Micropatterned surface electrode for massive selective stimulation of intraepidermal nociceptive fibres.

Publication date: Available online 9 September 2017
Source:Journal of Neuroscience Methods
Author(s): Massimo Leandri, Lucio Marinelli, Antonio Siri, Luca Pellegrino
BackgroundNo satisfactory neurophysiological test for nociceptive afferents is available to date. Laser stimuli present risks of skin damage, whilst electrical stimulation through specially designed electrodes is not selective enough.New methodWe present a new electrode designed according to critical issues identified in preliminary computer simulations concerning electric field gradient through the skin. To provide selective stimulation the activating electric field must be limited to intraepidermal free nerve endings. To this end, a new interdigitated electrode (IDE) was made of conductive rails arranged in a comb-like micropattern, situated only 150μm apart from each other (150 IDE) and alternately connected to the opposite poles of the stimulator.ResultsEvoked potentials recorded from the scalp were obtained after stimulation with the 150 IDE and with a similarly designed, but more widely spaced electrode (1000μm, or 1000 IDE). Small amplitude early and medium latency components were recorded with the 1000 IDE, suggesting activation of Aβ fibres. On the other hand, the 150 IDE only evoked late responses, confirming sufficient selectivity in small fibre activation.Comparison with Existing Method(s)The main differences with existing electrodes are: 1) Microspaced interdigitated conductive rails. 2) The potentially unlimited surface of stimulation and high efficiency per surface unit, resulting in large numbers of activated nociceptors.ConclusionsA new electrode providing selective stimulation of nociceptive nerve free endings is presented. It is non-invasive, and its surface can be enlarged at will. It is expected that it may greatly help in neurophysiological assessment of conditions affecting the nociceptive pathway.



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Lack of Apparent Survival Benefit from the Use of Androgen Deprivation Therapy in Patients with High-Risk Prostate Cancer Treated with Combined External Beam Radiotherapy and Brachytherapy

Publication date: Available online 9 September 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): David D. Yang, Vinayak Muralidhar, Brandon A. Mahal, Paul L. Nguyen, Phillip M. Devlin, Martin T. King, Peter F. Orio
PurposeWhile level 1 evidence has demonstrated a survival benefit from the addition of androgen deprivation therapy (ADT) to external beam radiation therapy (EBRT) for patients with high-risk prostate cancer, the benefits of ADT with combined EBRT and brachytherapy for high-risk patients are unclear. We examined the association between ADT and overall survival in a national cohort of high-risk patients treated with EBRT with or without brachytherapy.Methods and MaterialsWe identified 46,325 men in the National Cancer Database diagnosed from 2004 through 2011 with high-risk prostate cancer (Gleason 8-10, clinical T3-4, or prostate-specific antigen >20 ng/mL) who were treated with EBRT with or without brachytherapy and ADT. Multivariable Cox regression adjusting for sociodemographic and clinicopathologic factors was used to identify the association between ADT and overall survival.ResultsMedian follow-ups were 48.6 and 59.2 months for patients treated with EBRT only and combined modality radiotherapy, respectively. ADT was associated with an improvement in overall survival for the 85.0% (39,361) of the study cohort managed with EBRT alone (adjusted hazard ratio 0.91, P=0.001) but not for patients treated with combined modality radiotherapy (adjusted hazard ratio 1.05, P=0.496), with a significant interaction (Pinteraction=0.036).ConclusionsAs opposed to the known survival benefit when ADT is given with EBRT, our results suggest that ADT may not improve survival for high-risk patients treated with combined EBRT and brachytherapy. Given the significant adverse effects of ADT, particularly long-term therapy, a randomized controlled trial of combined EBRT and brachytherapy with or without ADT for select high-risk patients using a non-inferiority design should be undertaken.

Teaser

The benefits of androgen deprivation therapy (ADT) with combined external beam radiotherapy and brachytherapy for patients with high-risk prostate cancer are unknown. Using a large, national cohort of high-risk patients, we found that ADT was associated with an improvement in overall survival for patients managed with EBRT alone but not for patients treated with combined modality radiotherapy, suggesting that ADT may not improve overall survival for select high-risk patients treated with combined modality radiotherapy.


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Landscape attributes as drivers of the geographical variation in density of Sapajus nigritus Kerr, 1792, a primate endemic to the Atlantic Forest

Publication date: October 2017
Source:Acta Oecologica, Volume 84
Author(s): Carla D. Hendges, Geruza L. Melo, Alberto S. Gonçalves, Felipe O. Cerezer, Nilton C. Cáceres
Neotropical primates are among the most well studied forest mammals concerning their population densities. However, few studies have evaluated the factors that influence the spatial variation in the population density of primates, which limits the possibility of inferences towards this animal group, especially at the landscape-level. Here, we compiled density data of Sapajus nigritus from 21 forest patches of the Brazilian Atlantic Forest. We tested the effects of climatic variables (temperature, precipitation), landscape attributes (number of patches, mean inter-patch isolation distance, matrix modification index) and patch size on the population density using linear models and the Akaike information criterion. Our findings showed that the density of S. nigritus is influenced by landscape attributes, particularly by fragmentation and matrix modification. Overall, moderately fragmented landscapes and those surrounded by matrices with intermediate indexes of temporal modification (i.e., crop plantations, forestry) are related to high densities of this species. These results support the assumptions that ecologically flexible species respond positively to forest fragmentation. However, the non-linear relationship between S. nigritus density and number of patches suggests that even the species that are most tolerant to forest cover changes seem to respond positively only at an intermediate level of habitat fragmentation, being dependent of both a moderate degree of forest cover and a high quality matrix. The results we found here can be a common response to fragmentation for those forest dweller species that are able to use the matrix as complementary foraging sites.



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Constructing Experience: Event Models from Perception to Action

Publication date: Available online 9 September 2017
Source:Trends in Cognitive Sciences
Author(s): Lauren L. Richmond, Jeffrey M. Zacks
Mental representations of everyday experience are rich, structured, and multimodal. In this article we consider the adaptive pressures that led to human construction of such representations, arguing that structured event representations enable cognitive systems to more effectively predict the trajectory of naturalistic everyday activity. We propose an account of how cortical systems and the hippocampus (HPC) interact to construct, maintain, and update event representations. This analysis throws light on recent research on story comprehension, event segmentation, episodic memory, and action planning. It also suggests how the growing science base can be deployed to diagnose impairments in event perception and memory, and to improve memory for everyday events.



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Phosphate-arsenate relations to affect arsenic concentration in plant tissues, growth, and antioxidant efficiency of sunflower ( Helianthus annuus L.) under arsenic stress

Abstract

Relations between phosphate and arsenate are important but inconsistent to influence arsenic (As) phytotoxicity depending on many plant and soil factors. Present research aimed to investigate the phosphate and arsenate interactions in sunflower (Helianthus annuus L.) grown in alkaline calcareous soil for 18 weeks under natural environmental conditions at three arsenate [0 (As₀), 40 (As₄₀), and 80 (As₈₀) mg As kg⁻¹ soil as sodium arsenate] and three phosphate [0 (P₀), 100 (P₁₀₀), and 200 (P₂₀₀) mg P₂O₅ kg⁻¹ soil as diammonium phosphate] levels. The plants were grown in pots according to completely randomized design with five replications. Ionic and physiological parameters were measured at 40 days after treatment completion. Arsenic contamination with As₄₀ and As₈₀ increased root and shoot As concentration with relatively higher concentration in roots, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) while decreased plant P, chlorophyll, protein, and glutathione (GSH), and consequently plant growth, yield, and yield attributes. Addition of P₁₀₀ and P₂₀₀ under As stress reduced As transfer from soil to roots to shoots, MDA concentration, SOD, CAT, and POD activities while increased GSH, leaf protein, chlorophyll, and growth characteristics as well as achene yield compared to As-treated plants without additional P. In conclusion, P-induced inhibition of As transfer from soil to roots to shoots and reduction in MDA concentration accompanied with an increase in the synthesis of protein, chlorophyll, and GSH could be the main mechanisms responsible for lowered As toxicity in sunflower, leading to mitigation of potential risks of As contamination to food chain and human health.

http://ift.tt/2vWOz5d

Analytical insight into degradation processes of aminopolyphosphonates as potential factors that induce cyanobacterial blooms

Abstract

Aminopolyphosphonates (AAPs) are commonly used industrial complexones of metal ions, which upon the action of biotic and abiotic factors undergo a breakdown and release their substructures. Despite the low toxicity of AAPs towards vertebrates, products of their transformations, especially those that contain phosphorus and nitrogen, can affect algal communities. To verify whether such chemical entities are present in water ecosystems, much effort has been made in developing fast, inexpensive, and reliable methods for analyzing phosphonates. However, unfortunately, the methods described thus far require time-consuming sample pretreatment and offer relatively high values of the limit of detection (LOD). The aim of this study was to develop an analytical approach to study the environmental fate of AAPs. Four phosphonic acids, N,N-bis(phosphonomethyl)glycine (GBMP), aminotris(methylenephosphonic) acid (ATMP), hexamethylenediamine-N,N,N′,N′-tetrakis(methylphosphonic) acid (HDTMP), and diethylenetriamine penta(methylenephosphonic) acid (DTPMP) were selected and examined in a water matrix. In addition, the susceptibility of these compounds to biotransformations was tested in colonies of five freshwater cyanobacteria—microorganisms responsible for the so-called blooms in the water. Our efforts to track the AAP decomposition were based on derivatization of N-alkyl moieties with p-toluenesulfonyl chloride (tosylation) followed by chromatographic (HPLC-UV) separation of derivatives. This approach allowed us to determine seven products of the breakdown of popular phosphonate chelators, in nanomolar concentrations and in one step. It should be noted that the LOD of four of those products, aminemethylphosphonic acid (AMPA), N-phosphomethyl glycine (NPMG), N-(methyl)aminemethanephosphonic acid (MAMPA), and N-(methyl) glycine (SAR), was set below the concentration of 50 nM. Among those substances, N-(methylamino)methanephosphonic acid (MAMPA) was identified for the first time as the product of decomposition of the examined aminopolyphosphonates.

http://ift.tt/2jduQIn

Resistance of aerobic microorganisms and soil enzyme response to soil contamination with Ekodiesel Ultra fuel

