Publication date: 15 August 2018
Source:Molecular and Cellular Endocrinology, Volume 471
https://ift.tt/2JOg1oz
Πέμπτη 14 Ιουνίου 2018
Editorial Board
Integrated molecular analysis of Tamoxifen-resistant invasive lobular breast cancer cells identifies MAPK and GRM/mGluR signaling as therapeutic vulnerabilities
Publication date: 15 August 2018
Source:Molecular and Cellular Endocrinology, Volume 471
Author(s): Hillary Stires, Mary M. Heckler, Xiaoyong Fu, Zhao Li, Catherine S. Grasso, Michael J. Quist, Joseph A. Lewis, Uwe Klimach, Alan Zwart, Akanksha Mahajan, Balázs Győrffy, Luciane R. Cavalli, Rebecca B. Riggins
Invasive lobular breast cancer (ILC) is an understudied malignancy with distinct clinical, pathological, and molecular features that distinguish it from the more common invasive ductal carcinoma (IDC). Mounting evidence suggests that estrogen receptor-alpha positive (ER+) ILC has a poor response to Tamoxifen (TAM), but the mechanistic drivers of this are undefined. In the current work, we comprehensively characterize the SUM44/LCCTam ILC cell model system through integrated analysis of gene expression, copy number, and mutation, with the goal of identifying actionable alterations relevant to clinical ILC that can be co-targeted along with ER to improve treatment outcomes. We show that TAM has several distinct effects on the transcriptome of LCCTam cells, that this resistant cell model has acquired copy number alterations and mutations that impinge on MAPK and metabotropic glutamate receptor (GRM/mGluR) signaling networks, and that pharmacological inhibition of either improves or restores the growth-inhibitory actions of endocrine therapy.
https://ift.tt/2MrCo4N
Fighting breast cancer stem cells through the immune-targeting of the xCT cystine–glutamate antiporter
Abstract
Tumor relapse and metastatic spreading act as major hindrances to achieve complete cure of breast cancer. Evidence suggests that cancer stem cells (CSC) would function as a reservoir for the local and distant recurrence of the disease, due to their resistance to radio- and chemotherapy and their ability to regenerate the tumor. Therefore, the identification of appropriate molecular targets expressed by CSC may be critical in the development of more effective therapies. Our studies focused on the identification of mammary CSC antigens and on the development of CSC-targeting vaccines. We compared the transcriptional profile of CSC-enriched tumorspheres from an Her2+ breast cancer cell line with that of the more differentiated parental cells. Among the molecules strongly upregulated in tumorspheres we selected the transmembrane amino-acid antiporter xCT. In this review, we summarize the results we obtained with different xCT-targeting vaccines. We show that, despite xCT being a self-antigen, vaccination was able to induce a humoral immune response that delayed primary tumor growth and strongly impaired pulmonary metastasis formation in mice challenged with tumorsphere-derived cells. Moreover, immunotargeting of xCT was able to increase CSC chemosensitivity to doxorubicin, suggesting that it may act as an adjuvant to chemotherapy. In conclusion, our approach based on the comparison of the transcriptome of tumorspheres and parental cells allowed us to identify a novel CSC-related target and to develop preclinical therapeutic approaches able to impact on CSC biology, and therefore, hampering tumor growth and dissemination.
https://ift.tt/2MqJYNf
The importance of appropriate control groups in perioperative analgesic studies: One size does not fit all
Postoperative pain remains poorly treated [1]. Specifically in the United States, opioids continue to be the main weapon used by clinicians to optimize postoperative analgesia [2]. Nonetheless, opioids can worsen patient reported quality of postoperative recovery [3,4]. In addition, the current national focus in the US to reduce the prescription of opioid analgesics and, subsequently, opioid diversion makes the use of multimodal analgesic strategies a very important topic in the perioperative care of surgical patients [5].
https://ift.tt/2MsWpYW
We need more studies to guide the perioperative management of high risk seniors undergoing surgery
The number of surgical procedures in the ambulatory care setting in the United States has increased by over 300% during the past decade with over 30 million ambulatory surgeries (AS) being performed yearly [1]. Of these, 6 million are done in seniors (≥65years of age) and, with the aging of the US population, the number of seniors undergoing surgery will expand exponentially. In addition, more complex surgeries (e.g. hysterectomy, thyroidectomy, spine surgery) are also now conducted in the ambulatory setting [2–4].
https://ift.tt/2ymskY3
Postoperative outcomes in patients with a do-not-resuscitate (DNR) order undergoing elective procedures
Do-not-resuscitate (DNR) status has been shown to be an independent risk factor for mortality in the post-operative period. Patients with DNR orders often undergo elective surgeries to alleviate symptoms and improve quality of life, but there are limited data on outcomes for informed decision making.
https://ift.tt/2JET5vV
Hypnotic agents for induction of general anesthesia in cesarean section patients: A systematic review and meta-analysis of randomized controlled trials
An ideal induction drug for cesarean section (CS) must have quick action, with minimum side effects such as awareness, hemodynamic compromise, and neonatal depression. Thiopentone is frequently used; however, no reliable evidence is available to support its use as a dedicated hypnotic agent in this setting.
https://ift.tt/2JJ3Wkm
Infraclavicular and supraclavicular approaches to brachial plexus for ambulatory elbow surgery: A randomized controlled observer-blinded trial
To compare the effectiveness of supraclavicular and infraclavicular approaches to brachial plexus block for elbow surgery.
https://ift.tt/2Mq8OfY
Effects of arsenic methylation and metabolism on the changes of arsenic-related skin lesions
Abstract
Little was known about the arsenic metabolism and arsenic methylation associated with the changes of skin lesions after reducing the arsenic in drinking water (WAs). Therefore, urinary concentrations and proportions of arsenic species were determined for recovery (RC), improvement (IC), persistent (PE), aggravation (AC), new incidence (NC), and no sign (HC) groups based on the changes of skin lesions between before (in 2004) and after (in 2017) WAs reduction. The results indicate that the urinary concentrations of inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and total arsenic (TAs) were much higher for RC and IC groups than for the other groups in 2004, while these values varied slightly among the groups in 2017. The urinary %iAs of all the groups was significantly decreased after WAs reduction. In contrast, the urinary %DMA of RC, IC, AC, and NC groups was increased. From 2004 to 2017, the PE and HC groups had lower decrease rate of %iAs and %MMA, and increase rate of %DMA, primary methylation index (PMI), and secondary methylation index (SMI) after WAs reduction. The adjusted odd ratios (ORs) showed that the RC, IC, AC, and NC groups were positively related with %iAs and %MMA and were negatively correlated with %DMA, PMI, and SMI before WAs reduction. It can be concluded that higher urinary %iAs and %MMA before WAs reduction increased the probability of skin lesions recovery and improvement, and the risks of skin lesions aggravation and incidence. Higher increase rate of urinary %DMA was positively associated with of skin lesions recovery and improvement. Moreover, higher urinary %iAs and %MMA or lower increase rate of urinary %DMA might increase the risk of skin lesions aggravation.
https://ift.tt/2sYyzfv
Phospholipase PLA2G6, a Parkinsonism-Associated Gene, Affects Vps26 and Vps35, Retromer Function, and Ceramide Levels, Similar to α-Synuclein Gain
Publication date: Available online 14 June 2018
Source:Cell Metabolism
Author(s): Guang Lin, Pei-Tseng Lee, Kuchuan Chen, Dongxue Mao, Kai Li Tan, Zhongyuan Zuo, Wen-Wen Lin, Liping Wang, Hugo J. Bellen
Mutations in PLA2G6 (PARK14) cause neurodegenerative disorders in humans, including autosomal recessive neuroaxonal dystrophy and early-onset parkinsonism. We show that loss of iPLA2-VIA, the fly homolog of PLA2G6, reduces lifespan, impairs synaptic transmission, and causes neurodegeneration. Phospholipases typically hydrolyze glycerol phospholipids, but loss of iPLA2-VIA does not affect the phospholipid composition of brain tissue but rather causes an elevation in ceramides. Reducing ceramides with drugs, including myriocin or desipramine, alleviates lysosomal stress and suppresses neurodegeneration. iPLA2-VIA binds the retromer subunits Vps35 and Vps26 and enhances retromer function to promote protein and lipid recycling. Loss of iPLA2-VIA impairs retromer function, leading to a progressive increase in ceramide. This induces a positive feedback loop that affects membrane fluidity and impairs retromer function and neuronal function. Similar defects are observed upon loss of vps26 or vps35 or overexpression of α-synuclein, indicating that these defects may be common in Parkinson disease.
Graphical abstract
Teaser
Lin et al. show that loss of the fly homolog of the neurodegeneration gene PLA2G6 (PARK14) impairs retromer function, causes ceramide accumulation, and leads to lysosomal dysfunction, which causes neuronal dysfunction. Their further data suggest that the uncovered retromer/ceramide/lysosome pathway may be common in Parkinson disease.https://ift.tt/2JFy2ta
Supra-Additive Effects of Combining Fat and Carbohydrate on Food Reward
Publication date: Available online 14 June 2018
Source:Cell Metabolism
Author(s): Alexandra G. DiFeliceantonio, Géraldine Coppin, Lionel Rigoux, Sharmili Edwin Thanarajah, Alain Dagher, Marc Tittgemeyer, Dana M. Small
Post-ingestive signals conveying information about the nutritive properties of food are critical for regulating ingestive behavior. Here, using an auction task concomitant to fMRI scanning, we demonstrate that participants are willing to pay more for fat + carbohydrate compared with equally familiar, liked, and caloric fat or carbohydrate foods and that this potentiated reward is associated with response in areas critical for reward valuation, including the dorsal striatum and mediodorsal thalamus. We also show that individuals are better able to estimate the energy density of fat compared with carbohydrate and fat + carbohydrate foods, an effect associated with functional connectivity between visual (fusiform gyrus) and valuation (ventromedial prefrontal cortex) areas. These results provide the first demonstration that foods high in fat and carbohydrate are, calorie for calorie, valued more than foods containing only fat or carbohydrate and that this effect is associated with greater recruitment of central reward circuits.
Graphical abstract
Teaser
DiFeliceantonio et al. show that foods containing fat and carbohydrate are more reinforcing than equicaloric foods containing primarily fat or carbohydrate. This effect is independent of liking and is reflected by supra-additive responses in the striatum during food valuation. This may be one mechanism driving overconsumption of high-fat/-carbohydrate processed foods.https://ift.tt/2LQA7io
Short-Term Fasting Reveals Amino Acid Metabolism as a Major Sex-Discriminating Factor in the Liver
Publication date: Available online 14 June 2018
Source:Cell Metabolism
Author(s): Sara Della Torre, Nico Mitro, Clara Meda, Federica Lolli, Silvia Pedretti, Matteo Barcella, Luisa Ottobrini, Daniel Metzger, Donatella Caruso, Adriana Maggi
Sex impacts on liver physiology with severe consequences for energy metabolism and response to xenobiotic, hepatic, and extra-hepatic diseases. The comprehension of the biology subtending sex-related hepatic differences is therefore very relevant in the medical, pharmacological, and dietary perspective. The extensive application of metabolomics paired to transcriptomics here shows that, in the case of short-term fasting, the decision to maintain lipid synthesis using amino acids (aa) as a source of fuel is the key discriminant for the hepatic metabolism of male and female mice. Pharmacological and genetic interventions indicate that the hepatic estrogen receptor (ERα) has a key role in this sex-related strategy that is primed around birth by the aromatase-dependent conversion of testosterone into estradiol. This energy partition strategy, possibly the result of an evolutionary pressure enabling mammals to tailor their reproductive capacities to nutritional status, is most important to direct future sex-specific dietary and medical interventions.
