Alibertia edulis (L.C. Rich.) A.C. Rich – A potent diuretic arising from Brazilian indigenous species

Publication date: 20 January 2017
Source:Journal of Ethnopharmacology, Volume 196
Author(s): Diana Figueiredo de Santana Aquino, Cleide Adriane Signor Tirloni, Sara Emília Lima Tolouei Menegati, Claudia Andrea Lima Cardoso, Silvia Cristina Heredia Vieira, Maria do Carmo Vieira, Ana María Simonet, Francisco Antonio Macías, Arquimedes Gasparotto
Ethnopharmacological relevanceAlthough Alibertia edulis (L.C. Rich.) A.C. Rich decoction is used in Brazilian folk medicine due to its possible antihypertensive effect, this species has never been critically investigated as a hypotensive drug. So, the aim of this study was to evaluate the possible hypotensive and antihypertensive effects of the oral administration of Alibertia edulis aqueous extract (AEAE) in normotensive and hypertensive rats, and evaluate its inter-relation with a possible diuretic activity.Material and methodsDifferent doses of AEAE (20, 65 and 200mg/kg) were tested on the mean arterial pressure (MAP) of normotensive Wistar rats and after induction of renovascular hypertension (two-kidney, one-clip Goldblatt model). In addition, the diuretic effects of AEAE were compared with hydrochlorothiazide (HCTZ) in an acute and repeated-dose treatment for 7 days. Volume, sodium, potassium, chloride, calcium contents, pH and density were estimated in urine samples collected after 8 or 24h. Plasma sodium, potassium, total protein, urea, creatinine, AST and ALT concentrations were measured in samples collected at the end of the experimental period (seventh day). Finally, the antioxidant activity of the AEAE was assessed using the DPPH radical scavenging and ferric ions reducing power assay.ResultsThe intraduodenal administration of the HCTZ and AEAE significantly reduced, in a dose-dependent manner, the MAP in both normotensive and hypertensive rats. Otherwise, the heart rate was not affected by any treatment. Acute and prolonged oral administration of AEAE (200mg/kg) and HCTZ caused a significant increase in volume and urinary concentrations of sodium, potassium and chloride. Moreover, urinary calcium concentration was significantly increased after administration of AEAE (200mg/kg). Finally, AEAE was able to present important in vitro antioxidant properties.ConclusionThe results obtained have shown that AEAE presents potent diuretic activity and significant hypotensive and antihypertensive effect. In addition, this study may confirm part of the pharmacological activity popularly attributed to this species and opens perspective for the future use in various renal and cardiovascular diseases.

Graphical abstract

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A systematic review and network meta-analysis of neoadjuvant therapy combined with surgery for patients with resectable esophageal squamous cell carcinoma

Publication date: Available online 24 December 2016
Source:International Journal of Surgery
Author(s): Yuanwei Huang, Haidong Wang, Ganfeng Luo, Yanting Zhang, Li Wang, Ke Li
BackgroundThe role of neoadjuvant therapy combined with surgery for treating esophageal squamous cell carcinoma (ESCC) remains controversial. We performed a network meta-analysis to synthesize direct and indirect evidence to identify the optimal therapeutic method for ESCC.MethodsWe identified 15 randomized controlled trials that compared any of the following 4 therapeutic measures: surgery alone (S), preoperative chemotherapy followed by surgery (CTS), preoperative radiotherapy followed by surgery (RTS), and preoperative chemoradiotherapy followed by surgery (CRTS). The main outcomes were 5-year survival, rate of radical resection, operative mortality and postoperative complications.ResultsNetwork meta-analysis showed that CRTS was associated with improved survival as compared with S (OR = 1.50 [95% CI 1.21 to 1.97]) and decreased occurrence of complications as compared with RTS (OR = 0.50 [95% CI 0.22 to 0.99]). Direct evidence revealed CRTS associated with improved survival (OR = 1.61 [95% CI 1.01 to 2.57]) and radical resection (OR = 4.01 [95% CI 1.66 to 9.69]) as compared with S. In terms of radical resection, CTS was more effective than S (OR = 1.73 [95% CI 1.09 to 2.76]). Findings for CTS and RTS did not differ for 5-year survival, operative mortality and postoperative complications.ConclusionsOverall, CRTS might be the best choice for resectable ESCC because it could increase the radical resection rate and lower the occurrence of complications, thereby prolonging survival time.



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Mechanical properties of nanostructured films with an ultralow volume fraction of hard phase

Publication date: 27 January 2017
Source:Polymer, Volume 109
Author(s): Marion Chenal, Cyril Véchambre, Jean-Marc Chenal, Laurent Chazeau, Vincent Humblot, Laurent Bouteiller, Costantino Creton, Jutta Rieger
We demonstrate in this paper how polymerization induced self-assembly (PISA) using RAFT can be used to synthesize very asymmetric but monodisperse poly(acrylic acid)-b-poly(n-butyl acrylate) block copolymers, PAA-b-PBA, with a short PAA block and a long PBA block. In the course of the surfactant-free emulsion polymerization, core-shell particles form in water, with the short hydrophilic block located at the water-particle interface, and the long hydrophobic block constituting the particle core. Drying at room temperature creates films possessing an out of equilibrium structure, where the glassy PAA block generates a percolating network of shells. When deformed in uniaxial elongation, these films combine a high stiffness in small strains (considering the low volume fraction of PAA, of only 3 wt%), a yield stress and a significant extensibility before failure. The modulus, yield stress and extensibility can be tuned by modifying the composition of the latex serum with cations or positively charged low molar mass polymers, or by changing the copolymer composition. Of particular interest was the synthesis by PISA of particles of triblock copolymer PAA-b-PBA-b-PS. The out of equilibrium structure obtained had a very interesting combination of high stiffness, extensibility and high fracture toughness.

Graphical abstract

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Pleiotropic effects of oxidized phospholipids

Publication date: Available online 24 December 2016
Source:Free Radical Biology and Medicine
Author(s): Valery Bochkov, Bernd Gesslbauer, Christina Mauerhofer, Maria Philippova, Paul Erne, Olga V. Oskolkova
Oxidized phospholipids (OxPLs) are increasingly recognized to play a role in a variety of normal and pathological states. OxPLs were implicated in regulation of inflammation, thrombosis, angiogenesis, endothelial barrier function, immune tolerance and other important processes. Rapidly accumulating evidence suggests that OxPLs are biomarkers of atherosclerosis and other pathologies. In addition, successful application of experimental drugs based on structural scaffold of OxPLs in animal models of inflammation was recently reported. This review briefly summarizes current knowledge on generation, methods of quantification and biological activities of OxPLs. Furthermore, receptor and cellular mechanisms of these effects are discussed. The goal of the review is to give a broad overview of this class of lipid mediators inducing pleiotropic biological effects.



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Modulation of ventral striatal activity by cognitive effort

Publication date: 15 February 2017
Source:NeuroImage, Volume 147
Author(s): Ekaterina Dobryakova, Ryan K. Jessup, Elizabeth Tricomi
Effort discounting theory suggests that the value of a reward should be lower if it was effortful to obtain, whereas contrast theory suggests that the contrast between the costly effort and the reward makes the reward seem more valuable. To test these alternative hypotheses, we used functional magnetic resonance imaging (fMRI) as participants engaged in feedback-based learning that required low or high cognitive effort to obtain positive feedback, while the objective amount of information provided by feedback remained constant. In the low effort condition, a single image was presented with four response options. In the high effort condition, two images were presented, each with two response options, and correct feedback was presented only when participants responded correctly to both of the images. Accuracy was significantly lower for the high effort condition, and all participants reported that the high effort condition was more difficult. A region of the ventral striatum selected for sensitivity to feedback value also showed increased activation to feedback presentation associated with the high effort condition relative to the low effort condition, when controlling for activation from corresponding control conditions where feedback was random. These results suggest that increased cognitive effort produces corresponding increases in positive feedback-related ventral striatum activity, in line with the predictions made by contrast theory. The accomplishment of obtaining a hard-earned intrinsic reward, such as positive feedback, may be particularly likely to promote reward-related brain activity.



