Publication date: Available online 9 December 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Nicola A. Maffiuletti, Julien Gondin, Nicolas Place, Jennifer Stevens-Lapsley, Isabelle Vivodtzev, Marco A. Minetto
The clinical success of neuromuscular electrical stimulation (NMES) for neuromuscular rehabilitation is greatly compromised by the poor consideration of different physiological and methodological issues that are not always obvious for the clinicians. Therefore, the aim of this narrative review is to re-examine some of these fundamental aspects of NMES using a tripartite model perspective. First, we contend that NMES does not actually bypass the central nervous system but results in a multitude of neurally-mediated responses that contribute substantially to force generation and may engender neural adaptations. Second, we argue that too much emphasis is generally placed on externally-controllable stimulation parameters, while the major determinant of NMES effectiveness is the intrinsically-determined muscle tension generated by the current (i.e., evoked force). Third, we believe that a more systematic approach to NMES therapy is required in the clinic, and this implies a better identification of the patient-specific impairment and of the potential "responders" to NMES therapy. Based on these considerations, we suggest that the crucial steps for ensuring the clinical effectiveness of a NMES treatment should consist of: (1) identifying the neuromuscular impairment with clinical assessment; (2) implementing algorithm-based NMES therapy while (3) properly dosing the treatment with tension-controlled NMES and eventually amplifying its neural effects.
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Σάββατο 9 Δεκεμβρίου 2017
The Clinical Use of Neuromuscular Electrical Stimulation for Neuromuscular Rehabilitation: What Are We Overlooking?
Prior systemic treatment increased the incidence of somatic mutations in metastatic breast cancer
Source:European Journal of Cancer, Volume 89
Author(s): Takeo Fujii, Naoko Matsuda, Miho Kono, Kenichi Harano, Huiqin Chen, Rajyalakshmi Luthra, Sinchita Roy-Chowdhuri, Aysegul A. Sahin, Chetna Wathoo, Aron Y. Joon, Debu Tripathy, Funda Meric-Bernstam, Naoto T. Ueno
BackgroundUnderstanding the biology of breast cancer is important for guiding treatment strategies and revealing resistance mechanisms. Our objectives were to investigate the relationship between previous systemic therapy exposure and mutational spectrum in metastatic breast cancer and to identify clinicopathological factors associated with identified frequent somatic mutations.MethodsArchival tissues of patients with metastatic breast cancer were subjected to hotspot molecular testing by next-generation sequencing. The variables that significantly differed (P < 0.05) in univariate analysis were selected to fit multivariate models. Logistic models were fit to estimate the association between mutation status and clinical variables of interest. Five-fold cross-validation was performed to estimate the prediction error of each model.ResultsA total of 922 patients were included in the analysis. In multivariate analysis, previous systemic treatment before molecular testing (N = 186) was associated with a significantly higher rate of TP53 and PIK3CA mutations compared with the lack of systemic treatment (P < 0.001 for both).ConclusionSystemic treatment exposure is an independent risk factor for high rates of TP53 and PIK3CA mutation, which suggests the importance of testing samples after systemic therapy to accurately assess mutations. It is worth testing the gene profile when tumours become resistant to systemic treatments.
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Complete response of a metastatic porocarcinoma treated with paclitaxel, cetuximab and radiotherapy
Source:European Journal of Cancer
Author(s): C. Godillot, S. Boulinguez, L. Riffaud, V. Sibaud, C. Chira, E. Tournier, C. Paul, N. Meyer
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CONTENTS 1
Source:Materials Today, Volume 20, Issue 9
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CONTENTS 2
Source:Materials Today, Volume 20, Issue 9
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Diet Quality, Inflammation, and Quality of Life in Breast Cancer Survivors: A Cross-Sectional Analysis of Pilot Study Data
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Tonya S. Orchard, Rebecca R. Andridge, Lisa D. Yee, Maryam B. Lustberg
BackgroundModifiable lifestyle factors, such as diet quality, could reduce inflammation and improve quality of life (QOL) in breast cancer survivors, but data are inconclusive.ObjectiveTo determine whether diet quality, as measured by Healthy Eating Index-2010 (HEI-2010) score, is associated with inflammation, health status, or functional outcomes affecting QOL in survivors of early-stage breast cancer.DesignThis is a cross-sectional, secondary analysis of baseline data collected from breast cancer survivors after completion of primary therapy and before random assignment to a pilot nutritional intervention aimed at reducing side effects of aromatase inhibitor treatment.Participants/settingParticipants were 44 postmenopausal women with stage I to III endocrine receptor–positive breast cancer receiving outpatient care at a midwestern cancer center between November 2011 and October 2013.Main outcome measuresPrimary outcomes were serum proinflammatory cytokines (interleukin-6 [IL-6], IL-17, and tumor necrosis factor-α receptor 2 [TNFR-2]). Secondary outcomes included QOL measured by the Stanford Health and Disability Questionnaire and the Functional Assessment of Cancer Therapy–Breast with Endocrine Subscale.Statistical analyses performedPearson correlation coefficients (r) and linear regression models were used to evaluate the relationship of dietary variables with inflammatory cytokines and QOL measures.ResultsA higher overall HEI-2010 score (healthier diet) was associated with lower IL-6 (r=−0.46; P=0.002) and TNFR-2 (r=−0.41; P=0.006); however, associations were attenuated by body mass index (BMI) (IL=6 [r=−0.26; P=0.10]; TNFR-2 [r=−0.30; P=0.06]). In women with prior chemotherapy, a higher HEI-2010 score was strongly associated with lower IL-6 (r=−0.67; P=0.009) and TNFR-2 (r=−0.59; P=0.03) after BMI adjustment. There were no significant correlations between HEI-2010 score and QOL measures after adjustment for BMI.ConclusionsThese data suggest the need for more rigorous investigation into the relationship of diet quality, BMI, and inflammation in breast cancer survivors.
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Editorial Board
Source:Brain Stimulation, Volume 11, Issue 1
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Table of Contents
Source:Brain Stimulation, Volume 11, Issue 1
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Information for Authors
Source:Brain Stimulation, Volume 11, Issue 1
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Masthead
Source:Brain Stimulation, Volume 11, Issue 1
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Network-based brain stimulation selectively impairs spatial retrieval
Source:Brain Stimulation, Volume 11, Issue 1
Author(s): Kamin Kim, Amber Schedlbauer, Matthew Rollo, Suganya Karunakaran, Arne D. Ekstrom, Nitin Tandon
BackgroundDirect brain stimulation via electrodes implanted for intracranial electroencephalography (iEEG) permits the modulation of endogenous electrical signals with significantly greater spatial and temporal specificity than non-invasive approaches. It also allows for the stimulation of deep brain structures important to memory, such as the hippocampus, that are difficult, if not impossible, to target non-invasively. Direct stimulation studies of these deep memory structures, though, have produced mixed results, with some reporting improvement, some impairment, and others, no consistent changes.Objective/hypothesisWe hypothesize that to modulate cognitive function using brain stimulation, it is essential to modulate connected nodes comprising a network, rather than just alter local activity.MethodsiEEG data collected while patients performed a spatiotemporal memory retrieval task were used to map frequency-specific, coherent oscillatory activity between different brain regions associated with successful memory retrieval. We used these to identify two target nodes that exhibited selectively stronger coupling for spatial vs. temporal retrieval. In a subsequent session, electrical stimulation - theta-bursts with a fixed phase-lag (0° or 180°) – was applied to the two target regions while patients performed spatiotemporal retrieval.ResultsStimulation selectively impaired spatial retrieval while not affecting temporal retrieval, and this selective impairment was associated with theta decoupling of the spatial retrieval network.ConclusionThese findings suggest that stimulating tightly connected nodes in a functional network at the appropriate phase-lag may effectively modulate the network function, and while in this case it impaired memory processes, it sets a foundation for further network-based perturbation studies.
