-3) and their open-label, long-term extensions of patients with moderate-to-severe psoriasis.ResultsThe analysis included 4464 patients with 9161.8 patient-years of brodalumab exposure. The follow-up time–adjusted incidence rates of SIB events were comparable between the brodalumab and ustekinumab groups throughout the 52-week controlled phases (0.20 vs 0.60 per 100 patient-years). In the brodalumab group, 4 completed suicides were reported, 1 of which was later adjudicated as indeterminate; all patients had underlying psychiatric disorders or stressors.LimitationsThere was no comparator arm past week 52. Controlled study periods were not powered to detect differences in rare events such as suicide.ConclusionsComparison with controls and the timing of events do not indicate a causal relationship between SIB and brodalumab treatment.



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Scholar : These new articles for Archives and Manuscripts are available online

The online platform for Taylor & Francis Online content New for Archives and Manuscripts and online now on Taylor & Francis Online: Book Review Rogue archives: digital cultural memory and media fandom John Willsteed Pages: 1-2 | DOI: 10.1080/01576895.2017.1374157 Original Articles Applying radical empathy to Women's March documentation efforts: a reflection exercise Gina Watts Pages: 1-11 | DOI: 10.1080/01576895.2017.1373361 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.

Determination of the Influence of the Antiphlogistic Ingredients Panthenol and Bisabolol on the SPF Value in vivo

Background: Today, the sun protection factor (SPF) value of sunscreen products is determined in vivo with a standardized protocol (EN ISO 24444:2010), and the measured SPF biological end point is the visible skin erythema. However, many of the sunscreen products currently available on the market have antiphlogistic ingredients, which may potentially result in an overestimated SPF of the sunscreen. Aims: To investigate the potential influence of the antiphlogistic ingredients panthenol and bisabolol in sunscreens on the determined SPF value in vivo. Methods: Formulations with different concentrations of the antiphlogistic ingredients bisabolol or panthenol were tested. As a reference, a base formulation (vehicle) without antiphlogistic ingredients was used. First, the SPF of the sunscreen formulas with and without antiphlogistic ingredients was analyzed in vitro. To investigate whether the antiphlogistic ingredient may suppress the inflammatory response to ultraviolet (UV) irradiation, the SPF was determined in vivo. Finally, selected formulations were also analyzed in an erythema model for testing formulations on UV-induced inflammation. Results: It could be confirmed that no differences between the formula with and that without the active antiphlogistic ingredients bisabolol or panthenol exist when measured in vitro. However, there was also no statistically significant difference in the erythemal response between the vehicle (without an antiphlogistic active ingredient) and the test formulations with different concentrations of the antiphlogistic active ingredients in the in vivo determination of the SPF. Evidence of anti-inflammatory activity of the sunscreen antiphlogistics bisabolol and panthenol was also not apparent in the UV model over a time course of 48 h. Conlusion: The antiphlogistic ingredients panthenol and bisabolol incorporated in the tested sunscreen formula do not interfere with erythema reddening and thus do not affect the SPF value in vivo.
Skin Pharmacol Physiol 2017;30:284-291

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Clinical assessment of diode laser-assisted endoscopic intrasphenoidal vidian neurectomy in the treatment of refractory rhinitis

Abstract

For chronic rhinitis that is refractory to medical therapy, surgical intervention such as endoscopic vidian neurectomy (VN) can be used to control the intractable symptoms. Lasers can contribute to minimizing the invasiveness of ENT surgery. The aim of this retrospective study is to compare in patients who underwent diode laser-assisted versus traditional VN in terms of operative time, surgical field, quality of life, and postoperative complications. All patients had refractory rhinitis with a poor treatment response to a 6-month trial of corticosteroid nasal sprays and underwent endoscopic VN between November 2006 and September 2015. They were non-randomly allocated into either a cold instrument group or a diode laser-assisted group. Vidian nerve was excised with a 940-nm continuous wave diode laser through a 600-μm silica optical fiber, utilizing a contact mode with the power set at 5 W. A visual analog scale (VAS) was used to grade the severity of the rhinitis symptoms for quality of life assessment before the surgery and 6 months after. Of the 118 patients enrolled in the study, 75 patients underwent cold instrument VN and 43 patients underwent diode laser-assisted VN. Patients in the laser-assisted group had a significantly lower surgical field score and a lower postoperative bleeding rate than those in the cold instrument group. Changes in the VAS were significant in preoperative and postoperative nasal symptoms in each group. The application of diode lasers for vidian nerve transection showed a better surgical field and a lower incidence of postoperative hemorrhage. Recent advancements in laser application and endoscopic technique has made VN safer and more effective. We recommend this surgical approach as a reliable and effective treatment for patients with refractory rhinitis.