Graphical abstract
Teaser
Della Torre et al. show a major sex difference in the hepatic response to short-term fasting: females maintain the synthesis of energy storage molecules (lipids) at the expense of amino acids, and males simply slow down anabolic pathways. The mechanism is mediated by liver estrogen receptor alpha.https://ift.tt/2sVVurO
Postprandial Oxidative Metabolism of Human Brown Fat Indicates Thermogenesis
Publication date: Available online 14 June 2018
Source:Cell Metabolism
Author(s): Mueez U Din, Teemu Saari, Juho Raiko, Nobu Kudomi, Stefanie F. Maurer, Minna Lahesmaa, Tobias Fromme, Ez-Zoubir Amri, Martin Klingenspor, Olof Solin, Pirjo Nuutila, Kirsi A. Virtanen
Human studies suggest that a meal elevates glucose uptake in brown adipose tissue (BAT). However, in postprandial state the thermogenic activity and the metabolism of non-esterified fatty acids (NEFAs) in BAT remain unclear. Using indirect calorimetry combined with positron emission tomography and computed tomography (PET/CT), we showed that whole-body and BAT thermogenesis (oxygen consumption) increases after the ingestion of a mixed carbohydrate-rich meal, to the same extent as in cold stress. Postprandial NEFA uptake into BAT is minimal, possibly due to elevated plasma insulin inhibiting lipolysis. However, the variation in postprandial NEFA uptake is linked to BAT thermogenesis. We identified several genes participating in lipid metabolism to be expressed at higher levels in BAT compared with white fat in postprandial state, and to be positively correlated with BAT UCP1 expression. These findings suggest that substrates preferred by BAT in postprandial state are glucose or LPL-released NEFAs due to insulin stimulation.
Graphical abstract
Teaser
Using PET/CT imaging, U Din et al. show that eating a carbohydrate-rich meal triggers human brown adipose tissue (hBAT) thermogenesis to the same extent as cold stress, though the substrates used are different. Glucose and LPL-derived fatty acids are preferentially taken up by hBAT in the postprandial state.https://ift.tt/2LSoBD4
Reversible De-differentiation of Mature White Adipocytes into Preadipocyte-like Precursors during Lactation
Publication date: Available online 14 June 2018
Source:Cell Metabolism
Author(s): Qiong A. Wang, Anying Song, Wanze Chen, Petra C. Schwalie, Fang Zhang, Lavanya Vishvanath, Lei Jiang, Risheng Ye, Mengle Shao, Caroline Tao, Rana K. Gupta, Bart Deplancke, Philipp E. Scherer
Adipose tissue in the mammary gland undergoes dramatic remodeling during reproduction. Adipocytes are replaced by mammary alveolar structures during pregnancy and lactation, then reappear upon weaning. The fate of the original adipocytes during lactation and the developmental origin of the re-appearing adipocyte post involution are unclear. Here, we reveal that adipocytes in the mammary gland de-differentiate into Pdgfrα+ preadipocyte- and fibroblast-like cells during pregnancy and remain de-differentiated during lactation. Upon weaning, de-differentiated fibroblasts proliferate and re-differentiate into adipocytes. This cycle occurs over multiple pregnancies. These observations reveal the potential of terminally differentiated adipocytes to undergo repeated cycles of de-differentiation and re-differentiation in a physiological setting.
Graphical abstract
Teaser
Adipocytes in the mammary gland disappear during lactation. Wang et al. show that these mammary adipocytes fully de-differentiate into preadipocytes during lactation and readily re-differentiate during involution. The same adipocytes are therefore "recycled" over multiple rounds of pregnancies. De-differentiation constitutes a new possible fate for terminally differentiated adipocytes.https://ift.tt/2sWROFZ
Expression and localization of Forkhead transcription factor A1 in the three-dimensional reconstructed eccrine sweat glands
Source:Acta Histochemica
Author(s): Haihong Li, Liyun Chen, Mingjun Zhang, Sitian Xie, Liuhanghang Cheng
Previously studies showed that Forkhead transcription factor A1 (FoxA1) was associated with sweat secretion. To investigate the expression and localization of FoxA1 in the three-dimensional (3D) reconstructed eccrine sweat glands, eccrine sweat gland cells were transplanted subcutaneously into nude mice with Matrigel, and at 2, 3, 4, 5, 6, 8, 10 and 12 weeks post-transplantation, the reconstructed eccrine sweat glands were removed and immunostained for FoxA1 and co-immunostained for FoxA1 and eccrine sweat markers, K7, carbonic anhydrase II (CA Ⅱ), gross cystic disease fluid protein-15 (GCDFP-15) and α-smooth muscle actin (α-SMA), and FoxA1 and sweat secretion-related proteins, Na+-K+-ATPase α and Na+-K+-2Cl- cotransporter 1 (NKCC1). The results showed that FoxA1-positive cells weren't detected until 3 weeks post-implantation, a time point of the differntiation of secretory coil-like structures. From the fourth week on, the number of FoxA1-positive cells increased and thereafter maintained at a high number. Double immunofluorescence staining showed that FoxA1-positive cells co-expressed dark cell marker GCDFP-15 and myoepithelial cell marker α-SMA, as well as secretion-related proteins, Na+-K+-ATPase α and NKCC1 in both the native and reconstructed eccrine sweat glands. In conclusion, FoxA1 might be related to the development and differentiation of secretory coil-like structures, as well as the secretory function of the 3D reconstructed eccrine sweat glands.
https://ift.tt/2HQSRfd
Cutaneous squamous cell carcinoma progression during imiquimod treatment
To the Editor: We read with interest the paper by Que SKT et al regarding the management of cutaneous squamous cell carcinoma (cSCC)1 and the remarkable discussion about the field treatment with topical chemotherapy agents. Imiquimod is an immune response modifier that activates immune cells via toll-like receptor 7, initiating a cascade leading to the induction of cytokines, such as interferon alfa, interferon gamma, and interleukin 12, which promote a T helper 1 (TH1) immune response.2 The use of imiquimod for the treatment of invasive cSCC is not approved by the European Medicines Agency or Food and Drug Administration, but few reports have described its success in elderly patients and when other treatments and surgery are contraindicated.
https://ift.tt/2sYV0B1
Association of 25-hydroxyvitamin D levels and cutaneous melanoma: A nested case-control study of the Women's Health Initiative Observation Study
To the Editor: Exposure to ultraviolet radiation is an important risk factor for melanoma but is also the principal means by which the body synthesizes vitamin D in the skin. Prior studies on the association between 25-OH-D levels and melanoma occurrence and prognosis have shown conflicting results.1,2
https://ift.tt/2taZ5kO
Prognostic significance of tumor budding in cutaneous squamous cell carcinoma
To the Editor: We read with interest the article by Gonzalez-Guerrero et al1 reporting the prognostic significance of tumor buds in cutaneous squamous cell carcinoma (cSCC). The results of this study confirm and complement the results of 2 similar investigations published previously on the same topic,2,3 even though the methodology of these 3 studies was not identical. In our study,2 we compared 31 aggressive cSCCs, defined as tumors with subsequent local recurrences or metastases, with 21 nonaggressive cSCCs (which had been obtained from the same group of organ-graft recipients) and counted the number of tumor buds (defined as groups of 1-5 tumor cells) on 5 adjacent microscopic hot-spot fields at the invasive tumor front.
https://ift.tt/2sW2VPo
Dermatoses caused by cultural practices
With globalization and widespread immigration, physicians increasingly encounter patients from varying backgrounds and diverse customs. Although certain cultural practices are widely performed, there is limited medical literature describing their dermatologic and systemic effects and complications. Population diversity and sharing of traditions make it increasingly important for dermatologists to understand the role of cultural practices and recognize physiologic and pathologic sequelae. In addition, dermatologists are often adjured to assess skin findings that may be mistaken for abuse.
https://ift.tt/2JOMjzQ
Alopecia areata
To the Editor: Strazzulla et al1,2 have written instructive reviews on the clinical presentation, pathogenesis, and current treatment options for alopecia areata. In these articles, they describe and show photographs of the more common patchy subtype of the scalp and beard, as well as the less common ophiasis, androgenic-like, and diffuse subtypes. They also explain how trichoscopy and scalp biopsy are important tools in diagnosing alopecia areata. The authors mention that nail changes may be present in 10% to 20% of patients with alopecia areata and that severity of nail changes may correlate with more extensive hair loss; in addition, they list some of the more common nail changes, namely, regular pitting, longitudinal ridging, trachyonychia, and red lunulae.
https://ift.tt/2sXWpIe
Dermatoses caused by cultural practices
The second article in this continuing medical education series discusses cosmetic practices associated with cultural dermatoses, including hair care, traditional clothing, and skin decorations. Often, the steps individuals take to enhance their physical appearance are determined by cultural perceptions of beauty. Without awareness of cultural practices, a multitude of cutaneous dermatoses may be missed by the dermatologist. Recognition and understanding of patients' cultural backgrounds and habits will allow the practicing dermatologist to offer better counseling and treatment options while providing a more meaningful and understanding physician–patient relationship.