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Editorial Board
Source:Brain and Development, Volume 40, Issue 1
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Announcements and reports
Source:Brain and Development, Volume 40, Issue 1
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Cover
Source:Brain and Development, Volume 40, Issue 1
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Contents
Source:Brain and Development, Volume 40, Issue 1
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The in vitro effect of Antimicrobial Photodynamic Therapy on dental microcosm biofilms from partially erupted permanent molars: a pilot study
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Fabiana Sodré de Oliveira, Thiago Cruvinel, Daniela Alejandra Cusicanqui Méndez, Evandro José Dionísio, Daniel Rios, Maria Aparecida Andrade Moreira Machado
BackgroundThe aPDT could enhance the prevention of dental caries lesions in pits and fissures of partially erupted molars, by killing microorganisms from complex dental biofilms. This pilot study aimed to evaluate the effect of the Antimicrobial Photodynamic Therapy (aPDT) on the viability of specific microorganism groups of dental microcosm biofilms from occlusal surfaces of first permanent molars in eruption.MethodsDental microcosm biofilms grown on bovine enamel blocks, from dental plaque collected on occlusal surfaces of a partially erupted lower right first permanent molar, with McBain medium plus 1% sucrose in anaerobic condition at 37°C for 72h. The experiments were performed in eight groups: L-P-=no treatment (control), L18.75P-=18.75J/cm2 LED, L37.5P-=37.5J/cm2 LED, L75P-=75J/cm2 LED, L-P+=200mM TBO, L18.75P+=200mM TBO+18.75J/cm2 LED, L37.5P+=200mM TBO+37.5J/cm2 LED, and L75P+=200mM TBO+75J/cm2 LED. The counts of total microorganisms, total streptococci and mutans streptococci were determined on selective media agar plates by colony-forming units per mL. The log-transformed counts were analyzed by Kruskal-Wallis and post-hoc Dunn's test (P<0.05).ResultsThe counts of all microorganisms treated in the group L75P+ were statistically lower than those treated in L-P-. The aPDT promoted a significant reduction of microorganisms, with a trend of dose-dependent effect.ConclusionTBO-mediated aPDT was effective in reducing the viability of specific microbial groups in dental microcosm biofilms originated from occlusal of permanent molars in eruption.
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Analysis of the electromiographic activity of lower limb and motor function in hippotherapy practitioners with cerebral palsy
Publication date: Available online 9 December 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Mariane Fernandes Ribeiro, Ana Paula Espindula, Janaine Brandão Lage, Domingos Emanuel Bevilacqua Júnior, Luanna Honorato Diniz, Ednéia Corrêa de Mello, Alex Abadio Ferreira, Mara Lúcia Fonseca Ferraz, Vicente de Paula Antunes Teixeira
ObjectiveInvestigation of the effects of hippotherapy treatment on lower limb muscle activity and gross motor function in subjects with cerebral palsy (CP), comparing them to a group of subjects with adequate motor development.MethodsEvaluation was made of seven individuals with spastic diparetic CP, average age 9.3 (±3.3) years (CP group), Gross Motor Function Classification System (GMFCS) levels I and II, and eight individuals with adequate motor development, average age 10.9 (±3.2) years (control group). The groups were submitted to 25 sessions of hippotherapy, each lasting 30 min, on a weekly basis, and the muscle activity of the lower limbs was evaluated using surface electromyography during the 1st, 10th, 20th, and 25th sessions. For the CP group, Gross Motor Function Measurement (GMFM-88) was performed before and after hippotherapy treatment.ResultsThere was higher muscle activity in the 10th session, compared to the other sessions, with greater activity of the tibialis anterior muscles, for both groups studied. After treatment, the CP group showed significant improvement in the GMFM total score, and in the scores for dimensions D and E.ConclusionHippotherapy sessions improved the muscle responses in both groups, and improved the gross motor function of the subjects with CP.
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Cardiac autonomic response after cranial technique of the fourth ventricle (cv4) compression in systemic hypertensive subjects
Publication date: Available online 9 December 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Ana Christina Certain Curi, Alex Souto Maior Alves, Julio Guilherme Silva
ObjectiveThe aim of this study was to compare blood pressure (BP) behavior and heart rate variability (HRV) among hypertensive stage I and normotensive individuals who were submitted to the cranial technique of the 4th ventricle compression (CV4), an osteopathic technique.MethodsIn this experimental controlled study, thirty men between 40 and 60 years old were evaluated and divided into two groups: normotensive (NT) and hypertensive (HT). The CV4 maneuver was applied in both groups and BP was measured at 5 (five) different stages: pre and post-intervention, 5, 10 and 15min after technique. Time-frequency parameters were obtained from measurements of RR intervals. Data were analyzed using an ANOVA two-way for analysis of the condition factor (NT and HT) and times with p-value ≤ .05.ResultsThere was a reduction in the BP of the HT group. A significant intergroup difference (p = .01) was noticed, with respect to the standard deviation of successive normal R-R intervals (SDNN) values, mainly between pre-intervention and 15min stages. Concerning root mean square of the mean squared differences (RNSSD) values, the highlights were differences between pre-intervention and 10min (p = .01) only in the NT group. There was an increase in high frequencies (HF) values and a low frequencies (LF) attenuation in both groups at all different stages.ConclusionThe data showed a BP reduction in the HT group in pre-intervention/15min and an increase in parasympathetic activity and decreased sympathetic activity in both groups. This suggests a change in the sympathetic-vagal balance. However, further studies are needed to elucidate the data on BP reduction mechanisms with CV4.
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Temporal and spatial variations of 134Cs and 137Cs levels in the Sea of Japan and Pacific coastal region: Implications for dispersion of FDNPP-derived radiocesium
Publication date: February 2018
Source:Journal of Environmental Radioactivity, Volume 182
Author(s): M. Inoue, Y. Shirotani, S. Yamashita, H. Takata, H. Kofuji, D. Ambe, N. Honda, Y. Yagi, S. Nagao
To investigate the dispersion of Fukushima Dai-ichi Nuclear Power Plant (FDNPP)-derived radiocesium in the Sea of Japan and western Pacific coastal region and determine the sources of radiocesium in these areas, we examined the temporal and spatial variations of 134Cs and 137Cs concentrations (activities) during 2011–2016 in seawaters around the western Japanese Archipelago, particularly in the Sea of Japan. In May 2013, the surface concentration of 134Cs was ∼0.5 mBq/L (decay-corrected to March 11, 2011), and that of 137Cs exceeded the pre-accident level in this study area, where the effects of radiocesium depositions just after the FDNPP accident disappeared in surface waters in October 2011. Subsequently, radiocesium concentrations gradually increased during 2013–2016 (∼0.5–1 mBq/L for 134Cs), exhibiting approximately homogeneous distributions in each year. The temporal and spatial variations of 134Cs and 137Cs concentrations indicated that FDNPP-derived radiocesium around the western Japanese Archipelago, including the Sea of Japan, has been supported by the Kuroshio Current and its branch, Tsushima Warm Current, during 2013–2016. However, in the Sea of Japan, the penetration of 134Cs was limited to depths of less than ∼200 m during three years following the re-delivery of FDNPP-derived radiocesium.
