The prevalence and function of CD4+CXCR5+Foxp3+ follicular regulatory T cells in diffuse large B cell lymphoma

Publication date: August 2018
Source:International Immunopharmacology, Volume 61
Author(s): Zhanshan Cha, Haihui Gu, Yan Zang, Zi Wang, Jinqi Li, Weihua Huang, Aihua Qin, Lishuang Zhu, Xiaohua Tu, Ning Cheng, Haihan Song, Baohua Qian
CD4⁺CXCR5⁺Foxp3⁺ follicular regulatory T (Tfr) cells possess critical roles in suppressing the germinal center reaction, B cell activation, and follicular helper T cell (Tfh) cytokine secretion. Since diffuse large B cell lymphoma (DLBCL) can arise from B cells undergoing germinal center reaction and/or differentiation, we hypothesized that Tfr cells might be involved in DLBCL. In the present study, we recruited thirty-five DLBCL patients and twenty-five healthy controls. Data showed that DLBCL patients presented an enrichment of circulating CD4⁺CXCR5⁺Foxp3⁺ Tfr cells compared to controls. In the primary tumor isolated from enlarged lymph nodes, Tfr cells made up of roughly 3% to 16% of infiltrating T cells. Higher levels of tumor-infiltrating Tfr cells were observed in patients with less advanced DLBCL stages, and in patients that stayed in remission 24 months after the initial R-CHOP treatment. High BCL6 and high FOXP3 expression was observed in Tfr cells ex vivo. After anti-CD3/CD28 and IL-2 stimulation, the Tfr cells more closely resembled Treg cells and presented high IL10 and TGFB1 expression. CD4⁺CD25⁺CXCR5⁺ Tfr cells and CD4⁺CD25⁺CXCR5⁻ non-Tfr Treg cells could suppress CD4⁺CD25⁻ Tconv cell and CD8⁺ T cell proliferation with similar capacity. However, Tfr cells were less capable of suppressing IFNG expression than Treg cells, and although both cell types supported CD19⁺ tumor cell proliferation, Tfr cells were less supportive than the non-Tfr Treg cells. Overall, this study suggested that Tfr cells were involved in intratumoral immunity, were likely beneficial to DLBCL patients, and were functionally distinctive from non-Tfr Treg cells. The distribution pattern and the prognostic value of Tfr cells in DLBCL should be examined in further studies.



https://ift.tt/2JmeZmO

Impaired planning in patients with obsessive-compulsive disorder and unaffected first-degree relatives: Evidence for a cognitive endophenotype

Publication date: Available online 1 June 2018
Source:Journal of Anxiety Disorders
Author(s): Katharina Bey, Christian Kaufmann, Leonhard Lennertz, Anja Riesel, Julia Klawohn, Stephan Heinzel, Rosa Grützmann, Norbert Kathmann, Michael Wagner
Patients with obsessive-compulsive disorder (OCD) show deficient planning capacity in the Tower of London (TOL) problem solving task. Preliminary evidence for similar deficits in unaffected first-degree relatives suggests that impaired planning may constitute an endophenotype of OCD. However, results on this issue are inconsistent, possibly owing to small sample sizes and variability in problem structure across TOL tasks. Here, we adopted a computerized version of the TOL task featuring a 2 × 2 factorial design (high/low search depth × full/partial tower goal state) and examined a well-characterized sample of n = 72 OCD patients, n = 76 unaffected first-degree relatives and n = 102 healthy comparison subjects. Both OCD patients and relatives exhibited significantly less accurate problem solving than controls. Search depth, goal hierarchy, or the number of minimum moves did not moderate these group differences. Medication, OCD symptoms, and depressive comorbidity did not affect TOL performance in patients, suggesting a state-independent effect. In conclusion, we confirmed that OCD patients as well as unaffected first-degree relatives show deficient TOL performance across a range of task conditions, strongly supporting the role of impaired planning as an endophenotype of OCD, and contributing to the growing evidence for fronto-striatal dysfunctions in OCD.



https://ift.tt/2J83VKv

Cuba Si. Cancer No.

Publication date: Available online 1 June 2018
Source:Seminars in Oncology
Author(s): Antonio Tito Fojo
The current double issue of Seminars in Oncology brings 11 contributions from the Center for Genetic Engineering and Biotechnology, the Center of Molecular Immunology, and the Center of Medical and Surgical Research in Cuba. Having left Cuba in 1960, my interest in these submissions admittedly could go beyond the merely scientific. But others, I guarantee, will find EVERY article remarkably interesting and informative. In an era where the overwhelming majority of therapies in development as well as clinical trials being conducted are following well-traveled paths that bring us limited new information, the investigators from Cuba present us with rational, novel approaches to drug development. This is truly out of the box thinking, crafted in a country where resource limitations have clearly incentivized novel approaches. Their basic science is solid and their clinical validation is either mature or a work very much in progress. Cancer, one realizes reading these contributions, is a scourge across the world. Enjoy the refreshing and exciting approach of these investigators!!!



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Editorial Board

Publication date: July 2018
Source:Clinical Immunology, Volume 192





https://ift.tt/2HfMZMi

Editorial Board

Publication date: July 2018
Source:Clinical Immunology, Volume 192





https://ift.tt/2HfMZMi

Collagen secretion screening in Drosophila supports a common secretory machinery and multiple Rab requirements

Publication date: Available online 1 June 2018
Source:Journal of Genetics and Genomics
Author(s): Hongmei Ke, Zhi Feng, Min Liu, Tianhui Sun, Jianli Dai, Mengqi Ma, Lu-Ping Liu, Jian-Quan Ni, José Carlos Pastor-Pareja
Collagens are large secreted trimeric proteins making up most of the animal extracellular matrix. Secretion of collagen has been a focus of interest for cell biologists in recent years because collagen trimers are too large and rigid to fit into the COPII vesicles mediating transport from the endoplasmic reticulum (ER) to the Golgi. Collagen-specific mechanisms to create enlarged ER-to-Golgi transport carriers have been postulated, including cargo loading by conserved ER exit site (ERES) protein Tango1. Here, we report an RNAi screening for genes involved in collagen secretion in Drosophila. In this screening, we examined distribution of GFP-tagged Collagen IV in live animals and found 88 gene hits for which the knockdown produced intracellular accumulation of Collagen IV in the fat body, the main source of matrix proteins in the larva. Among these hits, only two affected collagen secretion specifically: PH4αEFB and Plod, encoding enzymes known to mediate posttranslational modification of collagen in the ER. Every other intracellular accumulation hit affected general secretion, consistent with the notion that secretion of collagen does not use a specific mode of vesicular transport, but the general secretory pathway. Included in our hits are many known players in the eukaryotic secretory machinery, like COPII and COPI components, SNAREs and Rab-GTPase regulators. Our further analysis of the involvement of Rab-GTPases in secretion shows that Rab1, Rab2 and RabX3, are all required at ERES, each of them differentially affecting ERES morphology. Abolishing activity of all three by Rep knockdown, in contrast, led to uncoupling of ERES and Golgi. We additionally present a characterization of a screening hit we named trabuco (tbc), encoding an ERES-localized TBC domain-containing Rab-GAP. Finally, we discuss the success of our screening in identifying secretory pathway genes in comparison to two previous secretion screenings in Drosophila S2 cells.



https://ift.tt/2HbBYMf

Radiological Study of the Ethmoidal Arteries in the Nasal Cavity and Its Pertinence to the Endoscopic Surgeon

Abstract

We studied the ethmoidal arteries using preexisting computer tomography of the paranasal sinuses (CT PNS) and statistically scrutinized data obtained between genders. A descriptive study from 77 CT PNS dated January 2016–December 2016 were collected and reviewed by two radiologists. A total of 54 (108 sides) CT PNS were studied of patients aged 18–77 years. 37 are male, 17 are female; with Bumiputera Sarawak predominance of 25 patients, 12 Malays, 16 Chinese and one Indian. Rate of identification are as follows: anterior ethmoidal artery (AEA)-100%, middle ethmoidal artery (MEA)-30%, posterior ethmoidal artery (PEA)-86%. The average distance from AEA–MEA is 8.1 ± 1.52 mm, MEA–PEA is 5.5 ± 1.29 mm and AEA–PEA is 12.9 ± 1.27 mm. The mean distance from PEA-the anterior wall of sphenoid is 7.7 ± 3.96 mm, and PEA-optic canal is 8.5 ± 3.1 mm with no statistical difference when compared between gender. AEA frequently presented with a long mesentery 57.4%, while 87.1% of PEA was hidden in a bony canal. The vertical distance of the AEA-skull base ranges from 0 to 12.5 mm whilst PEA-skull base is 0–4.7 mm. There is no statistical difference in distances of AEA, MEA nor PEA to skull base when analyzed between genders; t(82) = 1.663, p > 0.05, t(32) = 0.403, p > 0.05 and t(75) = 1.333, p > 0.05 respectively. We newly discovered, that 50% of MEA is hidden in a bony canal, and its distance to skull base ranged 0–5.3 mm. MEA and PEA less commonly have a short or long mesentery. Knowledge on the ethmoidal arteries especially in our unstudied population of diverse ethnicity, gains to assist surgeons worldwide, when embarking in endoscopic transnasal surgeries.

https://ift.tt/2JpnCwS

Alcohol consequences, not quantity, predict major depression onset among first-year female college students

Publication date: October 2018
Source:Addictive Behaviors, Volume 85
Author(s): Samantha R. Rosenthal, Melissa A. Clark, Brandon D.L. Marshall, Stephen L. Buka, Kate B. Carey, Robyn L. Shepardson, Michael P. Carey
Alcohol use and its consequences have often been associated with depression, particularly among female college students. Interpretation of this association has been challenging due to potential reverse causation. The current study sought to clarify the temporality of these relationships. We examined: (1) the association between alcohol consumption and onset depression among female college students, and (2) the association between drinking consequences and onset depression among drinkers only. We used a prospective longitudinal design. Participants were first-year female college students who completed a baseline survey at study entry, and monthly assessments of alcohol consumption, drinking consequences, and depression symptoms. Cox proportional hazards regression with time-varying covariates were constructed among the full sample (N = 412) and the drinkers only sample (N = 335). Adjusted hazard ratios accounted for known risk factors for depression such as race/ethnicity, academic challenge, not getting along with one's roommate, sexual victimization prior to college, marijuana use, and socioeconomic status. For each additional average drink per week, adjusting for all covariates, there was no (95% CI: -4%, +4%) increased risk of onset depression. For each additional alcohol consequence, adjusting for all covariates, there was a 19% (95% CI: 5%, 34%) increased risk of onset depression. This significant relationship remained after adjusting for quantity of alcohol consumption. Quantity of alcohol consumed did not predict incident depression. However, experiencing alcohol consequences, regardless of consumption, did increase the risk of incident depression. College substance use and mental health interventions should aim to reduce not only alcohol consumption, but also alcohol-related consequences.