https://ift.tt/2t8XTOV
Case 18-2018: A 45-Year-Old Woman with Hypertension, Fatigue, and Altered Mental Status
Presentation of Case. Dr. Sally A. Ingham (Medicine): A 45-year-old woman was admitted to this hospital because of dyspnea on exertion, fatigue, and confusion. The patient had been in her usual state of health until 18 months before the current admission, when the blood pressure was noted to be…
https://ift.tt/2JLbnaQ
A Shocking Turn of Events
In this Journal feature, information about a real patient is presented in stages (boldface type) to an expert clinician, who responds to the information by sharing relevant background and reasoning with the reader (regular type). The authors' commentary follows. A 38-year-old woman presented to her…
https://ift.tt/2sVGU3y
Editorial Board
Source:Critical Reviews in Oncology/Hematology, Volume 127
https://ift.tt/2t6Ksz6
ASSOCIATION OF FREE VITAMIN D3 CONCENTRATIONS AND ASTHMA TREATMENT FAILURES in the VIDA Trial
Publication date: Available online 14 June 2018
Source:Annals of Allergy, Asthma & Immunology
Author(s): John J. Lima, Mario Castro, Tonya S. King, Jason E Lang, Victor E. Ortega, Stephen P. Peters, Loren C. Denlinger, Elliot Israel, Christine A. Sorkness, Michael E. Wechsler, Sally E. Wenzel, Lewis J Smith
https://ift.tt/2tb3zIp
Decreased interleukin-35 serum levels in patients with chronic spontaneous urticaria
Source:Annals of Allergy, Asthma & Immunology
Author(s): Tao Chen, Li-xin Fu, Qiao-mei Sun, Pei-mei Zhou, Zai-pei Guo
https://ift.tt/2l9PeIp
Treatment of mucositis with combined 660- and 808-nm-wavelength low-level laser therapy reduced mucositis grade, pain, and use of analgesics: a parallel, single-blind, two-arm controlled study
Abstract
Oral squamous cell carcinoma (OSCC) is the most frequent oral malignant neoplasia. As consequence of OSCC treatment, oral mucositis (OM) is one of the most common adverse effects of OSCC treatment. Currently, there is no consensus for OM treatment. The purpose of the current study was to test the combination of red and infrared low-level laser therapy (LLLT) for OM treatment. Primary culture of human fibroblast was performed to identify LLLT dose. After laboratory tests, a two-arm parallel, single-blind, controlled study was conducted. The two arms were group 1, both 660- and 808-nm wavelengths (300 J/cm2, 9 J of total energy, 100 mW, spot size 3 mm2), and group 2, only 660-nm wavelength (300 J/cm2, 9 J of total energy, 100 mW, spot size 3 mm2). Both treatments were performed twice a week. Group 1 presented a reduction of mucositis grade in comparison to group 2. Group 1 also presented reduction of analgesics prescription. But no significant differences between groups 1 and 2 were observed according to the pain scale. In conclusion, the current study demonstrated that a combination of red and infrared at a higher dose (300 J/cm2) reduced both oral mucositis grade and analgesics prescription. The effects of the combination of RT and LLLT are unclear and need more studies.
https://ift.tt/2JBTMG8
Clinical and pharmacogenetic determinants of 5-fluorouracyl/leucovorin/irinotecan toxicity: Results of the PETACC-3 trial
Source:European Journal of Cancer, Volume 99
Author(s): Sabine Tejpar, Pu Yan, Hubert Piessevaux, Daniel Dietrich, Peter Brauchli, Dirk Klingbiel, Roberto Fiocca, Mauro Delorenzi, Fred Bosman, Arnaud D. Roth
PurposeIrinotecan (CPT-11) in combination with 5-fluorouracil (5FU) is widely used in the treatment of colorectal cancer. We assessed potential clinical variables that may predict toxicity and more specifically the role of UGT1A1 polymorphisms associated with irinotecan toxicity. We used data from the PETACC3 trial, which randomised patients in adjuvant setting to 6 months of leucovorin (LV) and 5FU (LV5/FU2) or LV5/FU2 + irinotecan.Patients and methodsClinical and toxicity data were available for 2982 patients, DNA was available for 1200 (40%) of these patients. We genotyped the polymorphisms UGT1A1*28 and UGT1A1-3156G > A. Risk factors for neutropenia and diarrhoea were assessed by univariable and multivariable analyses.ResultsIn univariable analysis, UGT1A*28 genotype was associated with an increased incidence of grade III–IV neutropenia (incidence: 44% versus 26%; odds ratio [OR]: 2.3; 95% confidence interval [CI]: 1.4–3.7). In multivariable analysis, the most important predictors (ordered in terms of contribution to R2) were baseline neutrophil count (OR for 1-unit (109/l) decrease: 1.8, 95% CI: 1.3–1.7), female sex (OR: 1.8, 95% CI: 1.1–3.0), body surface area (OR for 0.1-unit increase: 0.8, 95% CI: 0.7–1.0), UGT1A1 (OR: 2.8, 95% CI: 1.6–5.0), age (OR per 10 years: 1.3, 95% CI: 1.1–1.6) and poor performance status (OR: 1.6, 95% CI: 1.0–2.6). The main predictors for grade IV neutropenia were sex, age, performance score and UGT1A1. The main predictors for diarrhoea were sex and age.ConclusionsWe found that a complex of risk factors is involved in the development of toxicity, including UGT1A1. Parameters that are readily available in clinical practice, notably sex, age and performance status, are stronger predictors than the UGT1A1*28 genotype. Further studies beyond the UGT1A1*28 genotype are needed to fully understand the determinants of toxicity risk, notably in females.
https://ift.tt/2t06UdZ
A multifunctional two-photon fluorescent probe for detecting H2S in wastewater and GSH in vivo
Publication date: 1 October 2018
Source:Talanta, Volume 188
Author(s): Bin Yu, Chunyang Chen, Jiaxi Ru, Weifang Luo, Weisheng Liu
A novel turn-on fluorescent probe, which coumarin-fused coumarin was used as fluorophore to link with 2, 4- dinitrodiphenyl ether moiety that has high selectivity and sensitivity for H2S and thiols, was designed and synthesized. Our probe YB can sensitively react with H2S and GSH to release free fluorophore with strong fluorescence signals. The probe YB could use as a significant molecular imaging tool to study the endogenous GSH in living cell and a practical detector for H2S in the papermaking wastewater.
Graphical abstract
https://ift.tt/2sYtJ1H
Age-related differences in striatal, medial temporal, and frontal involvement during value-based decision processing
Publication date: September 2018
Source:Neurobiology of Aging, Volume 69
Author(s): Yu-Shiang Su, Jheng-Ting Chen, Yong-Jheng Tang, Shu-Yun Yuan, Anna C. McCarrey, Joshua Oon Soo Goh
Appropriate neural representation of value and application of decision strategies are necessary to make optimal investment choices in real life. Normative human aging alters neural selectivity and control processing in brain regions implicated in value-based decision processing including striatal, medial temporal, and frontal areas. However, the specific neural mechanisms of how these age-related functional brain changes modulate value processing in older adults remain unclear. Here, young and older adults performed a lottery-choice functional magnetic resonance imaging experiment in which probabilities of winning different magnitudes of points constituted expected values of stakes. Increasing probability of winning modulated striatal responses in young adults, but modulated medial temporal and ventromedial prefrontal areas instead in older adults. Older adults additionally engaged higher responses in dorso-medio-lateral prefrontal cortices to more unfavorable stakes. Such extrastriatal involvement mediated age-related increase in risk-taking decisions. Furthermore, lower resting-state functional connectivity between lateral prefrontal and striatal areas also predicted lottery-choice task risk-taking that was mediated by higher functional connectivity between prefrontal and medial temporal areas during the task, with this mediation relationship being stronger in older than younger adults. Overall, we report evidence of a systemic neural mechanistic change in processing of probability in mixed-lottery values with age that increases risk-taking of unfavorable stakes in older adults. Moreover, individual differences in age-related effects on baseline frontostriatal communication may be a central determinant of such subsequent age differences in value-based decision neural processing and resulting behaviors.
https://ift.tt/2HPm5vg
[18F]FMPEP-d2 PET imaging shows age- and genotype-dependent impairments in the availability of cannabinoid receptor 1 in a mouse model of Alzheimer's disease
Source:Neurobiology of Aging, Volume 69
Author(s): Jatta S. Takkinen, Francisco R. López-Picón, Anna K. Kirjavainen, Rea Pihlaja, Anniina Snellman, Tamiko Ishizu, Eliisa Löyttyniemi, Olof Solin, Juha O. Rinne, Merja Haaparanta-Solin
Contradictory findings on the role of the type 1 cannabinoid receptor (CB1R) during the pathogenesis of Alzheimer's disease (AD) have been reported. Here, we evaluated the CB1R brain profile in an AD mouse model using longitudinal positron emission tomography with an inverse agonist for CB1R, [18F]FMPEP-d2. APP/PS1-21 and wild-type (n = 8 in each group) mice were repeatedly imaged between 6 to 15 months of age, accompanied by brain autoradiography, western blot, and CB1R immunohistochemistry with additional mice. [18F]FMPEP-d2 positron emission tomography demonstrated lower (p < 0.05) binding ratios in the parietotemporal cortex and hippocampus of APP/PS1-21 mice compared with age-matched wild-type mice. Western blot demonstrated no differences between APP/PS1-21 and wild-type mice in the CB1R abundance, whereas significantly lower (p < 0.05) receptor expression was observed in male than female mice. The results provide the first demonstration that [18F]FMPEP-d2 is a promising imaging tool for AD research in terms of CB1R availability, but not expression. This finding may further facilitate the development of novel therapeutic approaches based on endocannabinoid regulation.
https://ift.tt/2sYtCTP
APOE ε4 status in healthy older African Americans is associated with deficits in pattern separation and hippocampal hyperactivation
Source:Neurobiology of Aging, Volume 69
Author(s): Neha Sinha, Chelsie N. Berg, Nicholas J. Tustison, Ashlee Shaw, Diane Hill, Michael A. Yassa, Mark A. Gluck
African Americans are 1.4 times more likely than European Americans to carry the apolipoprotein E (APOE) ε4 allele, a risk factor for Alzheimer's disease (AD). However, little is known about the neural correlates of cognitive function in older African Americans and how they relate to genetic risk for AD. In particular, no past study on African Americans has examined the effect of APOE ε4 status on pattern separation—mnemonic discrimination performance and its corresponding neural computations in the hippocampus. Previous work using the mnemonic discrimination paradigm has localized increased activation in the DG/CA3 hippocampal subregions as being correlated with discrimination deficits. In a case-control high-resolution functional magnetic resonance imaging study of 30 healthy African Americans, aged 60 years and older, we observed APOE ε4–related impairments in mnemonic discrimination, coincident with dysfunctional hyperactivation in the DG/CA3, and CA1 regions, despite no evidence of structural differences in the hippocampus between carriers and noncarriers. Our results add to the growing body of evidence that deficits in pattern separation may be an early marker for AD-related neuronal dysfunction.
https://ift.tt/2HOBGLz
Parkinsonism is associated with altered primary motor cortex plasticity in frontotemporal dementia–primary progressive aphasia variant
Publication date: September 2018
Source:Neurobiology of Aging, Volume 69
Author(s): Flavio Di Stasio, Suppa Antonio, Fabbrini Andrea, Marsili Luca, Asci Francesco, Conte Antonella, Trebbastoni Alessandro, De Lena Carlo, Berardelli Alfredo
In frontotemporal dementia (FTD), the behavioral variant (bv-FTD) and nonfluent variant of primary progressive aphasia (nfv-PPA) reflect a prominent neurodegenerative involvement of the frontal lobe networks, which may include the premotor and motor areas and thus cause heterogeneous clinical symptoms including parkinsonism. With the technique of transcranial magnetic stimulation, we investigated long-term potentiation– and long-term depression–like plasticity in the primary motor cortex of bv-FTD and nfv-PPA patients, with and without parkinsonism, by using the theta-burst stimulation (TBS) protocol. We applied the intermittent TBS and continuous TBS in 20 FTD patients and 18 age-matched healthy subjects. Results were also compared with those achieved in a cohort of age-matched patients with Parkinson's disease. The responses to TBS were abnormal in FTD patients with parkinsonism. By contrast, the TBS induced normal responses in patients with both nfv-PPA and bv-FTD without parkinsonism. Finally, responses to TBS were comparable in patients with FTD with parkinsonism and patients with Parkinson's disease. We provide evidence of abnormal primary motor cortex long-term potentiation–/long-term depression–like plasticity in patients with FTD and parkinsonism suggesting neurodegenerative processes in the corticobasal ganglia-thalamo-cortical motor networks in these patients.
