Nano-Diamino-Tetrac (NDAT) Enhances Resveratrol-Induced Antiproliferation by Action on the RRM2 Pathway in Colorectal Cancers

Abstract

Cancer resistance to chemotherapeutic agents is a major issue in the management of cancer patients. Overexpression of the ribonucleotide reductase regulatory subunit M2 (RRM2) has been associated with aggressive cancer behavior and chemoresistance. Nano-diamino-tetrac (NDAT) is a nanoparticulate derivative of tetraiodothyroacetic acid (tetrac), which exerts anticancer properties via several mechanisms and downregulates RRM2 gene expression in cancer cells. Resveratrol is a stilbenoid phytoalexin which binds to a specific site on the cell surface integrin αvβ3 to trigger cancer cell death via nuclear translocation of COX-2. Here we report that resveratrol paradoxically activates RRM2 gene expression and protein translation in colon cancer cells. This unanticipated effect inhibits resveratrol-induced COX-2 nuclear accumulation. RRM2 downregulation, whether achieved by RNA interference or treatment with NDAT, enhanced resveratrol-induced COX-2 gene expression and nuclear uptake which is essential to integrin αvβ3-mediated-resveratrol-induced antiproliferation in cancer cells. Elsewhere, NDAT downregulated resveratrol-induced RRM2 expression in vivo but potentiated the anticancer effect of the stilbene. These findings suggest that RRM2 appears as a cancer cell defense mechanism which can hinder the anticancer effect of the stilbene via the integrin αvβ3 axis. Furthermore, the antagonistic effect of RRM2 against resveratrol is counteracted by the administration of NDAT.

https://ift.tt/2Lnep9i

Effect of oral appliance on circulating leukocyte telomere length and SIRT1 in obstructive sleep apnea

Abstract

Objectives

The increased cardiovascular risk seen in patients with obstructive sleep apnea (OSA) may be due to combination of oxidative stress, systemic inflammation and damage to leukocyte telomere length (LTL) seen with aging. Another molecule, Sirtuin 1 (SIRT1), a histone/protein deacetylase, regulates endothelial nitric oxide synthase and is involved in different aspects of cardiovascular disease, aging and stress resistance. The aim of this study was to evaluate the effects of mandibular advancement device (MAD) on the circulating LTL and SIRT1 protein level in peripheral blood mononuclear cells (PBMCs) in patients with OSA.

Materials and methods

Forty patients with moderately severe to severe OSA who desired MAD and 20 healthy controls were prospectively enrolled. The LTL was measured by quantitative polymerase chain reaction while SIRT1 protein levels in PBMC was assessed using a Sirtuin 1 ELISA Kit. All study subjects underwent baseline sleep study, with OSA patients having repeat testing at 3 months after MAD.

Results

Compared to healthy subjects, patients with OSA at baseline had lower LTL and SIRT1 protein levels in PBMC. After 3 months of MAD, 24 OSA patients, designated as MAD responders, median (range) LTL increased from (0.556 [0.393–0.748]) to (0.708 [0.533–0.893]) and SIRT1 protein levels in PBMC increased from 0.58 ± 0.23 pg/μg of total protein to 0.95 ± 0.26 pg/μg of total protein. For the 16 MAD unresponsive patients, LTL and SIRT1 protein levels remained low.

Conclusions

Successful treatment of OSA with MAD can restore LTL and SIRT1 protein levels in PBMC.

Clinical relevance

LTL and SIRT1 protein levels in PBMC can be improved following effective treatment of OSA using MAD.

https://ift.tt/2LxQyk6

Visual and Positional Modulation of Pendular Seesaw Nystagmus: Implications for the Mechanism

Background: The mechanisms of pendular seesaw nystagmus (SSN) remain unknown. Methods: We evaluated modulation of pendular SSN by removal of visual fixation, convergence, and positional changes in 2 patients, one with bitemporal hemianopia due to a traumatic damage of the optic chiasm and the other with platybasia compressing the medulla and lower cerebellum. Results: In both patients, the pendular SSN markedly decreased or disappeared with convergence, without visual fixation in darkness, during static head tilt toward each shoulder while sitting and while supine. Conclusions: The similar patterns of nystagmus modulation observed in our patients with a different etiology indicate a common role of both visual and otolithic inputs in generating pendular SSN. Address correspondence to Ji-Soo Kim, MD, PhD, Department of Neurology, College of Medicine, Seoul National University Dizziness Center, Clinical Neuroscience Center, and Department of Neurology, Seoul National University Bundang Hospital, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Korea; E-mail: jisookim@snu.ac.kr J.-S. Kim serves as an Associate Editor of Frontiers in Neuro-otology and on the Editorial Boards of the Journal of Clinical Neurology, Frontiers in Neuro-ophthalmology, Journal of Neuro-ophthalmology, Journal of Neurology, Medicine, and Journal of Vestibular Research. The remaining authors report no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (https://ift.tt/2BFTkP1). © 2018 by North American Neuro-Ophthalmology Society

https://ift.tt/2O5bFf5

Anaerobic end-products and mitochondrial parameters as physiological biomarkers to assess the impact of urban pollutants on a key bioturbator

Abstract

The impact of long-term exposure (6 months) to highly or slightly polluted sediments on the energy metabolism of an ecosystem engineer (the oligochaete Limnodrilus hoffmeisteri) was investigated in laboratory conditions. We evaluated some mitochondrial parameters (respiratory chain activity and ATP production rate) and the accumulation of anaerobic end-products (lactate, alanine, succinate, and propionate). The sediments were collected from stormwater infiltration basins and presented high levels of heavy metals and polycyclic aromatic hydrocarbons (PAHs). These compounds had been drained by the runoff water on impervious surfaces of urban areas during rainfall events. A decrease in the activity of the mitochondrial electron transport chain was observed in worms exposed to the most polluted sediment. Urban contaminants disrupted both aerobic metabolism and mitochondrial functioning, forcing organisms to shift from aerobic to anaerobic metabolism (which is characteristic of a situation of functional hypoxia). Although L. hoffmeisteri is very tolerant to urban pollutants, long-term exposure to high concentrations can cause disruption in mitochondrial activity and therefore energy production. Finally, this study demonstrated that anaerobic end-products could be used as biomarkers to evaluate the impact of a mixture of urban pollutants on invertebrates.

https://ift.tt/2uAd717

Use of various biomarkers to explore the effects of GSM and GSM-like radiations on flowering plants

Abstract

Since last decade, GSM (Global System for Mobile Communication) technology has evidently revolutionized our digital world. It uses electromagnetic frequency radiations (EMFr), ranging 850–1900 MHz, and is being composed of three main units (i.e., mobile station, access and core networks). GSM technology has significant impact on our daily life as revealed by increased number of mobile users in the world over. The main goal of the present review is to critically revisit the available literature regarding the responses of various flowering plant species towards GSM and GSM-like radiations using physiological, biochemical, molecular and cytological markers using in vitro approaches. Different monocots (tomato, onion, wheat and maize etc.) and dicots (pulses, mustard and flax) have been studied using both GSM mobile phone and GSM simulators. Different studies revealed overall reductions in germination, root-shoot lengths, dry weight, in both dose and time-dependent manners. However, there could be found incline in various parameters at biochemical and molecular levels. Furthermore, there could be found disturbances at cytological levels upon exposure of roots of onion to EMFr radiations. The overall literature review shows the negative effects of GSM and GSM-like radiations on targeted plant species. In order to alleviate the stressful effects of EMFr radiations on plants, in vivo studies need to be done using various cost-effective approaches such as use of biochar and various organic amendments.

https://ift.tt/2zUHK6f

Salivary adiponectin, but not adenosine deaminase, correlates with clinical signs in women with Sjögren’s syndrome: a pilot study

Abstract

Objectives

To evaluate salivary adiponectin and adenosine deaminase (ADA) in women suffering from Sjögren's syndrome (SS).