Graphical abstract
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Spatial variations of 226Ra, 228Ra, 134Cs, and 137Cs concentrations in western and southern waters off the Korean Peninsula in July 2014
Source:Journal of Environmental Radioactivity, Volume 182
Author(s): M. Inoue, Y. Shirotani, S. Nagao, T. Aramaki, Y.I. Kim, K. Hayakawa
We examined the spatial distributions of 226Ra, 228Ra, 134Cs, and 137Cs concentrations (activities) in seawater off the western and southern Korean Peninsula in July 2014. Radium-228 (and 226Ra) concentrations in water samples varied widely from 5 to 14 mBq/L (2–4 mBq/L), showing a negative correlation with salinity, particularly at the surface off the western Korean Peninsula. This indicates that the seawaters in this area are fundamentally comprised of 228Ra-poor and high-saline Kuroshio Current water and 228Ra-rich and low-saline water (e.g., continental shelf water), with various mixing ratios. Although Fukushima Dai-ichi Nuclear Power Plant (FDNPP)-derived 134Cs was below the detection limit (<0.08 mBq/L) in waters off the western Korean Peninsula, low level 134Cs (0.1–0.2 mBq/L) was detected in waters off the southern Korean Peninsula accompanied by higher 137Cs concentrations (1.6–1.9 mBq/L) relative to that off the western Korean Peninsula. Combined with the lower radium concentrations, the detection of 134Cs is explained by mixing of FDNPP-derived radiocesium-contaminated Kuroshio Current water.
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A switch from GABA inhibition to excitation of vasopressin neurons exacerbates the development angiotensin II-dependent hypertension
Abstract
Hypothalamic magnocellular neurons secrete vasopressin into the systemic circulation to maintain blood pressure by increasing renal water reabsorption and by vasoconstriction. When blood pressure rises, baroreflex activation normally inhibits vasopressin neurons via activation of GABAergic inputs. However, plasma vasopressin levels are paradoxically elevated in several models of hypertension and in some patients with essential hypertension, despite increased blood pressure. We have previously shown that vasopressin neuron activity is increased early in the development of moderate angiotensin II-dependent hypertension via blunted baroreflex inhibition of vasopressin neurons. Here, we show that antagonism of vasopressin-induced vasoconstriction slows the development of hypertension and that local administration of a GABAA receptor antagonist inhibits vasopressin neurons during, but not before, the onset of hypertension. Taken together, our data suggest that vasopressin exacerbates the increase in blood pressure evident early in the development hypertension and that blunted baroreflex inhibition of vasopressin neurons is underpinned by an excitatory shift in their response to endogenous GABA signalling.
This article is protected by copyright. All rights reserved.
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Chapter 12 Therapeutic protein and drug imprinted nanostructures as controlled delivery tools
Publication date: 2018
Source:Design and Development of New Nanocarriers
Author(s): Handan Yavuz, Kemal Çetin, Semra Akgönüllü, Dilek Battal, Adil Denizli
Polymers play an enormous role in the drug delivery field owing to their flexibility, biocompatibility, and controllable size properties. With the advances in the polymer technology and nanotechnology, the novel drug delivery systems (DDSs) based on nanoparticles have been successfully developed. Nanoparticulate DDSs with an enhanced permeation allow targeted delivery of an intended therapeutic drug to the site of action with predetermined time and activity. Numerous applications have been reported which use nanoparticles as smart delivery systems for synthetic, semi-synthetic or natural drugs, which could be small molecules or huge molecules like proteins. In smart DDSs the critical point is to achieve tunable drug release. Diffusion, matrix degradation or both can control this property. In recent years the use of molecular imprinting technology to arrange the drug release properties from the polymer matrix is attracting significant attention. The basis of this approach is the affinity of an imprinted polymer for the drug molecule, which provides high loading capacity and sustained release profiles. Imprinting also allows for construction of responsive drug release systems based on competitive binding of the imprinted molecule with the weakly bound drug. The studies on the nanoparticle-based imprinted delivery systems will be summarized in this chapter.
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Cancer Immunotherapy in a Neglected Population: The Current Use and Future of T-cell-Mediated Checkpoint Inhibitors in Organ Transplant Patients
Source:Cancer Treatment Reviews
Author(s): Young Kwang Chae, Carlos Galvez, Jonathan F. Anker, Wade T. Iams, Manali Bhave
Although the indications for immune checkpoint inhibitors continue to grow, organ transplant recipients with advanced malignancies have been largely excluded from clinical trials testing the safety and efficacy of these therapies given their need for chronic immunosuppression and the risk of allograft rejection. With the rapid growth of transplant medicine and the increased risk of malignancy associated with chronic immunosuppression, it is critical that we systematically analyze the available data describing immune checkpoint blockade in the organ transplant population. Herein we provide a current and comprehensive review of cases in which immune checkpoint blockade was used on organ transplant recipients. Furthermore, we discuss the differences in efficacy and risk of allograft rejection between CTLA-4 and PD-1 inhibitors and make recommendations based on the limited available clinical data. We also discuss the future of immune checkpoint blockade in this subpopulation and explore the emerging data of promising combination therapies with mTOR, BRAF/MEK, and BTK/ITK inhibitors. Further clinical experience and larger clinical trials involving immune checkpoint inhibitors, whether as monotherapies or combinatorial therapies, will help develop regimens that optimize anti-tumor response and minimize the risk of allograft rejection in organ transplant patients.
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Safety and Efficacy of guselkumab in Japanese patients with moderate-to-severe plaque psoriasis: A Randomised, Placebo-Controlled, Ascending Dose Study
Summary
Background
The Interlukin-23 (IL-23)/Interlukin-17 (IL-17) pathway is central in the pathogenesis of psoriasis. The favourable efficacy and safety of guselkumab, an IL-23 specific monoclonal antibody, has been demonstrated in global Phase 3 studies of plaque psoriasis.
Objectives
To evaluate the safety, efficacy and pharmacokinetics of a single-dose subcutaneous guselkumab in Japanese patients with moderate-to-severe plaque psoriasis.
Methods
Patients with ≥ 10% of total body surface area (BSA) involvement and a Psoriasis Area and Severity Index (PASI) ≥12 were randomised (5:1) to receive guselkumab or placebo in 4 cohorts of this double-blind, placebo-controlled, single ascending dose, single-centre study. Safety, pharmacokinetics, and clinical response were monitored at baseline and specific time points over a 24-wk follow-up period.