https://ift.tt/2LRwFnJ
Stress-related deficits of older adults' spatial working memory: an EEG investigation of occipital alpha and frontal-midline theta activities
Publication date: September 2018
Source:Neurobiology of Aging, Volume 69
Author(s): Amanda C. Marshall, Nicholas Cooper, Livia Rosu, Steffan Kennett
Studies highlight cumulative life stress as a significant predictor of accelerated cognitive aging. This study paired electrophysiological with behavioral measures to explore how cumulative stress affects attentional and maintenance processes underpinning working memory retention. We collected electroencephalographic recordings from 60 individuals (30 older, 30 younger) reporting high or low levels of cumulative stress during the performance of a spatial Sternberg task. We measured mid-occipital alpha (8–12 Hz) and frontal-midline theta (4–6 Hz) as indicators of attentional and maintenance processes. Older, high-stress participants' behavioral performance lay significantly below than that of younger adults and low-stress older individuals. Impaired task performance coincided with reduced event-related synchronization in alpha and theta frequency ranges during memory maintenance. Electrophysiological findings suggest that older adults' reduced performance results from a stress-related impact on their ability to retain a stimulus in working memory and inhibit extraneous information from interfering with maintenance. Our results demonstrate the wide-ranging impact of cumulative stress on cognitive health and provide insight into the functional mechanisms disrupted by its influence.
https://ift.tt/2sWIkun
Screening emergency department patients for opioid drug use: A qualitative systematic review
Publication date: October 2018
Source:Addictive Behaviors, Volume 85
Author(s): Preet Kaur Sahota, Siri Shastry, Dana B. Mukamel, Linda Murphy, Narisu Yang, Shahram Lotfipour, Bharath Chakravarthy
IntroductionThe opioid drug epidemic is a major public health concern and an economic burden in the United States. The purpose of this systematic review is to assess the reliability and validity of screening instruments used in emergency medicine settings to detect opioid use in patients and to assess psychometric data for each screening instrument.MethodsPubMed/MEDLINE, PsycINFO, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Web of Science, Cumulative Index to Nursing and Allied Health Literature and ClinicalTrials.gov were searched for articles published up to May 2018. The extracted articles were independently screened for eligibility by two reviewers. We extracted 1555 articles for initial screening and 95 articles were assessed for full-text eligibility. Six articles were extracted from the full-text assessment.ResultsSix instruments were identified from the final article list: Screener and Opioid Assessment for Patients with Pain - Revised; Drug Abuse Screening Test; Opioid Risk Tool; Current Opioid Misuse Measure; an Emergency Medicine Providers Clinician Assessment Questionnaire; and an Emergency Provider Impression Data Collection Form. Screening instrument characteristics, and reliability and validity data were extracted from the six studies. A meta-analysis was not conducted due to heterogeneity between the studies.ConclusionsThere is a lack of validity and reliability evidence in all six articles; and sensitivity, specificity and predictive values varied between the different instruments. These instruments cannot be validated for use in emergency medicine settings. There is no clear evidence to state which screening instruments are appropriate for use in detecting opioid use disorders in emergency medicine patients. There is a need for brief, reliable, valid and feasible opioid use screening instruments in the emergency medicine setting.
https://ift.tt/2ym8j3R
AMPK/FIS1-Mediated Mitophagy Is Required for Self-Renewal of Human AML Stem Cells
Publication date: Available online 14 June 2018
Source:Cell Stem Cell
Author(s): Shanshan Pei, Mohammad Minhajuddin, Biniam Adane, Nabilah Khan, Brett M. Stevens, Stephen C. Mack, Sisi Lai, Jeremy N. Rich, Anagha Inguva, Kevin M. Shannon, Hyunmin Kim, Aik-Choon Tan, Jason R. Myers, John M. Ashton, Tobias Neff, Daniel A. Pollyea, Clayton A. Smith, Craig T. Jordan
Leukemia stem cells (LSCs) are thought to drive the genesis of acute myeloid leukemia (AML) as well as relapse following chemotherapy. Because of their unique biology, developing effective methods to eradicate LSCs has been a significant challenge. In the present study, we demonstrate that intrinsic overexpression of the mitochondrial dynamics regulator FIS1 mediates mitophagy activity that is essential for primitive AML cells. Depletion of FIS1 attenuates mitophagy and leads to inactivation of GSK3, myeloid differentiation, cell cycle arrest, and a profound loss of LSC self-renewal potential. Further, we report that the central metabolic stress regulator AMPK is also intrinsically activated in LSC populations and is upstream of FIS1. Inhibition of AMPK signaling recapitulates the biological effect of FIS1 loss. These data suggest a model in which LSCs co-opt AMPK/FIS1-mediated mitophagy as a means to maintain stem cell properties that may be otherwise compromised by the stresses induced by oncogenic transformation.
Graphical abstract
Teaser
Human acute myeloid leukemia stem cells (LSCs) depend on FIS1-mediated mitophagy for self-renewal and survival. AMPK is constitutively active in human LSCs, is upstream of FIS1, and acts to stimulate mitophagy. Disruption of AMPK signaling or FIS1 activity results in eradication of LSCs.https://ift.tt/2MrETEh
Modulating Cell Fate as a Therapeutic Strategy
Publication date: Available online 14 June 2018
Source:Cell Stem Cell
Author(s): Brian Lin, Priya Srikanth, Alison C. Castle, Sagar Nigwekar, Rajeev Malhotra, Jenna L. Galloway, David B. Sykes, Jayaraj Rajagopal
In injured tissues, regeneration is often associated with cell fate plasticity, in that cells deviate from their normal lineage paths. It is becoming increasingly clear that this plasticity often creates alternative strategies to restore damaged or lost cells. Alternatively, cell fate plasticity is also part and parcel of pathologic tissue transformations that accompany disease. In this Perspective, we summarize a few illustrative examples of physiologic and aberrant cellular plasticity. Then, we speculate on how one could enhance endogenous plasticity to promote regeneration and reverse pathologic plasticity, perhaps inspiring interest in a new class of therapies targeting cell fate modulation.
Teaser
In this Perspective, Lin et al. highlight examples of plasticity during normal regeneration and in aberrant situations in a variety of tissues. The authors also discuss the merits of enhancing endogenous plasticity to promote regeneration and reversing pathologic plasticity as potential therapeutic strategies.https://ift.tt/2taggD8
Esrrb Unlocks Silenced Enhancers for Reprogramming to Naive Pluripotency
Publication date: Available online 14 June 2018
Source:Cell Stem Cell
Author(s): Kenjiro Adachi, Wolfgang Kopp, Guangming Wu, Sandra Heising, Boris Greber, Martin Stehling, Marcos J. Araúzo-Bravo, Stefan T. Boerno, Bernd Timmermann, Martin Vingron, Hans R. Schöler
Transcription factor (TF)-mediated reprogramming to pluripotency is a slow and inefficient process, because most pluripotency TFs fail to access relevant target sites in a refractory chromatin environment. It is still unclear how TFs actually orchestrate the opening of repressive chromatin during the long latency period of reprogramming. Here, we show that the orphan nuclear receptor Esrrb plays a pioneering role in recruiting the core pluripotency factors Oct4, Sox2, and Nanog to inactive enhancers in closed chromatin during the reprogramming of epiblast stem cells. Esrrb binds to silenced enhancers containing stable nucleosomes and hypermethylated DNA, which are inaccessible to the core factors. Esrrb binding is accompanied by local loss of DNA methylation, LIF-dependent engagement of p300, and nucleosome displacement, leading to the recruitment of core factors within approximately 2 days. These results suggest that TFs can drive rapid remodeling of the local chromatin structure, highlighting the remarkable plasticity of stable epigenetic information.
Graphical abstract
Teaser
Rapid reprogramming of epiblast stem cells (EpiSCs) to induced pluripotent stem cells (iPSCs) allows a detailed analysis of epigenetic remodeling induced by transcription factors. The orphan nuclear receptor Esrrb plays a pioneering role in establishing a permissive chromatin environment for the recruitment of core pluripotency factors Oct4, Sox2, and Nanog.https://ift.tt/2t02aFd
Modulation of human Th17 cell responses through complement receptor 3 (CD11 b/CD18) ligation on monocyte-derived dendritic cells
Source:Journal of Autoimmunity
Author(s): Johannes Nowatzky, Olivier Manches, Shaukat Ali Khan, Emmanuelle Godefroy, Nina Bhardwaj
ObjectiveApoptotic cell receptors contribute to the induction of tolerance by modulating dendritic cell function following the uptake of apoptotic cells or microparticles. Dendritic cells that have bound or ingested apoptotic cells produce only low amounts of pro-inflammatory cytokines and fail to prime effector T cell responses. Specifically, ligation of the apoptotic cell receptor CR3 (CD11 b/CD18) on human monocyte-derived dendritic cells (moDC) down-modates proinflammatory cytokine secretion, but the consequences for human Th17 cell homeostasis and effector responses remain unknown. Here, we aimed to establish whether CD11b-ligated moDC modulate Th17 cell effector reponses to assess their potential for future use in moDC-based suppressive immunotherapy.MethodsWe generated a bead-based surrogate system to target CD11b on monocyte-derived human dendritic cells and examined the effects of CD11b ligation on Th17-skewing cytokine secretion, priming, expansion and functional plasticity in DC/T cell co-culture systems at the poly- and monoclonal level.ResultsWe show that Th17 cell expansion within the human memory CD4+ T cell compartment was efficiently constricted by targeting the CD11b receptor on moDC. This tolerogenic capacity was primarily dependent on cytokine skewing. Furthermore, ligation of CD11b on healthy homozygous carriers of the rs11143679 (ITGAM) variant – a strong genetic susceptibility marker for human systemic lupus erythematosus – also down-modulated the secretion of Th17-skewing cytokines.ConclusionOverall, our findings underline the potential of targeted CD11b ligation on human dendritic cells for the engineering of suppressive immunotherapy for Th17-related autoimmune disorders.
https://ift.tt/2ybQqoa
Simultaneous NO and SO 2 removal by aqueous persulfate activated by combined heat and Fe 2+ : experimental and kinetic mass transfer model studies
Abstract
This study evaluates the chemistry, kinetics, and mass transfer aspects of the removal of NO and SO2 simultaneously from flue gas induced by the combined heat and Fe2+ activation of aqueous persulfate. The work involves experimental studies and the development of a mathematical model utilizing a comprehensive reaction scheme for detailed process evaluation, and to validate the results of an experimental study at 30–70 °C, which demonstrated that both SO2 and Fe2+ improved NO removal, while the SO2 is almost completely removed. The model was used to correlate experimental data, predict reaction species and nitrogen-sulfur (N-S) product concentrations, to obtain new kinetic data, and to estimate mass transfer coefficient (KLa) for NO and SO2 at different temperatures. The model percent conversion results appear to fit the data remarkably well for both NO and SO2 in the temperature range of 30–70 °C. The conversions ranged from 43.2 to 76.5% and 98.9 to 98.1% for NO and SO2, respectively, in the 30–70 °C range. The model predictions at the higher temperature of 90 °C were 90.0 and 97.4% for NO and SO2, respectively. The model also predicted decrease in KLa for SO2 of 1.097 × 10−4 to 8.88 × 10−5 s−1 (30–90 °C) and decrease in KLa for NO of 4.79 × 10−2 to 3.67 × 10−2 s−1 (30–50 °C) but increase of 4.36 × 10−2 to 4.90 × 10−2 s−1 at higher temperatures (70–90 °C). This emerging sulfate-radical-based process could be applied to the treatment of flue gases from combustion sources.