Methods

Salivary adiponectin and ADA were measured in patients with SS (n = 17) and compared to their values in healthy controls (n = 13) and patients suffering from drug-induced xerostomia (non-SS sicca group; n = 19). A clinical history was made for each patient, patients were examined clinically, and xerostomia inventory (XI) was performed.

Results

Salivary adiponectin corrected by total protein was higher in patients with SS than in healthy individuals (P < 0.05) or patients with non-SS sicca (P < 0.01) and correlated with XI (r = 0.555; P < 0.05). Salivary ADA was higher in patients with SS and non-SS sicca compared to controls (P < 0.05 in both cases).

Conclusion

The results of the present study indicate that adiponectin and ADA are increased in the saliva of patients with SS.

Clinical relevance

Salivary adiponectin corrected by total protein can be a potential biomarker of SS.

Trial registration

NCT03156569

https://ift.tt/2zRvkMM

Case 260.

Related Articles

Case 260.

Radiology. 2018 Aug;288(2):621-623

Authors: Short RG, Tailor TD

Abstract
History A 31-year-old woman with a history of bilateral orthotopic lung transplantation performed 10 months earlier for cystic fibrosis presented for a routine follow-up appointment, with her chief symptom being a cough. The cough started approximately 1 month prior to this appointment and was minimally productive of clear to yellow phlegm. In addition to her cough, she reported increased sinus congestion and a sensation of "something in her upper chest." She denied shortness of breath, wheezing, hemoptysis, or cigarette smoking. Review of systems was negative for fever, chills, or night sweats. At physical examination, the patient was afebrile, borderline tachycardic (heart rate, 99 beats per minute), and mildly hypertensive (blood pressure, 138/99 mm Hg). Oxygen saturation was 96% on room air. Laboratory evaluation revealed a white blood cell count of 3.5 × 109/L (normal range, 3.2-9.8 × 109/L). Pulmonary function testing was notable for a newly decreased ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) of 64% (2.0 and 3.4 L, respectively) (normal FEV1-to-FVC ratio, 80%), suggesting an obstructive lung process. One month prior to presentation, the patient's sputum cultures grew Pseudomonas and methicillin-resistant Staphylococcus aureus. The patient showed no evidence of active infection at the time of bronchoscopy. Thus, the bacteria were favored to reflect colonization, and antibiotic therapy was not administered at that time. The patient was taking an immunosuppression regimen of mycophenalate mofetil (CellCept; Genentech, San Francisco, Calif) (1 g twice daily), prednisone (10 mg daily), and tacrolimus (Prograf; Astellas Pharma US, Northbrook, Ill) (goal therapeutic range, 12-14 ng/mL). The patient was sent for posteroanterior and lateral chest radiography followed by chest CT ( Figs 1 - 3 ) and fluorine 18 fluorodeoxyglucose PET/CT ( Fig 4 ). [Figure: see text][Figure: see text][Figure: see text][Figure: see text].

PMID: 30020871 [PubMed - in process]

https://ift.tt/2uMFwjM

Diesel engine emission analysis using fuel from diverse emulsification methods

Abstract

The focus of this work is to investigate the emission characteristics of a stationary diesel engine while utilizing an emulsion fuel from a novel preparation process. The emulsion preparation was performed in real time without using any surfactant. Instead of mechanically breaking the water down into droplets, the water is delivered thermally, by changing its phase from gas to liquid. Steam is used in this proposed process, where it will be converted into suspended water droplets once it meets colder diesel. The product is called steam-generated water-in-diesel emulsion fuel (S/D). The method is expected to reduce the moving components of a previous surfactant-less system; therefore, reducing costs and increasing the system reliability. The emission characteristics of S/D were compared with EURO 2 diesel (D2), and a conventional emulsion denoted as E10. E10 was prepared using 10% water (volumetric) and SPAN80 as a surfactant. The emission characterizations were carried out based on the exhaust gas of a single cylinder naturally aspirated CI engine fueled with D2, S/D, and E10. Compared to D2, both emulsions significantly reduced the emissions of nitrogen oxides (NOx) (E10 max ↓58.0%, S/D max ↓40.0%) and particulate matter (PM) (E10 max ↓20.0%, S/D max ↓57.0%).

https://ift.tt/2NvcA7D

Diagnostic performance of 18 F-PSMA-1007 PET/CT in patients with biochemical recurrent prostate cancer

Abstract

Purpose

The introduction of ligands targeting prostate-specific membrane antigen (PSMA), especially ⁶⁸Ga-PSMA-11, has changed the management of patients with prostate cancer (PCa). ¹⁸F-Labelled ligands can be produced in larger amounts and therefore can improve availability for a larger group of patients. The aim of this study was to evaluate the diagnostic performance of the recently introduced ¹⁸F-PSMA-1007 in patients with recurrent PCa.

Methods

This retrospective analysis included 100 consecutive patients with biochemical relapse (mean age 68.75 ± 7.6 years) referred for PSMA PET/CT. Whole-body PET/CT imaging (from the lower limbs to the skull) was performed in all patients 120 min after injection of 338 ± 44.31 MBq ¹⁸F-PSMA-1007. Prostatectomy, radiation beam therapy of the prostate bed and androgen-deprivation therapy had been performed in 92%, 45% and 27% of the patients, respectively. Radiation beam therapy of the prostate bed had been performed in addition to surgery in 38 patients (38%) and 10 patients (10%) had received all three therapy modalities. The probability of a ¹⁸F-PSMA-1007 PET/CT scan suggestive of pathology was compared with the Gleason score (GS) and PSA level.

Results

Of the 100 patients, 95 (95%) showed at least one pathological finding on ¹⁸F-PSMA-1007 PET/CT. The overall median PSA level was 1.34 ng/ml (range 0,04–41.3 ng/ml). The rates of pathological scans were 86%, 89%, 100% and 100% among patients with PSA levels ≤0.5, 0.51–1.0, 1.1–2.0 and > 2.0 ng/ml, respectively. The median GS was 7 (range 5–10). The majority of patients (70) with a GS available had a score in the range 7–9. The rate of pathological scans in these patients was 93% (65/70). The median SUV_max values of the pathological findings were 10.25, 14.32, 13.16 and 28.87 in patients with PSA levels ≤0.5, 0.51–1.0, 1.1–2.0 and >2.0 ng/ml, respectively. The median SUV_max in patients with a PSA level of >2.0 ng/ml was significantly higher than in all other PSA groups.

Conclusion

¹⁸F-PSMA-1007 PET/CT can detect recurrent PCa in a high percentage of patients with biochemical relapse. The probability of a pathological ¹⁸F-PSMA-1007 PET/CT scan seems to be high even in patients with a low PSA level ≤0.5 ng/ml, and this may have a significant impact on the management of this relevant group of patients.

https://ift.tt/2mur6AY

Robustness of eco-industrial symbiosis network: a case study of China

Abstract

As a complex network, eco-industrial symbiosis network is featured with complexity, openness, and non-linearity. A methodology is proposed to analyze and optimize the eco-industrial symbiosis network from the perspective of complex network theory. Structural robustness index and performance robustness index are established as the analysis model. Consequently, a robust method is developed to optimize the eco-industrial symbiosis network system based on the percolation theory. A conceptual framework is put forward to improve the robustness of eco-industrial symbiosis network system by introducing the "spare core" enterprise which is validated by quantitative analysis. The empirical results show that the robustness of eco-industrial symbiosis network varies under both random failure and intentional disturbance scenarios. However, eco-industrial symbiosis network system has strong self-regulation capability as long as the core enterprise is still in operation. It is recommended that supplementary chain could be added to those enterprises with lower network node connectivity to form "spare core" enterprise. This can not only effectively reduce the dependence of other enterprises on core enterprises, but also further improve the robustness of eco-industrial symbiosis network. This methodology is practically validated by a case analysis of eco-industrial park in China. The findings provide useful inputs to the design and operation of eco-industrial parks.