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Imbalance between the anti- and pro-inflammatory milieu in blood leukocytes of autistic children

Publication date: February 2017
Source:Molecular Immunology, Volume 82
Author(s): Sheikh F. Ahmad, Ahmed Nadeem, Mushtaq A. Ansari, Saleh A. Bakheet, Sabry M. Attia, Khairy M.A. Zoheir, Laila Yousef AL-Ayadhi, Mohammad Z. Alzahrani, Abdulaziz M.S. Alsaad, Moureq R. Alotaibi, Adel R.A. Abd-Allah
Accumulating evidence suggests an association between immune dysfunction and autism disorders in a significant subset of children. In addition, an imbalance between pro- and anti-inflammatory pathways has been proposed to play an important role in the pathogenesis of several neurodevelopmental disorders including autism; however, the role of anti-inflammatory molecules IL-27 and CTLA-4 and pro-inflammatory cytokines IL-21 and IL-22 has not previously been explored in autistic children. In the current study, we investigated the expression of IL-21, IL-22, IL-27, and CD152 (CTLA-4) following an in-vitro immunological challenge of peripheral blood mononuclear cells (PBMCs) from children with autism (AU) or typically-developing children (TD) with phorbol-12-myristate 13-acetate (PMA) and ionomycin. In our study, cells from children with AU had increased IL-21 and IL-22 and decreased CTLA-4 expression on CD4⁺ T cells as compared with cells from the TD control. Similarly, AU cells showed decreased IL-27 production by CD14⁺ cells compared to that of TD control cells. These results were confirmed by real-time PCR and western blot analyses. Our study shows dysregulation of the immune balance in cells from autistic children as depicted by enhanced pro-inflammatory cytokines, 'IL-21/IL-22' and decreased anti-inflammatory molecules, 'IL-27/CTLA-4'. Thus, further study of this immune imbalance in autistic children is warranted in order to facilitate development of biomarkers and therapeutics.



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Extensibility and Distensibility of the Thoracic Aorta in Patients with Aneurysm

Publication date: Available online 24 December 2016
Source:European Journal of Vascular and Endovascular Surgery
Author(s): H.W.L. de Beaufort, F.J.H. Nauta, M. Conti, E. Cellitti, C. Trentin, E. Faggiano, G.H.W. van Bogerijen, C.A. Figueroa, F.L. Moll, J.A. van Herwaarden, F. Auricchio, S. Trimarchi
ObjectivesReference values of aortic deformation during the cardiac cycle can be valuable for the pre-operative planning of thoracic endovascular aortic repair (TEVAR) and for facilitating computational fluid dynamics. This study aimed to quantify normal aortic extensibility (longitudinal extension) and distensibility (radial expansion), as well as pulsatile strain, in a group of 10 (>60 years) individuals with abdominal or thoracic aortic aneurysms.MethodsECG gated CT images of the thoracic aorta were reconstructed into virtual 3D models of aortic geometry. The centre lumen line length of the thoracic aorta and three longitudinal segments, and the aortic diameter and luminal areas of four radial intersections were extracted with a dedicated software script to calculate extensibility, longitudinal strain, distensibility, and circumferential area strain.ResultsMean extensibility and longitudinal strain of the entire thoracic aorta were 3.5 [1.3–6.8] × 10⁻³ N⁻¹, and 2.7 [1.0–4.5]%, respectively. Extensibility and longitudinal strain were most pronounced in the ascending aorta (20.6 [5.7–36.2] × 10⁻³ N⁻¹ and 15.9 [6.6–31.9]%) and smallest in the descending aorta (4.4 [1.6–12.3] × 10⁻³ N⁻¹ and 2.2 [0.7–4.7]%). Mean distensibility and circumferential area strain were most pronounced at the sinotubular junction (1.7 [0.5–2.9] × 10⁻³ mmHg⁻¹ and 11.3 [3.3–18.5]%, respectively). Distensibility varied between 0.9 [0.3–2.5] × 10⁻³ mmHg⁻¹ and 1.2 [0.3–3.3] × 10⁻³ mmHg⁻¹ at the intersections in the aortic arch and descending aorta.ConclusionsPulsatile deformations in both longitudinal and circumferential directions are considerable throughout the thoracic aorta. These findings may have implications for pre-operative TEVAR planning and highlight the need for devices that can mimic the significant aortic longitudinal and circumferential strains.



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Iliac Seal Zone Dynamics and Clinical Consequences After Endovascular Aneurysm Repair

Publication date: Available online 24 December 2016
Source:European Journal of Vascular and Endovascular Surgery
Author(s): F. Bastos Gonçalves, N.F. Oliveira, M. Josee van Rijn, K.H.J. Ultee, S.E. Hoeks, S. Ten Raa, R.J. Stolker, H.J.M. Verhagen
ObjectiveTo evaluate the dynamics of the iliac attachment zone after EVAR, and the association with clinical events.MethodsA tertiary institution's prospective EVAR database was searched to identify common iliac arteries at risk. Internally validated measurements were made, using centre lumen line reconstructions. Iliac dilatation and endograft limb retraction were the main endpoints. Associations between dilatation, retraction, oversizing, and distal seal length were investigated. Association with clinical events (sealing or occlusion) was also explored.ResultsOf 452 primary EVAR patients treated from 2004 to 2012, 341 were included (mean age 72 years, 12% female, 597 common iliac arteries). Median follow-up was 4.7 years. At 30 days, the mean iliac diameter increased from 14 mm to 15 mm (p < .001). Over follow-up, it increased to 18 mm (p < .001). Iliac dilatation ≥20% occurred in 295 cases (49.4%) and exceeded the implanted endograft diameter in 170 (28.7%). Limb retraction ≥5 mm was identified in 54 patients (9.1%) and was associated with iliac seal complications (p < 0.001). Iliac endograft extension diameter ≥24 mm (OR 3.3, 95% CI 1.7–6.4) and iliac artery dilatation beyond the endograft (OR 2.1, 95% CI 1.2–3.8) were independent risk factors. Overall, there were 34 (5.7%) iliac seal complications. Retraction of the iliac endograft (OR 1.17 per mm, 95% CI 1.10–1.24) and baseline AAA diameter (1.04 per mm, 95% CI 1.01–1.07) were independent risk factors for seal related complications. Greater initial post-operative iliac seal length was protective (OR 0.94 per mm, 95% CI 0.90–0.97).ConclusionsIliac dilatation and endograft retraction are common findings during follow-up, potentially leading to adverse clinical events. Optimisation of the iliac seal zone providing a long distal seal length and added attention to patients with large aneurysms or receiving ≥24 mm diameter iliac extensions are recommended. Also, long-term surveillance including CTA is advised to reveal and correct loss of seal at the iliac attachments before adverse clinical events occur.



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The arguments for and against cannabinoids application in glaucomatous retinopathy

Publication date: February 2017
Source:Biomedicine & Pharmacotherapy, Volume 86
Author(s): Yunes Panahi, Azadeh Manayi, Marjan Nikan, Mahdi Vazirian
Glaucoma represents several optic neuropathies leading to irreversible blindness through progressive retinal ganglion cell (RGC) loss. Reduction of intraocular pressure (IOP) is known as the only modifiable factor in the treatment of this disorder. Application of exogenous cannabinoids to lower IOP has attracted attention of scientists as potential agents for the treatment of glaucoma. Accordingly, neuroprotective effect of these agents has been recently described through modulation of endocannabinoid system in the eye. In the present work, pertinent information regarding ocular endocannabinoid system, mechanism of exogenous cannabinoids interaction with the ocular endocannabinoid system to reduce IOP, and neuroprotection property of cannabinoids will be discussed according to current scientific literature. In addition to experimental studies, bioavailability of cannabinoids, clinical surveys, and adverse effects of application of cannabinoids in glaucoma will be reviewed.



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Assessment of lead-time bias in estimates of relative survival for breast cancer

Publication date: February 2017
Source:Cancer Epidemiology, Volume 46
Author(s): Therese M.-L. Andersson, Mark J. Rutherford, Keith Humphreys
Relative survival ratios (RSRs) can be useful for evaluating the impact of changes in cancer care on the prognosis of cancer patients or for comparing the prognosis for different subgroups of patients, but their use is problematic for cancer sites where screening has been introduced due to the potential of lead-time bias. Lead-time is survival time that is added to a patient's survival time because of an earlier diagnosis irrespective of a possibly postponed time of death. In the presence of screening it is difficult to disentangle how much of an observed improvement in survival is real and how much is due to lead-time bias. Even so, RSRs are often presented for breast cancer, a site where screening has led to early diagnosis, with the assumption that the lead-time bias is small. We describe a simulation-based framework for studying the lead-time bias due to mammography screening on RSRs of breast cancer based on a natural history model developed in a Swedish setting. We have performed simulations, using this framework, under different assumptions for screening sensitivity and breast cancer survival with the aim of estimating the lead-time bias. Screening every second year among ages 40–75 was introduced assuming that screening had no effect on survival, except for lead-time bias. Relative survival was estimated both with and without screening to enable quantification of the lead-time bias. Scenarios with low, moderate and high breast cancer survival, and low, moderate and high screening sensitivity were simulated, and the lead-time bias assessed in all scenarios.



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How Do We Keep Information ‘Online’?