Graphical abstract
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https://ift.tt/2MtRhDB
Characterization of outdoor bronze monument patinas: the potentialities of near-infrared spectroscopic analysis
Abstract
The corrosion products usually found on outdoor bronzes are generated by the interaction between the metal alloy and the atmospheric pollutants. To protect the external surface of bronzes, different organic materials (natural or synthetic) can be applied, creating over time a patina consisting of a complex mixture of inorganic and organic degraded components. The correct chemical characterization of patina constituents is fundamental to define the state of conservation of a metal artwork and address proper restoration actions. In this paper, we evaluated the potentialities of near-infrared (NIR) reflectance microscopy (4000–7500 cm−1) as complementary method to mid-infrared (MIR) analyses for the characterization of bronze patinas. Although NIR spectroscopy has been already used in the field of heritage science, its application for the characterization of bronze patinas is almost unexplored. In this paper, several corrosion products usually found on the surface of outdoor bronze sculptures were synthesized, characterized, and submitted to the NIR-MIR total reflection analysis to build up a reference spectral database. We devoted particular attention to the NIR features of copper hydroxychlorides, such as atacamite and paratacamite, which have not been studied in detail up to now. A selection of organic-based formulations, commonly used by restorers to protect the bronze surface against the outdoor aggressive environment, were also considered as references. Successively, NIR-MIR reflectance microscopy was successfully employed for the analysis of patina micro-samples collected from the bronze statues of the Neptune Fountain (sixteenth century) located in Bologna. The obtained results demonstrate the ability of NIR spectroscopy to identify organic and inorganic patina constituents, even in mixtures. In addition, the study can be considered as a proof of concept for the possible future application of the technique for in situ diagnostic campaigns on bronze sculptures.
https://ift.tt/2ta8k4O
Herbicides in river water across the northeastern Italy: occurrence and spatial patterns of glyphosate, aminomethylphosphonic acid, and glufosinate ammonium
Abstract
Glyphosate and glufosinate ammonium are the active ingredients of commonly used herbicides. Active agricultural lands extend over a large part of the Veneto region (Eastern Po Valley, Italy) and glyphosate and glufosinate ammonium are widely used. Consequently, surface waters can be potentially contaminated. This study investigates the occurrence of glyphosate and glufosinate ammonium as well as aminomethylphosphonic acid (AMPA, the degradation product of glyphosate) in river water of Veneto. Eighty-six samples were collected in 2015 at multiple sampling points across the region. Samples were analyzed for the two target herbicides, AMPA as well as for other variables, including water temperature, pH, dissolved oxygen, conductivity, hardness, BOD, COD, inorganic ions, total nitrogen, total phosphorus, total suspended solids, arsenic, and lead. The average concentrations (all samples) were 0.17, 0.18, and 0.10 μg L−1 for glyphosate, AMPA, and glufosinate ammonium, respectively. The European upper tolerable level for pesticides (annual average 0.1 μg L−1) was often exceeded. Chemometric analysis was therefore applied to (i) investigate the relationships among water pollutants, (ii) detect the potential sources of water contamination, (iii) assess the effective water pollution of rivers by identifying river basins with anomalous pollution levels, and (iv) assess the spatial variability of detected sources. Factor analysis identified four factors interpreted as potential sources and processes (use of herbicides, leaching of fertilizers, urban/industrial discharges, and the biological activity on polluted or stagnant waters). A discriminant analysis revealed that the pollution from anthropogenic discharges is homogeneously present in surface water of Veneto, while biological activity and fertilizers present heterogeneous distributions. This study gives insights into the concentrations of herbicides in rivers flowing through a wide region that has heavy use of these chemicals in agriculture. The study also points out some hot-spots and suggests the future implementation of the current monitoring protocols and network.
https://ift.tt/2Mt9e5b
Nerve conduction velocity as a non-destructive biomarker in the earthworm Aporrectodea caliginosa exposed to insecticides
Abstract
Earthworms are important and useful soil organisms, but in agricultural soils, they are potentially exposed to a wide variety of pesticides. Insecticides represent the highest threat to earthworms and many are neurotoxic. There is a need for a reliable, relevant, simple biomarker to assess the sub-lethal effects of neurotoxic insecticides on earthworms under laboratory or field conditions. The Aporrectodea caliginosa earthworms were exposed to 0 (control), 0.5×, 1× (normal field application rate), and 5× concentrations of a carbamate (Pirimor®) and an organophosphate (Lorsban®) insecticides. The nerve conduction velocity (NCV) of the medial giant fibers of A. caliginosa earthworm was recorded on days 0, 1, 2, 3, 4, and 7 to quantify sub-lethal neurotoxic effects. Acetylcholinesterase (AChE) enzyme activity of A. caliginosa homogenates was measured at the conclusion of the experiment. Pirimor® but not Lorsban® induced a significant decrease in NCV on days 3, 4, and 7 at 1× and 5× doses. A significant dose-dependent decrease was observed on AChE activity to Pirimor® at the doses used but not Lorsban®. A clear relationship is observed between AChE activity and NCV in the case of Pirimor®. This study showed that NCV is a sensitive biomarker that correlates well with classical biomarker measurements such as AChE enzyme activity. This technique could be used to study the impact of insecticides on earthworms and also their recovery.
https://ift.tt/2JNzXrJ
Hymenoptera Venom Immunotherapy: Past, Present, and Future
We have learned a great deal about Hymenoptera immunotherapy since 1925 when Dr. Braun first reported the effective use of immunotherapy in a bee allergic patient. In his report, he described snipping off the posterior 1/8 inch of the body then grinding it up, extracting it in saline, and filtering the solution, demonstrating a positive skin test response and then using the same material to perform immunotherapy1. A plethora of publications in the 40 years after that first report reinforced the efficacy of whole body extract for immunotherapy to Hymenoptera.
https://ift.tt/2Mrxipf
FDA-approved peanut allergy treatment: the first wave is about to crest
As the prevalence of food allergy has increased in recent years, practicing allergists have seen an explosion of food allergy patient volume. For example, according to a nationwide telephone survey, between 1997 and 2008 there was a 3-fold rise in peanut allergy1,2. As illustrated in Figure 1, this trend has continued at the Northwest Asthma and Allergy Center in Washington State, where between 2006 and 2017 there was a similarly dramatic increase in the number of office visits for peanut allergy, tree nut allergy, and other food allergies.
https://ift.tt/2taJZMa
Vitamin D insufficiency, TH2 cytokines, and allergy markers in Puerto Rican children with asthma
TH2 cytokines, including IL-4, IL-5 and IL-13, are central to the development of atopic asthma, driving eosinophilia, bronchial hyperreactivity, and mucus hypersecretion.1 In recent years, treatment of severe atopic asthma has been expanded to include anti-IL-5 antibodies. In parallel, a growing body of evidence suggests that vitamin D may be beneficial in asthma management,2 perhaps through immune regulation.3
https://ift.tt/2sYEnFB
The Challenges of Preventing Food Allergy: lessons learned from LEAP and EAT
Driven by both the continuing rise in food allergy prevalence1, 2 and the lack of an effective cure, the last decade has seen an increase in clinical trials investigating the prevention of food allergy. Earlier wisdom, predominantly derived from the findings of observational studies, considered that allergy prevention was best achieved through allergen avoidance.3, 4 After testing under randomised controlled trial (RCT) conditions, allergen avoidance has not been deemed a suitable means of preventing food allergy.
https://ift.tt/2JQu8tC
Acute contrecoup epidural hematoma that developed without skull fracture in two adults: two case reports
The incidence of acute epidural hematoma not accompanied by fracture is low, and it mostly occurs right below the impact point in children. Acute epidural hematoma on the contralateral side of the impact point...
https://ift.tt/2l8mTCp
Iatrogenic pneumothorax during hypoglossal nerve stimulator implantation
Hypoglossal nerve stimulation is a promising new treatment for patients with obstructive sleep apnea. In the initial Stimulation Therapy for Apnea Reduction Trial, the overall rate of serious adverse events was <2% and no pneumothorax cases were reported. We present the case of an iatrogenic pneumothorax during placement of the chest sensor lead between the intercostal muscles. Following clinical and radiological evaluation, surgery was continued and the patient was treated expectantly. In the following review, we discuss pathophysiology, diagnosis, and expected outcomes.
https://ift.tt/2t8EKg1
The sources and dispersal of nitrate in multiple waters, constrained by multiple isotopes, in the Wudalianchi region, northeast China
Abstract
The Wudalianchi scenic area in NE China has been named an UNESCO "Global Geopark" and "Biosphere Reserve." During this investigation, the sources of nitrate and the hydrologic system through which it is dispersed were assessed using geochemical data and a multiple isotopic approach. The cold waters from the south and north springs originated from the deep subsurface. Isotopically, these waters exhibited relatively negative δD and δ18O values and nitrate in the water was substantially depleted 15N, suggesting that the mineral water was primarily derived from depth. Lakes within the Wudalianchi region were primarily composed of water from these deep mineral springs and precipitation. Chemical fertilizers were the primary source of nitrate to the Wudalianchi lakes. Groundwater was found in shallow mineral springs and wells plotted above the local meteoric water line, implying that shallow groundwater was primarily derived from precipitation. Elevated concentrations of nitrate in shallow mineral springs and well waters during the summer, autumn, and winter suggest that shallow groundwater within the Yaoquan volcanic area was also polluted by nitrate from human activities. Denitrification of shallow groundwater is slow, reducing the potential for "self-remediation". The concentration data are supported by nitrogen (N) isotope data; wells and springs exhibited N isotopic ratios between − 5‰ and + 5‰ (typical of fertilizers and precipitation) and exhibited higher oxygen (O) isotope values than water in the Wudalianchi lakes. These relationships suggest that nitrate in shallow mineral springs, wells, and lakes near the Yaoquan volcano was derived from the mixing of chemical fertilizers with local summer rainfall.