https://ift.tt/2JDfqVG

Arsenic removal from water by metal-organic framework MIL-88A microrods

Abstract

Fe-based metal-organic framework MIL-88A microrods were synthesized by hydrothermal method, which were used to adsorb As(V) in water for the first time. The experimental results indicated that MIL-88A has a very fast adsorption rate towards arsenic in water. The kinetic and isothermal data for arsenic removal were better fitted to the pseudo-second-order kinetic model and Langmuir model, respectively, implying a chemical and monolayer adsorption for As(V) on MIL-88A microrods. Two rate-controlling processes during adsorption were revealed by the intraparticle diffusion model. The maximum adsorption capacity of MIL-88A reached 145 mg g⁻¹, higher than those of Fe-based MIL adsorbents reported previously, which probably originates from its unique microstructure with abundant OH⁻ groups and an unusual large swelling towards water. These show that Fe-based MIL-88A is a good candidate for arsenic removal.

https://ift.tt/2uA2Xxh

Correction to: Effectiveness of adjunctive hyaluronic acid application in coronally advanced flap in Miller class I single gingival recession sites: a randomized controlled clinical trial

The figure 2 of the original version of this article was incorrect. Correct figure is presented below.

https://ift.tt/2uSkBfk

Dupilumab: A Review in Moderate-to-Severe Atopic Dermatitis

Abstract

Dupilumab (Dupixent^®), a subcutaneously administered, fully human IgG4 monoclonal antibody directed against the IL (interleukin)-4 receptor α subunit, blocks the signalling of IL-4 and IL-13, two T helper cell type 2 cytokines implicated in the immunopathology of atopic dermatitis (AD). It is the first biologic therapy to have been approved for the treatment of adult patients with moderate-to-severe AD in the EU and USA. In phase III trials in adults with moderate-to-severe AD who were inadequately controlled with topical medications and/or systemic treatments, such as ciclosporin, or for whom these therapies were not advisable, 16 weeks' treatment with dupilumab as monotherapy or in combination with topical corticosteroids (TCS) improved multiple measures of disease severity, pruritus, sleep disturbance, anxiety and depression, and quality of life compared with placebo. Moreover, the benefits of combination therapy at week 16 were maintained during long-term treatment for up to 1 year. Dupilumab, alone or added to TCS, was generally well tolerated, with low rates of serious adverse events and treatment discontinuations due to adverse events. Common adverse reactions included conjunctivitis, injection-site reactions and oral herpes. Thus, dupilumab represents a valuable new treatment option for adults with moderate-to-severe AD deemed appropriate for systemic therapy, a patient population for whom historically there has been a lack of safe and effective long-term treatments.

https://ift.tt/2NuqGWQ

Testosterone undecanoate and testosterone enanthate injections are both effective and safe in transmen over five years of administration

Clinical Endocrinology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2mtOFKf

Recommendations from the international evidence‐based guideline for the assessment and management of polycystic ovary syndrome

Clinical Endocrinology, EarlyView.


https://ift.tt/2uOYZQW

Correlation between attention‐deficit/hyperactivity disorder, its pharmacotherapy, and thyroid dysfunction: A nationwide population‐based study in Taiwan

Clinical Endocrinology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2mwoJgU

Independent association of serum vitamin D with anti‐Mullerian hormone levels in women with polycystic ovary syndrome

Clinical Endocrinology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2uOYFlc

Mifepristone in the treatment of the ectopic adrenocorticotropic hormone syndrome

Clinical Endocrinology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2msdExE

Fine‐needle aspiration in all thyroid incidentalomas at 18F‐FDG PET/CT: can EU‐TIRADS revise the dogma?

Clinical Endocrinology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2zUqT3t

Issue Information ‐ TOC and Editorial Board

Clinical Endocrinology, Volume 89, Issue 2, Page 117-118, August 2018.


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Cover Image, Volume 88, Issue 6

Clinical Endocrinology, Volume 89, Issue 2, Page i-i, August 2018.


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Issue Information ‐ Instructions for Authors

Clinical Endocrinology, Volume 89, Issue 2, Page 247-248, August 2018.


https://ift.tt/2mwov9y

Diagnostic accuracy of parathyroid hormon levels in washout samples of suspicious parathyroid adenomas: A single center retrospective cohort study

Clinical Endocrinology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2zU6ETP

Long‐term Use of Continuous Subcutaneous Hydrocortisone Infusion Therapy in Patients with Congenital Adrenal Hyperplasia

Clinical Endocrinology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2mwouCw

Melatonin secretion following brain midline irradiation is diminished, but not correlated to subjective sleep disturbances

Clinical Endocrinology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2zW3MWq

Linearized Solar Elastosis of the Legs: A Novel Presentation and Review of the Literature

Journal of Cutaneous Pathology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2LnIaGN

Calcinosis cutis dermatologic toxicity associated with fibroblast growth factor receptor inhibitor for the treatment of Wilms tumor

Journal of Cutaneous Pathology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2uPvU7M

A micorvenular hemangioma with a rare expression of progesterone receptor immunocreativity and a review of the literature

Journal of Cutaneous Pathology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2LnpV4C

Issue Information

Journal of Cutaneous Pathology, Volume 45, Issue 8, August 2018.


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Solitary fibrous tumor presenting on the scalp: a potential diagnostic pitfall

Journal of Cutaneous Pathology, Volume 45, Issue 8, Page 557-560, August 2018.


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Effect of a botanical cleansing lotion on skin sebum and erythema of the face: A randomized controlled blinded half‐side comparison

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2L97Iby

Male‐pattern baldness, common latent viruses, and microcompetition

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2JEBIGD

Multipolydioxanone scaffold improves upper lip and forehead wrinkles: A 12‐month outcome

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2LaS9QD

Evaluation of the efficacy of transdermal drug delivery of calcipotriol plus betamethasone versus tacrolimus in the treatment of vitiligo

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2JDa1xO

Wrinkles, brown spots, and cancer: Relationship between appearance‐ and health‐based knowledge and sunscreen use

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2LaS6Er

Severe vision loss caused by cosmetic filler augmentation: Case series with review of cause and therapy

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2Lykht8

Identification of a novel PLCD1 mutation in Chinese Han pedigree with hereditary leukonychia and koilonychia

Journal of Cosmetic Dermatology, EarlyView.


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Potential of four aquatic plant species to remove 60 Co from contaminated water under changing experimental conditions

Abstract

This study aimed to compare the potential of Lemna minor, Spirodela sp., Eichhornia crassipes and Pistia stratiotes to remove ⁶⁰Co from a realistic aquatic environment. Although all four plant species performed similarly well after 3 days of exposure to 50 kBq L^{−1 60}Co, Lemna minor and Spirodela sp. came forward as having higher ⁶⁰Co removal potential. This conclusion is, in first instance, based on the high ⁶⁰Co removal percentage obtained after a short contact time (e.g. more than 95% could be removed after 6 h by Spirodela sp.). Additionally, Lemna minor and Spirodela sp. accumulated a high amount of ⁶⁰Co per gram of biomass. For example, Lemna minor accumulated over three times more ⁶⁰Co per gram of biomass compared to Pistia stratiotes and Eichhornia crassipes. Both plants also performed well in the pH range 5–9. We used Lemna minor to test the influence of the initial ⁶⁰Co concentration (10, 50, 100 and 200 kBq L^{−1 60}Co) on its phytoremediation capacity but no differences could be observed in removal percentage. In addition, it was shown that by optimising the initial amount of biomass, radioactive waste production can be minimised whilst maintaining high ⁶⁰Co removal rates. Our study shows that these aquatic plants can be used for phytoremediation of ⁶⁰Co from contaminated water and can be considered as a "green" addition or alternative for conventional remediation techniques.

https://ift.tt/2NvDQD2

Persistent pruritic rash, fever, and joint pains in a young female

Australasian Journal of Dermatology, EarlyView.


https://ift.tt/2L6t21n

Giant fibroepithelial polyp of the vulva

Australasian Journal of Dermatology, EarlyView.


https://ift.tt/2JEfx3n

Porphyromonas gingivalis inhibits M2 activation of macrophages by suppressing α‐ketoglutarate production in mice

Molecular Oral Microbiology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2uPu8Dz

Diffuse erythema with ‘angel wings’ sign in Japanese patients with anti‐small ubiquitin‐like modifier activating enzyme antibody‐associated dermatomyositis

British Journal of Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2zST4jD

Mepacrine‐induced interstitial lung disease in discoid lupus erythematosus?