Abstract

This study determined the susceptibility of cultured soil microorganisms to the effects of Ekodiesel Ultra fuel (DO), to the enzymatic activity of soil and to soil contamination with PAHs. Studies into the effects of any type of oil products on reactions taking place in soil are necessary as particular fuels not only differ in the chemical composition of oil products but also in the composition of various fuel improvers and antimicrobial fuel additives. The subjects of the study included loamy sand and sandy loam which, in their natural state, have been classified into the soil subtype 3.1.1 Endocalcaric Cambisols. The soil was contaminated with the DO in amounts of 0, 5 and 10 cm³ kg⁻¹. Differences were noted in the resistance of particular groups or genera of microorganisms to DO contamination in loamy sand (LS) and sandy loam (SL). In loamy sand and sandy loam, the most resistant microorganisms were oligotrophic spore-forming bacteria. The resistance of microorganisms to DO contamination was greater in LS than in SL. It decreased with the duration of exposure of microorganisms to the effects of DO. The factor of impact (IF_DO) on the activity of particular enzymes varied. For dehydrogenases, urease, arylsulphatase and β-glucosidase, it had negative values, while for catalase, it had positive values and was close to 0 for acid phosphatase and alkaline phosphatase. However, in both soils, the noted index of biochemical activity of soil (BA) decreased with the increase in DO contamination. In addition, a positive correlation occurred between the degree of soil contamination and its PAH content.

http://ift.tt/2vXy88t

Contaminant characteristics and environmental risk assessment of heavy metals in the paddy soils from lead (Pb)-zinc (Zn) mining areas in Guangdong Province, South China

Abstract

In November 2016, the total metal concentrations in nine representative locations in lead (Pb)-zinc (Zn) mining areas, located in Guangdong Province, South China, were determined experimentally by flame atomic absorption spectrometer. The results indicated that the paddy soils were heavily contaminated with Cd (20.25 mg kg⁻¹), Pb (1093.03 mg kg⁻¹), and Zn (867.0 mg kg⁻¹), exceeding their corresponding soil quality standard values and background values. According to the results, the mean enrichment factor levels of the studied metals decreased in the following order: Cd > Zn > Pb > Cu > Ni > Mn > Cr. Among these metals, Cd, Pb, and Zn were predominantly influenced by widespread anthropogenic activities. The highest concentrations of the studied metal pollutants were distributed in the areas surrounding the mining activity district. Multivariate statistical analysis indicated that the major contributing sources of the studied metals were metal ore mining, smelting, and processing activities. However, the composition of soil background was another potential source. Moreover, the assessment results of environment risks showed that the potential ecological risks, in decreasing order, were Cd > Pb > Zn > Cu > Ni > Cr > Mn. Additionally, the non-carcinogenic risk represented the trend of HI _Pb > HI _Mn > HI _Zn > HI _Cu , and the carcinogenic risk ranked as CR _Cr > CR _Cd > CR _Ni . Among the environmental risk substances, Cd and Pb were the main contributors that pose ecological harm and health hazards through their serious pollution. Consequently, greater attention should be paid to this situation.

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Stability of BiFeO 3 nanoparticles via microwave-assisted hydrothermal synthesis in Fenton-like process

Abstract

Stable catalysts require high catalytic efficiency and repeated consecutive use, low mass loss, and metal leaching. This study investigated BiFeO₃ (BFO) composite with high stability and reusability using a one step microwave-assisted hydrothermal method (MAHS) to decompose bisphenol A (BPA) used as the target contaminant. After six consecutive reaction cycles in microwave-enhanced Fenton-like process (MW-Fenton-like), the removal rate of BPA decreased from 94 to 87.4% with low metal leaching ratio and mass loss. The morphology, crystal, reaction kinetics, and hydroxyl radical (·OH) were used to demonstrate the high stability of BFO-MAHS. The results indicated that the benign stability and reusability of BFO-MAHS probably occurred because (1) the thermal-effect of MW improved heating rate, which led to the rapid formation stable cube structure and (2) MW mechanical vibrations existed in the preparation process, which further enhanced the cube structure. Therefore, MAHS could be used as a green and environmental friendly method to apply in catalysts synthesis, which could immensely shorten preparation time and enhance the catalytic performance with no waste production.

http://ift.tt/2vXAoN5

Prenatal stress induced gender-specific alterations of N-methyl-d-aspartate receptor subunit expression and response to Aβ in offspring hippocampal cells

Publication date: 15 January 2018
Source:Behavioural Brain Research, Volume 336
Author(s): Yuan Fang, Hui Li, Lirong Chang, Yizhi Song, Longhui Ma, Liying Lu, Zunshu Du, Yan Li, Jinping Liu, Yan Wu
Prenatal stress (PS) is one of adverse life events during pregnancy, which may increase vulnerability to cognitive impairment in adult offspring. Aβ synaptotoxicity is one important pathological factor for cognitive impairment, and PS-induced cognitive disorder is closely associated with N-Methyl-d-Aspartate receptor (NMDAR), which acts as a key mediator of Aβ synaptotoxicity. In the present study, we tried to explore whether PS affects offspring's Aβ levels and NMDAR subunit expression in a gender-specific manner in hippocampal CA and DG subregions, and whether PS affects synaptic proteins and NMDAR subunit expression in cultured offspring hippocampal cells exposed to Aβ. Pregnant SD rats with restraint stress from gestation day 8–20 were used as PS model. Morris water maze, ELISA, immunofluorescence and western blot were tested on postnatal day 90 in male and female PS offspring. Our results showed that female offspring is more vulnerable to PS-induced cognitive impairment. Surprisingly, PS enhanced Aβ1-40 levels in the hippocampal DG subregion of male offspring. Furthermore, WB results implied that the decreased GluN2A in CA of female may contribute to the PS-induced cognitive impairment, while in DG, the increased GluN2A and decreased GluN2B contributed to protective effects against Aβ. Interestingly, we found PS could alleviate Aβ synaptotoxicity in male offspring's hippocampal cells. Overall, our results provided a fundamental understanding of PS-induced gender-specific alterations of NMDAR subunit expression and the susceptibility to Aβ, and paved the road for the development of timely preventive interventions on cognitive disorders of PS offspring.



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Effects of an acute therapeutic or rewarding dose of amphetamine on acquisition of Pavlovian autoshaping and ventral striatal dopamine signaling

Publication date: 15 January 2018
Source:Behavioural Brain Research, Volume 336
Author(s): D.R. Schuweiler, J.M. Athens, J.M. Thompson, S.T. Vazhayil, P.A. Garris
Rewarding doses of amphetamine increase the amplitude, duration, and frequency of dopamine transients in the ventral striatum. Debate continues at the behavioral level about which component of reward, learning or incentive salience, is signaled by these dopamine transients and thus altered in addiction. The learning hypothesis proposes that rewarding drugs result in pathological overlearning of drug-predictive cues, while the incentive sensitization hypothesis suggests that rewarding drugs result in sensitized attribution of incentive salience to drug-predictive cues.Therapeutic doses of amphetamine, such as those used to treat attention-deficit hyperactivity disorder, are hypothesized to enhance the ventral striatal dopamine transients that are critical for reward-related learning and to enhance Pavlovian learning. However, the effects of therapeutic doses of amphetamine on Pavlovian learning are poorly understood, and the effects on dopamine transients are completely unknown.We determined the effects of an acute pre-training therapeutic or rewarding amphetamine injection on the acquisition of Pavlovian autoshaping in the intact rat. We also determined the effects of these doses on electrically evoked transient-like dopamine signals using fast-scan cyclic voltammetry in the anesthetized rat. The rewarding dose enhanced the amplitude and duration of DA signals, caused acute task disengagement, impaired learning for several days, and triggered incentive sensitization. The therapeutic dose produced smaller enhancements in DA signals but did not have similar behavioral effects. These results underscore the necessity of more studies using therapeutic doses, and suggest a hybrid learning/incentive sensitization model may be required to explain the development of addiction.



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A randomized trial of clitoral vacuum suction versus vibratory stimulation in neurogenic female orgasmic dysfunction

Publication date: Available online 9 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Marcalee Alexander, Khurram Bashir, Craig Alexander, Lesley Marson, Raymond Rosen
ObjectiveTo examine safety and efficacy of use of a clitoral vacuum suction device (CVSD) versus vibratory stimulation (V) to treat orgasmic dysfunction in women with MS or SCI.DesignRandomized clinical trial.SettingTwo academic medical centers.ParticipantsThirty-one women including 20 with MS and 11 with SCI.InterventionA 12-week trial of the use of a CVSD versus VMain Outcome measuresFemale Sexual Function Inventory (FSFI) and Female Sexual Distress Scale (FSDS).Results23 women (18 MS; 5 SCI) completed the study including 13/16 randomized to CVSD and 10/15 randomized to V. There was a statistically significant increase in total FSFI score (p=.011), desire (p=. 009), arousal (p=.009), lubrication (p=.008), orgasm (p=.012), and satisfaction (p=.049) and a significant decrease in distress as measured by FSDS (p=.020) in subjects using the CVSD. In subjects who used V, there was a statistically significant increase in the orgasm subscale of the FSFI (p=.028). Subjects using the CVSD maintained improvements 4 weeks after treatment.ConclusionCVSD is safe and overall efficacious to treat female neurogenic sexual dysfunction related to MS and SCI. V is also safe and efficacious to female neurogenic orgasmic dysfunction; however, results were limited to the active treatment period. Due to ease of access and cost, clinicians can consider use of V for women with MS or SCI with orgasmic dysfunction. CVSD is recommended for women with multiple sexual dysfunctions or for whom V is ineffective.



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Comparative efficacy of intra-articular steroid injection and distension in patients with frozen shoulder: a systematic review and network meta-analysis

Publication date: Available online 9 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Meng-Ting Lin, Ming-Yen Hsiao, Yu-Kang Tu, Tyng-Guey Wang
ObjectiveTo compare the efficacy of intra-articular (IA) steroid injection and distension in patients with frozen shoulder.Data SourcesDatabases, including MEDLINE (via PubMed), EMBASE, Scopus and Cochrane Library, were searched for studies published up to November 2016.Study SelectionWe included all published randomized controlled trials (RCTs), quasi-experimental studies and observational studies investigating the effectiveness of IA steroid injection, distension and physiotherapy in patients with frozen shoulder. Sixteen RCTs and one observational study were enrolled in meta-analysis.Data ExtractionFull-texts were independently reviewed and quality of RCTs was assessed with The Cochrane Collaboration's tool. The primary outcome was functional improvement; the secondary outcomes included pain reduction and external rotation (ER) improvement.Data SynthesisIn pair-wise meta-analysis, pooled standardized mean difference (SMD) of functional improvement and pain reduction revealed equal efficacy at three follow-up time points. With respect to ER improvement, distension has a superior effect as compared to IA steroid injection at short term [2–4 weeks; SMD: −0.36; 95% confidence interval (CI): −0.68∼ −0.04] and at medium term (6–16 weeks; SMD: −0.80; 95% CI: −1.32∼ −0.29). The network meta-analysis indicated a better efficacy for distension than for IA steroid injection in ER improvement only at medium term (6–16 weeks; SMD: −0.70; 95% CI: −1.19∼ −0.21).ConclusionIA steroid injection was as effective as distension in shoulder-function improvement, pain reduction and increasing ER of shoulder. Distension yielded better ER improvement at medium term but to a minor extent in the long term. For patients with predominant ER limitation, early distension could be considered the primary choice of treatment.