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Chronic toxicity in Ceriodaphnia dubia induced by graphene oxide

Publication date: Available online 3 October 2017
Source:Chemosphere
Author(s): Jaqueline P. Souza, Francine P. Venturini, Fabrício Santos, Valtencir Zucolotto
The unique physico-chemical properties of nanomaterials have allowed their application in different areas including electronics, energy storage, nanomedicine, environmental remediation and biotechnology. Graphene and its derivatives, in particular, have been commercially available, with prediction for increasing their production in the next years, in a way that their release into aquatic environments is very likely to occur, and the impacts of such situation on organisms are still not completely understood. In this context, we evaluated graphene oxide (GO) effects on the freshwater cladoceran Ceriodaphnia dubia through acute and chronic toxicity, feeding rates, and reactive oxygen species (ROS) generation. The mean effective concentration (EC50) estimated during acute exposure was 1.25 mg L^-1 of GO. The chronic exposure resulted in significant decrease in the number of neonates. The feeding rates were also decreased by GO exposure. Sub-lethal concentrations of GO caused an increase in ROS generation in the organisms. Our results indicated that GO cause acute and chronic effects to C. dubia. In the presence of GO there was a shift in the available energy for self-maintenance rather than feeding or reproduction activities. This study provides useful information on GO concentrations that might impair the aquatic biota, and supports regulatory efforts concerning the environmental safety of this product.

Graphical abstract

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Cross-national mixed-methods comparative case study of recovery-focused mental health care planning and co-ordination in acute inpatient mental health settings (COCAPP-A).

This study suggests there is a commitment to safe, respectful, compassionate care in acute inpatient mental health settings but future research should investigate approaches that increase contact time with service users.

http://ift.tt/2ymj1q5

Assessing the impact and cost-effectiveness of needle and syringe provision and opioid substitution therapy on hepatitis C transmission among people who inject drugs in the UK: an analysis of pooled data sets and economic modelling.

Opiate substitution therapy together with needle/syringe programmes (NSPs) probably reduce the risk of hepatitis C acquisition; and NSPs are likely to be good value for money and even cost saving in some settings.

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A Very Early Rehabilitation Trial after stroke (AVERT): a Phase III, multicentre, randomised controlled trial.

Very early mobilisation was associated with a poorer outcome than usual care at 3 months

http://ift.tt/2yVxq9B

No differential effects to facial expressions under continuous flash suppression: An event-related potentials study

Publication date: December 2017
Source:NeuroImage, Volume 163
Author(s): Insa Schlossmacher, Markus Junghöfer, Thomas Straube, Maximilian Bruchmann
In recent years continuous flash suppression (CFS) has become a popular "blinding" technique for the investigation of nonconscious affective processing since it elicits potent and long-lasting suppression of conscious visual perception. While the majority of studies provides some positive evidence for nonconscious affective processing, there are also studies reporting their absence. Several methodological variations may give rise to this discrepancy: with respect to the experimental paradigm these variations pertain to the likelihood of residual stimulus visibility on the level of individual participants and single trials. Concerning the statistical analysis they relate to the procedures applied to assess whether detection performance is at chance level and whether the outcome measure does or does not depend on the affective stimulus category. In the present study we determined individual eye dominance and individual stimulus contrast in pretests, measured objective and subjective awareness online and applied Bayesian statistics to estimate the likelihood for the null hypothesis. Event-related potentials (ERPs) were measured while participants were subjected to fearful, happy, and neutral faces in a conscious as well as in a nonconscious CFS condition. In the conscious condition, expected emotion effects were observed in the ERP components N170/EPN and LPP. However, despite high statistical power, no effects of emotional expression were found in the nonconscious condition and the absence of nonconscious affective processing under the tested conditions was substantially more likely than its presence. We discuss whether CFS disrupts affective processing completely if thoroughly applied or whether positive and negative findings should be integrated under a two-threshold framework of nonconscious processing.



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Large-scale Retrieval for Medical Image Analytics: A Comprehensive Review

Publication date: Available online 2 October 2017
Source:Medical Image Analysis
Author(s): Zhongyu Li, Xiaofan Zhang, Henning Müller, Shaoting Zhang
Over the past decades, medical image analytics was greatly facilitated by the explosion of digital imaging techniques, where huge amounts of medical images were produced with ever-increasing quality and diversity. However, conventional methods for analyzing medical images have achieved limited success, as they are not capable to tackle the huge amount of image data. In this paper, we review state-of-the-art approaches for large-scale medical image analysis, which are mainly based on recent advances in computer vision, machine learning and information retrieval. Specifically, we first present the general pipeline of large-scale retrieval, summarize the challenges/opportunities of medical image analytics on a large-scale. Then, we provide a comprehensive review of algorithms and techniques relevant to major processes in the pipeline, including feature representation, feature indexing, searching, etc. On the basis of existing work, we introduce the evaluation protocols and multiple applications of large-scale medical image retrieval, with a variety of exploratory and diagnostic scenarios. Finally, we discuss future directions of large-scale retrieval, which can further improve the performance of medical image analysis.

Graphical abstract

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