British Journal of Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2mwv10m

Transepidermal water loss in healthy adults: a systematic review and meta‐analysis update

British Journal of Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2zRtw6r

Mosaicism due to postzygotic mutations in women with focal dermal hypoplasia

British Journal of Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2mwVvig

胃造口用于大疱性表皮松解

British Journal of Dermatology, Volume 179, Issue 1, Page e85-e85, July 2018.


https://ift.tt/2uNPOQB

职业性手部湿疹和转职

British Journal of Dermatology, Volume 179, Issue 1, Page e82-e82, July 2018.


https://ift.tt/2mteWs3

Gastrostomy for epidermolysis bullosa

British Journal of Dermatology, Volume 179, Issue 1, Page e71-e71, July 2018.


https://ift.tt/2zRtnzV

Methotrexate injections for psoriasis

British Journal of Dermatology, Volume 179, Issue 1, Page e73-e73, July 2018.


https://ift.tt/2mtXMKQ

FACE‐Q Skin Cancer Module: appearance satisfaction and QoL

British Journal of Dermatology, Volume 179, Issue 1, Page e70-e70, July 2018.


https://ift.tt/2uPlLrX

Nonalcoholic fatty liver disease in psoriasis

British Journal of Dermatology, Volume 179, Issue 1, Page e72-e72, July 2018.


https://ift.tt/2mteWbx

Editors Choice

British Journal of Dermatology, Volume 179, Issue 1, Page xi-xi, July 2018.


https://ift.tt/2uLBFUb

通过注射氨甲喋呤治疗银屑病

British Journal of Dermatology, Volume 179, Issue 1, Page e87-e87, July 2018.


https://ift.tt/2mu7wF2

Fibroblast injection vs. fibroblasts on amniotic membrane in RDEB

British Journal of Dermatology, Volume 179, Issue 1, Page e60-e60, July 2018.


https://ift.tt/2uPsa69

纤维母细胞注射与羊膜纤维母细胞治疗RDEB的对比

British Journal of Dermatology, Volume 179, Issue 1, Page e74-e74, July 2018.


https://ift.tt/2mstMiq

手部湿疹光疗试点试验

British Journal of Dermatology, Volume 179, Issue 1, Page e78-e78, July 2018.


https://ift.tt/2zST2bv

长期日晒与组蛋白乙酰化变化有关

British Journal of Dermatology, Volume 179, Issue 1, Page e75-e75, July 2018.


https://ift.tt/2mwjyxS

检测原位黑色素瘤的算法

British Journal of Dermatology, Volume 179, Issue 1, Page e77-e77, July 2018.


https://ift.tt/2zR8mp2

苏金单抗治疗化脓性汗腺炎

British Journal of Dermatology, Volume 179, Issue 1, Page e76-e76, July 2018.


https://ift.tt/2mwuYlc

Image Gallery: A new source of zoophilic dermatophyte infection

British Journal of Dermatology, Volume 179, Issue 1, Page e4-e4, July 2018.


https://ift.tt/2zR8vc4

银屑病患者中的非酒精性脂肪肝

British Journal of Dermatology, Volume 179, Issue 1, Page e86-e86, July 2018.


https://ift.tt/2ms9Axo

Ecthyma contagiosum (Orf): Reflectance confocal microscopy and histopathological correlates

Skin Research and Technology, EarlyView.


https://ift.tt/2LbzK6b

Reflectance confocal microscopy for the noninvasive diagnosis of cutaneous juvenile xanthogranuloma

Skin Research and Technology, EarlyView.


https://ift.tt/2LxSWaD

Intrinsic and extrinsic regulation of human skin melanogenesis and pigmentation

International Journal of Cosmetic Science, EarlyView.


https://ift.tt/2L97r8C

Standardized extract of wild apple fruit in alkyl‐polyglucoside‐based cosmetic cream – estimation of stability, safety, antioxidant activity and efficiency

International Journal of Cosmetic Science, Volume 40, Issue 3, Page 285-294, June 2018.


https://ift.tt/2JDm5PU

Preservative efficacy of selected antimicrobials of natural origin in a cosmetic emulsion

International Journal of Cosmetic Science, Volume 40, Issue 3, Page 276-284, June 2018.


https://ift.tt/2L97Ho6

Determination of fatty acid methyl esters in cosmetic castor oils by flow injection–electrospray ionization–high‐resolution mass spectrometry

International Journal of Cosmetic Science, Volume 40, Issue 3, Page 295-302, June 2018.


https://ift.tt/2JEaTCt

Hair colour and skin colour together influence perceptions of age, health and attractiveness in lightly pigmented young women

International Journal of Cosmetic Science, Volume 40, Issue 3, Page 303-312, June 2018.


https://ift.tt/2L97elQ

Issue Information

International Journal of Cosmetic Science, Volume 40, Issue 3, Page i-iv, June 2018.


https://ift.tt/2JD1Bq9

News and Notices

Clinical and Experimental Dermatology, Volume 43, Issue 6, Page 756-756, August 2018.


https://ift.tt/2JDQPQE

Issue Information

Clinical and Experimental Dermatology, Volume 43, Issue 6, Page i‐ii, 651-652, August 2018.


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Scholar : Journal of Early Childhood Teacher Education, Volume 39, Issue 3, July-September 2018 is now available online on Taylor & Francis Online

The online platform for Taylor & Francis Online content Journal of Early Childhood Teacher Education, Volume 39, Issue 3, July-September 2018 is now available online on Taylor & Francis Online. This new issue contains the following articles: Original Articles What measures of program quality tell us about the importance of executive function: implications for teacher education and preparation Jennifer Neitzel Pages: 181-192 | DOI: 10.1080/10901027.2018.1457580 Preparing early childhood preservice teachers for science teaching: aligning across a teacher preparation program Christine N. Lippard, Kristina Tank, Melissa C. Walter, Jackie Krogh & Karen Colbert Pages: 193-212 | DOI: 10.1080/10901027.2018.1457578 Mathematics in early childhood: Teacher educators' accounts of their work Kristin Lyn Whyte, M. Abigail Stein, Debbie Kim, Natalie Jou & Cynthia E. Coburn Pages: 213-231 | DOI: 10.1080/10901027.2017.1388306 Research to practice: understanding the role of implicit bias in early childhood disciplinary practices Jennifer Neitzel Pages: 232-242 | DOI: 10.1080/10901027.2018.1463322 The impact of an early intervention home visiting experience on student learning in a dual early childhood/special education graduate preservice program Bonnie Keilty & Sagarika Kosaraju Pages: 243-260 | DOI: 10.1080/10901027.2018.1457579 To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Gene expression profiling identifies distinct molecular signatures in thrombotic and obstetric antiphospholipid syndrome

Publication date: Available online 19 July 2018

Source: Journal of Autoimmunity

Author(s): Vera M. Ripoll, Francesca Pregnolato, Simona Mazza, Caterina Bodio, Claudia Grossi, Thomas McDonnell, Charis Pericleous, Pier Luigi Meroni, David A. Isenberg, Anisur Rahman, Ian P. Giles

Abstract

Antiphospholipid antibodies (aPL) cause vascular thrombosis (VT) and/or pregnancy morbidity (PM). Differential mechanisms however, underlying the pathogenesis of these different manifestations of antiphospholipid syndrome (APS) are not fully understood. Therefore, we compared the effects of aPL from patients with thrombotic or obstetric APS on monocytes to identify different molecular pathways involved in the pathogenesis of APS subtypes. VT or PM IgG induced similar numbers of differentially expressed (DE) genes in monocytes. However, gene ontology (GO) analysis of DE genes revealed disease-specific genome signatures. Compared to PM, VT-IgG showed specific up regulation of genes associated with cell response to stress, regulation of MAPK signalling pathway and cell communication. In contrast, PM-IgG regulated genes involved in cell adhesion, extracellular matrix and embryonic and skeletal development. A novel gene expression analysis based on differential variability (DV) was also applied. This analysis identified similar GO categories compared to DE analysis but also uncovered novel pathways modulated solely by PM or VT-IgG. Gene expression analysis distinguished a differential effect of VT or PM-IgG upon monocytes supporting the hypothesis that they trigger distinctive physiological mechanisms. This finding contributes to our understanding of the pathology of APS and may lead to the development of different targeted therapies for VT or PM APS.