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Group- and individual-level responsiveness of the 3-point Berg Balance Scale and 3-point Postural Assessment Scale for Stroke Patients

Publication date: Available online 9 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Yi-Jing Huang, Gong-Hong Lin, Shih-Chieh Lee, Yi-Miau Chen, Sheau-Ling Huang, Ching-Lin Hsieh
ObjectiveTo examine both group- and individual-level responsiveness of the 3-point Berg Balance Scale (BBS-3P) and 3-point Postural Assessment Scale for Stroke Patients (PASS-3P) in patients with stroke, and to compare the responsiveness of both 3-point measures versus their original measures (BBS and PASS) and their short forms (SFBBS and SFPASS) and between the BBS-3P and PASS-3P.DesignThe data were retrieved from a previous study wherein 212 patients were assessed at 14 and 30 days after stroke with the BBS and PASS.SettingMedical center.ParticipantsPatients with first onset of stroke within 14 days before hospitalization.Interventions.Not applicable.Main Outcome Measures.Group-level responsiveness was examined by the standardized response mean (SRM), and individual-level responsiveness was examined by the proportion of patients whose change scores exceeded the minimal detectable change of each measure. The responsiveness was compared using bootstrap approach.ResultsThe BBS-3P and PASS-3P had good group-level (SRM=0.60 and 0.56, respectively) and individual-level (48.1% and 44.8% of the patients with significant improvement, respectively) responsiveness. Bootstrap analyses showed that the BBS-3P generally had superior responsiveness to the BBS and SFBBS, and the PASS-3P had similar responsiveness to the PASS and SFPASS. The BBS-3P and PASS-3P were equally responsive to both group and individual's change.ConclusionsThe responsiveness of the BBS-3P and PASS-3P was comparable or superior to those of the original and short-form measures. We recommend the BBS-3P and PASS-3P as responsive outcome measures of balance for individuals with stroke.



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Long-term performance and user satisfaction with implanted neuroprostheses for upright mobility after paraplegia: Two to 14-year follow-up

Publication date: Available online 9 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Ronald J. Triolo, Stephanie Nogan Bailey, Kevin M. Foglyano, Rudi Kobetic, Lisa M. Lombardo, Michael E. Miller, Gilles Pinault
ObjectiveTo quantify the long-term (LT) (>2 years) effects of lower extremity (LE) neuroprostheses (NPs) for standing, transfers, stepping and seated stability after spinal cord injury.DesignSingle-subject design case series with participants acting as their own concurrent controls, including retrospective data review.SettingHospital-based clinical biomechanics laboratory with experienced (>20 years in the field) research biomedical engineers, physical therapist and medical monitoring review.ParticipantsTwenty-two (19 male, 3 female) LT (6.2 ± 2.7 years) at-home users of implanted NPs for trunk and LE function with chronic (14.4 ± 7.1 years) spinal cord injury resulting in full or partial paralysis.InterventionsTechnical and clinical performance measurements, along with user satisfaction surveys.Main Outcome MeasuresKnee extension moment, maximum standing time, body weight supported by lower extremities, three functional standing tasks, two satisfaction surveys, NP usage, and stability of implanted components.ResultsStimulated knee extension strength and functional capabilities were maintained with 94% of implant recipients reporting being "very" or "moderately" satisfied with their system. Greater than half (60%) of the participants were still using their implanted NPs for exercise and function for more than 10 minutes per day on nearly half or more of the days monitored, although maximum standing times and percentage body weight through LEs decreased slightly over the follow-up interval. Stimulus thresholds were uniformly stable. Six-year survival rates for the first-generation implanted pulse generator (IPG) and epimysial electrodes were close to 90%, while those for the second-generation IPG along with the intramuscular and nerve cuff electrodes were greater than 98%.ConclusionsObjective and subjective measures of the technical and clinical performances of implanted LE NPs generally remained consistent for 22 participants after an average of 6 years of unsupervised use at home. These findings suggest that implanted LE NPs can provide lasting benefits that recipients value.



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Pneumatosis from Esophagus to Rectum: A Comprehensive Review Focusing on Clinico-Radiological Differentiation Between Benign and Life-Threatening Causes

Publication date: Available online 9 September 2017
Source:Seminars in Ultrasound, CT and MRI
Author(s): Ulysses S. Torres, Camila D.F.M. Fortes, Priscila S. Salvadori, Dario A. Tiferes, Giuseppe D′Ippolito
Pneumatosis of the alimentary tract may occur from the esophagus to rectum as a result of a wide spectrum of conditions that range from benign to life-threatening. While distinguishing between these two groups is of paramount importance for an appropriate clinical management, it still remains a challenge for the radiologist in the daily practice. In the light of the current literature we provide in the present article a comprehensive review focusing on the clinical, laboratory and radiological findings that most consistently may allow such a differentiation. We also provide a pictorial essay illustrating this range of diagnoses, briefly discussing each one.



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Delayed Detection of Spontaneous Bilateral Tubal Ectopic Pregnancies After Methotrexate Treatment

Publication date: Available online 9 September 2017
Source:The Journal of Emergency Medicine
Author(s): Nicole E. Brown, Shereen A. Singer, Joe Suyama
BackgroundBilateral tubal ectopic pregnancies are a rare subset of ectopic pregnancy that can pose a diagnostic dilemma for clinicians. There is no distinct clinical presentation for bilateral tubal ectopic pregnancies, although they are typically associated with assistive reproductive techniques. In addition, there is no single diagnostic feature to help clinicians delineate bilateral tubal ectopic pregnancies from other types of ectopic pregnancy prior to passing the discriminatory zone (such as heterotopic pregnancy or twin ectopic [two gestational sacs in one tube]). Diagnosis is typically made via direct visualization intraoperatively and therefore treatment is usually surgical.Case ReportWe present a case of spontaneous bilateral tubal ectopic pregnancies diagnosed 7 days apart via transvaginal ultrasound. The patient presented to the emergency department with pelvic pain on the contralateral side of her previously diagnosed ectopic pregnancy and vaginal spotting. Bilateral adnexal masses were visualized on ultrasound and her serum beta–human chorionic gonadotropin level had a 5.9% decline from day 4 to day 7 after methotrexate administration 7 days prior; gynecology was consulted. The patient was successfully treated with an additional dose of intramuscular methotrexate without any complications.Why Should an Emergency Physician Be Aware of This?The implications of this case suggest that diagnosis of bilateral tubal ectopic pregnancies requires clinicians to have a high level of suspicion in any pregnant female with a suspected or known ectopic pregnancy who presents with pelvic pain regardless of prior diagnosis or treatment.



http://ift.tt/2eW5cGE

Does fear extinction in the laboratory predict outcomes of exposure therapy? A treatment analog study

Publication date: Available online 8 September 2017
Source:International Journal of Psychophysiology
Author(s): Eduard Forcadell, David Torrents-Rodas, Bram Vervliet, David Leiva, Miquel Tortella-Feliu, Miquel A. Fullana
Fear extinction models have a key role in our understanding of anxiety disorders and their treatment with exposure therapy. Here, we tested whether individual differences in fear extinction learning and fear extinction recall in the laboratory were associated with the outcomes of an exposure therapy analog (ETA). Fifty adults with fear of spiders participated in a two-day fear-learning paradigm assessing fear extinction learning and fear extinction recall, and then underwent a brief ETA. Correlational analyses indicated that enhanced extinction learning was associated with better ETA outcome. Our results partially support the idea that individual differences in fear extinction learning may be associated with exposure therapy outcome, but suggest that further research in this area is needed.



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A review of the effects of physical activity and sports concussion on brain function and anatomy

Publication date: Available online 8 September 2017
Source:International Journal of Psychophysiology
Author(s): Sara Tremblay, Alvaro Pascual-Leone, Hugo Théoret
Physical activity has been associated with widespread anatomical and functional brain changes that occur following acute exercise or, in the case of athletes, throughout life. High levels of physical activity through the practice of sports also lead to better general health and increased cognitive function. Athletes are at risk, however, of suffering a concussion, the effects of which have been extensively described for brain function and anatomy. The level to which these effects are modulated by increased levels of fitness is not known. Here, we review literature describing the effects of physical activity and sports concussions on white matter, grey matter, neurochemistry and cortical excitability. We suggest that the effects of sports concussion can be coufounded by the effects of exercise. Indeed, available data show that the brain of athletes is different from that of healthy individuals with a non-active lifestyle. As a result, sports concussions take place in a context where structural/functional plasticity has occurred prior to the concussive event. The sports concussion literature does not permit, at present, to separate the effects of intense and repeated physical activity, and the abrupt removal from such activities, from those of concussion on brain structure and function.



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Response to “Re: A Systematic Review and Meta-analysis of the Association Between C-reactive Protein and Major Cardiovascular Events in Patients with Peripheral Artery Disease”

Publication date: Available online 9 September 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Tejas P. Singh, Dylan R. Morris, Samuel Smith, Joseph V. Moxon, Jonathan Golledge




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Central sympathetic nervous system reinforcement in obstructive sleep apnoea

The available studies on cerebrovascular reactivity and cerebral oxygenation in obstructive sleep apnoea (OSA) patients brought conflicting results, yet the overall evidence suggests that resting state cerebral perfusion is diminished in these patients. Interestingly, in a group of healthy professional breath-hold divers who are exercising very long apnoeas - episodes corresponding to the ones observed in patients with OSA - demonstrated that cerebral oxygenation may remain stable at the expense of extreme sympathetic nervous system (SNS) activation.