https://ift.tt/2LRHiHk
Arbuscular mycorrhizal fungi enhance antioxidant defense in the leaves and the retention of heavy metals in the roots of maize
Abstract
In this study, we investigated the effects of the arbuscular mycorrhizal fungi (AMF) Funneliformis mosseae and Diversispora spurcum on the growth, antioxidant physiology, and uptake of phosphorus (P), sulfur (S), lead (Pb), zinc (Zn), cadmium (Cd), and arsenic (As) by maize (Zea mays L.) grown in heavy metal-polluted soils though a potted plant experiment. F. mosseae significantly increased the plant chlorophyll a content, height, and biomass; decreased the H2O2 and malondialdehyde (MDA) contents; and enhanced the superoxide dismutase (SOD) and catalase (CAT) activities and the total antioxidant capacity (T-AOC) in maize leaves; this effect was not observed with D. spurcum. Both F. mosseae and D. spurcum promoted the retention of heavy metals in roots and increased the uptake of Pb, Zn, Cd, and As, and both fungi restricted heavy metal transfer, resulting in decreased Pb, Zn, and Cd contents in shoots. Therefore, the fungi reduced the translocation factors for heavy metal content (TF) and uptake (TF′) in maize. Additionally, F. mosseae promoted P and S uptake by shoots, and D. spurcum increased P and S uptake by roots. Moreover, highly significant negative correlations were found between antioxidant capacity and the H2O2, MDA, and heavy metal contents, and there was a positive correlation with the biomass of maize leaves. These results suggested that AMF alleviated plant toxicity and that this effect was closely related to antioxidant activation in the maize leaves and increased retention of heavy metals in the roots.
https://ift.tt/2JSydRe
An empirical analysis of financial development and energy demand: establishing the role of globalization
Abstract
The rapid mode of globalization is experienced in the last few years. The acceleration in globalization expands economic activities through a share of knowledge and transfer of technology which influence energy demand. So, the objective of this empirical work is to explore the impact of financial development on energy demand incorporating globalization. The empirical finding is based on autoregressive distributed lag (ARDL) bound testing approach from 1980 to 2016 in case of China. Overall, we infer that financial development increases energy demand in China. Furthermore, the finding shows that globalization has a negative and significant impact on energy demand. The additional determinants, such as economic growth, and urbanization stimulate energy consumption. Besides, energy consumption granger cause financial development in the long-run path. Similarly, unidirectional causality is detected between globalization and energy consumption. The result gives direction to policymakers to preserve as well as to enhance efficient energy consumption and sustain economic growth in China with acceleration in globalization.
https://ift.tt/2laeoH5
Temporal and spatial characteristics of potential energy anomaly in Lake Taihu
Abstract
In this study, water temperature and meteorological data in Lake Taihu from June 11 to July 6, 2013, are collected to calibrate and verify the unstructured grid finite-volume community ocean model (FVCOM) coupled with a heat exchange module. The spatial and temporal variations of potential energy anomalies (PEA) in the lake, simulated by the calibrated FVCOM, are analyzed to explore the stratification and de-stratification processes in water body. The temporal variation of PEA primarily follows the diurnal cycles of solar radiation, while the spatial heterogeneity of PEA is jointly determined by solar radiation and vertical shear of horizontal velocity coupled with the topography of the lake. The maxima of PEA in the lake are not greater than 4 J/m3 in the summer and even smaller along shore regions and near the Pingtaishan station. This study is helpful to improve understanding of the effect of physical processes on the algae bloom in Lake Taihu.
https://ift.tt/2ydudGm
Malignant Triton tumour of the maxilla: A case report
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): W. Elleuch, S. Briki, H. Mnif, M. Abdelmoula
https://ift.tt/2y8O5KF
A falsely silent mass
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): X. Dubernard, E. Brenet, M. Makeieff
https://ift.tt/2MpRVSR
The Influence of Menopausal Hormone Therapy and Potential Lifestyle Interactions in Female Cancer Development—a Population-Based Prospective Study
Abstract
The past decades have seen contradictory research results on the health benefits and risks of menopausal hormone therapy (HT). In particular, long-term associations with overall cancer incidence and the potential interplay with other lifestyle factors remain undetermined. In a population-based prospective cohort, 29,152 women aged 50–64 years at entry (1993–1997) were followed through 2013 for incidence of cancer (99% complete follow-up). Cox' proportional hazards models were used to estimate cancer incidence according to baseline HT alone and in combination with lifestyle factors including alcohol intake, BMI, physical activity, diet, and smoking. Among 5484 women diagnosed with cancer, baseline HT was associated with an overall higher risk of cancer (HR 1.28; 95%CI, 1.21–1.36)—in particular, a higher risk of breast (HR 1.77; 95%CI, 1.61–1.95), ovarian (HR 1.68; 95%CI, 1.26–2.26), and endometrial (HR 1.86; 95%CI, 1.45–2.37) cancer. Combination with other lifestyle risk factors largely displayed additive associations. The risk of colorectal cancer was significantly lower (HR 0.79; 95%CI, 0.66–0.95). However, in the interaction analysis, only "healthy" subgroups of women using HT had a lower risk of colorectal cancer. With an overall higher risk of cancer among women on HT, this study underlined the importance of considering all female cancer risks in menopausal treatment guidelines. The largely additive associations between HT and the investigated lifestyle factors support the notion that high levels of hormones in itself play an important etiological role in female reproductive cancers, whereas the possible protective impact in colorectal cancer might be limited to women with an otherwise healthy lifestyle.
https://ift.tt/2Mm4KNX
Diagnosing Neuropathy in an Obese Patient
Source:Clinical Neurophysiology
Author(s): Elliot B. Bodofsky, Gregory T. Carter
https://ift.tt/2Mp3Tfk
Diagnostic Value of Somatosensory Evoked Potential Changes During Carotid Endarterectomy for 30-Day Perioperative Stroke
Source:Clinical Neurophysiology
Author(s): Rajiv P. Reddy, Indraneel S. Brahme, Tejas Karnati, Jeffrey Balzer, Donald J. Crammond, Katherine Anetakis, Parthasarathy D. Thirumala
ObjectivesSomatosensory evoked potentials (SSEPs) have proven useful as an intraoperative modality to predict perioperative stroke during carotid endarterectomy (CEA). However, the predictive value of SSEPs for predicting stroke 30 days postoperatively remains unclear. The primary objective is to evaluate the efficacy of intraoperative SSEP change in predicting the risk of stroke in the postoperative period beyond 24 hours but within 30 days. Our secondary aim is to evaluate the predictive value of each subcategory of SSEP change.MethodsWe performed a meta-analysis of 25 prospective/retrospective studies from PubMed, Web of Science, and Embase regarding SSEP monitoring for postoperative outcomes in symptomatic and asymptomatic CEA patients.ResultsA 8307-patient cohort composed the total sample population, of which 54.17% had symptomatic CS. For SSEP change and stroke greater than 24 hours but within 30 days, the diagnostic odds ratio was 8.68. The diagnostic odds ratio was 3.88 for transient SSEP change and stroke; 49.29 for persistent SSEP change and stroke; 36.45 for transient SSEP loss and stroke; and 281.35 for persistent SSEP loss and stroke.ConclusionsPatients with SSEP changes are at increased risk of perioperative stroke within the entire 30-day period. There is a noticeable step-wise increase in the predicted risk of stroke with the severity of SSEP changes.SignificanceSSEP changes can serve as a predictor for 30-day perioperative stroke during CEA.
https://ift.tt/2JPgR4x
Reply to “Diagnosing Neuropathy in an Obese Patient”: Measuring neuropathy in obese populations: Nerve conduction studies
Source:Clinical Neurophysiology
Author(s): Brian C. Callaghan, Eva L. Feldman
https://ift.tt/2sXis1E
Editorial Board
Source:Journal of Neuroscience Methods, Volume 305
https://ift.tt/2HNJX20
Is brain response to food rewards related to overeating? A test of the reward surfeit model of overeating in children
Source:Appetite, Volume 128
Author(s): Shana Adise, Charles F. Geier, Nicole J. Roberts, Corey N. White, Kathleen L. Keller
The reward surfeit model of overeating suggests that heightened brain response to rewards contributes to overeating and subsequent weight gain. However, previous studies have not tested whether brain response to reward is associated with food intake, particularly during childhood, a period of dynamic development in reward and inhibitory control neurocircuitry. We conducted functional magnetic resonance imaging (fMRI) with 7–11-year-old children (n = 59; healthy weight, n = 31; overweight, n = 28; 54% female) while they played a modified card-guessing paradigm to examine blood-oxygen-level-dependent (BOLD) response to anticipating and winning rewards (food, money, neutral). Food intake was assessed at three separate meals that measured different facets of eating behavior: 1) typical consumption (baseline), 2) overindulgence (palatable buffet), and 3) eating in the absence of hunger (EAH). A priori regions of interest included regions implicated in both reward processing and inhibitory control. Multiple stepwise regressions were conducted to examine the relationship between intake and BOLD response to rewards. Corrected results showed that a greater BOLD response in the medial prefrontal cortex for anticipating food compared to money positively correlated with how much children ate at the baseline and palatable buffet meals. BOLD response in the dorsolateral prefrontal cortex for winning food compared to money was positively correlated with intake at the palatable buffet meal and EAH. All aforementioned relationships were independent of child weight status. Findings support the reward surfeit model by showing that increased brain response to food compared to money rewards positively correlates with laboratory measures of food intake in children.
https://ift.tt/2JXItaZ
To check or not to check. Rectal ESBL colonization in hospitalized elderly patients
Source:American Journal of Infection Control
Author(s): Galina Goltsman, Yehuda Baumohl, Gilad Gal, Zvi Buckman, Valery Proshkin, Emily Lubart
BackgroundThe worldwide spread of extended-spectrum-beta-lactamase (ESBL) producing bacteria has affected health care. ESBL confers resistance to the majority of beta-lactam antibiotics.Materials and MethodsWe intended to quantify the rates of rectal ESBL-positive and negative patients that eventually developed fever and urinary tract infection (UTI). All rectal ESBL-positive patients were to be initially treated with the conventional antibiotics that have anti-ESBL activity (amikacin or ertapenem), while ESBL-negative patients were given ceftriaxone.ResultsMost patients were rectal ESBL-positive (60.7%). Fever was in 51% patients; 67.8% of them developed signs and symptoms of UTI. Most patients with UTI were urinary ESBL-positive (79%), most rectal ESBL-negative patients were urinary ESBL-negative (75%), (χ2 = 18.5, df = 1, P < .001). Overall mortality was higher in the febrile group (39, 34.8%) versus the afebrile (1, 0.9%) (χ2 = 42, df = 1, P < .001). The mortality rate in the febrile group was significantly higher in the rectal ESBL-positive patients (χ2 = 7.5, df = 1, P = .006).DiscussionThe direct correlation of rectal ESBL-positive and negative and respectively urinary ESBL-positive and negative patients' advocate for the use of antibiotics with anti-ESBL activity as an empiric treatment of rectal ESBL-positive patients with suspected UTI.ConclusionIn our opinion, it is worthwhile to identify rectal ESBL-positivity on hospital admission.