Publication date: Available online 24 December 2016
Source:Trends in Cognitive Sciences
Author(s): David Soto
New magnetoencephalography (MEG) results indicate that a putative marker of conscious processes – namely, the global broadcasting of information across large-scale cortical networks – can also operate during the maintenance of non-conscious input. I discuss the implications for the theoretical linkage between conscious awareness and working memory functions.



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Obituary – Michael Goitein

Publication date: Available online 24 December 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Herman Suit, George Chen, Thomas Bortfeld, Alfred Smith, Jay Loeffler, Edward Epp, Andrzej Niemierko, Gudrun Goitein




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Continuous Activity Monitoring during Concurrent Chemoradiotherapy

Publication date: Available online 25 December 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Nitin Ohri, Rafi Kabarriti, William R. Bodner, Keyur J. Mehta, Viswanathan Shankar, Balazs Halmos, Missak Haigentz, Bruce Rapkin, Chandan Guha, Shalom Kalnicki, Madhur Garg
BackgroundWearable activity monitors are widely available and marketed as fitness trackers. We performed a prospective trial testing the feasibility and utility of acquiring activity data as a measure of health status during concurrent chemoradiotherapy.MethodsAmbulatory patients who were planned for treatment with concurrent chemoradiotherapy with curative intent for cancers of the head and neck, lung, or gastrointestinal (GI) tract were provided with activity monitors prior to treatment initiation. Patients were asked to wear the devices continuously throughout the radiotherapy course. Step count data were downloaded at weekly during radiotherapy and two and four weeks after radiotherapy completion. The primary objective was to demonstrate feasibility, defined as collection of step counts for 80% of the days during study subjects' radiotherapy courses. Secondary objectives included establishing step count as a dynamic predictor of unplanned hospitalization risk.ResultsThirty-eight enrolled patients were treated with concurrent chemoradiotherapy. Primary diagnoses included head and neck cancer (n=11), lung cancer (n=13), and a variety of GI cancers (n=14). Step data were collected for 1524 out of 1613 days (94%) during patients' radiotherapy courses. Fourteen patients were hospitalized during radiotherapy or within four weeks of radiotherapy completion. Cox regression modeling demonstrated a significant association between recent step counts (3-day average) and hospitalization risk, with a 38% reduction in the risk of hospitalization for every 1,000 steps taken each day (HR = 0.62, 95% CI: 0.46 to 0.83, p=0.002). Inferior quality of life scores and impaired performance status were not associated with increased hospitalization risk.ConclusionContinuous activity monitoring during concurrent chemoradiotherapy is feasible and well-tolerated. Step counts may serve as powerful, objective, and dynamic indicators of hospitalization risk.

Teaser

We performed a prospective trial demonstrating the feasibility of collecting activity data using a commercial fitness tracker during concurrent chemoradiotherapy for cancers of the head and neck, lung, or gastrointestinal tract. We also found that daily step count was a powerful predictor of short-term hospitalization risk. Activity monitoring should be explored as a tool to aid in the evaluation and management of patients receiving cancer therapy.


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Investigating the use of appropriation in the writing of a child with autism: A case study

Publication date: Available online 24 December 2016
Source:Journal of Communication Disorders
Author(s): Jamie Maxwell, Christine Weill, Jack Damico
This case study investigated how a 10year old child with ASD (Autism Spectrum Disorder), Kameron (pseudonym), utilized appropriation as a writing strategy in the context of group therapy. Using the same questions as Lensmire and Beals (1994) in their study of a typically developing third-grader, written products were collected over the course of one semester and analyzed, along with video, audio, and participant observation data, to consider the following questions: 1) Where did the material come from? 2) What was taken? and 3) How was it used? Analysis of the process of Kameron's writing revealed utilization of appropriation as a strategy for 2 of the 4 written products. Material was appropriated from both adult authored texts performed via read alouds and from topics and values located in the local peer culture. Kameron's appropriation of shared experiences provided substance to initiate and engage in a shared peer culture. Increased engagement in the writing process and fewer off task behaviors were noted when appropriations were evidenced compared to the writing pieces where no appropriation occurred. The results demonstrate the powerful implications of both a process oriented and strength-based approach to writing and greater social awareness than expected in children with ASD.



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Heterogeneous kinetics, products, and mechanisms of ferulic acid particles in the reaction with NO3 radicals

Publication date: March 2017
Source:Atmospheric Environment, Volume 152
Author(s): Changgeng Liu, Peng Zhang, Xiaoying Wen, Bin Wu
Methoxyphenols, as an important component of wood burning, are produced by lignin pyrolysis and considered to be the potential tracers for wood smoke emissions. In this work, the heterogeneous reaction between ferulic acid particles and NO3 radicals was investigated. Six products including oxalic acid, 4-vinylguaiacol, vanillin, 5-nitrovanillin, 5-nitroferulic acid, and caffeic acid were confirmed by gas chromatography-mass spectrometry (GC-MS). In addition, the reaction mechanisms were proposed and the main pathways were NO3 electrophilic addition to olefin and the meta-position to the hydroxyl group. The uptake coefficient of NO3 radicals on ferulic acid particles was 0.17 ± 0.02 and the effective rate constant under experimental conditions was (1.71 ± 0.08) × 10⁻¹² cm³ molecule⁻¹ s⁻¹. The results indicate that ferulic acid degradation by NO3 can be an important sink at night.

Graphical abstract

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Assessment of the Non-Gaussianity and Non-Linearity Levels of Simulated sEMG Signals on Stationary Segments

Publication date: Available online 25 December 2016
Source:Journal of Electromyography and Kinesiology
Author(s): Noureddine Messaoudi, Raïs El'hadi Bekka, Philippe Ravier, Rachid Harba
The purpose of this paper was to evaluate the effects of the longitudinal single differential (LSD), the longitudinal double differential (LDD) and the normal double differential (NDD) spatial filters, the electrode shape, the inter-electrode distance (IED) on non-Gaussianity and non-linearity levels of simulated surface EMG (sEMG) signals when the maximum voluntary contraction (MVC) varied from 10% to 100% by a step of 10%. The effects of recruitment range thresholds (RR), the firing rate (FR) strategy and the peak firing rate (PFR) of motor units were also considered.A cylindrical multilayer model of the volume conductor and a model of motor unit (MU) recruitment and firing rate were used to simulate sEMG signals in a pool of 120 MUs for 5 seconds. Firstly, the stationarity of sEMG signals was tested by the runs, the reverse arrangements (RA) and the modified reverse arrangements (MRA) tests. Then the non-Gaussianity was characterised with bicoherence and kurtosis, and non-linearity levels was evaluated with linearity test.The kurtosis analysis showed that the sEMG signals detected by the LSD filter were the most Gaussian and those detected by the NDD filter were the least Gaussian. In addition, the sEMG signals detected by the LSD filter were the most linear. For a given filter, the sEMG signals detected by using rectangular electrodes were more Gaussian and more linear than that detected with circular electrodes. Moreover, the sEMG signals are less non-Gaussian and more linear with reverse onion-skin firing rate strategy than those with onion-skin strategy. The levels of sEMG signal Gaussianity and linearity increased with the increase of the IED, RR and PFR.



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Differences in therapeutic effects of topically applied corticosteroid and tacrolimus on atopic dermatitis-like symptoms in NC/Nga mice.

Publication date: Available online 24 December 2016
Source:Journal of Dermatological Science
Author(s): Atsushi Noguchi, Mitsutoshi Tominaga, Nobuaki Takahashi, Hironori Matsuda, Yayoi Kamata, Yoshie Umehara, Kyi Chan Ko, Yasushi Suga, Hideoki Ogawa, Kenji Takamori
BackgroundTopical corticosteroid and calcineurin inhibitor have similar therapeutic benefits in atopic dermatitis (AD), but the differences in therapeutic mechanisms of action of these agents against AD symptoms are not fully understood.ObjectiveThis study was performed to examine the different effects of topical betamethasone valerate (BMV), clobetasol propionate (CBP), and tacrolimus (TAC) on itch-related behavior and dermatitis in NC/Nga mice with AD-like symptoms.MethodsAD-like dermatitis was induced in the dorsal skin of NC/Nga mice by repeated topical application of Dermatophagoides farinae body (Dfb) ointment twice weekly for three weeks. Mice with dermatitis scores over 5 were divided into five groups with equal dermatitis scores and treated with BMV, CBP, TAC, or Vaseline (Vas) once daily for two consecutive days, or were not treated (NT). Scratching behavior was analyzed using a SCLABA^®-Real system. Transepidermal water loss (TEWL) before and after treatment was measured using a Tewameter^® TM210. Skin collected from each group was analyzed histologically.ResultsAfter the second treatment, dermatitis showed significantly greater improvement in the CBP and TAC-treated groups than in the Vas-treated and NT groups. The numbers of scratching bouts were significantly lower in CBP and TAC-treated mice than in Vas-treated mice. TEWL was significantly lower in TAC-, but not in CBP-, treated mice than in Vas-treated mice. Immunohistochemical examination showed that BMV, CBP and TAC did not reduce the increased densities of epidermal protein gene product 9.5- and substance P-immunoreactive fibers. The numbers of dermal CD4-immunoreactive T cells were significantly lower in BMV and CBP-treated mice than in Vas-treated and NT mice. The numbers of dermal eosinophils were significantly lower in BMV, CBP and TAC-treated mice than in Vas-treated and NT mice, with CBP showing the strongest effect. CBP significantly reduced epidermal thickness compared with Vas and NT. There were no significant differences in the numbers of interleukin-31-immunoreactive cells and mast cells, or in expression of epidermal thymic stromal lymphopoietin among all five groups.ConclusionThe therapeutic potency of TAC against AD-like symptoms, including pruritus, is equal to that of the corticosteroid CBP. Epidermal innervation of sensory nerves itself might not be related to the therapeutic effects of topical tacrolimus and corticosteroids in its early phase.