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Effectiveness of mechanical debridement with and without adjunct antimicrobial photodynamic therapy in the treatment of periodontal inflammation among patients with prediabetes

Publication date: Available online 9 September 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Mansour Al-Askar, Abdulaziz A. Al-Kheraif, Hameeda Bashir Ahmed, Sergio Varela Kellesarian, Hans Malmstrom, Fawad Javed
AimThe aim of the present study was to assess the effectiveness of mechanical debridement (MD) with and without adjunct antimicrobial photodynamic therapy (aPDT) in the treatment of periodontal inflammation among patients with prediabetes.MethodsDemographic information was collected using a questionnaire. Hemoglobin A1c (HbA1c) levels were measured at baseline and at 3 and 6 months' follow-up.Treatmentwise, individuals were randomly divided into 2 groups as follows: (a) Group-1, participants underwent full-mouth MD; and Group-2: participants underwent full-mouth MD with adjunct aPDT. In groups 1 and 2, full-mouth plaque index (PI), bleeding on probing (BOP) and probing pocket depth (PPD) were measured at baseline and at 3 and 6 months' follow-up. In both groups, full-mouth digital intraoral radiographs were also taken. Sample-size was estimated and statistical analysis was performed with level of significance set as P<0.05.ResultsIn total, 70 prediabetic male individuals (35 patients in group-1 and 35 in group-2) were included. At baseline, PI, BOP, number of sites with PPD ≥4mm were comparable among individuals in groups 1 and 2. In groups 1 and 2, PI (P<0.05), BOP (P<0.05), number of sites with PPD ≥4mm (P<0.05) were significantly higher at baseline compared with 3 months' follow-up. There was no statistically significant difference in PI, BOP, number of sites with PPD ≥4mm at 3 and 6 months' follow-up. At 6 months' follow-up, PI, BOP, number of sites with PPD ≥4mm were comparable to their respective baseline values. There was no statistically significant difference in CBL in both groups at 3 and 6 months' follow-up. There was no statistically significant difference in HbA1c levels among individuals in groups 1 and 2 at all-time intervals.ConclusionIn the short-term, MD is effective in reducing periodontal inflammation among patients with prediabetes. The contribution of adjunct aPDT in this regard is insignificant.



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Rare genetic variants in the sodium-dependent organic anion transporter SOAT (SLC10A6): Effects on transport function and membrane expression

Publication date: Available online 8 September 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Josefine Bennien, Thomas Fischer, Joachim Geyer
Sulfo-conjugated steroid hormones, such as dehydroepiandrosterone sulfate (DHEAS), pregnenolone sulfate or estrone-3-sulfate are abundant in the body, but are biologically inactive at classical androgen and estrogen steroid receptors. However, after carrier-mediated import and de-conjugation by the steroid sulfatase, these compounds participate in the overall steroid regulation of reproductive organs. The sodium-dependent organic anion transporter SOAT, coded by the SLC10A6 gene, is specific for the transport of steroid sulfates and is highly expressed in testicular germ cells, including pachytene spermatocytes, secondary spermatocytes, and round spermatids. Therefore, SOAT is supposed to be involved in the regulation of spermatogenesis and male fertility. In the present study, the SLC10A6 gene was analyzed for rare genetic variants, which might affect transport function or membrane expression of SOAT. Among the 31 SOAT variants analyzed, L44P, Q75R, P107L, G109S, S112F, N113K, S133F, G241D, G263E, G294R, and Y308N showed no transport activity for DHEAS at all. In the case of P107L, G241D, G263E, and Y308N, this was most likely due to significantly reduced expression in the plasma membrane. Other variants are located directly at (Q75R, S112F, N113K) or close to (G109S, S133F, and G263E) the supposed SOAT Na⁺ binding sites and thus could disable the sodium-coupled transport cycle. If these loss-of-function SOAT variants are more frequent in men with impaired spermatogenesis or infertility needs further investigation.



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CYP17A1 inhibitor abiraterone, an anti-prostate cancer drug, also inhibits the 21-hydroxylase activity of CYP21A2

Publication date: Available online 8 September 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Jana Malikova, Simone Brixius-Anderko, Sameer S. Udhane, Shaheena Parween, Bernhard Dick, Rita Bernhardt, Amit V. Pandey
Abiraterone is an inhibitor of CYP17A1 which is used for the treatment of castration resistant prostate cancer. Abiraterone is known to inhibit several drug metabolizing cytochrome P450 enzymes including CYP1A2, CYP2D6, CYP2C8, CYP2C9, CYP2C19, CYP3A4 and CYP3A5, but its effects on steroid metabolizing P450 enzymes are not clear. In preliminary results, we had observed inhibition of CYP21A2 by 1μM abiraterone. Here we are reporting the effect of abiraterone on activities of CYP21A2 in human adrenal cells as well as with purified recombinant CYP21A2. Cells were treated with varying concentrations of abiraterone for 24hours and CYP21A2 activity was measured using [³H] 17-hydroxyprogesterone as substrate. Whole steroid profile changes were determined by gas chromatography-mass spectrometry. Binding of abiraterone to purified CYP21A2 protein was measured spectroscopically. Computational docking was used to study the binding and interaction of abiraterone with CYP21A2. Abiraterone caused significant reduction in CYP21A2 activity in assays with cells and an inhibition of CYP21A2 activity was also observed in experiments using recombinant purified proteins. Abiraterone binds to CYP21A2 with an estimated Kd of 6.3μM. These inhibitory effects of abiraterone are at clinically used concentrations. A loss of CYP21A2 activity in combination with reduction of CYP17A1 activities by abiraterone could result in lower cortisol levels and may require monitoring for any potential adverse effects.



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Differential expression of vitamin D-associated enzymes and receptors in brain cell subtypes

Publication date: Available online 8 September 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Véréna Landel, Delphine Stephan, Xiaoying Cui, Darryl Eyles, François Feron
Accumulating evidence indicates that the active form of vitamin D, 1,25(OH)2D3, can be considered as a neurosteroid. However, the cerebral expression of vitamin D-associated enzymes and receptors remains controversial. With the idea of carrying out a comparative study in mind, we compared the transcript expression of Cyp27a1, Cyp27b1, Cyp24a1, Vdr and Pdia3 in purified cultures of astrocytes, endothelial cells, microglia, neurons and oligodendrocytes. We observed that endothelial cells and neurons can possibly transform the inactive cholecalciferol into 25(OH)D3. It can then be metabolised into 1,25(OH)2D3, by neurons or microglia, before being transferred to astrocytes where it can bind to VDR and initiate gene transcription or be inactivated when in excess. Alternatively, 1,25(OH)2D3 can induce autocrine or paracrine rapid non-genomic actions via PDIA3 whose transcript is abundantly expressed in all cerebral cell types. Noticeably, brain endothelial cells appear as a singular subtype as they are potentially able to transform cholecalciferol into 25(OH)D3 and exhibit a variable expression of Pdia3, according to 1,25(OH)2D3 level. Altogether, our data indicate that, within the brain, vitamin D may trigger major auto-/paracrine non genomic actions, in addition to its well documented activities as a steroid hormone.

Graphical abstract

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The relationship between 25-hydroxyvitamin D concentration and liver enzymes in overweight or obese adults: Cross-sectional and interventional outcomes

Publication date: Available online 9 September 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Negar Naderpoor, Aya Mousa, Maximilian de Courten, Robert Scragg, Barbora de Courten
Vitamin D deficiency is prevalent in individuals with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis. However, there is limited and inconsistent data on the effect of vitamin D supplementation on liver function. Hepatic enzymes have been used as surrogate markers for NAFLD and have been associated with metabolic syndrome. We examined the relationships between 25-hydroxyvitamin D (25(OH)D) and γ-glutamyl transferase (GGT), alanine aminotransferase (ALT), alkaline phosphatase (ALP) in 120 drug-naïve individuals with no history of liver disease. In addition, the effect of vitamin D supplementation (100,000 loading dose of cholecalciferol followed by 4000IU daily for 16 weeks) on hepatic enzymes was investigated in a subgroup of 54 vitamin D-deficient overweight or obese individuals (28 randomised to cholecalciferol and 26 to placebo). Hepatic enzymes, anthropometric parameters, lipid profile, insulin sensitivity (hyperinsulinaemic-euglycaemic clamp, M value) and high sensitivity C-reactive protein (hs-CRP) were measured before and after intervention. In the cross-sectional study, levels of GGT and ALT were higher in men compared to women (both p=0.001). There were no significant differences in GGT, ALT and ALP between vitamin D categories (25(OH)D<25 nmol/L, 25–50nmol/L, and >50nmol/L) and no relationships were found between the three enzymes and 25(OH)D before and after adjustment for age, sex, BMI, WHR, and insulin sensitivity (all p>0.5). In the randomised trial, 25(OH)D concentrations increased in the vitamin D group (mean change 57.0±21.3nmol/L) compared to the placebo group (mean change 1.9±15.1 nmol/L). Mean changes in GGT, ALT and ALP were not significantly different between vitamin D and placebo groups (all p>0.2). Change in 25(OH)D concentration was not correlated with changes in GGT, ALT and ALP before and after adjustments for age and sex (all p>0.1).In summary, 25(OH)D concentrations were not related to hepatic enzymes in drug-naive adults with no history of liver disease, and vitamin D supplementation had no effect on the serum levels of hepatic enzymes in vitamin D-deficient and overweight or obese, otherwise healthy individuals. Hence, vitamin D supplementation is unlikely to prevent incident NAFLD.



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Endocrine and physiological regulation of neutral fat storage in Drosophila

Publication date: Available online 8 September 2017
Source:Molecular and Cellular Endocrinology
Author(s): Michael Lehmann
After having revolutionized our understanding of the mechanisms of animal development, Drosophila melanogaster has more recently emerged as an equally valid genetic model in the field of animal metabolism. An increasing number of studies have revealed that many signaling pathways that control metabolism in mammals, including pathways controlled by nutrients (insulin, TOR), steroid hormone, glucagon, and hedgehog, are functionally conserved between mammals and Drosophila. In fact, genetic screens and analyses in Drosophila have identified new players and filled in gaps in the signaling networks that control metabolism. This review focuses on data that show how these networks control the formation and breakdown of triacylglycerol energy stores in the fat tissue of Drosophila.



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Molecular basis of androgen action on human sexual desire

Publication date: Available online 8 September 2017
Source:Molecular and Cellular Endocrinology
Author(s): Daniele Santi, Giorgia Spaggiari, Lisa Gilioli, Francesco Potì, Manuela Simoni, Livio Casarini
Reproduction is a fundamental process for the species maintenance and the propagation of genetic information. The energy expenditure for mating is overtaken by motivational stimuli, such as orgasm, finely regulated by steroid hormones, gonadotropins, neurotransmitters and molecules acting in the brain and peripheral organs. These functions are often investigated using animal models and translated to humans, where the androgens action is mediated by nuclear and membrane receptors converging in the regulation of both long-term genomic and rapid non-genomic signals. In both sexes, testosterone is a central player of this game and is involved in the regulation of sexual desire and arousal, and, finally, in reproduction through cognitive and peripheral physiological mechanisms which may decline with aging and circadian disruption. Finally, genetic variations impact on reproductive behaviours, resulting in sex-specific effect and different reproductive strategies. In this review, androgen actions on sexual desire are evaluated, focusing on the molecular levels of interaction.