https://ift.tt/2LbBIPF

Spanish adaptation of the Gambling Motives Questionnaire (GMQ): Validation in adult pathological gamblers and relationship with anxious-depressive symptomatology and perceived stress

Publication date: October 2018
Source:Addictive Behaviors, Volume 85
Author(s): Paula Jauregui, Ana Estevez, Jaione Onaindia
Gambling has been found to be related to different motives, such as enhancement, social, and behavioral and emotional coping. The most used instrument in this field is the Gambling Motives Questionnaire (GMQ; Stewart & Zack, 2008), which has not been validated in clinical samples. This study aimed to validate a Spanish version of the GMQ in a sample of adult pathological gamblers and to analyze its relationship with pathological gambling, anxiety, depression, and perceived stress. A sample of 164 gamblers was recruited from centers for the treatment of pathological gambling. The three-factor structure (enhancement, social, and coping motives) of the GMQ was validated through exploratory and confirmatory factorial analyses, and its convergent validity was proven. Gambling motives correlated with pathological gambling, anxiety, depression, and perceived stress. Enhancement motives predicted pathological gambling, while controlling for the effect of anxiety, depression, and perceived stress. These results are relevant for clinical evaluation and intervention with adult pathological gamblers.



https://ift.tt/2JoIggt

Exploring the role of positive metacognitions in explaining the association between the fear of missing out and social media addiction

Publication date: October 2018
Source:Addictive Behaviors, Volume 85
Author(s): Silvia Casale, Laura Rugai, Giulia Fioravanti
The present study aimed to investigate: a) the contribution of the fear of missing out (FoMO) in explaining social media problematic use taking also into account the fear of being negatively evaluated and the perception of low self-presentational skills; b) the mediating role of positive metacognitions about social media use in the relationship between FoMO and social media problematic use. A sample of 579 undergraduates was recruited (54.6% F; mean age = 22.39 ± 2.82). Among females, the assessed structural model produced good fit to the data [χ² = 101.11, df = 52, p < .001; RMSEA = 0.05 (90% C.I. =0.04–0.07), CFI = 0.98, SRMR = 0.05]. FoMO and self-presentational skills were both directly and indirectly associated with social media problematic use through the mediation of positive metacognitions. Fear of negative evaluation was not associated with social media problematic use. Among males, FoMO had both a direct and an indirect effect on social media problematic use mediated by positive metacognitions. The fear of negative evaluation and self-presentational skills were only indirectly associated with social media problematic use through positive metacognitions. The assessed structural model produced good fit to the data [χ² = 98.02, df = 55, p < .001; RMSEA = 0.05 (90% C.I. =0.04–0.07), CFI = 0.98, SRMR = 0.07]. The present study confirmed the role of FoMO with respect to social media problematic use and highlighted for the first time the mediating role of positive metacognitions in this relationship.



https://ift.tt/2LbxirZ

Photo-excitable hybrid nanocomposites for image-guided photo/TRAIL synergistic cancer therapy

Publication date: September 2018
Source:Biomaterials, Volume 176
Author(s): Gan Lin, Yang Zhang, Congqing Zhu, Chengchao Chu, Yesi Shi, Xin Pang, En Ren, Yayun Wu, Peng Mi, Haiping Xia, Xiaoyuan Chen, Gang Liu
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis in cancer cells without toxicity to normal cells. However, the efficiency is greatly limited by its short half-life and wild resistance in various cancer cells. In this study, we reported a micellar hybrid nanoparticle to carry TRAIL ligand (denoted as IPN@TRAIL) for a novel photo-excited TRAIL therapy. These IPN@TRAIL offered increased TRAIL stability, prolonged half-life and enhanced tumor accumulation, monitored by dual mode imaging. Furthermore, IPN@TRAIL nanocomposites enhanced wrapped TRAIL therapeutic efficiency greatly towards resistant cancer cells by TRAIL nanovectorization. More importantly, when upon external laser, these nanocomposites not only triggered tumor photothermal therapy (PTT), but also upregulated the expression of death receptors (DR4 and DR5), resulting in a greater apoptosis mediated by co-delivered TRAIL ligand. Such photo/TRAIL synergistic effect showed its great killing effects in a controllable manner on TRAIL-resistant A549 tumor model bearing mice. Finally, these nanocomposites exhibited rapid clearance without obvious systemic toxicity. All these features rendered our nanocomposites a promising theranostic platform in cancer therapy.



https://ift.tt/2sA1qp5

Blood-brain barrier shuttle peptides enhance AAV transduction in the brain after systemic administration

Publication date: September 2018
Source:Biomaterials, Volume 176
Author(s): Xintao Zhang, Ting He, Zheng Chai, R. Jude Samulski, Chengwen Li
The adeno-associated virus (AAV) vector has been used in preclinical and clinical trials of gene therapy for central nervous system (CNS) diseases. One of the biggest challenges of effectively delivering AAV to the brain is to surmount the blood-brain barrier (BBB). Herein, we identified several potential BBB shuttle peptides that significantly enhanced AAV8 transduction in the brain after a systemic administration, the best of which was the THR peptide. The enhancement of AAV8 brain transduction by THR is dose-dependent, and neurons are the primary THR targets. Mechanism studies revealed that THR directly bound to the AAV8 virion, increasing its ability to cross the endothelial cell barrier. Further experiments showed that binding of THR to the AAV virion did not interfere with AAV8 infection biology, and that THR competitively blocked transferrin from binding to AAV8. Taken together, our results demonstrate, for the first time, that BBB shuttle peptides are able to directly interact with AAV and increase the ability of the AAV vectors to cross the BBB for transduction enhancement in the brain. These results will shed important light on the potential applications of BBB shuttle peptides for enhancing brain transduction with systemic administration of AAV vectors.

Graphical abstract

https://ift.tt/2soqFvs

Editorial Board

Publication date: August 2018
Source:Biomaterials, Volume 175





https://ift.tt/2Hdw1y3

Contact dermatitis with concomitant contact urticaria syndrome due to multiple ingredients of oxidative hair dye

Publication date: Available online 1 June 2018
Source:Allergology International
Author(s): Jun-ichi Iwata, Naoko Inomata, Megumi Sato, Mami Miyakawa, Toshiko Kawaguchi, Michiko Aihara




https://ift.tt/2J8V8UN

The molecular allergology of subtropical grass pollen

Publication date: Available online 31 May 2018
Source:Molecular Immunology
Author(s): Thina Kailaivasan, Janet M. Davies
Grass pollens are amongst the most important aeroallergen sources world-wide triggering allergic rhinoconjunctivitis and asthma in sensitised patients. Much of what we know about the allergen components of grasses is informed by research on pollen of temperate (Pooideae) species that are abundant in the temperate climate zones. However, climate changes are altering the biogeographical distribution as well as timing and allergenicity of grass pollens. This provides an impetus for better understanding of the contribution of subtropical subfamilies of grasses to pollen allergy globally. Pollen of Chloridoideae (e.g. Cynodon dactylon; Bermuda grass) and Panicoideae (e.g. Paspalum notatum; Bahia grass or Sorghum halepense; Johnson grass) subfamilies are clinically important in subtropical zones of Australia, Asia, India, Africa, and America. These grasses differ ecologically and phylogenetically from temperate grasses and, importantly their allergen composition is qualitatively different. For example, subtropical grass pollens appear to lack the major group 5 grass pollen allergen family. In this review we summarize current knowledge of the epidemiology and immunology of subtropical Chloridoideae and Pancoideae pollen allergens, describe the biochemical characteristics of known isoforms and variants as well as properties and structures of subtropical pollen allergen components. Whilst only one subtropical allergen component; Cyn d 1 of Bermuda grass pollen, is available commercially for diagnostic use, in a natural purified form, a number of allergens of Panicoideae grass pollen; Zea m 1, Zea m 3 and Zea m 13 of maize, Pas n 1 and Pas n 13 of Bahia, as well as Sor h 1, Sor h 2, Sor h 13 and Sor h 23 of Johnson grass, have been discovered. Research effort is directed towards making available subtropical grass pollen allergen components as innovative treatment and diagnostic options that more specifically address the needs of patients from warmer regions of the globe.



https://ift.tt/2kGooaL

The molecular allergology of subtropical grass pollen

Publication date: Available online 31 May 2018
Source:Molecular Immunology
Author(s): Thina Kailaivasan, Janet M. Davies
Grass pollens are amongst the most important aeroallergen sources world-wide triggering allergic rhinoconjunctivitis and asthma in sensitised patients. Much of what we know about the allergen components of grasses is informed by research on pollen of temperate (Pooideae) species that are abundant in the temperate climate zones. However, climate changes are altering the biogeographical distribution as well as timing and allergenicity of grass pollens. This provides an impetus for better understanding of the contribution of subtropical subfamilies of grasses to pollen allergy globally. Pollen of Chloridoideae (e.g. Cynodon dactylon; Bermuda grass) and Panicoideae (e.g. Paspalum notatum; Bahia grass or Sorghum halepense; Johnson grass) subfamilies are clinically important in subtropical zones of Australia, Asia, India, Africa, and America. These grasses differ ecologically and phylogenetically from temperate grasses and, importantly their allergen composition is qualitatively different. For example, subtropical grass pollens appear to lack the major group 5 grass pollen allergen family. In this review we summarize current knowledge of the epidemiology and immunology of subtropical Chloridoideae and Pancoideae pollen allergens, describe the biochemical characteristics of known isoforms and variants as well as properties and structures of subtropical pollen allergen components. Whilst only one subtropical allergen component; Cyn d 1 of Bermuda grass pollen, is available commercially for diagnostic use, in a natural purified form, a number of allergens of Panicoideae grass pollen; Zea m 1, Zea m 3 and Zea m 13 of maize, Pas n 1 and Pas n 13 of Bahia, as well as Sor h 1, Sor h 2, Sor h 13 and Sor h 23 of Johnson grass, have been discovered. Research effort is directed towards making available subtropical grass pollen allergen components as innovative treatment and diagnostic options that more specifically address the needs of patients from warmer regions of the globe.



https://ift.tt/2kGooaL

Spectral Contrast Effects Produced by Competing Speech Contexts.