Results
Through week 24, 54% (11/20) of guselkumab patients and 50% (2/4) of placebo patients experienced ≥1 adverse event (AE). No deaths, serious AEs, or AEs leading to treatment discontinuation were reported. Maximum clinical response was seen at week 16 with PASI 75 response in 2/5 (10 mg), 4/5 (30 mg and 300 mg), and 3/5 (100 mg) patients and PASI 90 in 0/5 (10 mg), 3/5 (30 mg), 2 /5 (100 mg) and 3/5 (300 mg) patients. Mean Cmax and AUC∞ values increased in a dose-proportional manner with mean terminal t1/2 of 15.6-17.6 days and median tmax of 4-6 days.
Conclusions
Guselkumab was generally well-tolerated and exhibited sustained high levels of clinical response in Japanese patients with moderate-to-severe psoriasis.
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Which outcomes are reported in cellulitis trials? Results of a review of outcomes included in cellulitis trials and a patient priority setting survey
Summary
Background
There is an emerging need to develop consistent outcomes in clinical trials to allow effective comparison of treatment effects. No systematic review has previously looked at the reporting of outcome measures used in randomised controlled trials (RCTs) on treatment and prevention of cellulitis (erysipelas).
Objectives
The primary aim of this review was to describe the breadth of outcomes reported from RCTs on cellulitis treatment and prevention. The secondary aim was to identify outcome themes from patient and health care professionals' feedback from a cellulitis priority setting partnership (PSP).
Methods
We conducted a review of all outcome measures used in RCTs from two recent Cochrane reviews. Free text responses from a cellulitis priority setting survey were used to understand the perspectives of patients and healthcare professionals.
Results
Outcomes from 42 RCTs on treatment of cellulitis and six RCTs on prevention of cellulitis were reviewed. Only 28 trials stated their primary outcome. For trials assessing treatment of cellulitis, clinical response to treatment was categorised in 25 different ways. Five of these trials used an outcome that was in accordance with FDA guidance and only four trials incorporated either quality of life or patient satisfaction. For trials assessing prevention of cellulitis, recurrence was the key outcome measure. From the cellulitis PSP, prevention of recurrence, clinical features and long-term disease impact were the most important outcome themes for patients.
Conclusions
We have shown that in cellulitis treatment and prevention research, there is significant heterogeneity in clinical outcomes, inadequate focus on patient-reported outcomes, and a disparity between what is currently measured and what patients and healthcare professionals feel is important. We recommend that future cellulitis treatment trials consider the use of longer-term outcomes to capture recurrence and long-term morbidity, as well as short-term resolution of acute infection.
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Development and optimization of a new synthetic process for lorcaserin
Publication date: Available online 9 December 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Jérôme Cluzeau, Gaj Stavber
A two-step process to synthesize racemic lorcaserin was developed from 2-(4-chlorophenyl)ethanol via formation of bromide or tosylate derivatives. These derivatives were reacted with allylamine in neat conditions to provide pure N-(4-chlorophenethyl)allylammonium chloride. This compound was cyclized in neat conditions using aluminum or zinc chloride to give racemic lorcaserin. After resolution of enantiomers, the wrong enantiomer was racemized and recycled to give new R-lorcaserin.
Graphical abstract
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Antiobesity and emetic effects of a short-length peptide YY analog and its PEGylated and alkylated derivatives
Publication date: Available online 8 December 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Ayumu Niida, Yoko Kanematsu-Yamaki, Tomoko Asakawa, Yoshimasa Ishimura, Hisashi Fujita, Kouta Matsumiya, Naoki Nishizawa, Yusuke Adachi, Taisuke Mochida, Kazue Tsuchimori, Mariko Yoneyama-Hirozane, Junichi Sakamoto, Hideki Hirabayashi, Hideo Fukui, Shiro Takekawa, Taiji Asami
Neuropeptide Y2 receptor (Y2R) agonism is an important anorectic signal and a target of antiobesity drug discovery. Recently, we synthesized a short-length Y2R agonist, PYY-1119 (4-imidazolecarbonyl-[D-Hyp24,Iva25,Pya(4)26,Cha27,36,γMeLeu28,Lys30,Aib31]PYY(23–36), 1) as an antiobesity drug candidate. Compound 1 induced marked body weight loss in diet-induced obese (DIO) mice; however, 1 also induced severe vomiting in dogs at a lower dose than the minimum effective dose administered to DIO mice. The rapid absorption of 1 after subcutaneous administration caused the severe vomiting. Polyethylene glycol (PEG)- and alkyl-modified derivatives of 1 were synthesized to develop Y2R agonists with improved pharmacokinetic profiles, i.e., lower maximum plasma concentration (Cmax) and longer time at maximum concentration (Tmax). Compounds 5 and 10, modified with 20 kDa PEG at the N-terminus and eicosanedioic acid at the Lys30 side chain of 1, respectively, showed high Y2R binding affinity and induced significant body weight reduction upon once-daily administration to DIO mice. Compounds 5 and 10, with their relatively low Cmax and long Tmax, partially attenuated emesis in dogs compared with 1. These results indicate that optimization of pharmacokinetic properties of Y2R agonists is an effective strategy to alleviate emesis induced by Y2R agonism.
Graphical abstract
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Interpersonal and intrapersonal emotional processes in individuals treated for alcohol use disorder and non-addicted healthy individuals
Source:Addictive Behaviors, Volume 79
Author(s): Maciej Kopera, Elisa M. Trucco, Andrzej Jakubczyk, Hubert Suszek, Aneta Michalska, Aleksandra Majewska, Natalia Szejko, Agata Łoczewska, Aleksandra Krasowska, Anna Klimkiewicz, Kirk J. Brower, Robert A. Zucker, Marcin Wojnar
IntroductionPrior work largely confirms the presence of various emotional processing deficits among individuals with an alcohol use disorder (AUD); however, their specificity and relevance still warrant investigation. The aim of the current study was to compare selected aspects of emotional processing (i.e., mental state recognition, alexithymia, and emotional intelligence) between individuals treated for an AUD and healthy individuals.MethodsThe AUD sample consisted of 92 abstinent men with AUD who were participating in an 8-week inpatient abstinence-based treatment program in Warsaw, Poland. The healthy control (HC) group consisted of 86 men recruited from the Medical University of Warsaw and the Nowowiejski Hospital administrative staff. Baseline information about demographics, psychopathological symptoms, and severity of alcohol problems was obtained. Mental states recognition was assessed using the Reading the Mind in the Eyes Test (RMET). Alexithymia was measured with the Toronto Alexithymia Scale (TAS-20). The Schutte Self-Report Emotional Intelligence Test (SSEIT) was used to measure emotional intelligence (EI).Results and conclusionsAfter accounting for potentially confounding variables (demographics, severity of depression, anxiety symptoms) in MANCOVA models, patients with AUD presented deficits in identification and description of their own emotional states, as well as lower emotion regulation skills when compared to HCs. No between-group differences were observed in self-reported recognition of other people's emotions, social skills, and a behavioral measure of mental states recognition.Specific rather than general emotion-processing deficits in participants with AUD were identified, suggesting problems with processing of intrapersonal emotional signals.