https://ift.tt/2LRpSKO
Factors for compliance with infection control practices in home healthcare: findings from a survey of nurses' knowledge and attitudes toward infection control
Source:American Journal of Infection Control
Author(s): David Russell, Dawn W. Dowding, Margaret V. McDonald, Victoria Adams, Robert J. Rosati, Elaine L. Larson, Jingjing Shang
BackgroundInfection is a leading cause of hospitalization among home healthcare patients. Nurses play an important role in reducing infection among home healthcare patients by complying with infection control procedures. However, few studies have examined the compliance of home healthcare nurses with infection control practices or the range of sociocultural and organizational factors that may be associated with compliance.MethodsThis study analyzed survey responses from nurses at 2 large, certified home healthcare agencies (n = 359), to explore levels of compliance with infection control practices and identify associated demographic, knowledge, and attitudinal correlates.ResultsNurses reported a high level of infection control compliance (mean = 0.89, standard deviation [SD] = 0.16), correct knowledge (mean = 0.85, SD = 0.09), and favorable attitudes (mean = 0.81, SD = 0.14). Multivariate mixed regression analyses revealed significant positive associations of attitudinal scores with reported level of compliance (P < .001). However, knowledge of inflection control practices was not associated with compliance. Older (P < .05) and non-Hispanic black (P < .001) nurses reported higher compliance with infection control practices than younger and white non-Hispanic nurses.ConclusionThese findings suggest that efforts to improve compliance with infection control practices in home healthcare should focus on strategies to alter perceptions about infection risk and other attitudinal factors.
https://ift.tt/2JXIiwl
Sex bias of Acinetobacter baumannii nosocomial infection
Source:American Journal of Infection Control
Author(s): Wen-Li Yuan, Yan-Jun Shen, De-Yao Deng
https://ift.tt/2LRgC9E
Editorial Board and Contents
Source:Trends in Cell Biology, Volume 28, Issue 7
https://ift.tt/2t98Eku
The Role of Xist in X-Chromosome Dosage Compensation
Source:Trends in Cell Biology
Author(s): Anna Sahakyan, Yihao Yang, Kathrin Plath
In each somatic cell of a female mammal one X chromosome is transcriptionally silenced via X-chromosome inactivation (XCI), initiating early in development. Although XCI events are conserved in mouse and human postimplantation development, regulation of X-chromosome dosage in preimplantation development occurs differently. In preimplantation development, mouse embryos undergo imprinted form of XCI, yet humans lack imprinted XCI and instead regulate gene expression of both X chromosomes by dampening transcription. The long non-coding RNA Xist/XIST is expressed in mouse and human preimplantation and postimplantation development to orchestrate XCI, but its role in dampening is unclear. In this review, we discuss recent advances in our understanding of the role of Xist in X chromosome dosage compensation in mouse and human.
https://ift.tt/2Mp0e10
Toxic effects of cyhalofop-butyl on embryos of the Yellow River carp ( Cyprinus carpio var.): alters embryos hatching, development failure, mortality of embryos, and apoptosis
Abstract
As a universal environmental contaminant, the herbicide cyhalofop-butyl is considered to have infested effects on the embryonic development of aquatic species. The present study focused on an assessment of the impacts of cyhalofop-butyl on Yellow River carp embryos. It was found that cyhalofop-butyl inhibited the hatching of the embryos, and the hatching rate decreased with higher concentrations of the herbicide. The mortality rate was increased on exposure to cyhalofop-butyl and was significantly higher in the 1.6 and 2 mg/L treatment groups over 48 h. All of the embryos of the 2 mg/L treatment group died within the 48 h post-hatching stage. And the transcription of several embryos related to apoptosis was also influenced by cyhalofop-butyl exposure. Further, cyhalofop-butyl exposure leads to a series of morphological changes (pericardial edema, tail deformation, and spine deformation) in embryos, which were consistent with significant modifications in the associated genes. These results provided a scientific basis for further studies into the effects of cyhalofop-butyl on aquatic organisms.
https://ift.tt/2JMuK6L
Association of Cardiovascular Comorbidities With Hearing Loss in the Older Old
This cohort study investigates the association of cardiovascular disease–related risk factors with auditory function among adults older than 80 years.
https://ift.tt/2HN3cJp
https://ift.tt/2HN3cJp
Association Between Portable Music Player Use and Hearing Loss Among School-Aged Children
This population-based study examines the presence of early hearing loss in school-aged children in the Netherlands and its association with use of portable music players.
https://ift.tt/2JXFX4a
https://ift.tt/2JXFX4a
Can Your Smartphone Save Your Hearing?
The article in this issue of JAMA Otolaryngology–Head and Neck Surgery by le Clercq et al shows evidence that 1 in 7 children in Rotterdam, the Netherlands, has signs of hearing loss that may be attributed to noise exposure from portable music players (PMPs). The association of the apparent increased use of PMPs with hearing loss has been widely discussed in the popular press. Broad population-based data such as these are welcome contributions to the conversation. As with all such studies, they exist during times of change. In the period covered by this evaluation, a number of regulatory, technological, and cultural changes were happening.
https://ift.tt/2LNuzoS
https://ift.tt/2LNuzoS
Intralymphatic immunotherapy with two concomitant allergens, birch and grass - a RDBPC trial
Source:Journal of Allergy and Clinical Immunology
Author(s): Laila Hellkvist, Eric Hjalmarsson, Susanna Kumlien Georén, Agnetha Karlsson, Karin Lundkvist, Ola Winqvist, Ulla Westin, Lars Olaf Cardell
Teaser
Intralymphatic immunotherapy (ILIT) with only three lymph node-injections was performed with a combination of grass and birch allergen, with maintained safety and reduced reactivity at nasal grass allergen challenge.https://ift.tt/2sX4eh8
Epithelial proliferation in inflammatory skin disease is regulated by tetratricopeptide repeat domain 7 (Ttc7) in fibroblasts and lymphocytes
Publication date: Available online 14 June 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Ursina Nüesch, Andrea A. Mauracher, Lennart Opitz, Benjamin Volkmer, Katarzyna Michalak-Mićka, Jivko Kamarashev, Tom Hartwig, Ernst Reichmann, Burkhard Becher, Stefano Vavassori, Jana Pachlopnik Schmid
BackgroundMutations in tetratricopeptide repeat domain 7A (TTC7A) and its mouse orthologue, Ttc7, result in a multisystemic disease, mostly affecting the epithelial barriers and immune system. Despite successful hematopoietic stem cell transplantation, ongoing progression of gastrointestinal manifestations can be life-threatening in TTC7A-deficient patients.ObjectiveWe sought to identify whether TTC7A mutations dysregulate epithelial cells only or whether a cell-intrinsic defect in lymphocytes or other cells contributes to disease manifestations.MethodsTtc7-mutated (Ttc7fsn/fsn) mice were crossed to generate double-mutant (Rag2−/−Ttc7fsn/fsn) and triple-mutant (Rag2−/−IL2rg−/−Ttc7fsn/fsn) mice. These models, together with bone marrow chimeras, were used to explore the role of adaptive and innate lymphocytes in the flaky skin phenotype. The effect of the Ttc7fsn/fsn mutation on stromal cells was tested in a xenograft model in conjunction with transcriptomic analysis of Ttc7fsn/fsn fibroblasts.ResultsWe observed that the severity of epithelial hyperproliferation was accentuated by lymphocytes, whereas the phenotype was not induced by transfer of Ttc7-mutated hematopoietic cells. Furthermore, mice completely lacking the lymphocytic compartment were not protected from epithelial hyperproliferation. Ttc7-mutated mouse fibroblasts expressed increased transcript levels of insulin-like growth factor 1 (Igf1) and the antimicrobial protein regenerating islet-derived protein 3γ (Reg3γ). In a xenograft model Ttc7-mutated fibroblasts markedly increased epithelial proliferation of keratinocytes. Thus Ttc7-mutated fibroblasts were identified as potent instigators of epithelial hyperproliferation.ConclusionOur results reveal a previously unsuspected fundamental cell-extrinsic role of Ttc7. We have identified potential candidates for molecularly targeted treatment strategies that will need to be evaluated in future preclinical studies.
https://ift.tt/2HQqz4z
Mineralization and cementing properties of bio-carbonate cement, bio-phosphate cement, and bio-carbonate/phosphate cement: a review
Abstract
Due to high pollution associated with traditional Portland cement and bio-carbonate cement, a new generation of cementitious material needs to be developed. Bio-barium phosphate, magnesium phosphate, and ferric phosphate are synthesized by bio-mineralization. Firstly, the substrate is hydrolyzed by alkaline phosphatase secreted via phosphate-mineralization microbes, obtaining phosphate ions. Micro- and nano-scale phosphate minerals are prepared by phosphate ions reacting with different types of metal cation. The setting time of bio-BaHPO4 has a greater effect on the strength of sand columns when a mixing precipitation process is innovatively adopted. The strength of the sand columns increases as bio-BaHPO4 content (10~50%) increases. The optimum content of bio-BaHPO4 is 60%. Porosity and permeability of the sand columns decrease as bio-BaHPO4 content (10~60%) increases. Ammonium and ammonia can effectively be synthesized to magnesium ammonium phosphate by adding K2HPO4·3H2O to Sporosarcina pasteurii liquid. Permeability, porosity, and compressive strength of the sand columns are close to CJ1, CJ1.5, and CJ2 cementation. However, the fixation ammonia ratio of CJ2 is bigger than CJ1 and CJ1.5 (The mixture solutions of Sporosarcina pasteurii and K2HPO4·3H2O (1, 1.5, and 2 mol/L) are named as CJ1, CJ1.5, and CJ2) cementation. The results show that the Sporosarcina pasteurii liquid containing K2HPO4·3H2O (2 mol/L) and the mixture solution of MgCl2 and urea (3 mol/L) cemented loose sand particles best. Two types of bio-cement are environmentally friendly and can partially or completely replace bio-carbonate cement.
https://ift.tt/2t90UyS
Safety assessment of Morus nigra L. leaves: Acute and subacute oral toxicity studies in Wistar rats
Publication date: 5 October 2018
Source:Journal of Ethnopharmacology, Volume 224
Author(s): Kassia Caroline Figueredo, Camille Gaube Guex, Fernanda Ziegler Reginato, Andreia Regina Haas da Silva, Gabriela Buzatti Cassanego, Cibele Lima Lhamas, Aline Augusti Boligon, Gilberti Helena Hübscher Lopes, Liliane de Freitas Bauermann
Ethnopharmacological relevanceMorus nigra L. is a plant native to Asia, and well adapted to the Brazilian climate. It is popularly known as "amoreira preta", and is part of the National List of Plants of Interest to the Brazilian Unified Health System. It is used in folk medicine mainly to soften the effects of menopause, as anti-inflammatory, antidiabetic and antihypertensive. However, information on safe doses and use is still precarious.Aim of the studyTo identify the chemical composition of the ethanolic extract of Morus nigra L. leaves (EEMN), as well as perform a toxicological study in male and female rats.Materials and methodsThe chemical composition of the extract was performed by HPLC/DAD. In the acute study, the dose administered was 2000 mg/kg, and signs of toxicity and mortality was observed. In the sub-acute study, the extract was administered at doses of 500, 750 and 1000 mg/kg for 28 days. Behavioral changes, object recognition test, renal and hepatic tissue assessments, biochemical and hematological parameters were determined. The extract was administered orally to male and female rats in both studies.ResultsQuercetin and caffeic acid showed as major compounds in the extract. In the acute treatment, the extract was classified as safe (category 5), according to the protocol. In the subacute study, there was a decrease in AST in males (750 and 1000 mg/kg) and females (1000 mg/kg), reduction of total cholesterol in females (750 and 1000 mg/kg), and increase in renal and hepatic change the LPO levels.ConclusionThe present investigation showed that EEMN did not present significant toxic effects when administered orally. Moreover, presented a potentially protective action of organs and possesses hypocholesterolemic activity, thus, it is shown as a promising natural source to be used in pharmacology.
