Thermal behavior of Carrara marble after consolidation by ammonium phosphate, ammonium oxalate and ethyl silicate

Publication date: 15 April 2017
Source:Materials & Design, Volume 120
Author(s): Enrico Sassoni, Gabriela Graziani, Giovanni Ridolfi, Maria Chiara Bignozzi, Elisa Franzoni
The response to thermal variations is the primary cause of marble deterioration in ancient and modern buildings. In this study, the thermal behavior of Carrara marble after consolidation by an innovative hydroxyapatite-based treatment was investigated in comparison with ammonium oxalate and ethyl silicate. Samples were subjected to heating-cooling cycles up to 80°C. All the consolidating treatments were found to be fairly compatible, as in no case the residual strain after the thermal cycles was found to increase compared to the unweathered untreated marble. Anyway, the hydroxyapatite-treatment has the advantage of causing the highest increase in marble cohesion and the lowest residual strain, besides being more chromatically compatible and durable than the alternative commercial consolidants.

Graphical abstract

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Decoding Grasping Movements from the Parieto-Frontal Reaching Circuit in the Nonhuman Primate

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Prehension movements typically include a reaching phase, guiding the hand toward the object, and a grip phase, shaping the hand around it. The dominant view posits that these components rely upon largely independent parieto-frontal circuits: a dorso-medial circuit involved in reaching and a dorso-lateral circuit involved in grasping. However, mounting evidence suggests a more complex arrangement, with dorso-medial areas contributing to both reaching and grasping. To investigate the role of the dorso-medial reaching circuit in grasping, we trained monkeys to reach-and-grasp different objects in the dark and determined if hand configurations could be decoded from functional magnetic resonance imaging (MRI) responses obtained from the reaching and grasping circuits. Indicative of their established role in grasping, object-specific grasp decoding was found in anterior intraparietal (AIP) area, inferior parietal lobule area PFG and ventral premotor region F5 of the lateral grasping circuit, and primary motor cortex. Importantly, the medial reaching circuit also conveyed robust grasp-specific information, as evidenced by significant decoding in parietal reach regions (particular V6A) and dorsal premotor region F2. These data support the proposed role of dorso-medial "reach" regions in controlling aspects of grasping and demonstrate the value of complementing univariate with more sensitive multivariate analyses of functional MRI (fMRI) data in uncovering information coding in the brain.</span>

http://ift.tt/2lX7Evk

Cortical Thickness Abnormalities in Autism Spectrum Disorders Through Late Childhood, Adolescence, and Adulthood: A Large-Scale MRI Study

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Neuroimaging studies in autism spectrum disorders (ASDs) have provided inconsistent evidence of cortical abnormality. This is probably due to the small sample sizes used in most studies, and important differences in sample characteristics, particularly age, as well as to the heterogeneity of the disorder. To address these issues, we assessed abnormalities in ASD within the Autism Brain Imaging Data Exchange data set, which comprises data from approximately 1100 individuals (~6–55 years). A subset of these data that met stringent quality control and inclusion criteria (560 male subjects; 266 ASD; age = 6–35 years) were used to compute age-specific differences in cortical thickness in ASD and the relationship of any such differences to symptom severity of ASD. Our results show widespread increased cortical thickness in ASD, primarily left lateralized, from 6 years onwards, with differences diminishing during adulthood. The severity of symptoms related to social affect and communication correlated with these cortical abnormalities. These results are consistent with the conjecture that developmental patterns of cortical thickness abnormalities reflect delayed cortical maturation and highlight the dynamic nature of morphological abnormalities in ASD.</span>

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Relationships Between Morphologic and Functional Patterns in the Polymicrogyric Cortex