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Scholar : The American Journal of Family Therapy, Volume 46, Issue 2, March-April 2018 is now available online on Taylor & Francis Online

The online platform for Taylor & Francis Online content The American Journal of Family Therapy, Volume 46, Issue 2, March-April 2018 is now available online on Taylor & Francis Online. This new issue contains the following articles: Articles Understanding Infidelity: How Perceptions of Infidelity Behaviors Vary by Sex and One's Own Infidelity Experiences Nathaly Moreno & Emily Pearl Kahumoku-Fessler Pages: 107-121 | DOI: 10.1080/01926187.2018.1441760 Post-Adoption Services for High-Risk Families and Their Children: Preliminary Results of a State-Wide Intervention Raymond V. Burke, The Prevention Group Research Team, Cortney Schlueter, Erin Bader & Karen J. Authier Pages: 122-138 | DOI: 10.1080/01926187.2018.1450687 Neuroticism and Close Relationships: How Negative Affect is Linked with Relationship Disaffection in Couples Irum Saeed Abbasi, Neelam Rattan, Tehmina Kousar & Fatma Khalifa Elsayed Pages: 139-152 | DOI: 10.1080/01926187.2018.1461030 Trauma and Health Symptoms in a Community Sample: Examining the Influences of Gender and Daily Stress Kristin E. Silver, Meera Kumari, Danette Conklin & Gunnur Karakurt Pages: 153-167 | DOI: 10.1080/01926187.2018.1461031 The Role of Attachment Anxiety and Avoidance in Communication Modality and Relationship Quality of Romantic Relationships Initiated Online Eric T. Goodcase, David P. Nalbone, Lorna L. Hecker & Christopher Latty Pages: 168-183 | DOI: 10.1080/01926187.2018.1461032 Feasibility of Biological Sample Collection among a High-Risk Maternal Population for Child Maltreatment-Qualitative Pilot Findings Ashwini Tiwari & Shannon Self-Brown Pages: 184-194 | DOI: 10.1080/01926187.2018.1461033 Goal Effectiveness and Family Functioning Phillip Klever Pages: 195-212 | DOI: 10.1080/01926187.2018.1461581 To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : These new articles for Journal of Architectural Conservation are available online

The online platform for Taylor & Francis Online content New for Journal of Architectural Conservation and online now on Taylor & Francis Online: Original Articles Life cycle assessment and historic buildings: energy-efficiency refurbishment versus new construction in Norway | Fredrik Berg & Mie Fuglseth Pages: 1-16 | DOI: 10.1080/13556207.2018.1493664 To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : These new articles for Latin American Business Review are available online

The online platform for Taylor & Francis Online content New for Latin American Business Review and online now on Taylor & Francis Online: Errata Erratum Pages: 1-1 | DOI: 10.1080/10978526.2018.1483132 To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : These new articles for Activities, Adaptation & Aging are available online

The online platform for Taylor & Francis Online content New for Activities, Adaptation & Aging and online now on Taylor & Francis Online: Original Articles Effects of Exercise Interventions in Older Adults with Various Types of Dementia: Systematic Review Juyoung Park & Iris Cohen Pages: 1-35 | DOI: 10.1080/01924788.2018.1493897 Adaptation to Loss of Visual Function: Implications for Rehabilitation on Subtle Nuances of Communication Patrick Emeka Okonji, Catherine Bailey, Monique Lhussier & Mima Cattan Pages: 1-17 | DOI: 10.1080/01924788.2018.1500056 Older Adults' Perspectives on Volunteering in an Activity-Based Social Program for People with Dementia Areum Han, Diane Brown & Amber Richardson Pages: 1-19 | DOI: 10.1080/01924788.2018.1500055 FREE ACCESS: Health Care for Women International: Research on Women's Health in Africa: Issues, Challenges & Opportunities To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Treatment of synthetic dye baths by Fenton processes: evaluation of their environmental footprint through life cycle assessment

Abstract

Inorganic and organic constituents present in textile effluents have a noticeable effect on the performance of Fenton processes. However, studies have been focused on simple wastewater matrices that do not offer enough information to stakeholders to evaluate their real potential in large-scale facilities. Chemical auxiliaries, commonly present in textile wastewaters (NaCl = 30 g/L, Na₂CO₃ = 5 g/L, and CH₃COONa = 1 g/L), affect both the economic and environmental performance of the process because they increase the treatment time (from 0.5 to 24 h) and the consumption of H₂SO₄ (657%) and NaOH (148%) during conditioning steps. The life cycle assessment (LCA) performed with the IPCC-2013 method revealed that dyeing auxiliaries increase from 1.06 to 3.73 (252%) the emissions of carbon dioxide equivalent (CO₂-Eqv/m³). Electricity consumption can be considered an environmental hotspot because it represents 60% of the carbon footprint of the Fenton process. Also, the presence of auxiliaries is critical for the process because it results in the increase of the relative impact (between 50 and 80%) in all environmental categories considered by the ReCiPe-2008 method. Chemical auxiliaries increased the costs of the treatment process in 178% (US$2.22/m³) due to the higher energy consumption and the additional reagent requirements. It is worthwhile mentioning that the technical simplicity of the Fenton process and its low economic and environmental costs turn this process into an attractive alternative for the treatment of textile effluents in emerging economies.

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Measuring herpes zoster disease burden in São Paulo, Brazil: a clinico-epidemiological single-center study

OBJECTIVES: Herpes zoster is characterized by acute neuritis and post-herpetic neuralgia. Currently, data concerning the zoster-associated impact on quality of life and healthcare resource utilization in Brazil are scarce. This study measured the zoster-associated burden in a Brazilian population. METHODS: This was a prospective, observational, single-cohort study conducted in a primary hospital's emergency room in São Paulo, Brazil. Patients enrolled at various timepoints during a zoster episode were followed over 180 days. The Zoster Brief Pain Inventory and the Initial Zoster Impact Questionnaire assessed zoster-associated pain. The EuroQoL assessed the impact of herpes zoster and/or zoster-associated pain on quality of life. Healthcare resource utilization was assessed by patient-reported questionnaires. RESULTS: One-hundred forty-six zoster patients were enrolled [mean (SD) age of 69.9 (10.9) years]. Mean (SD) worst pain scores decreased from 5.3 (3.5) at baseline to 1.9 (3.0) 180 days following rash onset. Mean (SD) EuroQoL scores significantly decreased from 0.9 (0.2) before rash appearance to 0.7 (0.2) after rash onset (p<0.001), followed by gradual improvements in quality of life over 180 days, with pre-herpes zoster quality of life achieved at the end of the observation period. The majority of patients purchased prescription medications (89.7%) and required doctor's office visits (65.8%) for zoster episodes. CONCLUSIONS: Herpes zoster is associated with a significant disease burden, including zoster-associated pain, impaired quality of life and increased healthcare resource utilization in Brazil. These results support the implementation of early intervention and prevention programs such as vaccinations to reduce the herpes zoster-associated disease burden in Brazil.