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A neural signature of food semantics is associated with body-mass index

Publication date: Available online 9 September 2017
Source:Biological Psychology
Author(s): Giulio Pergola, Francesco Foroni, Paola Mengotti, Georgette Argiris, Raffaella Ida Rumiati
Visual recognition of objects may rely on different features depending on the category to which they belong. Recognizing natural objects, such as fruits and plants, weighs more on their perceptual attributes, whereas recognizing man-made objects, such as tools or vehicles, weighs more upon the functions and actions they enable. Edible objects are perceptually rich but also prepared for specific functions, therefore it is unclear how perceptual and functional attributes affect their recognition.Two event-related potentials experiments investigated: (i) whether food categorization in the brain is differentially modulated by sensory and functional attributes, depending on whether the food is natural or transformed; (ii) whether these processes are modulated by participants' body mass index. In experiment 1, healthy normal-weight participants were presented with a sentence (prime) and a photograph of a food. Primes described either a sensory feature ('It tastes sweet') or a functional feature ('It is suitable for a wedding party') of the food, while photographs depicted either a natural (e.g., cherry) or a transformed food (e.g., pizza). Prime-feature pairs were either congruent or incongruent. This design aimed at modulating N400-like components elicited by semantic processing. In experiment 1, N400-like amplitude was significantly larger for transformed food than for natural food with sensory primes, and vice versa with functional primes. In experiment 2, underweight and obese women performed the same semantic task. We found that, while the N400-like component in obese participants was modulated by sensory-functional primes only for transformed food, the same modulation was found in underweight participants only for natural food. These findings suggest that the level of food transformation interacts with participants' body mass index in modulating food perception and the underlying brain processing.



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Sustained Engagement of Attention is Associated with Increased Negative Self-Referent Processing in Major Depressive Disorder

Publication date: Available online 8 September 2017
Source:Biological Psychology
Author(s): Justin Dainer-Best, Logan T. Trujillo, David M. Schnyer, Christopher G. Beevers
This study investigated the link between self-reference and attentional engagement in adults with (n=22) and without (HC; n=24) Major Depressive Disorder (MDD). Event-related potentials (ERPs) were recorded while participants completed the Self-Referent Encoding Task (SRET). MDD participants endorsed significantly fewer positive words and more negative words as self-descriptive than HC participants. A whole-scalp data analysis technique revealed that the MDD participants had larger difference wave (negative words minus positive words) ERP amplitudes from 380–1000ms across posterior sites, which positively correlated with number of negative words endorsed. No group differences were observed for earlier attentional components (P1, P2). The results suggest that among adults with MDD, negative stimuli capture attention during later information processing; this engagement is associated with greater self-referent endorsement of negative adjectives. Sustained cognitive engagement for self-referent negative stimuli may be an important target for neurocognitive depression interventions.



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Too sweet to eat: Exploring the effects of cuteness on meat consumption

Publication date: 1 January 2018
Source:Appetite, Volume 120
Author(s): Janis H. Zickfeld, Jonas R. Kunst, Sigrid M. Hohle
Although daily meat consumption is a widespread habit, many individuals at the same time put a high value on the welfare of animals. While different psychological mechanisms have been identified to resolve this cognitive tension, such as dissociating the animal from the consumed meat or denying the animal's moral status, few studies have investigated the effects of the animal's appearance on the willingness to consume its meat. The present article explored how the perception of cuteness influences hypothetical meat consumption. We hypothesized that cuter animals would reduce the willingness to consume meat, and that this relationship would be mediated by empathy felt towards the animal. Across four pre-registered studies sampling 1074 US and Norwegian participants, we obtained some support for this prediction in the US but to a lesser degree in Norway. However, in all studies an indirect mediation effect of cuteness on meat consumption going through empathy towards the animal was observed. We also explored possible moderating and additional mediating mechanisms of trait pro-social orientation, caretaking intentions and sex effects for which we found mixed evidence. Theoretical and practical implications of the findings are discussed.



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Feasibility and reliability of digital imaging for estimating food selection and consumption from students’ packed lunches

Publication date: 1 January 2018
Source:Appetite, Volume 120
Author(s): Jennifer C. Taylor, Carolyn Sutter, Lenna L. Ontai, Adrienne Nishina, Sheri Zidenberg-Cherr
Although increasing attention is placed on the quality of foods in children's packed lunches, few studies have examined the capacity of observational methods to reliably determine both what is selected and consumed from these lunches. The objective of this project was to assess the feasibility and inter-rater reliability of digital imaging for determining selection and consumption from students' packed lunches, by adapting approaches previously applied to school lunches. Study 1 assessed feasibility and reliability of data collection among a sample of packed lunches (n = 155), while Study 2 further examined reliability in a larger sample of packed (n = 386) as well as school (n = 583) lunches. Based on the results from Study 1, it was feasible to collect and code most items in packed lunch images; missing data were most commonly attributed to packaging that limited visibility of contents. Across both studies, there was satisfactory reliability for determining food types selected, quantities selected, and quantities consumed in the eight food categories examined (weighted kappa coefficients 0.68–0.97 for packed lunches, 0.74–0.97 for school lunches), with lowest reliability for estimating condiments and meats/meat alternatives in packed lunches. In extending methods predominately applied to school lunches, these findings demonstrate the capacity of digital imaging for the objective estimation of selection and consumption from both school and packed lunches.



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A theoretical and empirical modeling of anxiety integrated with RDoC and temporal dynamics

Publication date: Available online 8 September 2017
Source:Journal of Anxiety Disorders
Author(s): Brandon Frank, Nicholas C. Jacobson, Landon Hurley, Dean McKay
The newly launched Research Domain Criteria (RDoC) emphasize specific mechanisms over diagnostic categories of psychopathology. In our view, RDoC provides a useful heuristic for mental health disorders, but does not capture the complexity of psychological data when proposed mechanisms are viewed as static entities. However, temporal and complex system dynamics may advance RDoC's utility. By investigating temporal patterns within trajectories and the interaction of complex networks, we propose that dynamic modeling provides comprehensive methods with which to investigate the etiopathology and maintenance of mental health disorders. We examine applications of dynamical systems to periphery physiology, an RDoC construct that has been widely used in psychological science. A review of the literature suggests methodological problems with aggregate and reductive models. We present a dynamical systems modeling of anxiety which suggests avenues for future biomarker research. This model appears congruent with RDoC and recent learning theory.



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Epithelial-mesenchymal transition of tumor budding in colorectal cancer: the mystery of CD44-positive stromal cells

Publication date: Available online 9 September 2017
Source:Human Pathology
Author(s): Simona Gurzu, Laura Banias, Zsolt Kovacs, Ioan Jung




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Angiomyomatous Hamartoma of Lymph Nodes, Revisited: Clinico-pathologic Study of 21 Cases, Emphasizing Its Distinction from Lymphangioleiomyomatosis of Lymph Nodes

Publication date: Available online 9 September 2017
Source:Human Pathology
Author(s): Michelle Moh, Ankur Sangoi, Joseph T. Rabban
Angiomyomatous hamartoma of lymph nodes (AMH-LN) is an uncommon benign proliferation of smooth muscle, blood vessels, collagenous stroma and adipocytes, most commonly affecting inguinal LN. A similar constellation of cell types constitutes various members of the perivascular epithelioid cell tumor (PEComa) family, including lymphangioleiomyomatosis (LAM) which can involve LN in women. Because some LN-LAM patients have tuberous sclerosis complex (TSC) and/or other PEComa family lesions, it is clinically relevant to distinguish LN-LAM from AMH-LN. Given their similar features, however, the possibility that AMH-LN is a morphologic variant of LN-LAM merits inquiry. The dual melanocytic and myoid immunophenotype distinguishes the PEComa family from its mimics. Cathepsin K has recently emerged as a more sensitive marker for the PEComa family than HMB-45, which can be weak and focal,but cathepsin K has not been studied in AMH-LN. This study evaluated 21 AMH-LN for clinical, morphologic and immunophenotypic features of LN-LAM. None (0/21) had TSC or PEComas. Thirteen (62%) were male, unlike LN-LAM which is restricted to women. All cases exhibited intraparenchymal proliferation of variable size, thick-walled blood vessels within collagenous stroma containing a sparse to focally cellular population of haphazardly distributed smooth muscle cells. Admixed adipocytes were commonly present. None exhibited classical features of LN-LAM such as subcapsular localization, extranodal extension, intralymphatic growth, compact nests, branching lymphatic channels, plump cell shape or foamy / clear cytoplasm. None exhibited any staining for cathepsin K, HMB45, or MiTF. There is no clinical, morphologic or immunohistochemical evidence to suggest that AMH-LN is a variant of LN-LAM.



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Characterization of genome-wide copy number aberrations in colonic mixed adenoneuroendocrine carcinoma and neuroendocrine carcinoma reveals recurrent amplification of PTGER4 and MYC genes

Publication date: Available online 9 September 2017
Source:Human Pathology
Author(s): Namita Sinha, Daniel Gaston, Daniel Manders, Marissa Goudie, Makoto Matsuoka, Tao Xie, Weei-Yuarn Huang
Colonic Mixed adenoneuroendocrine Carcinoma (MANEC) is an aggressive neoplasm with worse prognosis compared to adenocarcinoma. To gain a better understanding of the molecular features of colonic MANEC, we characterized the genome-wide copy number aberrations (CNA) of 14 MANECs and 5 neuroendocrine carcinomas using the OncoScan FFPE assay. Compared to 269 colonic adenocarcinomas, 19 of 42 chromosomal arms of MANEC exhibited a similar frequency of major aberrant events as adenocarcinomas, and 13 chromosomal arms exhibited a higher frequency of copy number gains. Among them, the most significant chromosomal arms were 5p (77% vs. 13%, P=1.2E-05) and 8q (85% vs. 33%, P=0.0018). The genomic identification of significant targets in cancers (GISTIC) algorithm identified seven peaks that drive the tumorgenesis of MANEC. For all except 5p13.1, the peaks largely overlapped with those of adenocarcinoma. Two tumors exhibited MYC amplification localized in 8q24.21 and two tumors exhibited PTGER4 amplification localized in 5p13.1. A total of eight tumors exhibited high copy number gain of PTGER4 and/or MYC. While the frequency of MYC amplification was similar to adenocarcinoma (10.5% vs. 4%, P=0.2), the frequency of PTGER4 amplification was higher than adenocarcinoma (10.5% vs. 0.3%, P=0.01). Our study demonstrates similar, but also distinct, CNAs in MANEC compared to adenocarcinoma and suggests an important role for the MYC pathway of colonic carcinoma with neuroendocrine differentiation. The discovery of recurrent PTGER4 amplification implies a potential of exploring targeting therapy to the prostaglandin synthesis pathways in a subset of these tumors.