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An overview of the infection of CMV, HSV 1/2 and EBV in Mexican patients with glioblastoma multiforme

Publication date: Available online 24 December 2016
Source:Pathology - Research and Practice
Author(s): Zavala-Vega Sergio, Castro-Escarpulli Graciela, Hernández-Santos Hector, Salinas-Lara Citlatepetl, Palma Icela, Mejía-Aranguré Juan Manuel, Gelista-Herrera Noemí, Rembao-Bojorquez Daniel, Sara A. Ochoa, Cruz-Córdova Ariadnna, Xicothencatl-Cortes Juan, Uribe-Gutiérrez Gabriel, Arellano-Galindo José
Several risk factors are involved in glioblastoma, including cytomegalovirus (CMV). This research was carried out to determine the rate of CMV infection, as well as HSV 1/2 and EBV in brain tissue, in patients with glioblastomamultiforme (GBM). The tissues were tested using immunohistochemistry, PCR, in situ hybridization and real-time PCR. At least, one HHV was detected in 21/29 (72%) patients as follows: single infections with HSV-1/2 in 4/21 (19%), EBV in 6/21 (28.6%) and CMV in 1/21 (4.8%). Mixed viral infection, HSV-1/2 and EBV were detected in 4/21 patients (19%), CMV and EBV in 5/21 (23.8%), and HSV-1/2, EBV, and CMV in 1/21. The CMV viral load ranged from 3×10² to 4.33×10⁵ genome/100ng of tissue. Genotype based on CMV gB was 3/7 where 2/3 was gB1 and 1/3 gB4). HSV, EBV and CMV were frequently found in brain tissues, more in mix in a population reported as highly seropositive.



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Corrigendum to “External conditions inversely change the RNA polymerase II elongation rate and density in yeast” [Biochim. Biophys. Acta 2013 Nov.;1829 (11):1248–1255]

Publication date: Available online 24 December 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Ana Miguel, Fernando Montón, Tianlu Li, Fernando Gómez-Herreros, Sebastián Chávez, Paula Alepuz, José E. Pérez-Ortín




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Sensorimotor gating in healthy adults tested over a 15 year period

Publication date: Available online 24 December 2016
Source:Biological Psychology
Author(s): Neal R. Swerdlow, Savita G. Bhakta, Brinda K. Rana, Justin Kei, Hsun-Hua Chou, Jo A. Talledo
BackgroundPrepulse inhibition (PPI) of startle, an operational measure of sensorimotor gating, is used to study normal and pathological brain function. From 2001 − 2016, we screened healthy subjects (HS) to establish their suitability for tests of drug effects on PPI. Because of the size and systematic characterization of this sample across variables of relevance to PPI, we now report these screening results.MethodsAcoustic startle and PPI were assessed in HS to identify those eligible for studies of drug effects on PPI from 2001-2016, yielding 457 "eligible" subjects.ResultsData confirmed the consistency of PPI across this 15-year period, and supported the role of several variables previously reported to moderate either startle or PPI.ConclusionsStartle and PPI are robust physiological measures that are predictably moderated by specific physiological variables in healthy adults. As such, these measures serve as robust markers of neurobiological processes in healthy and patient populations.



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Inside front cover continued (editorial board members)

Publication date: January 2017
Source:Biological Psychology, Volume 122





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Editorial board

Publication date: January 2017
Source:Biological Psychology, Volume 122





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Neurocognitive mechanisms modulating attention bias in anxiety: Current perspectives

Publication date: January 2017
Source:Biological Psychology, Volume 122
Author(s): Hadas Okon-Singer, Tatjana Aue




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Polysarcosine brush stabilized gold nanorods for in vivo near-infrared photothermal tumor therapy

Publication date: Available online 25 December 2016
Source:Acta Biomaterialia
Author(s): Hong Zhu, Ying Chen, Fang-Jie Yan, Jin Chen, Xin-Feng Tao, Jun Ling, Bo Yang, Qiao-Jun He, Zheng-Wei Mao
Gold nanorods (AuNRs) are suitable candidates for photothermal therapy in vivo, because of their excellent ability to transfer near-infrared (NIR) light into heat. However, appropriate surface should be generated on AuNRs before their in vivo application because of the low colloidal stability in complicate biological environment and relatively strong toxicity compared to their pristine stabilizer cetyltrimethylammonium bromide. In the current study, polysarcosine (PS), a non-ionic hydrophilic polypeptoid whose structure is similar to polypeptides, bearing repeating units of natural α-amino acid, was used to stabilize AuNRs due to its excellent hydrophilicity and biocompatibility.Polysarcosine with optimized molecular weight was synthesized and used to modify AuNRs by traditional ligand exchange. The grafting of PS on AuNRs was evidenced by fourier transform infrared (FTIR) spectroscopy and the alternation of surface zeta potential. The polysarcosine coated AuNRs (Au@PS) showed good stabilities in wide pH range and simulated physiological buffer with the ligand competition of dithiothreitol (DTT). The Au@PS NRs had neglectable cytotoxicity and showed efficient ablation of tumor cells in vitro. Moreover, Au@PS NRs had a longer circulation time in body that resulted in a higher accumulation in solid tumors after intravenous injection, compared to AuNRs capped with polyethylene glycol (PEG). Photothermal therapy in vivo demonstrated that the tumors were completely destroyed by single-time irradiation of NIR laser after one-time injection of the polysarcosine capped AuNRs. The Au@PS NRs did not cause obvious toxicity in vivo, suggesting promising potential in cancer therapy.SignificanceIn current study, polysarcosine (PS), a non-ionic hydrophilic polypeptoid whose structure is similar to polypeptides, bearing repeating units of natural α-amino acid, was used to stabilize AuNRs due to its excellent hydrophilicity and biocompatibility. The polysarcosine coated AuNRs (Au@PS) showed good stabilities in wide pH range and simulated physiological buffer. The Au@PS NRs had very low cytotoxicity and showed high efficacy for the ablation of cancer cells in vitro. Moreover, Au@PS NRs had a longer circulation time in blood that led to a higher accumulation in tumors after intravenous injection, compared to AuNRs capped with polyethylene glycol (PEG). In vivo photothermal therapy showed that tumors were completely cured without reoccurrence by one-time irradiation of NIR laser after a single injection of the polysarcosine modified AuNRs.

Graphical abstract

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Colossal permittivity and dielectric relaxation of (Li, In) Co-doped ZnO ceramics

Publication date: 25 March 2017
Source:Journal of Alloys and Compounds, Volume 698
Author(s): Dong Huang, Zhifu Liu, Yongxiang Li, Yun Liu
In this study, a colossal permittivity up to 3800 and a low dielectric loss of 0.11 at 1 kHz have been obtained from the (Li, In) co-doped ZnO ceramic [Zn(1−2x)(Li, In)xO] when x was 0.5%. Electric modulus spectroscopy and impedance analysis were used to investigate the origin of its high permittivity. Two relaxation peaks and a dielectric anomaly were observed in the temperature range of 293–363 K. According to the Debye relaxation theory, the low- and high-temperature relaxation peaks with activation energies of 0.09 eV and 0.29 eV, have been attributed to the hopping of singly and doubly charged oxygen vacancies, which are created by lithium and indium ions doping and oxygen deficiency during sintering process. After thermal treatment in an oxidizing atmosphere, the peaks related to the singly and doubly charged oxygen vacancies disappear and the permittivity reduces to ∼460 at room-temperature. From the X-ray photoelectron spectra (XPS), the concentrations of oxygen vacancies decrease after the O2-annealing process. The results reveal that the oxygen defects would be the main origin of the colossal permittivity of co-doped ZnO at room-temperature range.