Graphical abstract
https://ift.tt/2LLkgS8
The use of medicinal plants by pregnant women in Africa: A systematic review
Publication date: 5 October 2018
Source:Journal of Ethnopharmacology, Volume 224
Author(s): Seid Mussa Ahmed, Hedvig Nordeng, Johanne Sundby, Yesuf Ahmed Aragaw, Hugo J. de Boer
Ethnopharmacological relevanceMedicinal plant (MP) use during pregnancy is common in Africa and may have profound effects on both the mother and the developing foetus. A lack of overview complicates monitoring and regulating the use of MPs during pregnancy.Aim of the studyThis systematic review analyses prevalence of use of MPs during pregnancy, regional distribution, types and prevalence, MP properties, potential health risks, and consensus of MPs use, and suggests relevant measures to mitigate negative effects on pregnancy.Materials and methodsA search was undertaken using a range of scientific databases (Medline, Embase, African Journals OnLine, Google Scholar and Biological Abstracts), non-governmental organisations, various African universities and regulatory websites for original published and unpublished studies that assess and indicate the prevalence of use of MPs during pregnancy in Africa. Additional articles were located by exploring pertinent bibliographies, and contacting experts.ResultsA total of 3659 MP-use studies were found, but only 303 articles received full-text assessment for eligibility and finally only 50 scientific papers were eligible for the systematic review. The prevalence of MP use by pregnant women varied widely from 2% to 100%. Twenty-eight studies (56%) specified one or more plant species used as MP during pregnancy. The major reasons for MP use were relief of nausea and vomiting during pregnancy (NVP), stimulation of labour, and facilitation of childbirth. The most commonly cited MP species were Zingiber officinale Roscoe, Allium sativum L. and Cucurbita pepo L. and these were used for relief of NVP, motion sickness and as a nutritional supplement. Route of administration was most commonly oral, and few adverse effects were reported.ConclusionsThe use of MPs among pregnant women in Africa is prevalent, and the most commonly used plant species are not known to have harmful foetal effects during pregnancy. However, many of the MP species are poorly studied and teratogenic effects cannot be ruled out. Collaboration between healthcare providers and traditional practitioners to inform about the safe use of MPs may promote safer pregnancies and better health for mothers and infants.
Graphical abstract
https://ift.tt/2JPmItB
Anti-hepatitis B virus effects of the traditional Chinese herb Artemisia capillaris and its active enynes
Publication date: 5 October 2018
Source:Journal of Ethnopharmacology, Volume 224
Author(s): Chang-An Geng, Tong-Hua Yang, Xiao-Yan Huang, Jing Yang, Yun-Bao Ma, Tian-Ze Li, Xue-Mei Zhang, Ji-Jun Chen
Ethnopharmacological relevanceArtemisia capillaris (Yin-Chen) is a famous traditional Chinese medicine (TCM) for treating acute and chronic hepatitis in China. Enynes are one type of characteristic constituents in this herb, while their anti-hepatitis B virus (anti-HBV) properties have not been systemically investigated.Aim of the studyThis study is to reveal the active part of A. capillaris, and systemically investigate the enynes and their anti-HBV activity.Materials and methodsThe total extract and each fraction of A. capillaris were assayed for the anti-HBV activity to reveal the active part. Bioassay-guided fractionation using various chromatographic techniques yielded the enynes, whose structures were elucidated by spectroscopic analyses and ECD calculations. The anti-HBV properties inhibiting HBsAg and HBeAg secretions and HBV DNA replication were evaluated on HepG 2.2.15 cell line in vitro.ResultsACT-2 and ACT-3 was revealed to be the respective active and toxic part of A. capillaris. Twelve enynes (1–12) involving four new ones (1–4) and two unusual enyne analogs (13–14) were isolated from the active part (ACT-2). All the isolates were assayed for their anti-HBV activity, and the preliminary structure-activity relationships were summarized based on the structural features. In particular, compound 4 could significantly inhibit the secretions of HBsAg and HBeAg, and HBV DNA replication with IC50 values of 197.2 (SI > 5.1), 48.7 (SI > 20.5) and 9.8 (SI > 102) μM.ConclusionsEnynes are responsible for the anti-HBV effects of A. capillaris. Hydroxyl and glycosyl groups are preferable for maintaining activity. This is the first time to systematically investigate the anti-HBV activity of enynes in A. capillaris, which provides valuable information for understanding the ethnopharmacological application of Yin-Chen.
Graphical abstract
https://ift.tt/2LQxHAw
PRELIM II(EDI BOARD)
Source:Neuroscience Research, Volume 132
https://ift.tt/2l8uIYM
Descriptive survival study of nail melanoma patients treated with functional surgery versus distal amputation
Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1
Author(s): Suelen Montagner, Francisco Aparecido Belfort, Walter Belda Junior, Nilton Di Chiacchio
https://ift.tt/2HSnpO0
Prognostic significance of tumor budding in cutaneous squamous cell carcinoma
Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1
Author(s): Jean Kanitakis, Georgia Karayannopoulou
https://ift.tt/2JVSBRy
Table of Contents
Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1
https://ift.tt/2HOoGFu
Information for Readers
Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1
https://ift.tt/2JOu5ld
Melanoma staging: Varying precision and terminal digit clustering in Breslow thickness data is evident in a population-based study
Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1
Author(s): Marit B. Veierød, Christian M. Page, Stein Aaserud, Assia Bassarova, Kari D. Jacobsen, Per Helsing, Trude E. Robsahm
BackgroundErrors in Breslow thickness reporting can give misclassification of T category, an important classifier in melanoma staging.ObjectiveWe sought to investigate precision (number of digits) and terminal digit clustering in Breslow thickness and potential consequences for T category.MethodsAll first primary and morphologically verified invasive melanomas in Norway between 2008 and 2015 were included. A smoothing model was fitted to estimate the underlying Breslow thickness distribution without digit clustering.ResultsThickness was reported for 13,057 (97.5%) patients; the median was 1.0 mm (range, 0.09-85). It was reported as whole numbers (15.6%), to 1 decimal (78.2%) and 2 decimal places (6.2%)—thin tumors with more precision than thick tumors. Terminal digit clustering was found with marked peaks in the observed frequency distribution for terminal digits 0 and 5, and with drops around these peaks. Terminal digit clustering increased proportions of patients classified with T1 and T4 tumors and decreased proportions classified with T2 and T3.LimitationsBreslow thickness was not reported in 2.5% of cases.ConclusionsThe Norwegian recommendation of measurement to the nearest 0.1 mm was not followed. Terminal digit clustering was marked, with consequences for T category. Pathologists, clinicians, and epidemiologists should know that clustering of thickness data around T category cut points can impact melanoma staging with consequent effect on patient management and prognosis.
https://ift.tt/2HOowhm
JAAD Case Reports Article List
Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1
https://ift.tt/2JXlLjf
Journal Based CME Instructions and Information
Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1
https://ift.tt/2LNYDkg
Skin in the game: Existing and upcoming physician payment models in dermatology
Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1
Author(s): Oluwatobi A. Ogbechie-Godec, Arash Mostaghimi, Vinod E. Nambudiri
https://ift.tt/2JUOTY6
Dermatoses caused by cultural practices
Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1
Author(s): Neelam A. Vashi, Nicole Patzelt, Stephen Wirya, Mayra B.C. Maymone, Pedro Zancanaro, Roopal V. Kundu
With globalization and widespread immigration, physicians increasingly encounter patients from varying backgrounds and diverse customs. Although certain cultural practices are widely performed, there is limited medical literature describing their dermatologic and systemic effects and complications. Population diversity and sharing of traditions make it increasingly important for dermatologists to understand the role of cultural practices and recognize physiologic and pathologic sequelae. In addition, dermatologists are often adjured to assess skin findings that may be mistaken for abuse. Child abuse misdiagnosis can be traumatizing to all those involved, and immigrant families with limited English proficiency may have difficulty explaining their traditional practices. The first article of this 2-part continuing medical education series begins with a review of therapeutic cultural practices, including traditional Chinese medicine, Ayurveda, acupuncture, cupping, moxibustion, and coining, and the clinically relevant complications that may occur. Therapeutic practices can cause a range of complications, including contact dermatitis, heavy metal toxicity, and severe cutaneous adverse reactions.
https://ift.tt/2HM0raZ
Editorial Board
Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1
https://ift.tt/2JSiNfv
CME examination
Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1
https://ift.tt/2HOo9mY
Comparative effectiveness of targeted immunomodulators for the treatment of moderate-to-severe plaque psoriasis: A systematic review and network meta-analysis
Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1
Author(s): Anne M. Loos, Shanshan Liu, Celia Segel, Daniel A. Ollendorf, Steven D. Pearson, Jeffrey A. Linder
BackgroundThe comparative effectiveness of available targeted immunomodulators for moderate-to-severe psoriasis has not been evaluated.ObjectiveTo evaluate the comparative effectiveness of targeted immunomodulators for adults with moderate-to-severe plaque psoriasis.MethodsSystematic literature review of placebo-controlled and head-to-head randomized trials of 8 targeted immunomodulators that evaluated clinical benefits or harm. The primary outcome was a 75% improvement on the Psoriasis Area and Severity Index. We also conducted a network meta-analysis adjusted for placebo response to perform indirect comparisons between agents.ResultsIn the network meta-analysis, the targeted immunomodulators ordered by increasing relative risk (demonstrating greater likelihood) of achieving a 75% improvement on the Psoriasis Area and Severity Index relative to placebo were as follows: apremilast (6.2), etanercept (9.6), adalimumab (13.0), ustekinumab (14.0), secukinumab (15.4), infliximab (16.2), brodalumab (17.3), and ixekizumab (17.9). Ixekizumab, brodalumab, and infliximab were all statistically superior to ustekinumab, adalimumab, etanercept, and apremilast; results were similar to those of head-to-head studies where data were available.LimitationsMuch of the evidence is short-term (covering 10-16 weeks); limited direct comparisons.ConclusionsThe interleukin 17A inhibitors are more effective in achieving clearance than ustekinumab, and they are generally more effective than etanercept, adalimumab, and apremilast.
https://ift.tt/2JXlDjL
Answers to CME examination
Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1
https://ift.tt/2LPKlQd
Dermatoses caused by cultural practices
Publication date: July 2018
Source:Journal of the American Academy of Dermatology, Volume 79, Issue 1
Author(s): Neelam A. Vashi, Nicole Patzelt, Stephen Wirya, Mayra B.C. Maymone, Roopal V. Kundu
The second article in this continuing medical education series discusses cosmetic practices associated with cultural dermatoses, including hair care, traditional clothing, and skin decorations. Often, the steps individuals take to enhance their physical appearance are determined by cultural perceptions of beauty. Without awareness of cultural practices, a multitude of cutaneous dermatoses may be missed by the dermatologist. Recognition and understanding of patients' cultural backgrounds and habits will allow the practicing dermatologist to offer better counseling and treatment options while providing a more meaningful and understanding physician–patient relationship.
https://ift.tt/2JVqj9B
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