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Clinical Application of Atlantoaxial Pedicle Screw Placement Assisted by a Modified 3D-Printed Navigation Template

OBJECTIVES: To investigate the primary clinical value of atlantoaxial pedicle screw placement assisted by a modified 3D-printed navigation template. METHODS: We retrospectively analyzed the cases of 17 patients treated from June 2015 to September 2016 with atlantoaxial pedicle screw placement assisted by a modified 3D-printed navigation template. All procedures were performed prior to surgery, including thin-slice CT scanning, medical image sampling and computerized 3D modeling of the atlantoaxial joint, optimal pedicle screw trajectory determination, and anatomical trait acquisition for the atlantoaxial pedicle, spinous process of the axis, vertebral lamina and posterior lateral mass, and design of a reverse template. During surgery, a navigation template was tightly attached to the atlantoaxial joint to assist in pedicle screw placement. Surgeons subsequently used an electric drill to remove the template through a guide channel and then placed the atlantoaxial pedicle screw. Observed indexes included the VAS score, JOA improvement rate, surgery duration, and blood loss. RESULTS: Surgery was successful in all 17 patients, with an average operation duration of 106±25 min and an average blood loss of 220±125 ml. Three days postoperatively, the VAS score decreased from 6.42±2.21 to 3.15±1.26. Six months postoperatively, the score decreased to 2.05±1.56. The postoperative JOA score increased significantly from 7.68±2.51 to 11.65±2.72 3 d after surgery and to 13.65±2.57 after 6 months. Sixty-eight pedicle screws were inserted successfully, with 34 in the atlas and 34 in the axis. According to the Kawaguchi standard, 66 screws were in grade 0 (97.06%), and 2 were in grade 1 (2.94%). The pre- and postoperative transverse and sagittal screw angles showed no significant differences. CONCLUSIONS: Atlantoaxial pedicle screw placement assisted by a modified 3D-printed navigation template is worth recommending due to the improved accuracy in screw placement, improved patient safety and beneficial clinical effects.

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Scholar : These new articles for Critical Discourse Studies are available online

The online platform for Taylor & Francis Online content New for Critical Discourse Studies and online now on Taylor & Francis Online: Original Articles Religious solidarity, historical mission and moral superiority: construction of external and internal 'others' in AKP's discourses on Syrian refugees in Turkey Rabia Karakaya Polat Pages: 1-17 | DOI: 10.1080/17405904.2018.1500925 To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Regarding the Congruence Between 2 Circulating Tumor DNA Sequencing Assays—Reply

In Reply We thank Oxnard and Paweletz for their comments on our article. Kuderer et al demonstrated similar discrepancies comparing Guardant360 with tumor tissue, being more frequent at low variant allele fractions (VAFs). However, we disagree that including VAFs "would allow the reader to fully understand the data" because it could only partially explain the discrepancies, and its inclusion would be only mildly informative because it would be necessary to reanalyze the DNA to determine the true nature of these discrepancies with the caveat that other major factors such as timing and processing methods would not be considered.

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Analytical Validity and Clinical Utility of Tumor Biomarkers

To the Editor In his recent editorial, Dr Hayes correctly noted that "analytical validity and clinical utility" are needed for the adoption of a tumor biomarker test into clinical care. However, proving analytical validity with correlative or concordance studies is largely irrelevant without first proving clinical utility.

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A New Dark Skin Lesion in a 3-Year-Old Undergoing Acute Lymphoblastic Leukemia Induction Therapy

A 3-year-old girl with B-cell acute lymphoblastic leukemia and no known skin trauma presented with an asymptomatic skin lesion with violaceous to black plaque, a central hemorrhagic bulla, and surrounding hyperemia on the left lower back. What is your diagnosis?

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Regarding the Congruence Between 2 Circulating Tumor DNA Sequencing Assays

To the Editor We read with interest the article by Torga and Pienta. They address a timely and important subject, not just for liquid biopsies but also for other commercial next-generation sequencing offerings, and delve deeper into the need for rigorous analytical validation of assays that are used widely in patient care. Unfortunately, there are some key pieces of information missing to allow the reader to fully understand the data. The authors do not provide the variant type or allele frequencies (AFs) for called variants, which is important given different reporting criteria for different assays. Moreover, Stetson et al showed in a similar comparison much greater concordance for variants called at greater than 1% AFs, but striking variability with AFs of less than 1%. Having this information would allow for a discussion as to the difficulties in interpreting plasma next-generation sequencing with low AF results. The study by Torga and Pienta does succeed in cautioning the reader that not all laboratory-developed tests are created equal, and points to a need for rigorously validated reference materials for all assays to benchmark against in the pursuit of more consistent reporting of these important clinical results.

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Complementary Medicine, Refusal of Cancer Therapy, and Survival Among Patients With Curable Cancers

This cohort study compares overall survival, treatment adherence, and patient characteristics among patients with cancer receiving conventional cancer treatment with vs without complementary medicine.

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Regarding the Congruence Between 2 Circulating Tumor DNA Sequencing Assays

To the Editor Torga and Pienta reported low congruence between 2 circulating tumor DNA sequencing assays in 40 patients with metastatic prostate cancer. However, the mutant allele fraction (MAF) of reported genomic alterations, which may help clarify the cause of low congruence, is unmentioned in their report. Other than analytical factors, sampling error may affect the replicability of the circulating tumor DNA testing result when genomic alterations with low MAF are encountered. Five to 30 ng (ie, 1500-9000 genome equivalents) of cell-free DNA was used as input material in the Guardant360 assay. For example, for an alteration with an MAF of 0.1% and a cell-free DNA sample of 5 ng (ie, 1500 genome equivalents), the possibility that no single copy of the DNA molecule of the alteration is present in the sample is 22.3% (possibility that the DNA molecule of the alteration is not present in a given genome equivalent = 1 − 0.001 = 0.999; possibility that the DNA molecule of the alteration is not present in all 1500 genome equivalents = 0.999¹⁵⁰⁰ ≈ 0.223). In other words, 22.3% of testing results of the alteration are negative simply due to chance. Therefore, the possibility of congruence between 2 assays for this alteration is as low as 65.4% (possibility of negative results in both assays ≈ 0.223 × 0.223 ≈ 0.050; possibility of positive results in both assays ≈ 0.777 × 0.777 ≈ 0.604; possibility of congruence ≈ 0.050 + 0.604 = 0.654). Furthermore, the congruence may be even lower if analytical factors are considered. Thus, MAF data may provide insights into the root cause of low congruence between these 2 assays.

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Regarding the Congruence Between 2 Circulating Tumor DNA Sequencing Assays

To the Editor The recent analysis by Torga and Pienta attempted to evaluate 2 liquid biopsy test platforms (Guardant360 and PlasmaSELECT) and found "low congruence for the same patient-paired samples." However, having reanalyzed their available data, we conclude that the authors inappropriately performed a qualitative comparison of 2 quantitative tests with different reporting standards, resulting in a misrepresentation of the underlying data and misleading conclusions. Correcting for these issues, we instead find 91% patient-level concordance between the 2 tests and 100% concordance for results associated with indicated therapies.

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Regarding the Congruence Between 2 Circulating Tumor DNA Sequencing Assays

To the Editor The recent Research Letter comparing 2 cell-free DNA next-generation sequencing tests in prostate cancer has severe methodological flaws. It improperly confuses clinicians and implies that laboratory accreditation standards are lax. Published cell-free DNA test concordance study design criteria include:

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Monthly High-Dose Vitamin D Supplementation and Cancer Risk

This post hoc analysis of the Vitamin D Assessment randomized clinical trial assesses the association of monthly high-dose vitamin D supplementation vs placebo on cancer risk among New Zealand adults.

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Regarding the Congruence Between 2 Circulating Tumor DNA Sequencing Assays

To the Editor The blood-diagnostics field has evolved in the past decade, realizing the ability to detect driver mutations and resistance clones, allowing the application of targeted therapies and the concept of molecular selection and therapeutic monitoring using "liquid biopsy." Recently in JAMA Oncology, Torga and Pienta reported divergent results between 40 patient-paired blood samples in advanced prostate cancer using 2 commercially available cell-free circulating tumor DNA (ctDNA) tests (Guardant360 and PlasmaSelect). The results indicated low congruence between the 2 tests, and the authors concluded that the data were concerning with regard to standard clinical use of ctDNA.