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Synthesis of co-doped Yb3+-Er3+:ZrO2 upconversion nanoparticles and their applications in enhanced photovoltaic properties of quantum dot sensitized solar cells

Publication date: 25 March 2017
Source:Journal of Alloys and Compounds, Volume 698
Author(s): D. Ramachari, D. Esparza, T. López-Luke, V.H. Romero, L. Perez-Mayen, E. De la Rosa, C.K. Jayasankar
In this work, we explore the development of Yb³⁺-Er³⁺ co-doped ZrO2 nanoparticles to coat on TiO2/CdS/ZnS configuration to boost the photoconversion efficiency of quantum dot sensitized solar cells. Photovoltaic measurement results indicate that the Yb³⁺-Er³⁺:ZrO2 layer on TiO2/CdS/ZnS configuration offer a remarkable enhancement in open circuit voltage (593 mV) and fill factor (68.7%). This results proves that it is possible to increase the 55% of photoconversion efficiency (3.0%) in the CdS-based QDSSCs effectively by incorporating the Yb³⁺-Er³⁺:ZrO2 layer. Electrochemical impedance spectroscopy measurements confirm further the suppressed charge recombination process after coating with the Yb³⁺-Er³⁺:ZrO2 layer.



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Lymph node yield after rectal resection in patients treated with neoadjuvant radiation for rectal cancer: A systematic review and meta-analysis

Publication date: February 2017
Source:European Journal of Cancer, Volume 72
Author(s): Robert Mechera, Tibor Schuster, Robert Rosenberg, Benjamin Speich
BackgroundThe lymph node status represents a major prognostic factor in colorectal cancer. However, it was demonstrated that neoadjuvant chemoradiotherapy (CRT) decreases the numbers of lymph nodes in the specimen. Several studies describe less than 12 lymph nodes in the resected specimen of rectal cancer patients after neoadjuvant radiation. This meta-analysis quantifies the influence of neoadjuvant CRT or radiotherapy (RT) only on the lymph node yield in rectal cancer patients.MethodsWe performed a systematic review and searched PubMed, EMBASE and the Cochrane Library without any language restriction from 1st of January 1980 until 31st March 2015. Two reviewers examined all publications independently and extracted the relevant data if the study assessed lymph node counts or positive lymph node yields of patients who received neoadjuvant treatment compared with patients who did not receive neoadjuvant treatment. Meta-analyses were conducted to quantify the mean difference in lymph node yield.ResultsA total of 34 articles (including 37 datasets) were included in the meta-analyses. Neoadjuvant CRT resulted in a mean reduction of 3.9 lymph nodes (95% confidence interval [CI] 3.7–4.1) and an average reduction in harvested positive lymph nodes of 0.7 (95% CI 0.2–1.2) compared with patients who received no neoadjuvant therapy. Individuals who received neoadjuvant RT had, in average, 2.1 lymph node less (95% CI 1.7–2.5) resected compared with their counterparts who received no neoadjuvant treatment.ConclusionsNeoadjuvant CRT or RT only in rectal cancer patients leads to a decrease in lymph node harvest of approximately four and two lymph nodes, respectively. We therefore stress the importance of intensifying all efforts from involved subspecialities (i.e. surgeons and pathologists) to reach the benchmark harvest of 12 resected lymph nodes according to current guidelines.



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Organ or sphincter preservation for rectal cancer. The role of contact X-ray brachytherapy in a monocentric series of 112 patients

Publication date: February 2017
Source:European Journal of Cancer, Volume 72
Author(s): Anne Claire Frin, Ludovic Evesque, Jocelyn Gal, Karène Benezery, Eric François, Jean Gugenheim, Emmanuel Benizri, Yan Château, Serge Marcié, Jérome Doyen, Jean-Pierre Gérard
BackgroundContact X-ray brachytherapy (CXB) has been used at Centre Antoine Lacassagne since 2002 to increase the chance of conservative treatment (organ or sphincter preservation) in rectal cancer. A consecutive series of 112 patients (pts) is reported.MethodsThree protocols were used in selected rectal adenocarcinomas. Group 1: T1 N0 treated with local excision (LE) followed by adjuvant CXB. Group 2: T2 or 'early' T3 N0 treated with CXB combined with chemoradiotherapy (CRT) followed by surveillance or LE. Group 3: distal 'locally advanced' T3 N0-2 treated with CXB and CRT before total proctectomy.ResultsGroup 1: 27 pt (pTis: 3; pT1: 21; pT2: 3). After LE with CXB alone (20 pt) or CXB + CRT (7 pt) one local recurrence occurred. Organ preservation was achieved in 26 pt (96%). Group 2: 45 pt (T1: 2; T2: 23; T3: 20) treated with CXB alone (4 pt) or CXB + CRT or external beam radiotherapy (EBRT) (41 pt). A clinical complete response (cCR) was observed in 43/45 (96%) and 3 pt developed a local recurrence (11% at 5 years). The specific survival was 76% at 5 years and the rate of organ preservation was 89% (40/45 pt) with good bowel function in 36 pt. Group 3: 40 pt, anterior resection (with sphincter preservation) was possible in 35 pt (86%) with a 3-year local recurrence of 6%.ConclusionCXB usually combined as a boost with CRT or EBRT may safely increase the chance of a conservative treatment (organ or sphincter preservation) for selected rectal cancers.



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Correlation between severe infection and breast cancer metastases in the EORTC 10994/BIG 1-00 trial: Investigating innate immunity as a tumour suppressor in breast cancer

Publication date: February 2017
Source:European Journal of Cancer, Volume 72
Author(s): Nathan Touati, Konstantinos Tryfonidis, Franco Caramia, Hervé Bonnefoi, David Cameron, Leen Slaets, Belinda S. Parker, Sherene Loi
BackgroundBreast cancer cells which express an innate immune signature regulated by interferon regulatory factor 7 (IRF7) have reduced metastatic potential. Infections can induce interferon signalling and may activate an anti-tumour immune response. We investigated whether 'severe infection' can be a clinical surrogate of this phenomenon and/or the presence of high levels of the IRF7 signature at diagnosis before neo-adjuvant chemotherapy (NACT) is associated with a reduced distant relapse risk, specifically in bones.MethodsClinical data of the European Organisation for Research and Treatment of Cancer 10994/BIG 1-00 phase III trial which randomised 1856 patients treated with NACT between 2001 and 2006, were used. Severe infection was febrile neutropenia or any other grade III–IV infective adverse event during NACT. The IRF7 signature was calculated from gene expression data available for 160 patients on a pre-NACT biopsy. Cox models for distant relapse-free interval (DRFI) investigated the effect of the severe infection and IRF7. Fine and Gray models studied the occurrence of bone metastases as first distant relapse.ResultsMedian follow-up was 4.8 years. No association between severe infection and DFRI was observed in the entire population (n = 1615 eligible patients) hazard ratio [(HR] = 0.99, 90% CI, confidence interval [CI] = 0.81–1.20). For IRF7 (N = 160), a trend towards an association with DRFI was observed (HR = 0.89 for a 50 unit increase, 90% CI = 0.78–1.02, p = 0.081). Higher levels of the IRF7 signature were significantly associated with a decreased bone metastases risk: (HR = 0.76 for a 50 unit increase, 95% CI, 0.62–0.94, p = 0.012).ConclusionsIn this study it was shown that severe infection during NACT was not associated with decreased DRFI while high expression of the IRF7 gene signature was significantly associated with reduced bone relapse. This result may be useful for future adjuvant bisphosphonate/denosumab use.