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Polymicrogyria is a malformation of cortical folding and layering underlying different cognitive and neurological manifestations. The polymicrogyric cortex has heterogeneous morphofunctional patterns, qualitatively described at magnetic resonance imaging (MRI) by variable severity gradients and functional activations. We investigated the link between abnormal cortical folding and cortical function in order to improve surgical planning for patients with polymicrogyria and intractable epilepsy. We performed structural and functional MRI on 14 patients with perisylvian polymicrogyria and adopted surface-based methods to detect alterations of cortical thickness (CT) and local gyrification index (LGI) compared with normal cortex (30 age-matched subjects). We quantitatively assessed the grade of anatomic disruption of the polymicrogyric cortex and defined its relationship with decreased cortical function. We observed a good matching between visual analysis and morphometric measurements. CT maps revealed sparse clusters of thickening, while LGI maps disclosed circumscribed regions of maximal alteration with a uniformly decreasing centrifugal gradient. In polymicrogyric areas in which gyral and sulcal patterns were preserved, functional activation maintained the expected location, but was reduced in extent. Morphofunctional correlations, evaluated along cortico-cortical paths between maximum morphologic alterations and significant activations, identified an interindividual threshold for LGI (<span style="font-style:italic;">z-</span>value = −1.09) beyond which functional activations were no longer identifiable.</span>

http://ift.tt/2lXaHUp

Nationwide multi-institutional retrospective analysis of high-dose-rate brachytherapy combined with external beam radiotherapy for localized prostate cancer: An Asian Prostate HDR-BT Consortium

Publication date: Available online 17 February 2017
Source:Brachytherapy
Author(s): Hiromichi Ishiyama, Nobuhiko Kamitani, Hidemasa Kawamura, Shingo Kato, Manabu Aoki, Shinji Kariya, Taisei Matsumura, Motoki Kaidu, Ken Yoshida, Yaichiro Hashimoto, Yasutaka Noda, Keith H.C. Lim, Takatsugu Kawase, Takeo Takahashi, Koji Inaba, Motoyasu Kumano, Nobuhiko Yoshikawa, Yasuo Yoshioka, Katsumasa Nakamura, Junichi Hiratsuka, Jun Itami, Kazushige Hayakawa
PurposeTo report outcomes and risk factors of high-dose-rate (HDR) brachytherapy combined with external beam radiotherapy with or without androgen deprivation therapy (ADT) in prostate cancer patients.Materials and MethodsThis multi-institutional retrospective analysis comprised 3424 patients with localized prostate cancer at 16 Asian hospitals. One-thirds (27.7%) of patients received only neoadjuvant ADT, whereas almost half (49.5%) of patients received both neoadjuvant and adjuvant ADT. Mean duration of neoadjuvant and adjuvant ADT were 8.6 months and 27.9 months, respectively. Biochemical failure was defined by Phoenix ASTRO consensus. Biochemical control rate, clinical disease-free survival (cDFS), cause-specific survival, and overall survival (OS) were calculated.ResultsMedian followup was 66 months. Ten-year biochemical control, cDFS, cause-specific survival, and OS rate were 81.4%, 81.0%, 97.2%, and 85.6%, respectively. Receiving both neoadjuvant and adjuvant ADT was detected as a favorable factor for biochemical control, cDFS, and OS, but pelvic irradiation was detected as an adverse factor for cause-specific survival, and OS. Ten-year cumulative rates of late Grade ≥2 genitourinary and gastrointestinal toxicities were 26.8% and 4.1%, respectively; receiving both neoadjuvant and adjuvant ADT was detected as a favorable factor for preventing both toxicities.ConclusionsHDR combined with external beam radiotherapy was an effective and safe treatment for localized prostate cancer. Combination of long-term ADT was suggested to be necessary, even for HDR brachytherapy, and was useful in suppressing late toxicities. Meanwhile, pelvic irradiation was suggested to have an adverse effect on OS of our study population.



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Association between signs and symptoms of bruxism and presence of tori: a systematic review

Abstract

Objective

This systematic review aims to answer the question: "Is there an association between any specific signs and symptoms of bruxism and the presence of tori?"