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Improvement of the association between self-reported pill count and varenicline levels following exclusion of participants with misreported pill count: A commentary on Peng et al. (2017)
Source:Addictive Behaviors, Volume 79
Author(s): Annie R. Peng, Bernard Le Foll, Mark Morales, Caryn Lerman, Robert Schnoll, Rachel F. Tyndale
IntroductionWe previously reported poor associations between salivary varenicline and pill counts, and a substantial overestimation of adherence by pill counts in "Measures and predictors of varenicline adherence in the treatment of nicotine dependence" (Peng et al., 2017). We have since conducted supplementary analyses characterizing, and then excluding, individuals with established inaccurate pill count recall.MethodsBased on published varenicline pharmacokinetics (including drug levels, and the long half-life) and our detection limits, conservatively we should be able to detect varenicline in anyone who took at least one pill during the 48h prior to saliva collection; thus, those reporting 1 or more pills in this time frame but who had undetectable salivary varenicline were deemed to have inaccurate pill count recall. Correlations between pill counts and salivary varenicline, and Receiver Operating Characteristics curve analyses were conducted following exclusion of participants with inaccurate pill count recall.ResultsNearly 20% of our participants (N=67/376) had inaccurate self-reported pill counts. These participants were younger, non-white, lower income, and unmarried (evaluated using chi-square or Mann-Whitney U test). Following exclusion of these individuals, the correlations between salivary varenicline and pill count improved and the area under the curve (AUC) of pill counts for discriminating adherence improved modestly.ConclusionWhen the 20% of individuals with inaccurate pill count recall were excluded, an improved association between self-reported pill count and salivary varenicline was observed, albeit still weak. A substantial overestimation of adherence by pill counts relative to salivary varenicline is still observed even after exclusion of almost 20% of the group having established inaccurate reporting suggesting that these individuals, with identifiable inaccuracies, were only part of the overestimation of adherence.
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Identifying patterns of tobacco use among US middle and high school students: A latent class analysis
Source:Addictive Behaviors, Volume 79
Author(s): Mansoo Yu, Paul Sacco, Hye Jeong Choi, Jenna Wintemberg
ObjectivesThis study sought to (a) understand patterns of tobacco use among US middle and high school students based on their lifetime or current use of tobacco products: cigarettes, cigars, chewing tobacco, pipes, e-cigarettes, and hookah tobacco, and (b) examine differences in the underlying patterns by sociodemographic and tobacco-related characteristics (e.g., exposure to tobacco products, tobacco advertising, parental disapproval of tobacco use and feedback from healthcare providers).MethodsWe analyzed self-report data from the 2013 National Youth Tobacco Survey (n=18,046). Latent Class Analysis was conducted to identify patterns of tobacco use and tested how sociodemographic and tobacco-related characteristics are associated with such patterns.ResultsFour subtypes of tobacco use were identified: "Very Low Risk (VLR)," "Lifetime Smoking (LS)," "Lifetime Multiple Tobacco Use (LMT)," and "Past Month Multiple Tobacco Use (PMT)." Latino and Asian American youth were more likely to be in PMT. Compared with students in LS, students in VLR were less likely to receive advice not to use tobacco from their healthcare providers, but more likely to have parental disapproval of smoking. Students in LMT (vs. LS) were more likely to use tobacco coupons and promotional materials, report greater access to tobacco, and receive advice from a healthcare professional. Students in PMT (vs. LS) were more likely to use coupons, take part in tobacco promotions, and be exposed to smoking in a vehicle.ConclusionsOur study suggests that it may be important to consider the underlying patterns and correlates of tobacco use in designing tobacco control programs for youth.
http://ift.tt/2B40ks9
Comparison of Elliptical Excision versus Punch Incision for the Treatment of Epidermal Inclusion Cysts: A Prospective, Randomized Study
Publication date: Available online 9 December 2017
Source:Journal of the American Academy of Dermatology
Author(s): Justin Cheeley, Laura Delong Aspey, Jamie MacKelfresh, Michelle Pennie, Suephy Chen
http://ift.tt/2iIRPbh
Merkel Cell Carcinoma: an Update and Review Part 1. Pathogenesis, Diagnosis, and Staging
Publication date: Available online 9 December 2017
Source:Journal of the American Academy of Dermatology
Author(s): Kathleen Coggshall, Tiffany L. Tello, Jeffrey P. North, Siegrid S. Yu
Merkel cell carcinoma (MCC) is an uncommon primary cutaneous neuroendocrine cancer. It most commonly presents as an indurated plaque or nodule on sun-damaged skin in elderly patients and is characterized by high rates of local recurrence and nodal metastasis. Survival at five years is 51% for local disease and as low as 14% for distant disease, which underscores the aggressive nature of this tumor and challenges in management. Advances in immunology and molecular genetics have broadened our understanding of the pathophysiology of MCC and expanded our therapeutic arsenal. With this comprehensive review, we provide an update of MCC epidemiology, pathogenesis, clinical presentation, diagnostic evaluation and prognostic markers. Part II of this review will explore the evolving landscape in MCC management.
Teaser
Capsule Summary: word count not required for CME articles; please note that bulleted points appear at the start of each section but are not included in the total word counthttp://ift.tt/2kIuKcP
Anti-melanoma differentiation-associated gene 5 (MDA5) dermatomyositis: a concise review with an emphasis on distinctive clinical features
Publication date: Available online 9 December 2017
Source:Journal of the American Academy of Dermatology
Author(s): Drew JB. Kurtzman, Ruth Ann Vleugels
Melanoma differentiation-associated gene 5 (MDA5) is a recently described autoantigen target in a subset of patients with dermatomyositis (DM). Anti-MDA5 DM is characterized by a unique mucocutaneous and systemic phenotype that includes cutaneous and oral ulceration, painful palmar papules, alopecia, panniculitis, arthritis, a lower incidence of myositis, and, importantly, an elevated risk of interstitial lung disease, with a potentially fatal course. Because the clinical features may differ substantially from those typically observed in cutaneous DM, the diagnosis is often overlooked, which may negatively affect patient outcomes. This review aims to familiarize the clinician with the distinctive clinical features of anti-MDA5 DM in order to enhance its recognition and to facilitate an appropriate screening and management strategy.