Author: Feng, Lei; Oxenham, Andrew J.

DOI: 10.1037/xhp0000546

Publication Date: POST AUTHOR CORRECTIONS, 31 May 2018

https://ift.tt/2J8HCAh

Interplay between estrogen-related receptors and steroidogenesis-controlling molecules in adrenals. In vivo and in vitro study

Publication date: Available online 31 May 2018
Source:Acta Histochemica
Author(s): A. Pacwa, E. Gorowska-Wojtowicz, A. Ptak, P. Pawlicki, A. Milon, M. Sekula, K. Lesniak, B. Bilinska, A. Hejmej, M. Kotula-Balak
Estrogen-related receptors (ERRs) α, β and γ appear to be novel molecules implicated in estrogen signaling. We blocked and activated ERRs in mouse (C57BL/6) adrenals and adrenocortical cells (H295R) using pharmacological agents XCT 790 (ERRα antagonist) and DY131 (ERRβ/γ agonist), respectively. Mice were injected with XCT 790 or DY131 (5 μg/kg bw) while cells were exposed to XCT 790 or DY131 (0.5 μg/L). Irrespectively of the agent used, changes in adrenocortical cell morphology along with changes in lutropin, cholesterol levels and estrogen production were found. Diverse and complex ERRs regulation of multilevel-acting steroidogenic proteins (perilipin; PLIN, cytochrome P450 side-chain cleavage; P450scc, translocator protein; TSPO, steroidogenic acute regulatory protein; StAR, hormone sensitive lipase; HSL and HMG-CoA reductase; HMGCR) was revealed. Blockage of ERRα decreased P450scc, StAR and TSPO expressions. Activation of ERRβ/γ increased P450scc, StAR and HMGCR while decreased HSL expressions. PLIN expression increased either after XCT 790 or DY131 treatment. Additionally, treatment with both XCT 790 or DY131 decreased activity of Ras/Raf, Erk and Akt indicating their involvement in control of morphology and steroidogenic function of cortex cells. ERRs are important in maintaining morpho-function of cortex cells through action in specific, opposite, or common manner on steroidogenic molecules.



https://ift.tt/2sALfYV

Stereotactic radiation therapy in the strategy of treatment of metastatic renal cell carcinoma: A study of the Getug group

Publication date: July 2018
Source:European Journal of Cancer, Volume 98
Author(s): Emmanuel Meyer, David Pasquier, Guillemette Bernadou, Gilles Calais, Pierre Maroun, Alberto Bossi, Christine Theodore, Laurence Albiges, Dinu Stefan, Renaud D.E. Crevoisier, Christophe Hennequin, Jean-Léon Lagrange, Jean-Michel Grellard, Bénédicte Clarisse, Idlir Licaj, Jean-Louis Habrand, Christian Carrie, Florence Joly
BackgroundRenal cell carcinoma (RCC) is usually considered radioresistant, but stereotactic radiation therapy (SRT) may increase local disease control. This study aimed to assess the benefit of SRT in the management of metastatic RCC patients.MethodsData of all RCC patients who received SRT between 2008 and 2015 with curative intent were retrospectively collected in six French referral centres. Local control (LC), progression-free survival (PFS), local recurrence-free survival (LRFS), time to systemic therapy (TTS) and overall survival (OS) were assessed.ResultsOne hundred and eighty-eight patients treated with SRT for 252 RCC metastases (brain [n = 120]; spine [n = 75]; and others [n = 57]) were recensed. SRT was performed for oligoprogressive disease (101 patients), oligometastatic disease (80 patients) or residual tumour after a partial response to systemic treatment (7 patients). The median biologically effective dose was 78 Gy. For the whole population, local control rates at 6, 12 and 24 months were 87.5%, 82.9% and 77.6%, respectively; median PFS, LRFS, TTS and OS were 8.5, 23.2, 13.2 and 29.2 months, respectively. Among patients treated for oligoprogressive/oligometastatic disease, the median PFS, TTS, and OS were 8.6/7.6, 10.5/14.2 and 23.2/33.9 months, respectively. Among the 7 patients treated with SRT after partial response to systemic treatment, no relapse occurred for 3 of them after a median follow-up of 22 months. Acute and late severe toxicities were noted in 5 (2.6%) patients.ConclusionsSRT is effective and safe for oligometastatic and oligoprogressive RCC patients and may delay introduction or change of systemic therapy.



https://ift.tt/2szBg5Y

Biology, taxonomy, and IPM strategies of Bactrocera tau Walker and complex species (Diptera; Tephritidae) in Asia: a comprehensive review

Abstract

Bactrocera flies are the serious pests of fruit, vegetables, and nuts over the world. Bactrocera tau Walker is an economically important pest of agricultural crops. In Asia, approximately 30–40% losses of agricultural products are caused by B. tau infestation every year. In Asia, the B. tau contains a complex of sibling species that called the tau complex. However, the basic studies of B. tau and complex species are very important for integrated management. A comprehensive review of the B. tau and complex species has not been provided elsewhere. So, considering the importance of B. tau and complex species, this study provides the published information on ecology, nomenclature, identification tools, geographical distribution, potential invasion, and IPM tactics of B. tau and complex species, which would be more informative for publication facilitating related to integrated pest management (IPM) strategies of B. tau and complex species. In IPM of B. tau and complex species, the phytochemical and biological controls have not been applied successfully in Asia; there is an urgent need to study and applications of these two mentioned control techniques against the B. tau and complex species in Asia.

https://ift.tt/2Le7Im5

Monitoring system for investigating the effect of temperature change on optical properties

Abstract

Knowledge about the changes in optical properties is needed for planning safer and more accurate laser treatments. A monitoring system was developed to study how the optical properties of a lipid emulsion are affected by temperature changes. A double-integrating-sphere system is modified with a controlled heating apparatus to measure the temperature-dependent diffuse reflectance and total transmittance values. The absorption and reduced scattering coefficients were estimated from the reflectance and transmittance values using an inverse adding-doubling method. The total transmittance showed positive correlation with temperature while the diffuse reflectance was found to be negatively correlated. Although the absorption coefficient did not demonstrate a statistically significant change with temperature, the reduced scattering coefficient was negatively correlated. By using the obtained optical properties, Monte Carlo simulations were performed to observe the difference in light propagation within a tissue. The results indicate that temperature-dependent changes in optical properties should be taken into consideration for a safer laser treatment.

https://ift.tt/2JjooLT

Synthesis, Structure-Activity Relationship and Molecular Docking Studies of 3-O-Flavonol Glycosides as Cholinesterase Inhibitors

Publication date: Available online 1 June 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Ehsan Ullah Mughal, Asif Javid, Amina Sadiq, Shahzad Murtaza, Muhammad Naveed Zafar, Bilal Ahmad Khan, Sajjad Hussain Sumra, Muhammad Nawaz Tahir, Kanwal, Khalid Mohammed Khan
The prime objective of this research work is to prepare readily soluble synthetic analogues of naturally occurring 3-O-flavonol glycosides and then investigate the influence of various substituents on biological properties of synthetic compounds. In this context, a series of varyingly substituted 3-O-flavonol glycosides have been designed, synthesized and characterized efficiently. The structures of synthetic molecules were unambiguously corroborated by IR, ¹H-, ¹³C-NMR and ESI-MS spectroscopic techniques. The structure of compound 22 was also analyzed by X-ray diffraction analysis. All the synthetic compounds (21-30) were evaluated for in vitro inhibitory potential against cholinesterase enzymes. The results displayed that most of the derivatives were potent inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with varying degree of IC50 values. The experimental results were further encouraged by molecular docking studies in order to explore their binding behavior with the active pocket of AChE and BChE enzymes. The experimental and theoretical results are in parallel with one another.

Graphical abstract

https://ift.tt/2swqUE1

Synthesis and biological evaluation of novel N-substituted nipecotic acid derivatives with an alkyne spacer as GABA uptake inhibitors

Publication date: Available online 1 June 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Krisztián Tóth, Georg Höfner, Klaus T. Wanner
In this study, we present the synthesis and structure-activity relationships (SAR) of novel N–substituted nipecotic acid derivatives closely related to SNAP-5114 (2) in the pursuit of finding new and potent mGAT4 selective inhibitors. By the use of iminium ion chemistry, a series of new N-substituted nipecotic acid derivatives containing a variety of heterocycles, and an alkyne spacer were synthesized. Biological evaluation of the prepared compounds showed, how the inhibitory potency and subtype selectivity for the murine GABA transporters (mGATs) were influenced by the performed modifications.

Graphical abstract

https://ift.tt/2kLxkvH

Levels of retinal IAPP are altered in Alzheimer's disease patients and correlate with vascular changes and hippocampal IAPP levels

Publication date: September 2018
Source:Neurobiology of Aging, Volume 69
Author(s): Nina Schultz, Elin Byman, Malin Wennström
Islet amyloid polypeptide (IAPP) forms toxic aggregates in the brain of patients with Alzheimer's disease (AD). Whether IAPP also affects the retina in these patients is still unknown. Levels of IAPP in soluble and insoluble homogenate fractions of retina and hippocampus from AD patients and nondemented controls were analyzed using ELISA. Number of pericytes and vessel length were determined by analysis of immunostained retina and hippocampus. Insoluble retinal fractions of AD patients contained lower levels of unmodified IAPP, whereas soluble retinal fractions contained increased levels of the same. Total IAPP levels and pericyte numbers in retina mirrored corresponding variables in the hippocampus. Moreover, levels of total unmodified IAPP correlated negatively with the vessel length both in retina and hippocampus across the group and positively with pericyte numbers in retina in AD patients. Our studies indicate that changes in brain IAPP are reflected by corresponding levels in the retina. Our results also suggest modification of IAPP as an important event implicated in vascular changes associated with AD.



https://ift.tt/2sFLGkP

A simple and clinically relevant combination of neuroimaging and functional indexes for the identification of those at highest risk of Alzheimer's disease

Publication date: September 2018
Source:Neurobiology of Aging, Volume 69
Author(s): Hossein Tabatabaei-Jafari, Erin Walsh, Marnie E. Shaw, Nicolas Cherbuin
The current challenge in clinical practice is to identify those with mild cognitive impairment (MCI), who are at greater risk of Alzheimer's disease (AD) conversion in the near future. The aim of this study was to assess a clinically practical new hippocampal index—hippocampal volume normalized by cerebellar volume (hippocampus to cerebellum volume ratio) used alone or in combination with scores on the Mini–Mental State Examination, as a predictor of conversion from MCI to AD. The predictive value of the HCCR was also contrasted to that of the hippocampal volume to intracranial volume ratio. The findings revealed that the performance of the combination of measures was significantly better than that of each measure used individually. The combination of Mini–Mental State Examination and hippocampal volume, normalized by the cerebellum or by intracranial volume, accurately discriminated individuals with MCI who progress to AD within 5 years from other MCI types (stable, reverters) and those with intact cognition (area under receiver operating curve of 0.88 and 0.89, respectively). Normalization by cerebellar volume was as accurate as normalization by intracranial volume with the advantage of being more practical, particularly for serial assessments.