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Relation between plasma trough concentration of abiraterone and prostate-specific antigen response in metastatic castration-resistant prostate cancer patients

Publication date: February 2017
Source:European Journal of Cancer, Volume 72
Author(s): E. Carton, G. Noe, O. Huillard, L. Golmard, J. Giroux, A. Cessot, N.E.B. Saidu, M. Peyromaure, M. Zerbib, C. Narjoz, J. Guibourdenche, A. Thomas, M. Vidal, F. Goldwasser, B. Blanchet, J. Alexandre
BackgroundAbiraterone (ABI) is a major oral agent for the treatment of metastatic castration-resistant prostate cancer (mCRPC) patients but its systemic exposure is subject to a large inter-individual variability. We aimed to explore the relationship between ABI trough plasma concentration and prostate-specific antigen (PSA) response in mCRPC patients and to identify the critical determinants for its activity.Patients and methodsThis is a monocentric prospective observational study in mCRPC patients treated with ABI. The plasmatic concentration of ABI at steady state was measured using liquid chromatography with fluorescence detection. The primary objective was to study the relationship between mean ABI plasma exposure (ABI Cmin) and 3-month PSA response.ResultsFrom 2012 to 2016, 61 mCRPC patients were eligible for pharmacokinetic/pharmacodynamic assessment. Thirty-eight patients experienced PSA response (62%, [confidence interval {CI} 95% 50–78]). In univariate analysis, ABI Cmin was 1.5-fold higher in responders: 12.0 ng/mL (CI 95% 9.4–15.6) versus 8.0 ng/mL (CI 95% 5.8–11.6; P = 0.0015). In multivariate analysis, only ABI Cmin was independently associated with PSA response (odds ratio = 1.12 [CI 95% 1.01–1.25], P = 0.004). By receiver operating characteristic analysis, the optimal threshold for ABI Cmin was 8.4 ng/mL. Progression-free survival (PFS) was significantly higher in patients with ABI Cmin above 8.4 ng/mL (hazard ratio 0.55, [CI 95% 0.31–0.99], 12.2 [CI 95% 9.2–19.5] versus 7.4 [CI 95% 5.5–14.7] months otherwise, P = 0.044).ConclusionsWe showed that ABI trough concentration correlates with PSA response and PFS. Moreover, we could determine a cut-off value of plasmatic concentration for PSA response. Altogether, ABI concentration monitoring appears as a new approach to improve clinical outcome in mCPRC patients.



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18F-FDG PET/CT surveillance for the detection of recurrence in patients with head and neck cancer

Publication date: February 2017
Source:European Journal of Cancer, Volume 72
Author(s): Shin-Ae Kim, Jong-Lyel Roh, Jae Seung Kim, Jeong Hyun Lee, Sang Hoon Lee, Seung-Ho Choi, Soon Yuhl Nam, Sang Yoon Kim
BackgroundPosttreatment detection of recurrence may lead to salvage treatment and prognostic prediction in patients with head and neck squamous cell carcinoma (HNSCC). We evaluated the diagnostic and prognostic values of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/computed tomography (CT) after definitive treatment of HNSCC.MethodsThis prospective study included 278 consecutive patients who underwent curative surgery (n = 143, 51.4%) or definitive radiotherapy/chemoradiotherapy (n = 135, 48.6%) for previously untreated HNSCC. The patients were regularly followed up and evaluated by ¹⁸F-FDG PET/CT, head and neck CT/magnetic resonance imaging (MRI), and chest CT at regular intervals after treatment. The imaging interpretations were compared with the histological results for recurrence. Receiver operating characteristics curves analysis, McNemar's test and logistic regression using generalised estimating equations were used to compare the diagnostic accuracy of ¹⁸F-FDG PET/CT and standard imaging of CT/MRI or chest CT, and a Cox proportional hazards model was used to assess the prognostic value of PET/CT.ResultsDuring a median follow-up of 44 months (range, 24–62 months), 73 patients (26.3%) had recurrence or persistent diseases. The area under curves for ¹⁸F-FDG PET/CT and CT/MRI were 0.975 (0.964–0.992) and 0.789 (0.713–0.874), respectively (P < 0.001). ¹⁸F-FDG PET/CT detected 65 of 66 recurrences (98.5%) not suggested by physical examination and endoscopy. Positive findings on ¹⁸F-FDG PET/CT scans were independent predictors of poorer cancer-specific and overall survival outcomes (P < 0.01).ConclusionsPosttreatment ¹⁸F-FDG PET/CT surveillance helps to properly detect recurrence and to predict the survival following treatment of HNSCC.



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Major infections, secondary cancers and autoimmune diseases occur in different clinical subsets of chronic lymphocytic leukaemia patients

Publication date: February 2017
Source:European Journal of Cancer, Volume 72
Author(s): Andrea Visentin, Silvia Imbergamo, Carmela Gurrieri, Federica Frezzato, Valentina Trimarco, Veronica Martini, Filippo Severin, Flavia Raggi, Edoardo Scomazzon, Monica Facco, Francesco Piazza, Gianpietro Semenzato, Livio Trentin
BackgroundMajor infections (MIs), secondary cancers (SCs) and autoimmune diseases (ADs) are the most common and relevant complications in patients with chronic lymphocytic leukaemia.MethodsWe performed a single-centre retrospective study to investigate the prevalence of the above quoted complications, the association with most important prognostic markers and their impact on survival (n = 795).ResultsAlmost one out of three patients experienced at least one complication and only 0.9% of the cohort developed all three complications. One hundred and twenty (20%) subjects developed SC, 98 MI (12%) and 80 AD (10%); these complications seem to occur in a mutually exclusive manner. By Kaplan–Meier analysis we estimated that after 20 years from the diagnosis SC, MI and AD occurred in 48%, 42% and 29% of patients, respectively. Furthermore, we showed that some clinical and biological markers are skewed among patients with different complications and that subjects with MI and SC had a worse prognosis than those with AD and all other patients (p < 0.0001).ConclusionsThis study reveals the existence of different clinical subsets of chronic lymphocytic leukaemia patients characterised by an increased and different risk for developing specifically MI, SC and AD.



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Erratum to “Systematic versus on-demand early palliative care: A randomised clinical trial assessing quality of care and treatment aggressiveness near the end of life” [Eur J Cancer 69 (2016) 110–118]

Publication date: Available online 24 December 2016
Source:European Journal of Cancer
Author(s): Marco Maltoni, Emanuela Scarpi, Monia Dall'Agata, Stefania Schiavon, Claudia Biasini, Carla Codecà, Chiara Maria Broglia, Elisabetta Sansoni, Roberto Bortolussi, Ferdinando Garetto, Luisa Fioretto, Maria Teresa Cattaneo, Alice Giacobino, Massimo Luzzani, Giovanna Luchena, Sara Alquati, Silvia Quadrini, Vittorina Zagonel, Luigi Cavanna, Daris Ferrari, Paolo Pedrazzoli, Giovanni Luca Frassineti, Antonella Galiano, Andrea Casadei Gardini, Manlio Monti, Oriana Nanni




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Estimation of net survival for cancer patients: Relative survival setting more robust to some assumption violations than cause-specific setting, a sensitivity analysis on empirical data

Publication date: February 2017
Source:European Journal of Cancer, Volume 72
Author(s): Robin Schaffar, Bernard Rachet, Aurélien Belot, Laura M. Woods
Net survival is the survival that would be observed if the only possible underlying cause of death was the disease under study. It can be estimated with either cause-specific or relative survival data settings, if the informative censoring is properly considered. However, net survival estimators are prone to specific biases related to the data setting itself. We examined which data setting was the most robust against violation of key assumptions (erroneous cause of death and inappropriate life tables).We identified 4285 women in the Geneva Cancer Registry, diagnosed with breast, colorectal, lung cancer and melanoma between 1981 and 1991 and estimated net survival up to 20 years using cause-specific and relative survival settings. We used weights to tackle informative censoring in both settings and performed sensitivity analyses to evaluate the impact of misclassification of cause of death in the cause-specific setting or of using inappropriate life tables on net survival estimates in the relative survival setting.For all the four cancers, net survival was highest when using the cause-specific setting and the absolute difference between the two estimators increased with time since diagnosis. The sensitivity analysis showed that (i) the use of different life tables did not compromise net survival estimation in the relative survival setting, whereas (ii) a small level of misclassification for the cause of death led to a large change in the net survival estimate in the cause-specific setting.The relative survival setting was more robust to the above assumptions violations and is therefore recommended for estimation of net survival.



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EGFR-independent Elk1/CIP2A signalling mediates apoptotic effect of an erlotinib derivative TD52 in triple-negative breast cancer cells

Publication date: February 2017
Source:European Journal of Cancer, Volume 72
Author(s): Chun-Yu Liu, Tzu-Ting Huang, Chun-Teng Huang, Ming-Hung Hu, Duen-Shian Wang, Wan-Lun Wang, Wen-Chun Tsai, Chia-Han Lee, Ka-Yi Lau, Hsiu-Ping Yang, Ming-Huang Chen, Chung-Wai Shiau, Ling-Ming Tseng, Kuen-Feng Chen
ObjectivesCancerous inhibitor of protein phosphatase 2A (CIP2A) has emerged as a therapeutic determinant mediating the anti-cancer effects of several new agents. We investigated the efficacy and mechanism of TD52, an erlotinib derivative with minimal p-EGFR inhibition but significant CIP2A downregulation, in triple-negative breast cancer (TNBC) cells.MethodsTNBC lines were used for in vitro studies. Cell apoptosis was examined by flow cytometry and Western blot. Signal transduction pathways in cells were assessed by Western blot. In vivo efficacy of TD52 was tested in xenograft nude mice.ResultsWe explored the CIP2A mRNA expression in a publically available database and found that higher levels of CIP2A mRNA is associated with worse recurrence-free survival in patients with TNBC. TD52-enhanced apoptosis accompanied with CIP2A downregulation and CIP2A overexpression protected cells from TD52-mediated apoptosis. The activity of protein phosphatase 2A (PP2A) was also increased in TD52-treated cells. TD52-induced apoptosis and p-Akt downregulation was attenuated by PP2A antagonist okadaic acid. Furthermore, TD52 indirectly downregulated CIP2A transcription via disturbing the binding of Elk1 to the CIP2A promoter. Importantly, TD52 showed anti-tumour activity in mice bearing TNBC xenograft tumours and downregulated CIP2A and p-Akt in these xenografted tumours. Interestingly, higher Elk1 mRNA expression was also associated with worse recurrence-free survival in TNBC patients by Kaplan–Meier survival analysis.ConclusionOur findings indicated that EGFR-independent pharmacological modulation on Elk1/CIP2A signalling mediates the apoptotic effect of TD52 in TNBC cells, suggesting the potential therapeutic strategy.