Teaser
Anti-MDA5 dermatomyositis exhibits unique clinical features including mucocutaneous ulceration, palmar papules, non-scarring alopecia, panniculitis, arthritis, and interstitial lung disease.Early intervention may reduce disease-related morbidity and improve survival in affected individuals.Knowledge of the salient features of anti-MDA5 dermatomyositis enhances its recognition and facilitates treatment.http://ift.tt/2iGS32C
‘‘Intralesional Drainage Injection’ of Triamcinolone acetonide for Epidermal Cyst’
Publication date: Available online 9 December 2017
Source:Journal of the American Academy of Dermatology
Author(s): Deepak Jakhar, Ishmeet Kaur
http://ift.tt/2kIb7lf
Merkel Cell Carcinoma: An Update and Review. Part II: Current and Future Therapy
Publication date: Available online 9 December 2017
Source:Journal of the American Academy of Dermatology
Author(s): Tiffany L. Tello, Kathleen Coggshall, Sue S. Yom, Siegrid S. Yu
Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin associated with a high risk of local recurrence and distant metastases. It most commonly occurs on sun-exposed areas of Caucasian patients over the age of 65.1,2 The Merkel cell polyomavirus (MCV) is thought to be responsible for malignant transformation in approximately 80% of cases in the northern hemisphere,3 while ultraviolet radiation induced DNA damage is implicated in MCV-negative tumors.4 The overall incidence of MCC is low, with approximately 1600 cases diagnosed annually in the United States. The rate is much higher in patients with lymphoproliferative malignancies, solid organ transplants, and HIV infection.5–9 The low overall incidence of this tumor makes it challenging to conduct prospective clinical trials with sufficient power.10 As a result, most management recommendations are based on case series, retrospective reviews, and expert opinion.The pathogenesis, diagnosis, and staging of MCC are discussed in Part I of this review. Part II focuses on current management guidelines and promising new therapies in development. Due to the complexity, aggressive nature, and individuality of each case, MCC is best treated by a multidisciplinary team.
Teaser
Capsule Summary: word count not required for CME articles as these appear before each section and are included in the text word counthttp://ift.tt/2iKNggG
Dermoscopy as an evolving tool to assess vitiligo activity
Publication date: Available online 9 December 2017
Source:Journal of the American Academy of Dermatology
Author(s): Abhijeet Kumar Jha, Sidhath Sonthalia, Aimilios Lallas
http://ift.tt/2kIaVT3
Catalytic valorization of biomass derived glycerol under methane: Effect of catalyst synthesis method
Publication date: 15 March 2018
Source:Fuel, Volume 216
Author(s): Danielle Austin, Aiguo Wang, Peng He, Hui Qian, Hongbo Zeng, Hua Song
The feasibility of upgrading glycerol using Zn, Cu and Ga modified ZSM-5 was investigated. Different catalyst synthesis techniques were compared for their performance on the aromatization of glycerol under a methane environment at 400 °C and initial pressure of 5 bar. GC–MS analysis showed that the catalyst synthesized using deposition precipitation (DP) resulted in the best performance in terms of the highest yield of monoaromatics in the liquid product when compared with the other synthesis techniques. XRD, NH3-TPD, Pyridine DRIFT, TEM, CO Chemisorption and XAS were employed to better understand the influencing parameters. High crystallinity, high acidity with a higher proportion of medium acid sites and high metal dispersion were identified as the most important factors influencing aromatization performance. Evidently, the deposition precipitation synthesis technique is effective in obtaining each of these attributes. Additionally, a methane environment increased aromatic production when compared to an inert environment. Methane was found to not only maintain high metal dispersion throughout the reaction, but may participate in the reaction as well. The synthesis technique utilized for the upgrading of glycerol can influence the distribution of products, allowing for increased selectivity of the desired product. The demonstrated feasibility and excellent upgrading performance of the DP synthesized catalyst could make the production of biodiesel more economical and environmentally friendly.
http://ift.tt/2AJoyWd
Prediction of soil parameters using the spectral range between 350 and 15,000nm: A case study based on the Permanent Soil Monitoring Program in Saxony, Germany
Publication date: 1 April 2018
Source:Geoderma, Volume 315
Author(s): Frank Riedel, Michael Denk, Ingo Müller, Natalja Barth, Cornelia Gläßer
In this study, we tested the potential of visible-near infrared (VNIR, 350–2500nm) and mid-infrared spectroscopy (MIR, 2500–15,000nm) for quantification and prediction of soil parameters to support the Saxon Permanent Soil Monitoring Program. As Saxony is characterised by a large variety of soil metal concentrations which can negatively affect essential soil functions, the presented study is strongly focused on the forecast of soil metal contents. As data basis, a total of 203 soil samples of the Saxon Permanent Soil Monitoring Program, collected between 1998 and 2013 at 48 representative locations with respect to soil type, parent material, land use and climate conditions, were used. The chemical analysis provided information regarding total soil organic carbon content (TOC) and pH-value as well as element concentrations (Al, As, Ca, Cu, Fe, K, Mn, Na, Ni, Pb, Zn). VNIR-spectra were collected utilising an ASD FieldSpec Pro FR while an Agilent 4300 Handheld FTIR spectrometer was applied to cover the MIR wavelength region. Spectra pre-processing comprised the application of multi scatter correction (MSC), standard normal variate (SNV), continuum removal (CR) and the first and second derivatives. To model the relationship between soil spectral and chemical properties, and to predict element concentration, the spectra and chemical data were used as input for Partial Least Square Regression (PLSR) models. The definition of training data was realised on Kennard-Stone sampling algorithm and we selected 103 samples for model calibration and 100 samples for model validation. In general, the MIR-spectra and the MSC- and SNV-pre-processing improved the model performance. We obtained promising model results for TOC, Al, Fe, K and Ni with R2-values between 0.70 and 0.88. Moderate results were obtained for Ca (R2=0.61) and Mn (R2=0.43). We conclude that VNIR and MIR spectroscopy has the potential to quickly provide reliable information regarding major soil parameters and metal contents and is thus a promising alternative approach to support soil analysis within the Saxon Permanent Soil Monitoring Program.
http://ift.tt/2AHJkFk
AC impedance spectroscopy on Al/p-Si/ZnTPyP/Au heterojunction for hybrid solar cell applications
Publication date: 5 March 2018
Source:Journal of Alloys and Compounds, Volume 736
Author(s): M.M. Shehata, T.G. Abdel-Malik, K. Abdelhady
A p-Silicon/Zn-tetra pyridyl-porphyrin (ZnTPyP) heterojunction was fabricated by forming a ZnTPyP layer on a p-type Si single crystal substrate using a conventional thermal evaporation technique. Complex impedance measurements of the Al/p-Si/ZnTPyP/Au heterojunction were carried out at applied AC-voltage range from 0.2 V to 1 V, temperature range from 303 K to 353 K and over the frequency range from 100HZ to 2 MHz. Impedance spectra of the heterojunction under the standard illumination ranged from 0 to 40 mW/cm2 were reported and analysed.
Graphical abstract
http://ift.tt/2A8FEeH
Exploiting Metabolic Vulnerabilities of Cancer with Precision and Accuracy
Source:Trends in Cell Biology
Author(s): Adam J. Wolpaw, Chi V. Dang
Links between oncogenic drivers and cancer cell metabolism have emerged over the past several decades, indicating that constitutive oncogenic growth signaling can render cancers susceptible to metabolic interventions. While significant progress has been achieved in the identification of metabolic vulnerabilities of cancer cells, the complexity of the tumor microenvironment (TME) and the dynamic nature of organismal circadian metabolism challenge the precision of targeting cancer metabolism. Here current progress in the areas of cancer metabolism and TME metabolism is reviewed, highlighting how cancer metabolism can be accurately and precisely targeted.