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Reciprocal relationships between daily sleep and mood: A systematic review of naturalistic prospective studies

An intimate relationship exists between sleep and affective states. Disturbances in sleep are common across a spectrum of psychopathologies, and are recognised as precipitating or prodromal factors for mood disorders. Conversely, affective states can impact sleep quality and ability to fall asleep. However, one of the main limitations of this literature is that studies have typically assessed sleep and mood at one time point and studies are often laboratory-based, where measurement of both sleep and mood has dubious ecological validity.

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Connecting the immune system, systemic chronic inflammation and the gut microbiome: The role of sex

Publication date: Available online 1 June 2018
Source:Journal of Autoimmunity
Author(s): Lisa Rizzetto, Francesca Fava, Kieran M. Tuohy, Carlo Selmi
Unresolved low grade systemic inflammation represents the underlying pathological mechanism driving immune and metabolic pathways involved in autoimmune diseases (AID). Mechanistic studies in animal models of AID and observational studies in patients have found alterations in gut microbiota communities and their metabolites, suggesting a microbial contribution to the onset or progression of AID. The gut microbiota and its metabolites have been shown to influence immune functions and immune homeostasis both within the gut and systematically. Microbial derived-short chain fatty acid (SCFA) and bio-transformed bile acid (BA) have been shown to influence the immune system acting as ligands specific cell signaling receptors like GPRCs, TGR5 and FXR, or via epigenetic processes. Similarly, intestinal permeability (leaky gut) and bacterial translocation are important contributors to chronic systemic inflammation and, without repair of the intestinal barrier, might represent a continuous inflammatory stimulus capable of triggering autoimmune processes. Recent studies indicate gender-specific differences in immunity, with the gut microbiota shaping and being concomitantly shaped by the hormonal milieu governing differences between the sexes. A bi-directional cross-talk between microbiota and the endocrine system is emerging with bacteria being able to produce hormones (e.g. serotonin, dopamine and somatostatine), respond to host hormones (e.g. estrogens) and regulate host hormones' homeostasis (e.g by inhibiting gene prolactin transcription or converting glucocorticoids to androgens). We review herein how gut microbiota and its metabolites regulate immune function, intestinal permeability and possibly AID pathological processes. Further, we describe the dysbiosis within the gut microbiota observed in different AID and speculate how restoring gut microbiota composition and its regulatory metabolites by dietary intervention including prebiotics and probiotics could help in preventing or ameliorating AID. Finally, we suggest that, given consistent observations of microbiota dysbiosis associated with AID and the ability of SCFA and BA to regulate intestinal permeability and inflammation, further mechanistic studies, examining how dietary microbiota modulation can protect against AID, hold considerable potential to tackle increased incidence of AID at the population level.



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The Revision Rhinoplasty Consult: The Art of Managing Expectations.

Facial plast Surg 2018; 34: 287-289
DOI: 10.1055/s-0038-1655734

Rhinoplasty is widely acknowledged to be a challenging operation. The success of the operation has long been measured in anecdotal ways. As the surgeon—do I think the outcome is good? Does the patient tell me they are happy? At hand is an obvious issue with patients sometimes not returning to their original doctor. Other times they may have minor concerns that take minimal effort to correct. Does that constitute a revision? In most circles, the ultimate definition of revision rhinoplasty is a return to surgery with the intent to correct a functional or aesthetic concern that arose after the original procedure.
[...]

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Functional Compromise in the Middle Vault in the Management of Revision Rhinoplasty

Facial plast Surg 2018; 34: 239-244
DOI: 10.1055/s-0038-1654677

As rhinoplasty procedures become more common, the need for revision surgeries increases as well. Unlike primary rhinoplasties, revision rhinoplasties can be more challenging because of anatomic differences from initial surgery, a lack of available cartilage, tissue remodeling responses, and other complications. As such, surgeons should be prepared to address revision rhinoplasty patients differently from primary rhinoplasty patients. Here, the authors describe a generalizable approach to revision functional rhinoplasty patients and detail some of the surgical techniques that can be employed to achieve optimal outcomes, with particular attention paid to procedures that can be used in the middle vault.
[...]

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Use of Translucent Template in the Reconstruction of Nasal Defects: A Novel Technique

Facial plast Surg 2018; 34: 339-340
DOI: 10.1055/s-0038-1653991

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Failure of Synthetic Implants: Strategies and Management

Facial plast Surg 2018; 34: 245-254
DOI: 10.1055/s-0038-1654676

Dorsal augmentation with synthetic implants is the most commonly performed rhinoplasty procedure, especially in the East-Asian region. However, as in all other surgical procedures, complications are inevitable. Complications that need to be managed surgically include displacement, deviation, suboptimal aesthetic outcome, extrusion, inflammation, infection, and changes in skin quality. Most complications can be easily managed with revision surgery. After the removal of the synthetic implant from the nasal dorsum, different dorsal implant materials such as dermofat, alloderm, or fascia-wrapped diced cartilage, conchal cartilage with perichondrial attachment, and costal cartilage are preferred. An irreversible change in the skin/soft tissue envelope poses a challenge that usually requires reconstructive surgery with a local flap. Therefore, early detection and prompt management of the complication are essential for minimizing the severity of the deformity and the complexity of the surgical procedures.
[...]

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Bilateral Tessier Type 3 Cleft—Repairment in a Single Session

Facial plast Surg 2018; 34: 335-336
DOI: 10.1055/s-0038-1653985

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The Twisted Nose: What to Do When It's Not Straight

Facial plast Surg 2018; 34: 255-260
DOI: 10.1055/s-0038-1653987

Septorhinoplasty is among the most common facial plastic and reconstructive surgeries and its complexities are reflected in a relatively high revision rate. The patient with a postoperative twisted nose presents an additional challenge and requires that the surgeon display empathy and possess a deep knowledge of the aesthetic and functional intricacies of the nose. Correction of the twisted nose should be approached in a systematic fashion with unique considerations for each "third" of the nose. While there are many options in the overall surgical armamentarium, each surgeon will find specific techniques that are most efficacious and reproducible for their individual practice. This article discusses select surgical "pearls" and techniques that can aid the surgeon in their own surgical decision-making.
[...]

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Dissatisfaction with Nasal Tip Shape: Secondary Tip Maneuvers

Facial plast Surg 2018; 34: 278-286
DOI: 10.1055/s-0038-1653988

Dissatisfaction with the appearance of the nasal tip is a common compliant in patients seeking revision surgery after rhinoplasty. Revision rhinoplasty is more technically difficult and unpredictable given the frequent presence of scar contracture, impaired skin envelope quality, and missing alar cartilage. This article describes some of the more common causes for tip revision surgery and techniques to address these abnormalities.
[...]

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Dorsal Failures: From Saddle Deformity to Pollybeak

Facial plast Surg 2018; 34: 261-269
DOI: 10.1055/s-0038-1653990

The nasal dorsum is an important component of a rhinoplasty and may be the primary motivation for seeking surgery. The nasal dorsum is a complex three-dimensional shape that is shrouded by local anesthetic and edema during surgery. This makes an accurate assessment of the surgical changes challenging. Complications related to dorsal modification include imbalances from over- or underresection of the structures of the nasal dorsum, inadequate or overaugmentation, an open-roof deformity, pollybeak, saddle nose, inverted-V, warped cartilage, visible grafts, contour problems, graft malposition, and extrusion. This review will discuss the common problems that can occur with dorsal modification during rhinoplasty.
[...]

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Cleft Rhinoplasty: Strategies for the Multiply Operated Nose

Facial plast Surg 2018; 34: 290-297
DOI: 10.1055/s-0038-1653986

Rhinoplasty, as a surgical procedure to improve the appearance of the nose while preserving or improving function, is complicated and difficult to master. Revision cleft rhinoplasty offers another tier of challenge. The symmetry, proportions, and definition of the nose are affected by the native cleft deformity but also previous surgical scars, cartilage grafts, and skin excisions. Our preferred approach is to use structural cartilage grafting to establish septal and lower lateral cartilage resiliency. Internal lining deficiency is addressed with skin or lining transfer, while excess nasal tip thickness is contoured to improve definition. Of the utmost importance, the cleft nasal deformity cannot be considered in isolation, but rather a combined amalgamation of the lip muscle and scar, dentofacial occlusion, and skeletal maxillary deficiency.
[...]

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The Art of Camouflage: When Can a Revision Rhinoplasty Be Nonsurgical?

Facial plast Surg 2018; 34: 270-277
DOI: 10.1055/s-0038-1653989

Rhinoplasty surgery is known to have revision rates up to 20%. Surgical revisions include the risk of anesthesia and scarring. The skilled injector may offer nonsurgical alternatives to patients when considering revision surgery. Injections can be done to improve symmetry or improve/camouflage deformities that are possibly too minor for surgery but bothersome to the patient. Injections can be performed using different filler materials, but these treatments also carry inherent risks.
[...]

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Surgical Tips for the Management of the Wide Nasal Base

Facial plast Surg 2018; 34: 337-338
DOI: 10.1055/s-0038-1653984

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Rhinoplasty: Why Do Revisions Still Occur?