Material and methods

Observational studies, which evaluated the association between signs and symptoms of bruxism and tori, were selected. Signs and symptoms of bruxism (such as teeth grinding, jaw clenching, abnormal tooth wear, facial muscle hypertrophy, pain, or fatigue) had to be determined by questionnaire or anamnesis and tori within clinical assessment. Search-strategies were developed for five databases, in addition to three gray literature's databases. The risk of bias was evaluated using the "Meta-Analysis of Statistics Assessment and Review Instrument". A summary of overall strength of evidence was estimated using GRADE's Summary of findings table.

Results

Among 575 studies, five were included. Two studies were categorized as moderate risk of bias and three as high risk of bias. Self-report of teeth grinding and/or clenching presented contradictory results. Presence of abnormal tooth wear increased the odds of having tori, mainly for torus mandibularis. The overall quality of evidence ranged from low to very low.

Conclusion

Based on available evidence, the presence of abnormal tooth wear might be associated with tori, mainly torus mandibularis. There is no sufficient evidence to credit or discredit the association of tori and other signs and/or symptoms of bruxism.

Clinical relevance

Bruxism diagnosis is a challenge. The association between signs and symptoms of bruxism and tori could help clinicians on the recognition of patients susceptible to bruxism. This knowledge might also aid to the understanding of tori's development and stimulate new relevant research.

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Presence of root canal treatment has no influence on periodontal bone loss

Abstract

Aim

The aim of this study was to compare the interproximal bone level at root canal-filled teeth and non-root canal-filled teeth.

Materials and methods

The records of patients from the department were consecutively screened from January 2009 to October 2011. The distance between the coronal reference point to the alveolar bone crest (AC) was assessed at the mesial and distal aspects of root canal-filled teeth (RCF+) and their contralateral non-root canal-filled teeth (RCF−) on periapical radiographs. Generalised linear mixed-effects models were applied.

Results

The sample consisted of 128 pairs of teeth comprising data from 72 patients. The results for AC revealed a median distance of 3.2 mm for RCF+ and 3.4 mm for RCF− (p = 0.61). Using the maximal distance on either the distal or the mesial tooth surface, a median distance of 3.6 mm was detected for RCF+ and 3.8 mm for RCF−, respectively (p = 0.42). Even after taking several tooth- and subject-specific variables into account, the differences between AC on RCF+ and RCF− were statistically not significant (p > 0.05).

Conclusion

The interproximal bone loss did not differ statistically significant between root canal-filled teeth and non-root canal-filled teeth.

Clinical relevance

Existence of appropriately done root canal fillings in periodontitis patients has no effect on the prognosis of periodontal disease.

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Improving Radiation Oncology Providers' Workload and Performance: Can Simulation-based Training Help?

Publication date: Available online 17 February 2017
Source:Practical Radiation Oncology
Author(s): Lukasz M. Mazur, Prithima R. Mosaly, Gregg Tracton, Marjorie P. Stiegler, Robert Adams, Bhishamjit Chera, Lawrence B. Marks
PurposeTo help with ongoing safety challenges in radiation therapy (RT) the objective of this research was to develop and assess the impact of simulation-based training intervention on radiation oncology providers' workload and performance during treatment planning and quality assurance (QA) tasks.Methods and materials18 radiation oncology professionals completed routine treatment planning and QA tasks on two clinical scenarios in a simulation laboratory, as part of a prospective IRB-approved study. Workload was measured at the end of each assessment/scenario using the NASA Task-Load Index (NASA-TLX). Performance was quantified based on procedural compliance (adherence to pre-set/standard QA tasks), time-to-scenario completion, and clinically relevant performance. Participants were then randomized to receive (vs. not receive) simulation-based training intervention (e.g., standardized feedback on workload and performance) and underwent repeat measurements of workload and performance. Pre- and post-intervention changes in workload and performance from participants who received (vs. did not receive) were compared using two-way analysis of variance (ANOVA).ResultsSimulation-based training was associated with significant improvements in procedural compliance (p=0.01) and increases in time-to-scenario completion (p=0.01), but had no significant impact on subjective workload or clinically relevant performance.ConclusionSimulation-based training may be a tool to improve procedural compliance of RT professionals and to acquire new skills and knowledge to proactively maintain RT professionals' preoccupation with patient safety.