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Histone 3.3 Mutations in Giant Cell Tumor and Giant Cell-Rich Sarcomas of Bone

Publication date: Available online 9 September 2017
Source:Human Pathology
Author(s): Alberto Righi, Irene Mancini, Marco Gambarotti, Piero Picci, Gabriella Gamberi, Cristina Marraccini, Angelo Paolo Dei Tos, Lisa Simi, Pamela Pinzani, Alessandro Franchi
Mutually exclusive histone 3.3 gene mutations have been recognized in chondroblastoma and giant cell tumor of bone (GCTB), which may be useful for differential diagnostic purposes in morphologically ambiguous cases. While over 90% of GCTB presents histone 3.3 variants exclusively in the H3F3A gene, chondroblastoma is mutated mainly in H3F3B. In this study we examined a series of giant cell rich primary bone tumors, aiming to evaluate the possible diagnostic role of histone 3.3 mutations in the differential diagnosis between GCTB and giant cell rich sarcomas. Sixteen cases of non-metastatic GCTB, 9 GCTB with lung metastases, and 35 giant cell-rich sarcomas were selected from our institutional archives. Eight chondroblastomas were used as controls. Direct sequencing for the presence of H3F3A and H3F3B variants in coding region between codons 1 and 42, including the hot spot codons (28, 35 and 37) was performed on DNA extracted from formalin-fixed paraffin-embedded tissue using conventional polymerase chain reaction (PCR) and fast COamplification at Lower Denaturation temperature-PCR (COLD-PCR). Overall, 24 GCTB (96%) presented a mutation in the H3F3A gene (15 of 16 non metastatic and 9 of 9 metastatic). Five sarcomas harbored a H3F3A mutation (3 p.G35 W, 1 p.G35 L and 1 p.G35E), and these were all secondary malignant GCTB. In conclusion, we confirm that H3F3A mutational testing may be a useful adjunct to differentiate GCTB from giant cell rich sarcomas. Although the presence of H3F3A mutations does not exclude with certainty a diagnosis of sarcoma, the possibility of a malignant evolution of GCTB should also be considered.



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Expression of YES-associated protein (YAP) and its clinical significance in breast cancer tissues

Publication date: Available online 9 September 2017
Source:Human Pathology
Author(s): Lanqing Cao, Ping-Li Sun, Min Yao, Meng Jia, Hongwen Gao
The transcriptional co-activator YES-associated protein (YAP) has been reported to act as both an oncogene and tumor suppressor in breast cancers. In this study, we evaluated YAP expression immunohistochemically in 324 breast cancer tissues and correlated the expression with clinicopathological findings and patient survival data. Additionally, we reviewed the literature to clarify the role of YAP in breast cancer. We detected YAP, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth receptor-2 (HER2) expression and a Ki67 labeling index >20% in 53.4%, 49.0%, 45.0%, 28.3%, and 57.4% of invasive ductal carcinoma (IDC) tissues, respectively. YAP is mainly localized within the tumor cell nuclei, and its expression was associated with the PR status and Luminal A subtype. YAP expression also inversely correlated with the HER2 and Ki67 levels and lymph node metastasis. Kaplan–Meier curves revealed associations of YAP expression with favorable disease-free survival (DFS) and overall survival (OS) in patients with Luminal A subtype breast cancer and with favorable DFS association among patients with IDC, Luminal B (HER2-) and Luminal B (HER2+) subtype breast cancers. A multivariate Cox analysis revealed that YAP expression and PR status were independent favorable predictors of DFS and OS, respectively, among patients with breast cancer, whereas TNM stage and an old age were independent predictors of a poor DFS. Our results, together with the literature review findings, suggest that YAP could be a prognostic marker in patients with breast cancer.



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Small bowel stenosis: a manifestation of chronic graft-versus-host disease in children?

Publication date: Available online 9 September 2017
Source:Human Pathology
Author(s): Mickael Tordjman, Marie Ouachee, Arnaud Bonnard, Bogdana Tilea, Karima Yakouben, Jerome Viala, Michel Peuchmaur, Dominique Berrebi
Digestive graft versus host disease (GVHD) is a frequent complication after bone marrow transplantation (BMT), but small bowel obstruction is an extremely rare event. We present herein the first pediatric series of 4 cases of small bowel obstruction after BMT with detailed gross, histological data and their genetic status of the NOD2 gene. All patients had a history of severe acute GVHD treated by immunosuppressive agents and/or infliximab (in 3 cases). Acute or progressively worsening abdominal pain accompanied by small bowel occlusion occurred 5–16months after graft and CT-scan revealed multiple small intestinal stenosis. Failure of intensive medical treatment led to surgical resection of affected loops. Stigmata of acute (apoptosis of crypts and satellitosis) and chronic GVHD features (submucosal fibrosis and serosae sclerolipomatosis), as well as extensive ulcerations, were observed in all ileal specimens. NOD2 mutation was found in only one patient. The follow up showed successful outcome after surgery.



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Copyright

Publication date: October 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 5





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Contributors

Publication date: October 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 5





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Contents

Publication date: October 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 5





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Forthcoming Issues

Publication date: October 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 5





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Gene Therapy

Publication date: October 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 5
Author(s): Daniel E. Bauer, Donald B. Kohn




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Historical Perspective on the Current Renaissance for Hematopoietic Stem Cell Gene Therapy

Publication date: October 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 5
Author(s): Donald B. Kohn

Teaser

Gene therapy using hematopoietic stem cells (HSC) has developed over the past 3 decades, with progressive improvements in the efficacy and safety. Autologous transplantation of HSC modified with murine gammaretroviral vectors first showed clinical benefits for patients with several primary immune deficiencies, but some of these patients suffered complications from vector-related genotoxicity. Lentiviral vectors have been used recently for gene addition to HSC and have yielded clinical benefits for primary immune deficiencies, metabolic diseases, and hemoglobinopathies, without vector-related complications. Gene editing using site-specific endonucleases is emerging as a promising technology for gene therapy and is moving into clinical trials.


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Integrating Vectors for Gene Therapy and Clonal Tracking of Engineered Hematopoiesis

Publication date: October 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 5
Author(s): Luca Biasco, Michael Rothe, Juliane W. Schott, Axel Schambach

Teaser

Gene therapy using autologous or allogeneic cells offers promising possibilities to treat inherited and acquired diseases, ideally leading to a long-lasting therapeutic correction. This article summarizes efforts that use integrating vectors derived from retroviruses and transposons, and briefly explains integrating vector biology and integration site analysis and recent successful application of this technology in clinical trials. Moreover, outlined is how these vectors can be used for cancer gene discovery and clonal tracking of benign and malignant hematopoiesis to gain insights into the dynamics of hematopoiesis.


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Nonintegrating Gene Therapy Vectors

Publication date: October 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 5
Author(s): Takis Athanasopoulos, Mustafa M. Munye, Rafael J. Yáñez-Muñoz

Teaser

Gene delivery vectors that do not rely on host cell genome integration offer several advantages for gene transfer, chiefly the avoidance of insertional mutagenesis and position effect variegation. However, unless engineered for replication and segregation, nonintegrating vectors will dilute progressively in proliferating cells, and are not exempt of epigenetic effects. This article provides an overview of the main nonintegrating viral (adenoviral, adeno-associated viral, integration-deficient retro-lentiviral, poxviral), and nonviral (plasmid vectors, artificial chromosomes) vectors used for preclinical and clinical cell and gene therapy applications. Particular emphasis is placed on their use in hematologic disease.


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In Vivo Hematopoietic Stem Cell Transduction

Publication date: October 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 5
Author(s): Maximilian Richter, Daniel Stone, Carol Miao, Olivier Humbert, Hans-Peter Kiem, Thalia Papayannopoulou, André Lieber

Teaser

Current protocols for hematopoietic stem cell (HSC) gene therapy, involving the transplantation of ex vivo lentivirus vector-transduced HSCs into myeloablated recipients, are complex and not without risk for the patient. In vivo HSC gene therapy can be achieved by the direct modification of HSCs in the bone marrow after intraosseous injection of gene delivery vectors. A recently developed approach involves the mobilization of HSCs from the bone marrow into peripheral the blood circulation, intravenous vector injection, and re-engraftment of genetically modified HSCs in the bone marrow. We provide examples for in vivo HSC gene therapy and discuss advantages and disadvantages.


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Gene Editing

Publication date: October 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 5
Author(s): Dale Ando, Kathleen Meyer

Teaser

The clinical application and regulatory strategy of genome editing for ex vivo cell therapy is derived from the intersection of two fields of study: viral vector gene therapy trials; and clinical trials with ex vivo purification and engraftment of CD34⁺ hematopoietic stem cells, T cells, and tumor cell vaccines. This article covers the regulatory and translational preclinical activities needed for a genome editing clinical trial modifying hematopoietic stem cells and the genesis of this current strategy based on previous clinical trials using genome-edited T cells. The SB-728 zinc finger nuclease platform is discussed because this is the most clinically advanced genome editing technology.


http://ift.tt/2wPI83v

Gene Therapy Approaches to Hemoglobinopathies

Publication date: October 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 5
Author(s): Giuliana Ferrari, Marina Cavazzana, Fulvio Mavilio

Teaser

Gene therapy for hemoglobinopathies is currently based on transplantation of autologous hematopoietic stem cells genetically modified with a lentiviral vector expressing a globin gene under the control of globin transcriptional regulatory elements. Preclinical and early clinical studies showed the safety and potential efficacy of this therapeutic approach as well as the hurdles still limiting its general application. In addition, for both beta-thalassemia and sickle cell disease, an altered bone marrow microenvironment reduces the efficiency of stem cell harvesting as well as engraftment. These hurdles need be addressed for gene therapy for hemoglobinopathies to become a clinical reality.


http://ift.tt/2fbfb84

Gene Therapy for Hemophilia

Publication date: October 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 5
Author(s): Amit C. Nathwani, Andrew M. Davidoff, Edward G.D. Tuddenham

Teaser

The best currently available treatments for hemophilia A and B (factor VIII or factor IX deficiency, respectively) require frequent intravenous infusion of highly expensive proteins that have short half-lives. Factor levels follow a saw-tooth pattern that is seldom in the normal range and falls so low that breakthrough bleeding occurs. Most hemophiliacs worldwide do not have access to even this level of care. In stark contrast, gene therapy holds out the hope of a cure by inducing continuous endogenous expression of factor VIII or factor IX following transfer of a functional gene to replace the hemophilic patient's own defective gene.


http://ift.tt/2wPnzE8

Gene Therapy Approaches to Human Immunodeficiency Virus and Other Infectious Diseases

Publication date: October 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 5
Author(s): Geoffrey L. Rogers, Paula M. Cannon