Facial plast Surg 2018; 34: 237-238
DOI: 10.1055/s-0038-1654678

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Satisfaction with Facial Appearance and Quality of Life after Treatment of Face Scars with a Transparent Facial Pressure Mask

Facial plast Surg
DOI: 10.1055/s-0038-1648249

Treatment of facial hypertrophic scars and deformities has developed from the use of elastic fabric hoods to transparent facemasks. The clinical effects of these masks have been described. However, the psychological impact of wearing such a mask is not well documented. The aim of this study was to assess patients' satisfaction with their current facial appearance, to assess the end result of facemask therapy, and to assess the decision to have undergone facemask therapy by means of four different FACE-Q questionnaires. Out of the eligible 87 patients who completed the facemask therapy between January 2012 and November 2017, 42 filled out the questionnaires. These patients wore a custom-fabricated facemask because of facial hypertrophic scars and severe postsurgical facial irregularities. Patients who wore the mask 12 to 16 hours per day were significantly more satisfied with the end result compared with those who wore it 4 to 8 hours daily. Also, patients who wore the mask 8 to 12 and 12 to 16 hours each day were more satisfied to have undergone therapy compared with those who wore it 4 to 8 hours daily. Furthermore, patients who finished therapy 3 to 4 years and 4 to 5 years ago reported a significant higher satisfaction with facial appearance compared with those who completed therapy in a time period shorter than 1 year ago. Patients who finished therapy 3 to 4 years ago reported higher satisfaction with their facial appearance compared with those who finished therapy 2 to 3 years ago. Additionally, the Patient and Observer Scar Assessments Score (POSAS) showed a significant reduction between start and end of therapy. This study shows facemask therapy to result in long-lasting stable results. It also shows a longer daily wearing of the facemask to result in the highest satisfaction according to patients.
[...]

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Go with the Flow: Cerebrospinal Fluid Flow Regulates Neural Stem Cell Proliferation

Publication date: 1 June 2018
Source:Cell Stem Cell, Volume 22, Issue 6
Author(s): Naoko Kaneko, Kazunobu Sawamoto
Adult neural stem cells in the wall of brain ventricles make direct contact with cerebrospinal fluid. In this issue of Cell Stem Cell, Petrik et al. (2018) demonstrate that these neural stem cells sense the flow of cerebrospinal fluid through a transmembrane sodium channel, ENaC, which regulates their proliferation.

Teaser

Adult neural stem cells in the wall of brain ventricles make direct contact with cerebrospinal fluid. In this issue of Cell Stem Cell, Petrik et al. (2018) demonstrate that these neural stem cells sense the flow of cerebrospinal fluid through a transmembrane sodium channel, ENaC, which regulates their proliferation.


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Intestinal Stem Cell Dynamics: A Story of Mice and Humans

Publication date: 1 June 2018
Source:Cell Stem Cell, Volume 22, Issue 6
Author(s): Michael C. Hodder, Dustin J. Flanagan, Owen J. Sansom
Stem cell dynamics define the probability of accumulating mutations within the intestinal epithelium. In this issue of Cell Stem Cell, Nicholson et al. (2018) report that human intestinal stem cell dynamics differ significantly from those of mice and establish that oncogenic mutations are more likely to expand; therefore, "normal" epithelium may carry multiple mutations.

Teaser

Stem cell dynamics define the probability of accumulating mutations within the intestinal epithelium. In this issue of Cell Stem Cell, Nicholson et al. (2018) report that human intestinal stem cell dynamics differ significantly from those of mice and establish that oncogenic mutations are more likely to expand; therefore, "normal" epithelium may carry multiple mutations.


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Lnc’ed in to Cardiogenesis

Publication date: 1 June 2018
Source:Cell Stem Cell, Volume 22, Issue 6
Author(s): Makoto Sahara, Elif Eroglu, Kenneth R. Chien
Despite the continuous discovery of long noncoding RNAs (lncRNAs) with critical developmental roles, our knowledge of lncRNAs that control cardiac lineage commitment is still limited. In this issue, Guo et al. (2018) report a novel lncRNA-mediated multiprotein complex assembly that directly regulates the key transcriptional programs of murine cardiogenesis.

Teaser

Despite the continuous discovery of long noncoding RNAs (lncRNAs) with critical developmental roles, our knowledge of lncRNAs that control cardiac lineage commitment is still limited. In this issue, Guo et al. (2018) report a novel lncRNA-mediated multiprotein complex assembly that directly regulates the key transcriptional programs of murine cardiogenesis.


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Stem-Cell-Derived Cardiomyocytes Grow Up: Start Young and Train Harder

Publication date: 1 June 2018
Source:Cell Stem Cell, Volume 22, Issue 6
Author(s): Joshua T. Maxwell, Chunhui Xu
Engineering cardiac tissue that accurately recapitulates adult myocardium is critical for advancing disease modeling, drug screening, and regenerative medicine. Ronaldson-Bouchard et al. report a new strategy for generating cardiac tissues from stem-cell-derived cardiomyocytes that reach a maturation level closer to human adult cardiac structure and function.

Teaser

Engineering cardiac tissue that accurately recapitulates adult myocardium is critical for advancing disease modeling, drug screening, and regenerative medicine. Ronaldson-Bouchard et al. report a new strategy for generating cardiac tissues from stem-cell-derived cardiomyocytes that reach a maturation level closer to human adult cardiac structure and function.


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Spotlight on Glycolysis: A New Target for Cord Blood Expansion

Publication date: 1 June 2018
Source:Cell Stem Cell, Volume 22, Issue 6
Author(s): Andrea M. Patterson, Louis M. Pelus
Umbilical cord blood (UCB) is a highly valuable but low-quantity source of hematopoietic stem cells (HSCs) for life-saving transplantations. Recently in Nature Medicine, Guo et al. (2018) found that antagonism of a glycolysis-blocking pathway enhances ex vivo expansion of long-term HSCs from human UCB.

Teaser

Umbilical cord blood (UCB) is a highly valuable but low-quantity source of hematopoietic stem cells (HSCs) for life-saving transplantations. Recently in Nature Medicine, Guo et al. (2018) found that antagonism of a glycolysis-blocking pathway enhances ex vivo expansion of long-term HSCs from human UCB.


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Stem Cells in the Clinic

Publication date: 1 June 2018
Source:Cell Stem Cell, Volume 22, Issue 6
Author(s): Sheila Chari, Anh Nguyen, Jonathan Saxe




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Mentoring the Next Generation: Janet Rossant

Publication date: 1 June 2018
Source:Cell Stem Cell, Volume 22, Issue 6

Mentor-mentee relationships are essential for professional development, but developing these interpersonal skills is not often highlighted as a priority in scientific endeavors. In a yearlong series, Cell Stem Cell interviews prominent scientists who have prioritized mentorship over the years. Here, we chat with Dr. Janet Rossant about her views.



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Ask the Expert: Luigi Naldini

Publication date: 1 June 2018
Source:Cell Stem Cell, Volume 22, Issue 6

New technologies are revolutionizing the potential of hematopoietic stem cell transplantation (HSCT) to effectively treat many hematologic disorders and malignancies. Here we chat with Dr. Luigi Naldini about the remaining challenges for successful transplantation, cutting-edge new technologies, and what exciting breakthroughs he looks forward to seeing on the horizon.



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CIRM Alpha Stem Cell Clinics: Collaboratively Addressing Regenerative Medicine Challenges

Publication date: 1 June 2018
Source:Cell Stem Cell, Volume 22, Issue 6
Author(s): Catriona H.M. Jamieson, Maria T. Millan, Abla A. Creasey, Geoff Lomax, Mary E. Donohoe, Mark C. Walters, Mehrdad Abedi, Daniela A. Bota, John A. Zaia, John S. Adams
The California Institute for Regenerative Medicine (CIRM) Alpha Stem Cell Clinic (ASCC) Network was launched in 2015 to address a compelling unmet medical need for rigorous, FDA-regulated, stem cell-related clinical trials for patients with challenging, incurable diseases. Here, we describe our multi-center experiences addressing current and future challenges.

Teaser

The California Institute for Regenerative Medicine (CIRM) Alpha Stem Cell Clinic (ASCC) Network was launched in 2015 to address a compelling unmet medical need for rigorous, FDA-regulated, stem cell-related clinical trials for patients with challenging, incurable diseases. Here, we describe our multi-center experiences addressing current and future challenges.


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Organoid Center Strategies for Accelerating Clinical Translation

Publication date: 1 June 2018
Source:Cell Stem Cell, Volume 22, Issue 6
Author(s): Takanori Takebe, James M. Wells, Michael A. Helmrath, Aaron M. Zorn
The meteoric rise in stem-cell-derived organoid technologies has ushered in a new era of "organoid medicine." Here we discuss how an organoid center can accelerate the translation of laboratory proof-of-principle experiments into clinical practice by developing and utilizing shared platforms for commercial and medical applications.

Teaser

The meteoric rise in stem-cell-derived organoid technologies has ushered in a new era of "organoid medicine." Here we discuss how an organoid center can accelerate the translation of laboratory proof-of-principle experiments into clinical practice by developing and utilizing shared platforms for commercial and medical applications.


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Stem Cell Therapies for Treating Diabetes: Progress and Remaining Challenges

Publication date: 1 June 2018
Source:Cell Stem Cell, Volume 22, Issue 6
Author(s): Julie B. Sneddon, Qizhi Tang, Peter Stock, Jeffrey A. Bluestone, Shuvo Roy, Tejal Desai, Matthias Hebrok
Restoration of insulin independence and normoglycemia has been the overarching goal in diabetes research and therapy. While whole-organ and islet transplantation have become gold-standard procedures in achieving glucose control in diabetic patients, the profound lack of suitable donor tissues severely hampers the broad application of these therapies. Here, we describe current efforts aimed at generating a sustainable source of functional human stem cell-derived insulin-producing islet cells for cell transplantation and present state-of-the-art efforts to protect such cells via immune modulation and encapsulation strategies.

Teaser

Sneddon et al. describe current efforts aimed at generating a sustainable source of functional human stem cell-derived insulin-producing islet cells for cell transplantation for the treatment of diabetes and present state-of-the-art efforts to protect such cells via immune modulation and encapsulation strategies.


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Mesenchymal Stromal Cells: Clinical Challenges and Therapeutic Opportunities

Publication date: 1 June 2018
Source:Cell Stem Cell, Volume 22, Issue 6
Author(s): Jacques Galipeau, Luc Sensébé
Mesenchymal stromal cells (MSCs) have been the subject of clinical trials for more than a generation, and the outcomes of advanced clinical trials have fallen short of expectations raised by encouraging pre-clinical animal data in a wide array of disease models. In this Perspective, important biological and pharmacological disparities in pre-clinical research and human translational studies are highlighted, and analyses of clinical trial failures and recent successes provide a rational pathway to MSC regulatory approval and deployment for disorders with unmet medical needs.