http://ift.tt/2A8BpQj
A New Textured Polyphosphazene Biomaterial with Improved Blood Coagulation and Microbial Infection Responses
Publication date: Available online 8 December 2017
Source:Acta Biomaterialia
Author(s): Li-Chong Xu, Zhongjing Li, Zhicheng Tian, Chen Chen, Harry R. Allcock, Christopher A. Siedlecki
A new poly[bis(octafluoropentoxy) phosphazene] (OFP) was synthesized for the purpose of blood contacting medical devices. OFP was further either developed into crosslinkable polyphosphazene (X-OFP) or blended with polyurethane (PU) as the mixture (OFP/PU) for improvement of mechanical property of polyphosphazene polymers. All the materials were fabricated as smooth films or further textured with submicron pillars for the assay of antimicrobial and antithrombotic properties. Results showed that crosslinkable OFP (X-OFP) and blends of OFP/PU successfully improved the mechanical strength of OFP and fewer defects of pillars were found on the textured polyphosphazene surfaces. The antithrombotic experiments showed that polyphosphazene OFP materials reduced human Factor XII activation and platelet adhesion, thereby being resistant to plasma coagulation and thrombosis. The bacterial adhesion and biofilm experiments demonstrated that OFP materials inhibited staphylococcal bacterial adhesion and biofilm formation. The surface texturing further reduced the platelet adhesion and bacterial adhesion, and inhibited biofilm formation up to 23 days. The data suggested that textured OFP materials may provide a practical approach to improve the biocompatibility of current biomaterials in the application of blood contacting medical devices with significant reduction in risk of pathogenic infection and thrombosis.Statement of SignificanceThe thromboembolic events and microbial infection have been the significant barriers for the long term use of biomaterials in blood-contacting medical devices. The development of new materials with multiple functions including anti-thrombosis and antibacterial surfaces is a high research priority. This study synthesized new biostable and biocompatible polyphosphazene polymers, poly[bis(octafluoropentoxy)phosphazene] (OFP) and crosslinkable OFP, and successfully improved the mechanical strength of polyphosphazenes. Polymers were fabricated into textured films with submicron pillars on the surfaces. The antimicrobial and antithrombotic assays demonstrated that new materials combined with surface physical modification have significant reduction in risk of pathogenic infection and thrombosis, and improve the biocompatibility of current biomaterials in the application of blood-contacting medical devices. It would be interest to biomaterials and bioengineering related communities.
Graphical abstract
http://ift.tt/2AObiBC
Fabrication of Hybrid Crosslinked Network with Buffering Capabilities and Autonomous Strengthening Characteristics for Dental Adhesive
Publication date: Available online 8 December 2017
Source:Acta Biomaterialia
Author(s): Linyong Song, Qiang Ye, Xueping Ge, Anil Misra, Candan Tamerler, Paulette Spencer
Ingress of bacteria and fluids at the interfacial gaps between the restorative composite biomaterial and the tooth structure contribute to recurrent decay and failure of the composite restoration. The inability of the material to increase the pH at the composite/tooth interface facilitates the outgrowth of bacteria. Neutralizing the microenvironment at the tooth/composite interface offers promise for reducing the damage provoked by cariogenic and aciduric bacteria. We address this problem by designing a dental adhesive composed of hybrid network to provide buffering and autonomous strengthening simultaneously. Two amino functional silanes, 2-hydroxy-3-morpholinopropyl (3-(triethoxysilyl)propyl) carbamate and 2-hydroxy-3-morpholinopropyl (3-(trimethoxysilyl)propyl) carbamate were synthesized and used as co-monomers. Combining free radical initiated polymerization (polymethacrylate-based network) and photoacid-induced sol-gel reaction (polysiloxane) results in the hybrid network formation. Resulting formulations were characterized with regard to real-time photo-polymerization, water sorption, leached species, neutralization, and mechanical properties. Results from real-time FTIR spectroscopic studies indicated that ethoxy was less reactive than methoxy substituent. The neutralization results demonstrated that the methoxy-containing adhesives have acute and delayed buffering capabilities. The mechanical properties of synthetic copolymers tested in dry conditions were improved via condensation reaction of the hydrolyzed organosilanes. The leaching from methoxy containing copolymers was significantly reduced. The sol-gel reaction provided a chronic and persistent reaction in wet condition-performance that offers potential for reducing secondary decay and increasing the functional lifetime of dental adhesives.Statement of SignificanceThe interfacial gaps between the restorative composite biomaterial and the tooth structure contributes to recurrent decay and failure of the composite restoration. The inability of the material to increase the pH at the composite/tooth interface facilitates the outgrowth of more cariogenic and aciduric bacteria.This paper reports a novel, synthetic resin that provides buffering capability and autonomous strengthening characteristics. In this work, two amino functional silanes were synthesized and the effect of alkoxy substitutions on the photoacid-induced sol-gel reaction was investigated. We evaluated the neutralization capability (monitoring the pH of lactic acid solution) and the autonomous strengthening property (monitoring the mechanical properties of the hybrid copolymers under wet conditions and quantitatively analyzing the leachable species by HPLC). The novel resin investigated in this studyoffersthe potential benefits of reducing the risk of recurrent decay and prolonging the functional lifetime of dental adhesives.
Graphical abstract
http://ift.tt/2ANpVVA
Acoustic Characterization of Echogenic Polymersomes Prepared From Amphiphilic Block Copolymers
Source:Ultrasound in Medicine & Biology
Author(s): Lang Xia, Fataneh Karandish, Krishna Nandan Kumar, James Froberg, Prajakta Kulkarni, Kara N. Gange, Yongki Choi, Sanku Mallik, Kausik Sarkar
Polymersomes are a class of artificial vesicles prepared from amphiphilic polymers. Like lipid vesicles (liposomes), they too can encapsulate hydrophilic and hydrophobic drug molecules in the aqueous core and the hydrophobic bilayer respectively, but are more stable than liposomes. Although echogenic liposomes have been widely investigated for simultaneous ultrasound imaging and controlled drug delivery, the potential of the polymersomes remains unexplored. We prepared two different echogenic polymersomes from the amphiphilic copolymers polyethylene glycol–poly-DL-lactic acid (PEG-PLA) and polyethylene glycol–poly-L-lactic acid (PEG-PLLA), incorporating multiple freeze-dry cycles in the synthesis protocol to ensure their echogenicity. We investigated acoustic behavior with potential applications in biomedical imaging. We characterized the polymeric vesicles acoustically with three different excitation frequencies of 2.25, 5 and 10 MHz at 500 kPa. The polymersomes exhibited strong echogenicity at all three excitation frequencies (about 50- and 25-dB enhancements in fundamental and subharmonic, respectively, at 5-MHz excitation from 20 µg/mL polymers in solution). Unlike echogenic liposomes, they emitted strong subharmonic responses. The scattering results indicated their potential as contrast agents, which was also confirmed by clinical ultrasound imaging.