Teaser

Advances in gene therapy technologies, particularly in gene editing, are suggesting new avenues for the treatment of human immunodeficiency virus and other infectious diseases. This article outlines recent developments in antiviral gene therapies, including those based on the disruption of entry receptors or that target viral genomes using targeted nucleases, such as the CRISPR/Cas9 system. In addition, new ways to express circulating antiviral factors, such as antibodies, and approaches to harness and engineer the immune system to provide an antiviral effect that is not naturally achieved are described.


http://ift.tt/2faAsPh

Hematopoietic Stem Cell Approaches to Cancer

Publication date: October 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 5
Author(s): Jennifer E. Adair, Sara P. Kubek, Hans-Peter Kiem

Teaser

Hematopoietic stem cells (HSCs) are unique in their ability to self-renew and generate all blood lineages for the entire life. HSC modification affects red blood cells, platelets, lymphocytes, and myeloid cells. Chemotherapy can result in myelosuppression, limiting effective chemotherapy administration. For diseases like glioblastoma, high expression of methlylguanine methyltransferase can inactivate alkylating agent chemotherapy. Here we discuss how HSCs can be modified to overcome this resistance, permitting sensitization of tumors to chemotherapy while simultaneously protecting the hematopoietic system. We also discuss how HSCs can be harnessed to produce powerful tumor killing T cells, potentially benefitting and complementing T-cell–based immunotherapies.


http://ift.tt/2wPNICG

Gene Modified T Cell Therapies for Hematological Malignancies

Publication date: October 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 5
Author(s): Ulrike Abramowski-Mock, Juliette M. Delhove, Waseem Qasim

Teaser

This article focuses on clinical applications of T cells transduced to express recombinant T cell receptor and chimeric antigen receptor constructs directed toward hematological malignancies, and considers newer strategies incorporating gene-editing technologies to address GvHD and host-mediated rejection. Recent data from clinical trials are reviewed, and an overview is provided of current and emerging manufacturing processes; consideration is also given to new developments in the pipeline.


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Blockage of regulatory T cells augments induction of protective immune responses by influenza virus-like particles in aged mice

Publication date: Available online 9 September 2017
Source:Microbes and Infection
Author(s): Zhiyuan Wen, Xi Wang, Ke Dong, Huizhong Zhang, Zhigao Bu, Ling Ye, Chinglai Yang
Elderly humans over 65 years old are at great risk to pathogenesis by influenza virus infection. However, although influenza vaccines provide effective protection in healthy young adults, protection of elderly adults is substantially lower even with a good match between the vaccine and the circulating influenza virus. To gain insight of the underlying mechanism for the reduced immunogenicity of influenza vaccines in the aged population, we investigated immunogenicity of influenza virus-like particle vaccines in aged mice, which represent a useful model for studying aging associated impairment in immune responses. Specifically, we investigated the effect of inhibiting regulatory T cells in aged mice on induction of protective immune responses by influenza vaccines. Our results showed that injecting anti-CD25 antibodies could down-regulate CD25 on the surface of regulatory T cells and significantly increase the levels of antibody responses induced by VLP immunization in aged mice. Further, the profiles of antibody responses were also changed towards Th1 type by regulatory T cell blockage in aged mice. Moreover, aged mice that were treated by anti-CD25 antibodies prior to vaccination were more effectively protected against lethal influenza virus challenge.



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Single immunization with MF59-adjuvanted inactivated whole-virion H7N9 influenza vaccine provides early protection against H7N9 virus challenge in mice

Publication date: Available online 9 September 2017
Source:Microbes and Infection
Author(s): Haiyan Chang, Jie Duan, Peng Zhou, Ling Su, Dan Zheng, Fenghua Zhang, Fang Fang, Xiaoman Li, Ze Chen
H7N9 influenza infection in humans would result in severe respiratory illness. Vaccination is the best way to prevent influenza virus. In this paper, we investigated the effect of early protection provided by inactivated whole-virion H7N9 influenza vaccine in a mouse model.Mice were immunized intramuscularly once with different doses of inactivated whole-virion H7N9 influenza vaccine alone or in combination with MF59 adjuvant. Specific IgM and IgG antibody titers in sera of mice were detected by ELISA 3, 5 and 7days after immunization. To evaluate the early protection provided by the vaccine, mice were challenged with lethal dose (40LD50) of homologous virus 3, 5 and 7 days after immunization respectively. The survival rate and body weight change of mice during 21 days after challenge and the residual lung virus titer on 3^rd day after challenge were determined. The results demonstrated that mice could obtain effective protection 3 days after immunization with the vaccine at a high dose, and 5-7 days after immunization even at a low dose. Thus early immune responses induced by inactivated whole-virion H7N9 vaccine could provide effective protection.



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The caspase-8/Bid/cytochrome c axis links signals from death receptors to mitochondrial reactive oxygen species production

Publication date: November 2017
Source:Free Radical Biology and Medicine, Volume 112
Author(s): Wan-Sung Kim, Kwang-Soon Lee, Ji-Hee Kim, Chun-Ki Kim, Gwangsoo Lee, Jongseon Choe, Moo-Ho Won, Tae-Hyoung Kim, Dooil Jeoung, Hansoo Lee, Ji-Yoon Kim, Mi Ae Jeong, Kwon-Soo Ha, Young-Guen Kwon, Young-Myeong Kim
Ligation of the death receptors for TNF-α, FasL, and TRAIL triggers two common pathways, caspase-dependent intrinsic apoptosis and intracellular reactive oxygen species (ROS) generation. The apoptotic pathway is well characterized; however, a signaling linker between the death receptor and ROS production has not been clearly elucidated. Here, we found that death receptor-induced ROS generation was strongly inhibited by mitochondrial complex I and II inhibitors, but not by inhibitors of NADPH oxidase, lipoxygenase, cyclooxygenase or xanthine oxidase, indicating that ROS are mostly generated by the impairment of the mitochondrial respiratory chain. ROS generation was accompanied by caspase-8 activation, Bid cleavage, and cytochrome c release; it was blocked in FADD- and caspase-8-deficient cells, as well as by caspase-8 knockdown and inhibitor. Moreover, Bid knockdown abrogated TNF-α- or TRAIL-induced ROS generation, whereas overexpression of truncated Bid (tBid) or knockdown of cytochrome c spontaneously elevated ROS production. In addition, p53-overexpressing cells accumulated intracellular ROS via cytochrome c release mediated by the BH3-only protein Noxa induction. In a cell-free reconstitution system, caspase-8-mediated Bid cleavage and recombinant tBid induced mitochondrial cytochrome c release and ROS generation, which were blocked by Bcl-xL and antioxidant enzymes. These data suggest that anti-apoptotic Bcl-2 proteins play an important role in mitochondrial ROS generation by preventing cytochrome c release. These data provide evidence that the FADD/caspase-8/Bid/cytochrome c axis is a crucial linker between death receptors and mitochondria, where they play a role in ROS generation and apoptosis.

Graphical abstract

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Immune mechanisms of food allergy and its prevention by early intervention

Publication date: October 2017
Source:Current Opinion in Immunology, Volume 48
Author(s): Victor Turcanu, Helen A Brough, George Du Toit, Ru-Xin Foong, Tom Marrs, Alexandra F Santos, Gideon Lack
The environmental factors driving the increase in food allergies are unclear and possibly involve dual exposure to allergens, microbiome-driven effects or other mechanisms. Until they can be better understood, early intervention aiming at establishing oral tolerance provides an effective way to decrease the window-of-risk when children may develop allergic sensitisation to foods due to the absence of a protective immune response. Thus, the recent LEAP (Learning Early About Peanut allergy) and LEAP-On studies achieved a high level of peanut allergy prevention by early introduction of peanuts in the infants diet and conveyed more information regarding the evolution of IgE and IgG4 antibody responses to food antigens over time.



http://ift.tt/2fbmyMR

Skin burns following cryotherapy in misdiagnosed pediatric injuries

Publication date: Available online 8 September 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): N.K. Sferopoulos
Superficial local cryotherapy is frequently and safely used for pain relief following musculoskeletal injury or disease. However, serious skin complications have been reported in adults following inappropriate application. Skin burns following superficial local cryotherapy have not been previously reported in children.The consequences of inappropriate use of various forms of cryotherapy in four children following sport injuries are presented. They were all primarily misdiagnosed with a soft tissue injury. The incorrect usage was due to the high severity of the local symptoms and signs. They were all referred with partial thickness skin burns. Diagnosis on referral indicated a bone injury in all of them. The value of the initial clinical examination is emphasized considering that fractures, including physeal injuries, are more common than ligamentous lesions, and the high incidence of the radiographically occult acute injuries in children. The use of superficial local cryotherapy following injuries in children should always follow the rules of proper usage and should be avoided in cases that the clinical examination cannot exclude a potential sprain or fracture to prevent further ligament, joint or bone damaging.



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Pilates Reformer exercises for fall risk reduction in older adults: A randomized controlled trial

Publication date: Available online 9 September 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Margaret Roller, Aimie Kachingwe, Janna Beling, Dawn-Marie Ickes, Allyson Cabot, Gabrielle Shrier
ObjectiveTo investigate the effects of Pilates exercises using a Reformer on measures of fall risk, balance and mobility, self-efficacy, and active range of motion in adults age 65 and over at risk for falls compared to a control group.DesignRandomized Controlled Trial.Methods55 subjects (27 Pilates intervention, 28 control; 38 females, 17 males; mean age 77.6 years, range 65–95) were randomly assigned to either a Pilates Reformer intervention group or a control group (no intervention). Subjects in the intervention group attended a Pilates Reformer exercise program in a group format once a week over a 10-week period. The primary outcome measures were the Sensory Organization Test (SOT) composite scores on the NeuroCom^® system, Timed Up-and-Go (TUG), and Activities-specific Balance Confidence (ABC) scale. The secondary outcome measures were the Adaptation Test (ADT), straight leg raise, hip extension, and ankle dorsiflexion active range of motion (AROM), Berg Balance Scale (BBS), and 10 Meter Walk Test (10MWT).ResultsThere was a significant interaction between group and time on the TUG, BBS, 10MWT, and SLR, hip extension, and ankle dorsiflexion AROM measurements. Over time, subjects in the Pilates intervention group improved their scores significantly on all mentioned measures, whereas subjects in the control group did not (P ≤ 0.05). Significantly improved AROM was found between groups following the Pilates intervention for hip extension, left SLR, and right ankle dorsiflexion.ConclusionPilates Reformer exercises performed once per week for 10 weeks resulted in reduced fall risk and significant improvements in static and dynamic balance, functional mobility, balance self-efficacy, and lower extremity AROM in adults age 65 and older at risk for falling, whereas the control group did not significantly improve in any measures. Pilates Reformer exercises are more effective compared to no exercise intervention at improving hip and ankle AROM.