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Impact of industry collaboration on randomised controlled trials in oncology

Publication date: February 2017
Source:European Journal of Cancer, Volume 72
Author(s): Anne Linker, Annie Yang, Nitin Roper, Evans Whitaker, Deborah Korenstein
BackgroundIndustry funders can simply provide money or collaborate in trial design, analysis or reporting of clinical trials. Our aim was to assess the impact of industry collaboration on trial methodology and results of randomised controlled trials (RCT).MethodsWe searched PubMed for oncology RCTs published May 2013 to December 2015 in peer-reviewed journals with impact factor > 5 requiring reporting of funder role. Two authors extracted methodologic (primary end-point; blinding of the patient, clinician and outcomes assessor; and analysis) and outcome data. We used descriptive statistics and two-sided Fisher exact tests to compare characteristics of trials with collaboration, with industry funding only, and without industry funding.ResultsWe included 224 trials. Compared to those without industry funding, trials with collaboration used more placebo control (RR 3·59, 95% CI [1·88–6·83], p < 0001), intention-to-treat analysis (RR 1·32, 95% CI [1·04–1·67], p = 02), and blinding of patients (RR 3·05, 95% CI [1·71–5·44], p < 0001), clinicians (RR 3·36, 95% CI [1·83–6·16], p≤·001) and outcomes assessors (RR 3·03, 95% CI [1·57–5·83], p = 0002). They did not differ in use of overall survival as a primary end-point (RR 1·27 95% CI [0·72–2·24]) and were similarly likely to report positive results (RR 1·11 95% CI [0·85–1·46], p = 0.45). Studies with funding only did not differ from those without funding.ConclusionsOncology RCTs with industry collaboration were more likely to use some high-quality methods than those without industry funding, with similar rates of positive results. Our findings suggest that collaboration is not associated with trial outcomes and that mandatory disclosure of funder roles may mitigate bias.



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Analysis of plutonium isotope ratios including 238Pu/239Pu in individual U–Pu mixed oxide particles by means of a combination of alpha spectrometry and ICP-MS

Publication date: 1 April 2017
Source:Talanta, Volume 165
Author(s): Fumitaka Esaka, Kenichiro Yasuda, Daisuke Suzuki, Yutaka Miyamoto, Masaaki Magara
Isotope ratio analysis of individual uranium–plutonium (U–Pu) mixed oxide particles contained within environmental samples taken from nuclear facilities is proving to be increasingly important in the field of nuclear safeguards. However, isobaric interferences, such as ²³⁸U with ²³⁸Pu and ²⁴¹Am with ²⁴¹Pu, make it difficult to determine plutonium isotope ratios in mass spectrometric measurements. In the present study, the isotope ratios of ²³⁸Pu/²³⁹Pu, ²⁴⁰Pu/²³⁹Pu, ²⁴¹Pu/²³⁹Pu, and ²⁴²Pu/²³⁹Pu were measured for individual Pu and U–Pu mixed oxide particles by a combination of alpha spectrometry and inductively coupled plasma mass spectrometry (ICP-MS). As a consequence, we were able to determine the ²⁴⁰Pu/²³⁹Pu, ²⁴¹Pu/²³⁹Pu, and ²⁴²Pu/²³⁹Pu isotope ratios with ICP-MS after particle dissolution and chemical separation of plutonium with UTEVA resins. Furthermore, ²³⁸Pu/²³⁹Pu isotope ratios were able to be calculated by using both the ²³⁸Pu/(²³⁹Pu+²⁴⁰Pu) activity ratios that had been measured through alpha spectrometry and the ²⁴⁰Pu/²³⁹Pu isotope ratios determined through ICP-MS. Therefore, the combined use of alpha spectrometry and ICP-MS is useful in determining plutonium isotope ratios, including ²³⁸Pu/²³⁹Pu, in individual U–Pu mixed oxide particles.

Graphical abstract

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Optimization and evaluation of MALDI TOF mass spectrometric imaging for quantification of orally dosed octreotide in mouse tissues

Publication date: 1 April 2017
Source:Talanta, Volume 165
Author(s): Tai Rao, Boyu Shen, Zhangpei Zhu, Yuhao Shao, Dian Kang, Xinuo Li, Xiaoxi Yin, Haofeng Li, Lin Xie, Guangji Wang, Yan Liang
Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry imaging (MALDI-TOF-MSI) has received considerable attention in recent years since it allows molecular mapping of diverse bimolecular in animal/plant tissue sections, although some barriers still exist in absolute pixel-to-pixel quantification. Octreotide, a synthetic somatostatin analogue, has been widely used to prevent gastrointestine bleeding in the clinic. The aim of the present study is to develop a MALDI-TOF-MSI method for quantitatively visualizing spatial distribution of octreotide in mouse tissues. In this process, a structurally similar internal standard was spotted onto tissue section together with matrix solution to minimize signal variation and give excellent quantitative results. The 2,5-dihydroxybenzoic acid was chosen as the most suitable matrix via comparing the signal/noise generated by MALDI-TOF-MSI after cocrystallization of octreotide with different matrix candidates. The reliability of MALDI-TOF-MSI, with respect to linearity, sensitivity and precision, was tested via measuring octreotide in fresh tissue slices at different concentrations. The validated method was then successfully applied to visualize the distribution of octreotide in mouse tissues after oral administration of octreotide at 20mg/kg. The results demonstrated that MALDI-TOF-MSI could not only clearly visualize the spatial distribution of octreotide, but also make the calculation of the key pharmacokinetic parameters (Tmax and t1/2) possible. More importantly, the tissue concentration-time curves of octreotide determined by MALDI-TOF-MSI agreed well with those measured based on LC–MS/MS.These findings illustrate the potential of MALDI-TOF-MSI in pharmacokinetic profiling during drug development.

Graphical abstract

http://ift.tt/2hdZgnG

Novel turn-on fluorescent detection of alkaline phosphatase based on green synthesized carbon dots and MnO2 nanosheets

Publication date: 1 April 2017
Source:Talanta, Volume 165
Author(s): Fengli Qu, Haimeng Pei, Rongmei Kong, Shuyun Zhu, Lian Xia
Using sterculia lychnophora seeds as precursors for the first time, fluorescent carbon dots (CDs) were synthesized by simple hydrothermal treatment. The quantum yield of as-synthesized CDs was 6.9% by using quinine sulfate as the reference. The fluorescence of CDs could be effectively quenched by a MnO2 nanosheet based on fluorescence resonance energy transfer (FRET). Ascorbic acid (AA) could reduce MnO2 to Mn²⁺ and result in the destruction of the MnO2 nanosheets, which could induce the fluorescence recovery of the CDs. In particular, alkaline phosphatase (ALP) could bio-catalyze acid 2-phosphate (AAP) hydrolysis to AA. Here, an efficient fluorescence probe based on a CDs-MnO2 nanosheet for rapid and selective detection of ALP was reported for the first time. Excellent performance for the detection of ALP was observed with high sensitivity and a detection limit of 0.4U/L owing to the low background. The detection of ALP in human serum was conducted with satisfactory results, demonstrating its potential applications in clinical diagnosis.