Teaser

In this Perspective, Galipeau and Sensébé highlight important biological and pharmacological disparities in pre-clinical research and human translational studies. The authors also analyze clinical trial failures and recent successes to discuss a rational pathway toward MSC regulatory approval and deployment for disorders with unmet medical needs.


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Regenerating Eye Tissues to Preserve and Restore Vision

Publication date: 1 June 2018
Source:Cell Stem Cell, Volume 22, Issue 6
Author(s): Jeffrey H. Stern, Yangzi Tian, James Funderburgh, Graziella Pellegrini, Kang Zhang, Jeffrey L. Goldberg, Robin R. Ali, Michael Young, Yubing Xie, Sally Temple
Ocular regenerative therapies are on track to revolutionize treatment of numerous blinding disorders, including corneal disease, cataract, glaucoma, retinitis pigmentosa, and age-related macular degeneration. A variety of transplantable products, delivered as cell suspensions or as preformed 3D structures combining cells and natural or artificial substrates, are in the pipeline. Here we review the status of clinical and preclinical studies for stem cell-based repair, covering key eye tissues from front to back, from cornea to retina, and including bioengineering approaches that advance cell product manufacturing. While recognizing the challenges, we look forward to a deep portfolio of sight-restoring, stem cell-based medicine.Video Abstract

Teaser

Stern et al. review the status of clinical and preclinical studies for stem cell-based repair, covering key eye tissues from front to back, from cornea to retina, and including bioengineering approaches that advance cell product manufacturing.


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A First-in-Human, Phase I Study of Neural Stem Cell Transplantation for Chronic Spinal Cord Injury

Publication date: 1 June 2018
Source:Cell Stem Cell, Volume 22, Issue 6
Author(s): Erik Curtis, Joel R. Martin, Brandon Gabel, Nikki Sidhu, Teresa K. Rzesiewicz, Ross Mandeville, Sebastiaan Van Gorp, Marjolein Leerink, Takahiro Tadokoro, Silvia Marsala, Catriona Jamieson, Martin Marsala, Joseph D. Ciacci
We tested the feasibility and safety of human-spinal-cord-derived neural stem cell (NSI-566) transplantation for the treatment of chronic spinal cord injury (SCI). In this clinical trial, four subjects with T2–T12 SCI received treatment consisting of removal of spinal instrumentation, laminectomy, and durotomy, followed by six midline bilateral stereotactic injections of NSI-566 cells. All subjects tolerated the procedure well and there have been no serious adverse events to date (18–27 months post-grafting). In two subjects, one to two levels of neurological improvement were detected using ISNCSCI motor and sensory scores. Our results support the safety of NSI-566 transplantation into the SCI site and early signs of potential efficacy in three of the subjects warrant further exploration of NSI-566 cells in dose escalation studies. Despite these encouraging secondary data, we emphasize that this safety trial lacks statistical power or a control group needed to evaluate functional changes resulting from cell grafting.

Graphical abstract

Teaser

After promising results were seen in a pre-clinical human-spinal-cord-derived neural stem cell NSI-566 transplantation study for spinal cord injury in rats, a phase I clinical trial for NSI-566 transplantation was initiated in patients with complete thoracic SCI.


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Phase I Trial: Cirmtuzumab Inhibits ROR1 Signaling and Stemness Signatures in Patients with Chronic Lymphocytic Leukemia

Publication date: 1 June 2018
Source:Cell Stem Cell, Volume 22, Issue 6
Author(s): Michael Y. Choi, George F. Widhopf, Emanuela M. Ghia, Reilly L. Kidwell, Md Kamrul Hasan, Jian Yu, Laura Z. Rassenti, Liguang Chen, Yun Chen, Emily Pittman, Minya Pu, Karen Messer, Charles E. Prussak, Januario E. Castro, Catriona Jamieson, Thomas J. Kipps
Cirmtuzumab is a humanized monoclonal antibody (mAb) that targets ROR1, an oncoembryonic orphan receptor for Wnt5a found on cancer stem cells (CSCs). Aberrant expression of ROR1 is seen in many malignancies and has been linked to Rho-GTPase activation and cancer stem cell self-renewal. For patients with chronic lymphocytic leukemia (CLL), self-renewing, neoplastic B cells express ROR1 in 95% of cases. High-level leukemia cell expression of ROR1 is associated with an unfavorable prognosis. We conducted a phase 1 study involving 26 patients with progressive, relapsed, or refractory CLL. Patients received four biweekly infusions, with doses ranging from 0.015 to 20 mg/kg. Cirmtuzumab had a long plasma half-life and did not have dose-limiting toxicity. Inhibition of ROR1 signaling was observed, including decreased activation of RhoA and HS1. Transcriptome analyses showed that therapy inhibited CLL stemness gene expression signatures in vivo. Cirmtuzumab is safe and effective at inhibiting tumor cell ROR1 signaling in patients with CLL.

Graphical abstract

Teaser

Choi et al. find that cirmtuzumab, a humanized mAb specific for the cancer stem cell antigen ROR1, was well tolerated and stable in clinical testing in patients with relapsed chronic lymphocytic leukemia. Treatment inhibited activation of Rho-GTPase and HS1 in vivo and reversed the stemness gene expression signatures in leukemia cells.


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Food-induced Anaphylaxis in Infants and Children

Publication date: Available online 1 June 2018
Source:Annals of Allergy, Asthma & Immunology
Author(s): Waheeda Samady, Jennifer Trainor, Bridget Smith, Ruchi Gupta
BackgroundRecent recommendations to introduce peanut products to infants for peanut allergy prevention requires a focused assessment of infant anaphylaxis.ObjectiveThis study describes the symptomatology of food-induced anaphylaxis (FIA) in infants (<12 months) compared to older pediatric cohorts.MethodsRetrospective review between June 2015 and June 2017 of children presenting with FIA at a large urban children's hospital emergency department (ED).ResultsA total of 357 cases of FIA were evaluated: 47 in infants (<12 months), 43 in toddlers (12 to 24 months), 96 in young children (2 to 6 years), and 171 in school-aged children (>6 years). Infants presented with gastrointestinal (GI) involvement more frequently than any other age group (89% vs 63% [P = .003], 60% [P <.001], and 58% [P <.001]). Additionally, infants and young children presented with skin involvement more frequently than school-aged children (94% and 91% vs 62% [P <.001]). Respiratory symptoms were more common in older cohorts (17% in infants vs 44% in young children [P <.001] and 54% in school-aged children [P <.001]). Egg and cow's milk were more common causes of FIA in infants compared to school-aged children (egg, 38% vs 1% [P <.001]; milk, 17% vs 7% [P =.03]). Only 21% of infants with FIA had eczema and 36% had a history of food allergy.ConclusionInfants with FIA primarily presented with GI and skin manifestations. Egg was the most common food trigger in infants. Most infants with FIA did not have eczema or a history of food allergy.



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Changes in chronic rhinosinusitis symptoms differentially associate with improvement in general health-related quality of life

Publication date: Available online 1 June 2018
Source:Annals of Allergy, Asthma & Immunology
Author(s): Marlene M. Speth, Lloyd P. Hoehle BA, Katie M. Phillips, David S. Caradonna, Stacey T. Gray, Ahmad R. Sedaghat




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Are there different subtypes of eosinophilic esophagitis?

Publication date: Available online 1 June 2018
Source:Annals of Allergy, Asthma & Immunology
Author(s): Jay Adam Lieberman




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Bedroom Exposure to Airborne Allergens in the Chicago Area Using a Patient-Operated Sampling Device

Publication date: Available online 1 June 2018
Source:Annals of Allergy, Asthma & Immunology
Author(s): Julian Gordon, Paul Detjen, Sai Nimmagadda, Laura Rogers, Sanjay Patel, James Thompson, Rachel Reboulet, Prasanthi Gandhi
Background: In current practice, allergens in vacuum collected dust are used as surrogates for inhalable allergens. We developed an airsampling device that can be used by patients themselves for direct measurement of airborne allergen concentrations in their own homes.Objective: To demonstrate the use of this device to establish allergen concentration reference ranges in a target population. To evaluate relationships of patient-reported information to measured allergen concentrations.Methods: Patients from 5 allergist's practices in the Chicagoland region were provided with instructions, questionnaire, informed consent forms and samplers to run for 5 days in their bedrooms. Samples were collected from cartridges and assayed by multiplex immunoassays for 12 common household allergens and ELISA for ragweed.Results: Unique allergen profiles were obtained for 102 patient homes. Samples with allergen concentrations above the limit of detection were: total dust mite: 28%; cat, 61%; dog, 64%; mouse, 12%; rat, 0%; cockroach, 4%; Alternaria, 6%; Aspergillus, 21%; birch pollen 1%; grass, 8%; ragweed, 5%. Of those, 75 completed questionnaires, providing meta-data for further analysis. Pet allergens correlated significantly with number of pets owned. Humidity correlated with dust mite allergens, open windows with Alternaria and mouse allergens, HEPA filter use with reduced levels of several allergens. Many other variables showed no significant correlations.Conclusion: The combination of ease of use, high air sampling rate and sensitive immunoassays permitted the measurement of airborne allergens concentrations in homes and establishment of reference ranges. Patientreported information permitted identification of factors that could relate to allergen concentrations and suggest remedial measures.



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Static Measurements of Vowel Formant Frequencies and Bandwidths: A Review

Publication date: Available online 1 June 2018
Source:Journal of Communication Disorders
Author(s): Raymond D. Kent, Houri K. Vorperian
PurposeData on vowel formants have been derived primarily from static measures representing an assumed steady state. This review summarizes data on formant frequencies and bandwidths for American English and also addresses (a) sources of variability (focusing on speech sample and time sampling point), and (b) methods of data reduction such as vowel area and dispersion.MethodSearches were conducted with CINAHL, Google Scholar, MEDLINE/PubMed, SCOPUS, and other online sources including legacy articles and references. The primary search items were vowels, vowel space area, vowel dispersion, formants, formant frequency, and formant bandwidth.ResultsData on formant frequencies and bandwidths are available for both sexes over the lifespan, but considerable variability in results across studies affects even features of the basic vowel quadrilateral. Origins of variability likely include differences in speech sample and time sampling point. The data reveal the emergence of sex differences by 4 years of age, maturational reductions in formant bandwidth, and decreased formant frequencies with advancing age in some persons. It appears that a combination of methods of data reduction provide for optimal data interpretation.ConclusionThe lifespan database on vowel formants shows considerable variability within



https://ift.tt/2sD7XzI

The extent of vestibular impairment is important in recovery of canal paresis of patients with vestibular neuritis

We questioned whether the extent of vestibular impairment affected the recovery of vestibular function in acute vestibular neuritis (VN). The objective of this study was to identify how the extent of vestibular impairment influenced the recovery from canal paresis (CP) in patients with VN.