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Stress-Activated Chaperones: A First Line of Defense

Publication date: Available online 8 September 2017
Source:Trends in Biochemical Sciences
Author(s): Wilhelm Voth, Ursula Jakob
Proteins are constantly challenged by environmental stress conditions that threaten their structure and function. Especially problematic are oxidative, acid, and severe heat stress which induce very rapid and widespread protein unfolding and generate conditions that make canonical chaperones and/or transcriptional responses inadequate to protect the proteome. We review here recent advances in identifying and characterizing stress-activated chaperones which are inactive under non-stress conditions but become potent chaperones under specific protein-unfolding stress conditions. We discuss the post-translational mechanisms by which these chaperones sense stress, and consider the role that intrinsic disorder plays in their regulation and function. We examine their physiological roles under both non-stress and stress conditions, their integration into the cellular proteostasis network, and their potential as novel therapeutic targets.



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Neuropeptide discovery in Proasellus cavaticus: prediction of the first large-scale peptidome for a member of the Isopoda using a publicly accessible transcriptome

Publication date: Available online 8 September 2017
Source:Peptides
Author(s): Andrew E. Christie
In silico transcriptome mining is one of the most effective methods for neuropeptide discovery in crustaceans, particularly for species that are small, rare or from geographically inaccessible habitats that make obtaining the large pools of tissue needed for other peptide discovery platforms impractical. Via this approach, large peptidomes have recently been described for members of many of the higher crustacean taxa, one notable exception being the Isopoda; no peptidome has been predicted for any member of this malacostracan order. Using a publicly accessible transcriptome for the isopod Proasellus cavaticus, a subcentimeter subterranean ground water dweller, the first in silico-predicted peptidome for a member of the Isopoda is presented here. BLAST searches employing known arthropod neuropeptide pre/preprohormone queries identified 49 transcripts as encoding putative homologs within the P. cavaticus transcriptome. The proteins deduced from these transcripts allowed for the prediction of 171 distinct mature neuropeptides. The P. cavaticus peptidome includes members of the adipokinetic hormone-corazonin-like peptide, allatostatin A, allatostatin B, allatostatin C, allatotropin, bursicon α, bursicon β, CCHamide, crustacean cardioactive peptide, crustacean hyperglycemic hormone/molt-inhibiting hormone, diuretic hormone 31, eclosion hormone, elevenin, FMRFamide-like peptide, glycoprotein hormone α2, leucokinin, myosuppressin, neuroparsin, neuropeptide F, pigment dispersing hormone, pyrokinin, red pigment concentrating hormone, RYamide, short neuropeptide F, sulfakinin, tachykinin-related peptide and trissin families, as well as many linker/precursor-related sequences that may or may not represent additional bioactive molecules. Interestingly, many of the predicted P. cavaticus neuropeptides possess structures identical (or nearly so) to those previously described from members of several other malacostracan orders, i.e., the Decapoda, Amphipoda and Euphausiacea, a finding that suggests broad phylogenetic conservation of bioactive peptide structures, and possibly functions, may exist within the Malacostraca.



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Hypothyroidism in the “Arnolfini Portrait” (1434) by Jan Van Eyck (1390–1441)

Abstract

Background

The Arnolfini portrait painted by Jan van Eyck in 1434 remains one of the most puzzling yet alluring paintings of prerenaissance western art.

Purpose

The painting is renowned for its exactitude in brush strokes, textures and the distinctive morphology of the main character Arnolfini. The nature of these requires pathological consideration.

Methods

Diagnostic and pathological analysis of the painting.

Results

A number of pathological abnormalities are noted in the face of the main character including loss of outer third of the eyebrow (Sign of Hertoghe), bilateral ptosis and melasma of the forehead. These together support a diagnosis of hypothyroidism.

Conclusions

This novel diagnosis offers an additional perspective to this enigmatic portrait, and can add to the comprehension of the method, origin and pathological associations of this prominent painting from a genius artist.

http://ift.tt/2xThLGq

Are children playgrounds safe play areas? Inorganic analysis and lead isotope ratios for contamination assessment in recreational (Brazilian) parks

Abstract

In city playgrounds, there is a potential risk of harming children's health by contamination coming from anthropogenic activities. With the aim to determinate the sources and the risk of hazardous elements, soil samples were collected in 19 selected playgrounds of different urban and rural areas from the Rio Grande do Sul state (Brazil). The concentration of 23 metals and metalloids and lead isotopic ratios were determined by ICP-MS. The methodology proposed here, firstly, classified the parks according to the average metal content by means of the NWACs (Normalized-and-Weighted Average Concentrations) and assess the contamination risk determining the Contamination Factors (CFs). Finally, statistical tools (correlation analysis and principal component analysis) were used to identify the most important contamination sources. The statistical tools used, together with lead isotopic composition analysis of the samples, revealed that coal combustion is the main source of contamination in the area. Vegetation was identified as a barrier for the contamination coming from the city. Nonetheless, some of the soils present a possible toxicological risk for humans. In fact, Cr, Sb, and Pb concentrations were higher than the Residential Intervention Values (VIRs) defined by the Environmental Protection Agency of the State of São Paulo, also in Brazil.

http://ift.tt/2wQRKu1

The dissipation and risk assessment of 2,4-D sodium, a preharvest anti-fruit-drop plant hormone in bayberries

Abstract

Preharvest fruit-drop is a challenge to bayberry production. 2,4-D sodium as a commonly used anti-fruit-drop hormone on bayberry can reduce the yield loss caused by preharvest fruit-drop. The persistence and risk assessment of 2,4-D sodium after applying on bayberries were investigated. A method for determining 2,4-D sodium in bayberry was established based on LC-MS-MS. The average recoveries of 2,4-D sodium were at the range of 93.7–95.8% with relative standard deviations (RSDs) ranging from 0.9 to 2.8%. The dissipation rates of 2,4-D sodium were described using first-order kinetics, and its half-life ranged from 11.2 to 13.8 days. A bayberry consumption survey was carried out for Chinese adults for the first time. The safety assessments of 2,4-D sodium were conducted by using field trail data as well as monitoring data. Results showed that the chronic risk quotient and the acute risk quotient were calculated to be 0.23–0.59 and 0.02–0.05%, respectively, for Chinese adults, indicating low dietary risk for adults and children. In the end, the household cleaning steps were compared, and results showed that water rinsing for 1 min can remove 49.9% 2,4-D sodium residue, which provides pesticide removal suggestion for consumers.

http://ift.tt/2wh75Ae

Brevibacillus laterosporus isolated from the digestive tract of honeybees has high antimicrobial activity and promotes growth and productivity of honeybee’s colonies

Abstract

The development of novel antimicrobial drugs, as well as the discovery of novel compounds able to promote honeybee's growth, represents major challenges for modern entomology. The main aim of this study was to investigate whether Brevibacillus laterosporus isolated from the digestive tract of Saudi honeybees, Apis mellifera, was able to stimulate colony strength parameters of honeybees and to evaluate its ability to produce antimicrobial agents. Honeybees were collected in Dirab, Riyadh Region, Saudi Arabia, and microorganisms were isolated and identified by 16S ribosomal RNA analysis. Microscopic identification of the microorganism in its native state was facilitated by atomic force microscopy at high-resolution imaging. Active biological compounds were produced by submerged fermentation with B. laterosporus. The fermented broth was subjected to extraction and purification, and then semi-pure compounds were analyzed by gas chromatography–mass spectrometry. The effectiveness of the crude extract and semi-pure compounds as antimicrobial agents was evaluated by susceptibility assays. More than 22% of the microorganisms isolated from the digestive tract of healthy honeybees have been identified as B. laterosporus, this kind of species has a unique shape and morphological structure. The cyclic dipeptide cyclo(Leu-Pro) produced by B. laterosporus showed biological activity against several pathogenic microorganisms. Furthermore, the total counts of workers, closed brood, and open brood, as well as the production of bee pollen and honey, were better in honeybees treated with a B. laterosporus suspension. The data indicated that the B. laterosporus strain isolated from a healthy honeybee might be a novel probiotic and a producer of important biological compounds.

http://ift.tt/2wgAT0b

Morphology evolution of nanorods decorated on electrospun nanofibers and their applications in SERS and catalysis

Publication date: 5 December 2017
Source:Materials & Design, Volume 135
Author(s): Lu Bai, Zhaodong Yan, Lu Jia, Zhicheng Liu, Yaqing Liu
Understanding the structure-property relationships of functional materials with changing nanostructures is essential for their practical applications. In this work, the nanorods-decorated electrospun nanofibers underwent a morphology evolution upon simple thermal treatment. The nanorods became short, and finally round with the increasing thermal treating time. As results of the morphology evolution, the SERS properties and the catalytic properties of the changing nanostructures showed different trends. The SERS activity firstly increased and then decreased with the thermal treating time. However, the catalytic property decreased with the thermal treating time. The revealed connections between the practical performance and the morphology evolution might be helpful for the control of functionality of nanomaterials under certain conditions.

Graphical abstract

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The Ice Test to Differentiate Essential tremor from Parkinson’s disease tremor

Publication date: Available online 8 September 2017
Source:Clinical Neurophysiology
Author(s): Aparna Wagle Shukla, Michael Okun, David Vaillancourt, Lisa Warren




http://ift.tt/2wS8rDK

Standard computerized EEG reporting - it’s time to even the score

Publication date: Available online 8 September 2017
Source:Clinical Neurophysiology
Author(s): William O. Tatum




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Processing of visual food cues during bitter taste perception in female patients with binge-eating symptoms: a cross-modal ERP study

Publication date: Available online 8 September 2017
Source:Clinical Neurophysiology
Author(s): Anne Schienle, Wilfried Scharmüller, Daniela Schwab
ObjectiveIn healthy individuals, the perception of an intense bitter taste decreased the reward value of visual food cues, as reflected by the reduction of a specific event-related brain potential (ERP), frontal late positivity. The current cross-modal ERP study investigated responses of female patients with binge-eating symptoms (BES) to this type of visuo-gustatory stimulation.MethodsWomen with BES (n = 36) and female control participants (n = 38) viewed food images after they rinsed their mouth with either bitter wormwood tea or water.ResultsRelative to controls, the patients showed elevated late positivity (LPP: 400-700 ms) to the food images in the bitter condition. The LPP source was located in the medial prefrontal cortex. Both groups did not differ in the ratings for the fluids (intensity, bitterness, disgust).ConclusionsThis ERP study showed that a bitter taste did not decrease late positivity to visual food cues (reflecting food reward) in women with BES.SignificanceThe atypical bitter responding might be a biological marker of this condition and possibly contributes to overeating. Future studies should additionally record food intake behavior to further investigate this mechanism.



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