Graphical abstract

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Fabrication of novel metal-free “graphene alloy” for the highly efficient electrocatalytic reduction of H2O2

Publication date: 1 April 2017
Source:Talanta, Volume 165
Author(s): Tingting Zhang, Cong Li, Yue Gu, Xiaoyi Yan, Bo Zheng, Yaru Li, He Liu, Nannan Lu, Zhiquan Zhang, Guodong Feng
Hydrogen peroxide (H2O2) is becoming significant due to its extensive applications, so determination of H2O2 is very important topic in analytical chemistry. Metal-free "graphene alloy" – nitrogen (N) and sulfur (S) heteroatoms co-doped reduced graphene oxide (NS-rGO) was produced via a simple one-step thermal annealing procedure using a mixture of 5-amino-2-mercapto-1,3,4-thiadiazole (AMT) and graphene oxide (GO). The obtained metal-free NS-rGO composite showed better electrocatalytic activity toward the reduction of H2O2 compared with the reduced graphene oxide (rGO). The enhanced performance was caused by the synergistic effect of N and S co-doping. Under optimum conditions, the constructed sensor demonstrated a linear response to H2O2 in the range of 7–18000μM, with a lower detection limit of 0.45μM (S/N=3), even better than some reported sensors based on noble metal nanoparticles. Moreover, the proposed sensor exhibited excellent analytical performance in terms of acceptable selectivity, excellent reproducibility and long-time stability. These results indicated that the NS-rGO composite was a promising metal-free electrocatalytic material for constructing H2O2 sensors. Additionally, NS-rGO composite was expected to be applied as catalysts for fuel cell applications, even for applications beyond fuel cells.

Graphical abstract

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Fabrication of a polymeric ionic liquid-based adsorbent for multiple monolithic fiber solid-phase microextraction of endocrine disrupting chemicals in complicated samples

Publication date: 1 April 2017
Source:Talanta, Volume 165
Author(s): Miao Pei, Zirui Zhang, Xiaojia Huang, Yuanfei Wu
A multiple monolithic fiber solid-phase microextraction (MMF-SPME) utilizing polymeric ionic liquid-based adsorbent was prepared. The adsorbent was obtained by in situ copolymerization of an ionic liquid, 1-trimethyl-(4-vinylbenzyl) aminium chloride and dual cross-linkers (divinylbenzene and ethylenedimethacrylate). The effect of preparation conditions including the content of ionic liquid and porogen in the polymerization mixture on extraction performance was studied in detail. Infrared spectroscopy, elemental analysis, scanning electron microscopy and mercury intrusion porosimetry were used to inspect the physicochemical properties of the new adsorbent. The applicability of the new MMF-SPME was demonstrated by the extraction of trace endocrine disrupting chemicals (EDCs). Results indicated that the prepared MMF-SPME could extract EDCs effectively through multi-interactions such as ion-exchange, π-π and hydrophobic interactions. After optimization of extraction parameters, a method of MMF-SPME coupled to high performance liquid chromatography/diode array detection was conducted to detect trace EDCs in complicated samples including environmental water and human urine. The limits of detection (S/N=3) and quantification (S/N=10) for targeted compounds were 0.011–0.065μg/L and 0.036–0.21μg/L, respectively. Satisfactory precision was also achieved by evaluating the repeatability and intermediate precision with relative standard deviations (RSDs) of less than 9% and 10%, respectively. At the same time, the proposed method was successfully applied for the determination of EDCs in water and human urine with spiking recoveries ranged from 70.6% to 119%.

Graphical abstract

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Facile preparation of rare-earth based fluorescence/MRI dual-modal nanoprobe for targeted cancer cell imaging

Publication date: 1 April 2017
Source:Talanta, Volume 165
Author(s): Sa Huang, Peng Chen, Chen Xu
Nowadays, cancer has become a serious threat to public health worldwide. Early and precise diagnosis is critical for the detection, monitoring and management of cancer. Herein, a facile strategy for developing a fluorescence/MRI dual-modal nanoprobe (FA-PEI-NaGdF4:Eu nanoparticles) has been reported for targeted cancer cell imaging. The fluorescence/MRI nanoprobes have strong fluorescence and the high signal-to-noise ratio, which is suitable for the fluorescence imaging. Moreover, the FA-PEI-NaGdF4:Eu nanoprobes have high longitudinal relaxivity, making them suitable for T1-weighted MR imaging. Additionally, due to modification with FA, the fluorescence/MRI nanoprobes could target cancer cells that possessed large numbers of folate receptors. The results of the cytotoxicity assay revealed that the nanoprobes had the excellent biocompatibility. With the high biocompatibility, excellent imaging performance and superior targeting, the FA-PEI-NaGdF4:Eu nanoprobes can be used as a promising candidate for targeted fluorescence/MRI cancer cell imaging and would bring more opportunities for the biomedical applications.

Graphical abstract

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Graphene oxide and carboxylated graphene oxide: Viable two-dimensional nanolabels for lateral flow immunoassays

Publication date: 1 April 2017
Source:Talanta, Volume 165
Author(s): Li Yu, Peiwu Li, Xiaoxia Ding, Qi Zhang
Graphene oxide (GO) and carboxylated GO were used as labels for lateral flow immunoassays, instead of the conventionally used colloidal gold and colored latex labels. A sensor is demonstrated that enables fast screening for aflatoxin B1 (AFB1) as a model analyte using the antibody-GO complex as the recognition element. The visual limit of detection and cut-off value for AFB1 are 0.3 and 1ng/mL, respectively. It is shown that GO and carboxylated GO are viable black labels for use in lateral flow assays, one typical advantage being the saving cost (compared to the use of colloidal gold). Qualitative results are achieved within 15min, and the analytical results were in good agreement with the reference LC MS/MS method. The method was successfully applied to the on-site determination of AFB1 in agricultural products. In our perception, it opens new possibilities for the screening of other toxins by lateral flow immunoassays using GO and carboxylated GO as labels.



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Air assisted emulsification liquid-liquid microextraction based on deep eutectic solvent for preconcentration of methadone in water and biological samples

Publication date: 1 April 2017
Source:Talanta, Volume 165
Author(s): N. Lamei, M. Ezoddin, K. Abdi
Nowadays, a deep eutectic solvent (DES) has recently been considered as a green ion liquid analogue. In this study, a new compound of DES has been synthesized as an extraction solvent in air assistedemulsification liquid–liquid microextraction method (DES-AAELLME) for preconcentration and extraction of methadone followed by gas chromatographyflame ionization detector (GC–FID). To obtain an efficient water-miscible deep eutectic solvent, choline chloride (ch-cl) and 5,6,7,8-Tetrahydro-5,5,8,8-tetramethylnaphthalen-2-ol (TNO) were mixed at a molar ratio of 1:2 and tetrahydrofuran (THF) was used as a demulsifier solvent into homogeneous solution for providing a turbid state. The solution was rapidly sucked up and injected 10 times using a 10-mL glass syringe to enhance the turbidity of solution and disperse the aggregated DES droplets into aqueous phase. Some important parameters affecting extraction recovery were investigated. Under optimum conditions, the calibration curve was linear in the concentration range from 2 to 8000µgL⁻¹. The limit of detection and the limit of quantification were found 0.7µgL⁻¹ and 2.3µgL⁻¹ respectively with preconcentration factor of 270. The precision, as the relative standard deviation (RSD) (n=6), was <6% respectively. This method was successfully applied to determine methadone in water and biological samples with an appropriate recovery about 98.4–101.2%.

Graphical abstract

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Update of Ireland's national average indoor radon concentration – Application of a new survey protocol

Publication date: April 2017
Source:Journal of Environmental Radioactivity, Volumes 169–170
Author(s): A. Dowdall, P. Murphy, D. Pollard, D. Fenton
In 2002, a National Radon Survey (NRS) in Ireland established that the geographically weighted national average indoor radon concentration was 89 Bq m⁻³. Since then a number of developments have taken place which are likely to have impacted on the national average radon level. Key among these was the introduction of amending Building Regulations in 1998 requiring radon preventive measures in new buildings in High Radon Areas (HRAs). In 2014, the Irish Government adopted the National Radon Control Strategy (NRCS) for Ireland. A knowledge gap identified in the NRCS was to update the national average for Ireland given the developments since 2002. The updated national average would also be used as a baseline metric to assess the effectiveness of the NRCS over time.A new national survey protocol was required that would measure radon in a sample of homes representative of radon risk and geographical location. The design of the survey protocol took into account that it is not feasible to repeat the 11,319 measurements carried out for the 2002 NRS due to time and resource constraints. However, the existence of that comprehensive survey allowed for a new protocol to be developed, involving measurements carried out in unbiased randomly selected volunteer homes. This paper sets out the development and application of that survey protocol. The results of the 2015 survey showed that the current national average indoor radon concentration for homes in Ireland is 77 Bq m⁻³, a decrease from the 89 Bq m⁻³ reported in the 2002 NRS. Analysis of the results by build date demonstrate that the introduction of the amending Building Regulations in 1998 have led to a reduction in the average indoor radon level in Ireland.



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Editorial Board

Publication date: January 2017
Source:Cancer Treatment Reviews, Volume 52





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