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Safety and immunogenicity of the novel H4:IC31 tuberculosis vaccine candidate in BCG-vaccinated adults: Two phase I dose escalation trials

Publication date: Available online 17 February 2017
Source:Vaccine
Author(s): Maria Norrby, Timo Vesikari, Lars Lindqvist, Markus Maeurer, Raija Ahmed, Shahnaz Mahdavifar, Sean Bennett, J. Bruce McClain, Barbara M. Shepherd, Daner Li, David A. Hokey, Ingrid Kromann, Søren T. Hoff, Peter Andersen, Adriëtte W. de Visser, Simone A. Joosten, Tom H.M. Ottenhoff, Jan Andersson, Susanna Brighenti
BackgroundNovel vaccine strategies are required to provide protective immunity in tuberculosis (TB) and prevent development of active disease. We investigated the safety and immunogenicity of a novel TB vaccine candidate, H4:IC31 (AERAS-404) that is composed of a fusion protein of M. tuberculosis antigens Ag85B and TB10.4 combined with an IC31® adjuvant.MethodsBCG-vaccinated healthy subjects were immunized with various antigen (5, 15, 50, 150μg) and adjuvant (0, 100, 500nmol) doses of the H4:IC31 vaccine (n=106) or placebo (n=18) in two randomized, double-blind, placebo-controlled phase I studies conducted in a low TB endemic setting in Sweden and Finland. The subjects were followed for adverse events and CD4⁺ T cell responses.ResultsH4:IC31 vaccination was well tolerated with a safety profile consisting of mostly mild to moderate self-limited injection site pain, myalgia, arthralgia, fever and post-vaccination inflammatory reaction at the screening tuberculin skin test injection site. The H4:IC31 vaccine elicited antigen-specific CD4⁺ T cell proliferation and cytokine production that persisted 18weeks after the last vaccination. CD4⁺ T cell expansion, IFN-γ production and multifunctional CD4⁺ Th1 responses were most prominent after two doses of H4:IC31 containing 5, 15, or 50μg of H4 in combination with the 500nmol IC31 adjuvant dose.ConclusionsThe novel TB vaccine candidate, H4:IC31, demonstrated an acceptable safety profile and was immunogenic, capable of triggering multifunctional CD4⁺ T cell responses in previously BCG-vaccinated healthy individuals. These dose-escalation trials provided evidence that the optimal antigen-adjuvant dose combinations are 5, 15, or 50μg of H4 and 500nmol of IC31.Trial registration: ClinicalTrials.gov, NCT02066428 and NCT02074956.



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Effect of stepwise perinatal immunization education: A cluster-randomized controlled trial

Publication date: Available online 17 February 2017
Source:Vaccine
Author(s): Aya Saitoh, Akihiko Saitoh, Isamu Sato, Tomohiro Shinozaki, Hajime Kamiya, Satoko Nagata
BackgroundPerinatal immunization education is important for improving the immunization outcomes of infants; however, the content of educational materials used at each perinatal period has not been carefully evaluated. We hypothesized that stepwise education offered at different perinatal periods would improve infant immunization status and enhance maternal immunization knowledge.MethodsIn this cluster-randomized controlled trial, pregnant women were recruited from nine obstetric sites in Niigata, Japan. The intervention group received a stepwise, interactive education intervention (prenatally, postnatally, and 1month after birth). The control group received a leaflet containing general information on immunization. Infant immunization status was evaluated at 6months of age, and maternal immunization knowledge was evaluated by a written survey after each intervention.ResultsAmong 188 study participants, 151 (80.3%) replied to the final post-intervention survey. At 6months of age, the percentage of children who completed three doses of inactivated polio, diphtheria, tetanus toxoid, and acellular pertussis (DTaP-IPV) vaccine was higher in the intervention group than in the control (p=0.04); however, no differences between groups were observed for the Haemophilus influenzae type b (Hib) (p=0.67) or 13-valent pneumococcal conjugate (PCV13) vaccines (p=0.20). The duration to the completion of the third dose of the DTaP-IPV, Hib, and PCV13 vaccines was shorter in the intervention group than in the control (p=0.03, p<0.01, and p<0.01, respectively). Furthermore, maternal knowledge scores exhibited significantly greater improvement in the intervention group over time compared with those of the control group (p=0.02).ConclusionsStepwise perinatal immunization education improved immunization schedule adherence for required vaccines and improved maternal immunization knowledge.