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Transforming Growth Factor β Polymorphism C−509T and Radiation-Induced Fibrosis in Breast Cancer

This cohort study of female participants with stage 0 to IIA breast cancer treated with breast-conserving surgery and whole-breast irradiation assesses whether radiation-induced toxicities of normal breast tissue 3 years after radiotherapy are associated with the transforming growth factor β gene variant C−509T.

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Ethical Implications of Direct-to-Consumer Hereditary Cancer Tests

This Viewpoint examines the ethics of informed consent and test result disclosure associated with direct-to-consumer genetic testing for hereditary cancer susceptibility.

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A Study of Anlotinib in Recurrent/Metastatic Head and Neck Adenocarcinomas

Conditions:   Head and Neck Carcinoma;   Adenocarcinoma;   Recurrent Disease;   Distantly Metastatic Malignant Neoplasm
Intervention:   Drug: Anlotinib
Sponsor:   Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
Not yet recruiting

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Effectiveness of Manual Therapy vs Exercises With Foam Rolling for Tension Headache

Condition:   Tension-type Headache
Interventions:   Other: Manual Therapy protocol;   Other: Foam Rolling protocol;   Other: Placebo control
Sponsor:   University of Valencia
Recruiting

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Editorial Board

Publication date: August 2018

Source: Autoimmunity Reviews, Volume 17, Issue 8

Author(s):

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The pH-altering agent omeprazole affects rate but not the extent of ibrutinib exposure

Abstract

Purpose

This drug-interaction study evaluated the effect of omeprazole, a proton-pump inhibitor, on ibrutinib's pharmacokinetics (PK) in healthy participants.

Methods

This open-label, sequential-design study included 20 healthy adults aged 18–55 years. Ibrutinib (560 mg, single dose) was administered after an overnight fast alone on day 1 and with omeprazole on day 7. Omeprazole (40 mg) alone was administered on days 3–6, 1 h before breakfast; and after an overnight fast on day 7, followed by ibrutinib 2 h later. Blood was sampled on days 1 and 7 for up to 48 h postdose, and the standard PK parameters for ibrutinib and PCI-45227 were summarized using descriptive statistics. The effect of omeprazole on ibrutinib's PK was determined by assessing geometric mean ratios (GMRs) and 90% CIs. Mechanistic modeling was performed using the BTK-receptor occupancy (RO) model.

Results

AUC_48h and AUC_last of ibrutinib plus omeprazole versus ibrutinib alone showed a modest decrease (GMR [90% CI] 98.3% [83.1–116.3] and 92.5% [77.8–109.9], respectively); C_max decreased by 62.5% (GMR [90% CI] 37.5% [26.4–53.4]), with delayed t_max (1−2 h) and terminal half-life unaffected. Mean AUC for PCI-45227 (primary metabolite) was ~ 20% lower with ibrutinib plus omeprazole versus ibrutinib alone. Model predictions showed no impact of decreased C_max on BTK target engagement. No new safety signals were identified with the use of ibrutinib in this study.

Conclusions

The decrease in C_max without a corresponding decrease in AUC by omeprazole was not clinically relevant for ibrutinib's bioavailability. No dose adjustments are recommended during ibrutinib's co-administration with omeprazole or other pH-altering agents.

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Phase II study of pazopanib in combination with paclitaxel in patients with metastatic melanoma

Abstract

Purpose

This phase II study evaluated the safety and clinical activity of pazopanib, a potent and mutlitargeted tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptors (VEGFRs)-1, -2 and -3, platelet-derived growth factor receptor (PDGFR)-α and β, and cKit, in combination with metronomic paclitaxel in patients with metastatic melanoma.

Experimental design

Sixty chemotherapy-naive patients received pazopanib at a starting dose of 800 mg daily in combination with metronomic dosing of paclitaxel 80 mg/m² weekly thrice every 4 weeks. The primary endpoint was 6-month progression-free survival (PFS) rate, while secondary endpoints included 1-year overall survival rate, RECIST response rates, progression-free survival rates and median overall survival. Prior BRAF-targeted therapy or checkpoint inhibitors were permitted.

Results

The 6-month PFS rate was 68%, with a 1-year OS rate of 48%. Objective response rate was 37% comprising one complete and 20 partial responses. Stable disease at 8 weeks was noted in 32 patients (55%) with an overall clinical benefit rate of 93%. Six-month median progression-free survival was 8 months and median OS was 12.7 months. The most frequently (> 15%) reported non-hematologic, treatment-related adverse events were fatigue, diarrhea, hypertension, transaminitis and peripheral neuropathy. Treatment-related non-fatal bowel perforation, a known class effect, occurred in one patient. No significant association was noted between plasma levels of pazopanib and response.

Conclusions

The combination of pazopanib and metronomic paclitaxel was well-tolerated, demonstrating significant activity in metastatic melanoma. Further evaluation of this combination is warranted.

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Clinical pharmacokinetics and safety profile of single agent arsenic trioxide by continuous slow-rate infusion in patients with newly diagnosed acute promyelocytic leukemia

Abstract

Purpose

This study evaluated pharmacokinetics (PK) and safety profiles of single agent arsenic trioxide (ATO, As₂O₃) administrated as continuous slow-rate infusion in patients with newly diagnosed acute promyelocytic leukemia.

Patients and methods

Patients received 0.16 mg/kg ATO per day. ATO was given for 40 min infusion on the first day followed by 18–20 h daily at a very slow rate with infusion speed of 8 drips/min. During the first week, plasma samples were collected immediately before next administration on each day, and 0.5, 1, 2, 4, 8, 12 h after administration, at the end of infusion (18 h) on day 7. Total arsenic was determined by ICPMS. Arsenic species, arsenious acid (As^III) and its metabolites, monomethylarsonic acid (MMA^V) and dimethylarsinic acid (DMA^V), were quantified by UHPLC-ICPMS. Safety assessment and PK analysis was conducted.

Results

Hyperleukocytosis occurred in two patients and no severe toxicity was observed. Total arsenic gradually accumulated from 15.84 to 34.12 ng/mL during the first week of therapy. MMA^V/iAs increased and remained stable at value about 0.6 after day 4, while DMA^V/MMA^V declined under 2 after day 4. Compared with 2 h infusion, clearance (CL) of As^III was significantly lower (0.8 ± 0.2 vs. 2.7 ± 1.7 L/kg/h, P = 0.002) while AUC_0–t of As^III was significantly increased (213.9 ± 38.6 vs. 82.6 ± 55.7 L/kg/h, P = 0.028).

Conclusion

Continuous slow-rate ATO infusion provided an alternative administration for ATO therapy with few toxic effects. Degree of methylation from MMA to DMA is inconsistent with that from iAs to MMA. PK of arsenic species is considered important for clinical use of ATO.

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The association of polymorphisms in folate-metabolizing genes with response to adjuvant chemotherapy of colorectal cancer

Abstract

Background

Colorectal cancer (CRC) is one of the major health issues worldwide. 5-Fluorouracil (5-FU) is a cornerstone of chemotherapy for CRC and the major targets of 5-FU are folate-metabolizing enzymes.

Methods

A total of 103 CRC patients with complete clinical data were included in this prospective cohort study. Genotyping was performed using polymerase chain reaction (PCR) followed by sequencing. Using Kaplan–Meier curves, log-rank tests, and Cox proportional hazard models, we evaluated associations between functional polymorphisms in four genes MTHFR (1298A>C and 677C>T), DPYD (496A>G and 85T>C), DHFR 19 bp del, and MTR (2756 A>G) with disease-free survival (DFS).