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Reply to: comment on “Liquid nitrogen cryotherapy for chronic recalcitrant interdigital candidiasis of toe-spaces – an uncontrolled pilot study”

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About melanocyte activation in idiopathic guttate hypomelanosis by 5-fluorouracil tattooing

https://ift.tt/2J5wRio

Folliculitis Decalvans: Effectiveness of Therapies and Prognostic Factors In A Multicenter Series of 60 Patients With Long-Term Follow-Up

https://ift.tt/2snKjI8

Safety and efficacy of hydrogen peroxide topical solution, 40% (w/w) in patients with seborrheic keratoses: results from two identical, randomized, double-blind, placebo-controlled, phase 3 studies (A-101-SEBK-301/302)

Capsule Summary

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Influence of age and marital status on stage at diagnosis and survival of patients with Merkel cell carcinoma: a SEER based cohort study

https://ift.tt/2J310CR

A cross-sectional study of clinical distinctions between neuropathic and inflammatory pruritus

https://ift.tt/2xzmTUW

REPLY to MS#JAAD-D-18-00380

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“Soft corn versus Candidiasis!”

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A systematic review and meta-analysis of the prevalence and phenotype of adult-onset atopic dermatitis

Previous studies found conflicting results about whether atopic dermatitis (AD) begins in adulthood.

https://ift.tt/2sr9eu9

Microscopic morphology and seasonal variation of health effect arising from heavy metals in PM2.5 and PM10: One-year measurement in a densely populated area of urban Beijing

Publication date: 1 November 2018
Source:Atmospheric Research, Volume 212
Author(s): Yang Gao, Hongbing Ji
In order to study the sustained impact of particulate matter on urban residents, 572 PM2.5 and PM10 samples in all were attained simultaneously from a densely populated area of Beijing from September 2015 to August 2016. 11 types of heavy metals were determined as to better ascertain the seasonal variation characteristics of particle composition. In the course of the year, the mean concentrations of PM2.5 and PM10 were detected to be 102.45 μg m⁻³ and 144.75 μg m⁻³, respectively. From general perspective, winter turned out to be the longest in haze day quantity and the highest in particle concentration, followed by spring, autumn and summer, successively. The mass concentrations of numerous PM2.5 elements fluctuated evidently in the decreasing order of Ba, Zn, Mn, Sr, Cu, Pb, Cr, V, Ni, Cd and Sb. In contrast with other seasons, winter displayed the most evident increase of metal content in particulates, especially under the condition of haze. Relationship between different size particles was also reckoned with in this study. High concentration ratio of PM2.5 and PM10 (0.76–0.84) was detected during haze period, and PM2.5 was accounted as a primary pollutant during haze-fog day in Beijing. Moreover, the carcinogenic and non-carcinogenic risk posed by detected heavy metals was investigated. Cr posed the highest carcinogenic risk, and in the meantime, as compared with other non-carcinogenic metals, value of Pb was the highest in Hazard Quotient. Risk arising from Cr and Cd in winter shall be noteworthy, and accordingly it may pose danger or potential risk to adults in haze days. Eventually, a large amount of fly ash and soot particles in winter samples were indicated from SEM-EDX analysis results, whereas those are rarely detected in summer samples.

Graphical abstract

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The transformation behaviors of heavy metals and dewaterability of sewage sludge during the dual conditioning with Fe2+-sodium persulfate oxidation and rice husk

Publication date: October 2018
Source:Chemosphere, Volume 208
Author(s): Qiao Xiong, Min Zhou, Mengjia Liu, Shijie Jiang, Haobo Hou
This study focused on the behavior of heavy metals (HMs) in sewage sludge after conditioning based on total HMs concentration, fractionation and leaching tests. Fe²⁺-sodium persulfate (SPS) oxidation was applied as chemical conditioner and rice husk (RH) was added as a physical conditioner to improve the dewaterability of sewage sludge. Combined the response surface methodology analysis and our previous research, the capillary suction time (CST) and the water content of sludge cake reduced by 93.8% and 25%, respectively, after conditioned by 125 mg g⁻¹ dry solid (DS) SPS, 33 mg g⁻¹ DS Fe²⁺, 333 mg g⁻¹ DS RH at original pH of sludge. The HMs analysis indicated that the concentrations of Cu, Pb, Cd, Zn and Cr were increased in liquid phase after conditioning process. And after conditioned by Fe²⁺/SPS with RH, the leaching toxicity reduction are 79%, 100%, 93%, 80% and 68% for Cu, Pb, Cd, Zn and Cr, respectively. Results showed that RH combined with Fe²⁺/SPS oxidation has a synergistic effect on risk reduction and immobilization of HMs. The chemical species of HMs were redistributed and the risk of Pb was reduced from medium risk to no risk after sludge conditioning process according to the risk assessment.



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Synthesis and characterization of zinc substituted magnetite nanoparticles and their application to magneto-motive ultrasound imaging

Publication date: 1 November 2018
Source:Journal of Magnetism and Magnetic Materials, Volume 465
Author(s): Yaser Hadadian, Diego R.T. Sampaio, Ana P. Ramos, Antonio A.O. Carneiro, Morteza Mozaffari, Luciana C. Cabrelli, Theo Z. Pavan
Biomedical application of magnetic nanoparticles is a rapidly growing research field. For medical diagnostic purposes, these nanoparticles are mostly used as imaging contrast agents. Magneto-motive ultrasound (MMUS) is an example of imaging techniques where superparamagnetic nanoparticles are used as contrast agent. Since it is a relatively new technique, much research is yet in progress to optimize the magnetic properties of these contrast agents. In this study, Zn-substituted magnetic (nominal composition ZnxFe1−xFe2O4, x = 0.0, 0.1, 0.2, 0.3 and 0.4) nanoparticles with aim of enhancing the saturation magnetization were successfully synthesized by the coprecipitation method. The effect of zinc on morphology, structure and magnetic properties of the prepared nanoparticles was studied and their potential for MMUS imaging was investigated. X-Ray diffraction results showed that all samples had spinel structure and incorporating zinc in magnetite structure led to an increase in its lattice parameter, on the other hand TEM images revealed that particle size was decreased with zinc concentration. EDX analysis of the samples confirmed the incorporation of zinc in magnetite structure with a relatively good agreement with nominal values. Low, room and high temperature magnetic properties of the samples were investigated using vibrating sample magnetometer (VSM). Room temperature M-H curves along with zero-field-cooling measurements showed all samples were superparamagnetic and saturation magnetization at x = 0.1 zinc concentration increased drastically. All prepared samples were examined as contrast agents in MMUS imaging and the results confirmed the direct role of magnetization in enhancement of MMUS signals.



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Growth, the Mediterranean diet and the buying power of adolescents in Greece

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


https://ift.tt/2Hdkq29

Removal efficiency and enzymatic mechanism of dibutyl phthalate (DBP) by constructed wetlands

Abstract

Four vertical-flow constructed wetland systems were set up in the field in order to study the removal efficiency and possible enzymatic mechanism of the constructed wetlands in treating sewage containing different concentrations of dibutyl phthalate (DBP). Under DBP spiked concentrations of 0.5, 1.0, and 2.0 mg/L, good DBP removal rates of 62.08, 82.17, and 84.17% were achieved, respectively. Meanwhile, certain removal effects of general water quality parameters were observed in all four constructed wetlands: with high average removal rates of nitrate nitrogen (NO₃⁻-N) and chemical oxygen demand (COD) of 91.10~93.89 and 82.83~89.17%, respectively, with moderate removal efficiencies of total nitrogen (TN), total phosphorus (TP), ammonia nitrogen (NH₄⁺-N) of 44.59~49.67, 30.58~37.18, and 28.52~37.45%, respectively. Compared to the control, an increase of enzyme activities of urease, phosphatase, dehydrogenase, and nitrate reductase was observed in the treatments with DBP addition. In the presence of 0.5 mg/L of DBP concentration, the urease, phosphatase, and dehydrogenase activities reached the highest levels, with an increase of 350.02, 36.57, and 417.88% compared with the control, respectively. It appeared that the low concentration of DBP might better stimulate the release of enzymes.

https://ift.tt/2LOYii4

Post-Partum Thrombotic Thrombocytopenic Purpura (TTP) in a Patient with known Idiopathic (Immune) Thrombocytopenic Purpura: a case report and review of the literature

Incidences of immune thrombocytopenic purpura occur in 1 in every 1000–10,000 pregnancies accounting for 3% of all thrombocytopenic pregnancies. A pre-existing immune thrombocytopenic purpura is known to be a ...

https://ift.tt/2kEuXue

Postpartum acute fatty liver of pregnancy: a case report

Acute fatty liver of pregnancy can be a very dramatic clinical event with significant risk of mortality to healthy women. The pathogenesis is still unknown. It usually occurs in the third trimester or in the i...

https://ift.tt/2HckbED

Clinical data supporting a 2-dose schedule of MenB-FHbp, a bivalent meningococcal serogroup B vaccine, in adolescents and young adults

Publication date: Available online 1 June 2018
Source:Vaccine
Author(s): Johannes Beeslaar, Judith Absalon, Paul Balmer, Amit Srivastava, Roger Maansson, Laura J. York, John L. Perez
Invasive meningococcal disease (IMD) caused by Neisseria meningitidis is a potentially devastating condition that can result in death and is associated with serious long-term sequelae in survivors. Vaccination is the preferred preventative strategy. Quadrivalent polysaccharide-based vaccines that protect against infection caused by meningococcal serogroups A, C, W, and Y are not effective against meningococcal serogroup B (MenB), which was responsible for approximately 60% and 35% of confirmed IMD cases in the European Union and the United States in 2016, respectively. A recombinant protein MenB vaccine (MenB-FHbp [bivalent rLP2086; Trumenba®]) has been approved for protection against MenB infection in persons 10–25 years of age in the United States and Canada and for individuals ≥10 years of age in the European Union and Australia. In these regions, MenB-FHbp is approved as a 2- or 3-dose primary vaccination schedule. This report will review the current evidence supporting administration of MenB-FHbp as a 2-dose primary vaccination schedule. Different contexts in which a 2- or 3-dose primary vaccination schedule might be preferred (eg, routine prospective vaccination vs outbreak control) are reviewed.