http://ift.tt/2ARk4hY
Reduced empathic responses for sexually objectified women: an fMRI investigation
Source:Cortex
Author(s): Carlotta Cogoni, Andrea Carnaghi, Giorgia Silani
Sexual objectification is a widespread phenomenon characterized by a focus on the individual´s physical appearance over his/her mental state. This has been associated with negative social consequences, as objectified individuals are judged to be less human, competent, and moral. Moreover, behavioral responses toward the person change as a function of the degree of the perceived sexual objectification. In the present study, we investigated how behavioral and neural representations of other social pain are modulated by the degree of sexual objectification of the target. Using a within-subject fMRI design, we found reduced empathic feelings for positive (but not negative) emotions toward sexually objectified women as compared to non-objectified (personalized) women when witnessing their participation to a ball-tossing game. At the brain level, empathy for social exclusion of personalized women recruited areas coding the affective component of pain (i.e., anterior insula and cingulate cortex), the somatosensory components of pain (i.e., posterior insula and secondary somatosensory cortex) together with the mentalizing network (i.e., middle frontal cortex) to a greater extent than for the sexually objectified women. This diminished empathy is discussed in light of the gender-based violence that is afflicting the modern society.
http://ift.tt/2Aow8IO
Scholar : Asian Englishes, Volume 19, Issue 3, November 2017 is now available online on Taylor & Francis Online
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Scholar : These new articles for Amyloid are available online
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Imbalance in DNA repair machinery is associated with BRAFV600E mutation and tumor aggressiveness in papillary thyroid carcinoma
Source:Molecular and Cellular Endocrinology
Author(s): Bruna S. Lutz, Natalia M. Leguisamo, Nicole K. Cabral, Helena C. Gloria, Keli C. Reiter, Grasiela Agnes, Virgilio Zanella, Erika L.S. Meyer, Jenifer Saffi
The involvement of alterations in MLH1, an essential mismatch repair component, in BRAFV600E mutated papillary thyroid carcinoma (PTC) has been suggested to be associated with features of tumor aggressiveness. Thirty-two PTC and surrounding normal thyroid tissues were evaluated for 11 representative DNA repair genes expression. BRAFV600E mutational status assessment and clinicopathological correlations were evaluated for their gene and protein expression. BRAFV600E PTC is associated with lower levels of XPD and MLH1 gene expression. Decrease in MLH1 and XPD mRNA levels in BRAFV600E PTC (but not their protein products) are associated with predictors of poor patient outcomes. Considering the complete subset of patients, MGMT and XRCC2 genes were shown down and upregulated, respectively, in PTC tissues. Low expression of MGMT gene and weak XRCC2 protein expression were correlated with characteristics of tumor aggressiveness. These results suggest that an imbalance in DNA repair gene expression in PTC is associated with aggressive clinicopathological features and BRAFV600E mutation.
http://ift.tt/2AojREd
Scholar : These new articles for Canadian Art Therapy Association Journal are available online
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Scholar : These new articles for International Journal of Rail Transportation are available online
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Cyclic fatigue and torsional strength of three different thermally treated reciprocating nickel-titanium instruments
Abstract
Objectives
The aim of this study was to evaluate the cyclic and torsional fatigue resistance of the reciprocating single-file systems Reciproc Blue 25.08 (VDW GmbH, Munich, Germany), Prodesign R 25.06 (Easy Dental Equipment, Belo Horizonte, Brazil), and WaveOne Gold 25.07 (Dentsply/Tulsa Dental Specialties, Tulsa, OK, USA).
Materials and methods
Sixty reciprocating instruments of the systems Reciproc Blue R25 (RB #25 .08 taper), Prodesign R (PDR #25 .06 taper), and WaveOne Gold (WOG #25 .07 taper) (n = 20) were used. Cyclic fatigue resistance testing was performed by measuring the time to failure in an artificial stainless steel canal with a 60° angle of curvature and a 5-mm radius located 5 mm from the tip (n = 10). The torsional test (ISO 3630-1) evaluated the torque and angle of rotation at failure of new instruments (n = 10) in the portion 3 mm from the tip. The fractured surface of each fragment was also observed using scanning electron microscopy (SEM). In addition, a supplementary examination was performed to measure the cross-sectional area of each instrument 3 and 5 mm from the tip. The data were analyzed using one-way ANOVA and Tukey's test, and the level of significance was set at 5%.
Results
The cyclic fatigue resistance values of PDR 25.06 were significantly higher (P < 0.05). RB 25.08 showed higher fatigue resistance than WOG 25.07 (P < 0.05). The torsional test showed that PDR 25.06 had lower torsional strength (P < 0.05). No differences were observed between RB 25.08 and WOG 25.07 (P > 0.05). PDR 25.06 showed higher angular rotation values than RB 25.08 and WOG 25.07 (P < 0.05). RB 25.08 presented higher angular rotation than WOG 25.07 (P < 0.05). The cross-sectional area analysis showed that PDR 25.06 presented the smallest cross-sectional areas at 3 and 5 mm from the tip (P < 0.05).
Conclusion
PDR 25.06 presented the highest cyclic fatigue resistance and angular rotation until fracture compared to RB 25.08 and WOG 25.07. In addition, RB 25.08 and WOG 25.07 had higher torsional strength than PDR 25.06.
Clinical relevance
In endodontic practice, thermally treated reciprocating instruments have been used for the root canal preparation of curved and constricted canals; therefore, these instruments should present high flexibility and suitable torsional strength to minimize the risk of instrument fracture.
http://ift.tt/2A6ieGU
Relationship between caries experience and demarcated hypomineralised lesions (including MIH) in the permanent dentition of 15-year-olds
Abstract
Objective
This cross-sectional study compared the caries experience in 15-year-olds with and without demarcated hypomineralised lesions (DHL) in permanent teeth.
Material and methods
One thousand three hundred and two 15-year-old adolescents from two ongoing birth cohorts (GINIplus15 and LISAplus15) were examined to determine non-cavitated carious lesions (NCCL) and the DMF index. Furthermore, DHL was scored on all permanent teeth/surfaces according to the molar-incisor hypomineralisation criteria of the European Academy of Paediatric Dentistry (MIH/EAPD). Adolescents with DHL were categorised into those with a minimum of one DHL in the permanent dentition (DHL ≥ 1), with DHL on at least one first permanent molar (MIH/EAPD) and with DHL on at least one first permanent molar and permanent incisor (MIH/Severe). The study was conducted in the metropolitan area of Munich.
Results
The proportion of children without caries amounted to 63.7% (DMF > 0) and 26.0% (D1-4MF > 0); the caries experience was mean = 4.0(SD = 5.2) NCCL/T and 0.9(1.7) DMF/T. Existence of DHL ≥ 1, MIH/EAPD and MIH/Severe was detected in 40.2, 17.2 and 9.8% of all adolescents, respectively. The corresponding DMF/T values were: no DHL 0.9(1.7); DHL ≥ 1 1.0(1.7); MIH/EAPD 1.1(1.6); MIH/Severe 1.1(1.7). The group of adolescents with MIH/EAPD and MIH/Severe were found to have statistically higher caries rates in comparison to those with no DHL.
Conclusions
Caries and DHL are prevalent and influenced the dental health of 15-year-old adolescents. A significant positive association existed between the presence of caries and DHL.
Clinical relevance
Children with MIH/EAPD or MIH/Severe had a higher probability to develop carious lesions in the permanent dentition.
http://ift.tt/2AGUdri
Scholar : Ibsen Studies, Volume 17, Issue 2, November 2017 is now available online on Taylor & Francis Online
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Scholar : These new articles for Activities, Adaptation & Aging are available online
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Scholar : These new articles for Critique: Studies in Contemporary Fiction are available online
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Summary Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an un...
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