Results

The minor allele frequencies of MTHFR 1298A>C, MTHFR 677C>T, DPYD 496A>G, DPYD 85T>C, DHFR 19 bp del, and MTR 2756 A>G were 0.364, 0.214, 0.116, 0.209, 0.383, and 0.097, respectively. CRC patients carrying the homozygous GG genotype in DPYD 496A>G had 4.36 times shorter DFS than wild-type AA carriers, (DFS_GG vs _AA: 8.0 ± 4 vs 69.0 ± 10 months; HR 4.36, 95% CI 1.04–18; p = 0.04). Moreover, female carriers of homozygous CC genotype of DPYD 85T>C had shorter DFS compared to either heterozygous or wild-type genotypes, and were 12.7 times shorter than wild-type TT carriers (DFS_{CC vs TT}: 5.0 ± 1.5 vs 42.0 ± 7.6 months; HR 12.7, 95% CI 2.2–71.4; p = 0.004). However, there were no significant associations with the other studied polymorphisms.

Conclusion

Genetic polymorphism in DPYD seems to be associated with DFS in CRC patients receiving an adjuvant regimen of 5-FU/capecitabine-based chemotherapy. Further studies are needed to verify these findings.

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Therapeutic drug monitoring and dose adaptation of cisplatin in a newborn with hepatoblastoma: a case report

Abstract

Purpose

Chemotherapy dosing in neonates represents a major clinical challenge because of a lack of clinical pharmacology information in this patient population. In this study, we investigate the use of cisplatin dose adaptation based on therapeutic drug monitoring in a 2-week-old neonate with localized hepatoblastoma.

Methods

Cisplatin concentrations were determined in plasma and ultrafiltrate samples collected on each of six cycles of a monotherapy regimen, beginning with a dose of 1.6 mg/kg at 16 days of age. Pharmacokinetic data were analyzed to generate clearance (CL) and area under the curve (AUC_0–∞) for each administration. Toxicity and clinical response were monitored.

Results

The first cisplatin dose (1.6 mg/kg) resulted in an AUC_0–∞ of 535 µg/mL · min, was well tolerated and associated with a good response. This AUC was, therefore, considered as an appropriate target for this patient. Increases in cisplatin CL were observed across consecutive treatment cycles, and, therefore, dose was gradually increased to finally reach 2.5 mg/kg on the sixth cycle. Treatment was well tolerated over the six courses and resulted in a good response, with the patient remaining in remission at 15 months. Cisplatin CL was significantly correlated to age (p = 0.013) and weight (p = 0.013).

Conclusions

Our study provides useful data on the pharmacokinetics of cisplatin monotherapy in neonates treated within the first few weeks of life. These data provide a reference point to support clinicians in determining appropriate dosing regimens for neonates and support the implementation of therapeutic drug monitoring in such challenging patients.

https://ift.tt/2uzV9vD

A pharmacodynamic study of sirolimus and metformin in patients with advanced solid tumors

Abstract

Background

Sirolimus is a mammalian target of rapamycin (mTOR) inhibitor. Metformin may potentiate mTOR inhibition by sirolimus while mitigating its adverse effects. We conducted a pilot study to test this hypothesis.

Methods

Patients with advanced solid tumor were treated with sirolimus for 7 days followed by randomization to either sirolimus with metformin (Arm A) or sirolimus (Arm B) until day 21. From day 22 onwards, all patients received sirolimus and metformin. The primary aim was to compare the change in phospho-p70S6K (pp70S6K) in peripheral blood mononuclear cells (PBMC) from day 8 to day 22 using a two-sample t test. Secondary aims were objective response rate, toxicity, and other serum pharmacodynamic biomarkers (e.g., fasting glucose, triglycerides, insulin, C-peptide, IGF-1, IGF-1R, IGF-BP, and leptin).

Results

24 patients were enrolled, with 18 evaluable for the primary endpoint. There was no significant difference in mean change in pp70S6K in arm A vs. arm B (− 0.12 vs. − 0.16; P = 0.64). Similarly, there were no significant differences in other serum pharmacodynamic biomarkers. There were no partial responses. There were no dose-limiting or unexpected toxicities.

Conclusions

Adding metformin to sirolimus, although well tolerated, was not associated with significant changes in pp70S6K in PBMC or other serum pharmacodynamic biomarkers.

Impact

Combining metformin with sirolimus did not improve mTOR inhibition.

https://ift.tt/2A2pNTJ

Relationship of peak serum methotrexate concentration to prognosis and drug tolerance in non-metastatic extremity osteosarcomas

Abstract

Purpose

This study aimed to explore whether peak serum methotrexate concentration (C_max) correlated with adverse events, overall survival (OS) and event-free survival (EFS) in patients with primary extremity osteosarcoma.

Methods

Patients with extremity osteosarcoma who were treated at our center between 2005 and 2015 were retrospectively studied. All the patients were Enneking stage II and had received standard perioperative chemotherapy composed of high-dose methotrexate, doxorubicin, cisplatin and ifosfamide. C_max and treatment-associated toxicities of each cycle were recorded. OS and EFS were estimated and compared by Kaplan–Meier survival analysis, and Cox regression models were performed for univariate comparisons.

Results

In total, 567 patients were followed for an average of 53 months (24–104 months). The estimated 3- and 5-year EFS were 71.7 and 63.1%, and the 3- and 5-year OS were 78.2 and 72.9%, respectively. C_max ranged from 527 to 2495 µmol/L with a mean value of 931 ± 106 µmol/L. No significant differences in EFS and OS (p = 0.18 and p = 0.28) were observed among patients with a mean C_max > 1500, > 1000, > 700 and < 700 µmol/L. However, patients with a mean C_max > 1500 µmol/L had significantly increased rates of grade 3–5 toxicity. In the univariate analysis, C_max was not a prognostic factor for EFS (p = 0.08) or OS (p = 0.16).

Conclusions

C_max did not correlate significantly with the oncologic prognosis of non-metastatic extremity osteosarcoma patients treated by multi-agent chemotherapy; however, C_max correlated closely with toxicities and complications. The persistent inclusion of methotrexate in classical multidisciplinary chemotherapy was questioned and should be examined in future trials.

https://ift.tt/2uvg571

Reply to: Relationship between LAT1 expression and resistance to chemotherapy in pancreatic ductal adenocarcinoma

https://ift.tt/2A2pKav

Over-adherence to capecitabine: a potential safety issue in breast and colorectal cancer patients

Abstract

Purpose

The aim of the OCTO clinical study was to measure patients' adherence to capecitabine-based treatment.

Methods

A cohort of ambulatory patients treated with capecitabine monotherapy for either locally advanced or metastatic, breast or colorectal cancer was monitored for 6 cycles. Adherence was assessed in all patients by self-completed questionnaires on disease, pill-count and pharmacological dosage of FBAL (metabolite of capecitabine); and in half of the cohort by electronic medication event monitoring systems (MEMS™) recording the opening times of the device.

Results

Forty patients were enrolled between November 2008 and September 2011 and treated by capecitabine for an average of 4.75 cycles (range 1–6). Hand-foot syndrome (HFS) was the most frequently reported toxicity (35% patients), and to a lesser extent fatigue and/or asthenia (21%), nausea and/or vomiting (13%) and diarrhea (11%). In the MEMS™ cohort, 20 patients were included. Patients' adherence was excellent with very few missing occasions (23/2272 records). Close analysis of MEMS™ data revealed unexpected medication patterns, such as patients taking extra days of medication beyond planned cycle, patients taking extra doses per day and patients missing a day of dosing and "compensating" by taking extra the following day (N = 7, 18%). A trend was found between over-adherence and high-grade toxicity (grades 3 and/or 4): OR 4.74 [0.65–45.2], p = 0.13 and higher AUC (p = 0.16). There was a trend towards increased AUC of FBAL in over-adherent patients (p = 0.16).

Conclusion

Adherence to oral anticancer chemotherapy was found excellent in this population suggesting over-adherence to capecitabine and potential safety implications for outpatients' drugs.

https://ift.tt/2uwE2Lk