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Meetings of Interest

Publication date: June 2018
Source:Pediatric Neurology, Volume 83





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Dramatic improvement of a rare syndrome with high dose riboflavin treatment

Publication date: Available online 1 June 2018
Source:Pediatric Neurology
Author(s): Eva B Forman, A. Reghan Foley, Mary D King




https://ift.tt/2J8BmZn

Laser additive manufacturing of Zn metal parts for biodegradable applications: Processing, formation quality and mechanical properties

Publication date: 5 October 2018
Source:Materials & Design, Volume 155
Author(s): Peng Wen, Maximilian Voshage, Lucas Jauer, Yanzhe Chen, Yu Qin, Reinhart Poprawe, Johannes Henrich Schleifenbaum
Zn based metals have exhibited promising applications for biodegradable implants. Only a handful of very recent reports were found on additive manufacturing of Zn metal by selective laser melting (SLM). This work provided a systematic study on densification, surface roughness and mechanical properties regarding SLM of Zn metal. Single track surface after laser melting was rugged and twisted with a large amount of attached particles due to severe Zn evaporation. For SLM produced solid parts, the relative density was more than 99.50%; the surface roughness Sa was 9.15–10.79 μm for as-melted status and 4.83 μm after sandblasting, both comparable to optimal results obtained by SLM of common metals. The microstructure was made up of fine columnar grains. The average values of hardness, elastic modulus, yield strength, ultimate strength and elongation were 42 HV, 23GPa, 114 MPa, 134 MPa, and 10.1% respectively, better than those obtained by most manufacturing methods. The superior mechanical properties were attributed to high densification and fine grains resulted by optimal processing control of Zn evaporation and laser energy input. Cardiovascular stents were printed out to demonstrate additive manufacturing ability for complicated structures. All the results indicate the encouraging prospect of additive manufacturing of Zn based metals for biodegradable applications.

Graphical abstract

https://ift.tt/2J4tfB0

Design and fabrication of melt electrowritten tubes using intuitive software

Publication date: 5 October 2018
Source:Materials & Design, Volume 155
Author(s): Erin McColl, Jürgen Groll, Tomasz Jungst, Paul D. Dalton
This study approaches the accurate continuous direct-writing onto a cylindrical collector from a mathematical perspective, taking into account the winding angle, cylinder diameter and length required for the final 3D printed tube. Using an additive manufacturing process termed melt electrowriting (MEW), porous tubes intended for tissue engineering applications are fabricated from medical-grade poly(ε-caprolactone) (PCL), validating the mathematically-derived method. For the fabricated tubes in this study, the pore size, winding angle and printed length can all be planned in advance and manufactured as designed. The physical dimensions of the tubes matched theoretical predictions and mechanical testing performed demonstrated that variations in the tubular morphology have a direct impact on their strength. MEWTubes, the web-based application developed and described here, is a particularly useful tool for planning the complex continuous direct writing path required for MEW onto a rotating, cylindrical build surface.

Graphical abstract

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Modelling fatigue delamination growth in fibre-reinforced composites: Power-law equations or artificial neural networks?

Publication date: 5 October 2018
Source:Materials & Design, Volume 155
Author(s): Giuliano Allegri
This paper discusses two alternative modelling approaches for describing fatigue delamination growth (FDG) in polymer-based fibre-reinforced composites, i.e. semi-empirical equations having a power-law form and artificial neural networks. Barenblatt's self-similarity principles are applied for identifying a suitable expression of the delamination driving force in terms of the square-rooted energy-release-rate range and the associated peak values. The general dependency of pre-factors and exponents of FDG power-laws on the stress-ratio and mode-mixity is discussed in detail. Single-hidden-layer neural networks (SHLNN) with the support of self-similarity principles are here proposed as an alternative to semi-empirical power laws for describing FDG in composites. A example application of SHLNN to mixed-mode and variable stress-ratio FDG is provided for the carbon/epoxy system T800H/#3631. The SHLNN predictions are compared to a semi-empirical fit based on a modified Hartman-Schijve power-law.

Graphical abstract

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Advances and controversies in the classification and grading of pituitary tumors

Abstract

Background

Pituitary tumors are common lesions, and they represent the second most frequent primary brain tumor. Their classification has undergone several changes over time. The World Health Organization conducts periodic expert review/consensus meetings and publishes the results as recommendations for changes in classification, based on advances in molecular and genetic advances. This paper summarizes the results of the 2017 WHO Classification, which recommends several important changes.

Purpose

This paper provides a review of the major changes and issues leading to an understanding of the basis for a new pituitary tumor classification. They include the rejection and modification of prior conceptual and pathological characteristics of these neoplasms. There is also considerable concern related to invasive and recurrent pituitary tumors which follow a less benign course than the typical pituitary adenoma.

Methods

A review of the outcome data for the previously designated "atypical" pituitary tumor category revealed that the former criteria were not adequate to support their ability to predict with accuracy the clinical course of a given tumor. A similar review was accomplished regarding the role of the p53 tumor suppressor mutation. Again, there was no reliable contribution of p53 status to tumor aggressiveness. Other changes have occurred regarding the cytogenetic lineage of the various subtypes of pituitary adenoma. The transcription factors Pit-1, SF-1, and TPit play a major role in determining tumor subtypes and have become part of the classification criteria.

Results

These advances now help provide the background for more reliable and consistent classification of pituitary adenomas. Further definition of aggressive characteristics such as cavernous sinus and dural invasion remain to be considered in the quest to make more accurate prognostic projections based on histopathological analysis.

Conclusions

The 2017 WHO Classification of Pituitary Tumors provides a more solid basis for accurate and reliable prognostic assessment of these lesions. Further progress undoubtedly will be made as the recommendations of this update are incorporated in to routine use.

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Keine Überlegenheit der Protonentherapie gegenüber der IMRT beim lokal fortgeschrittenen NSCLC

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EDITORIAL

Publication date: June 2018
Source:Seminars in Cancer Biology, Volume 50





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Editorial Board & Publication Information

Publication date: June 2018
Source:Seminars in Cancer Biology, Volume 50





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Erratum to “Plasma magnesium is inversely associated with Epstein-Barr virus load in peripheral blood and Burkitt lymphoma in Uganda” [Cancer Epidemiol. 52 (2018) 70–74]

Publication date: Available online 1 June 2018
Source:Cancer Epidemiology
Author(s): Juan Ravell, Isaac Otim, Hadijah Nabalende, Ismail D. Legason, Steven J. Reynolds, Martin D. Ogwang, Christopher M. Ndugwa, Vickie Marshall, Denise Whitby, James J. Goedert, Eric A. Engels, Kishor Bhatia, Michael J. Lenardo, Sam M. Mbulaiteye




https://ift.tt/2Jmcl0g

TNFAIP3 (A20) – The Immunological Rheostat

Publication date: Available online 1 June 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Asher Maroof, Dhavalkumar D. Patel




https://ift.tt/2LQui5C

Auto-antibodies to IgE and FceRI and the Natural Variability of SYK Expression in Basophils

Publication date: Available online 1 June 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Donald MacGlashan
BackgroundSecretion from human basophils and mast cells requires the activity of SYK but expression of SYK is highly variable in the general population and this variability predicts the magnitude of IgE-mediated secretion. One known mechanism of modulating SYK expression in human basophils is aggregation of FceRI.ObjectiveThis study examines the possibility that functional auto-antibodies are present in a wide variety of subjects and in particular, subjects whose basophils poorly express SYK. It also tests whether any found antibodies could modulate SYK expression in maturing basophils and whether interaction with FcgRIIb/CD32b modulates the effect.MethodsAn experimental algorithm for classifying the nature of histamine release induced by serum from 3 classes of subjects was developed.ResultsThe frequency of functional auto-antibodies that produce characteristics concordant with FceRI-mediated secretion was zero in 34 subjects without chronic spontaneous urticaria (CSU). In subjects with CSU, the frequency was lower than expected, approximately 7%. For the 5/68 unique CSU sera tested that contained anti-FceRI or anti-IgE Abs, these antibodies were found to induce down-regulation of SYK in both peripheral blood basophils and basophils developed from CD34+ progenitors. Blocking interaction of these antibodies with CD32b did not alter their ability to down-regulate SYK expression.ConclusionsThis study establishes that functional auto-antibodies to IgE/FceRI do not provide a good explanation for the variability in SYK expression in basophils in the general population. They do show that if antibodies with these characteristics are present, they are capable of modulating SYK expression in developing basophils.

Teaser

The wide variability in the critical signaling tyrosine kinase SYK observed in the general population is not explained by the presence of auto-antibodies to IgE or FceRIalpha.


https://ift.tt/2J89vbV

Lexico-syntactic features are activated but not selected in bare noun production: Electrophysiological evidence from overt picture naming

Publication date: Available online 31 May 2018
Source:Cortex
Author(s): Man Wang, Yiya Chen, Niels O. Schiller
To produce a word, speakers need to retrieve the lexico-syntactic representation of the word and encode the phonological form for articulation. It is not precisely known yet if a word's syntactic features (e.g. number, gender, etc.) are automatically activated and selected in bare noun production. Cubelli and colleagues (2005) proposed that only in languages that have a complex morphological structure (e.g. Italian), the selection of grammatical gender is required. In languages with a relatively simpler morphological structure, the selection of grammatical gender is by-passed. Here, we investigated this issue further by employing a language with an extremely simple morphological structure, i.e. Mandarin Chinese. Using the picture-word interference paradigm, we manipulated the congruency of the lexico-syntactic classifier feature (comparable to grammatical gender) between the target picture and the superimposed distractor word. We measured participants' naming latencies and their electroencephalogram (EEG). As a result, relative to the classifier-congruent condition, classifier incongruency elicited a stronger N400 effect in the ERP analyses, suggesting the automatic activation of lexico-syntactic features in bare noun production. However, classifier congruency did not affect naming latencies, suggesting that the lexico-syntactic feature is not selected in bare noun naming when it is irrelevant for production.



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