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Dynamics of APC recruitment at the site of injection following injection of vaccine adjuvants

Publication date: Available online 17 February 2017
Source:Vaccine
Author(s): Susan van Aalst, Irene Stephanie Ludwig, Peter Johannes Sylvester van Kooten, Ruurd van der Zee, Willem van Eden, Femke Broere
Vaccines often contain adjuvants to strengthen the response to the vaccine antigen. However, their modes of action at the site of injection (SOI) are poorly understood. Therefore, we assessed the local effects of adjuvant on the innate immune system in mice. We investigated the safe, widely used adjuvants MF59 and aluminum hydroxide (alum), as well as trehalose-6,6′-dibehenate (TDB), Complete Freund's Adjuvant (CFA) and the Toll-Like-Receptor-ligands lipopolysaccharide (LPS) and Pam3CysSerLys4 (Pam3CSK4). We assessed muscle immune cell infiltration after adjuvant injection and observed 16h post immunization (hpi) an increased influx with CFA, MF59 and TDB, but not with alum, LPS or Pam3CSK4. An elevated influx with the latter three became visible only 72hpi. Contribution of granulocytes, macrophages and dendritic cells to the influx differed per adjuvant and in time. Adjuvants generally induced a local pro-inflammatory micro-milieu that was transient except for CFA and TDB. The gene expression of CXCL-1, CCL-2 and CCL-5, involved in recruitment of immune cells, varied per adjuvant and corresponded grossly with the observed influx of granulocytes and monocytes/macrophages. Muscles injected with CFA or MF59 (when co-injected with peptide) resulted in APC ex vivo capable to induce proliferation of peptide-specific T-cells. By adding in vitro an excess of peptide to the APC/T cell co-cultures, we observed an adjuvant-enhanced co-stimulation or antigen presentation by APC after CFA- but not MF59-injection. After TDB-injection this effect was observed only at 72hpi, but not 24hpi. Thus the cellular influx profile and the local cytokine and chemokine micro-milieu in the muscle were strongly influenced by the type of adjuvant. Additionally, the capacity of muscle APC to load and present antigen was affected by the adjuvant. These findings may assist the development of novel adjuvanted vaccines in a more rational manner.



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Corrigendum to “Sustained localized presentation of RNA interfering molecules from in situ forming hydrogels to guide stem cell osteogenic differentiation” [Biomaterials 35/24 (2014) 6278–6286]

Publication date: May 2017
Source:Biomaterials, Volume 125
Author(s): Minh K. Nguyen, Oju Jeon, Melissa D. Krebs, Daniel Schapira, Eben Alsberg




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Polyester fabric sheet layers functionalized with graphene oxide for sensitive isolation of circulating tumor cells

Publication date: May 2017
Source:Biomaterials, Volume 125
Author(s): Jiyoon Bu, Young Jun Kim, Yoon-Tae Kang, Tae Hee Lee, Jeongsuk Kim, Young-Ho Cho, Sae-Won Han
The metastasis of cancer is strongly associated with the spread of circulating tumor cells (CTCs). Based on the microfluidic devices, which offer rapid recovery of CTCs, a number of studies have demonstrated the potential of CTCs as a diagnostic tool. However, not only the insufficient specificity and sensitivity derived from the rarity and heterogeneity of CTCs, but also the high-cost fabrication processes limit the use of CTC-based medical devices in commercial. Here, we present a low-cost fabric sheet layers for CTC isolation, which are composed of polyester monofilament yarns. Fabric sheet layers are easily functionalized with graphene oxide (GO), which is beneficial for improving both sensitivity and specificity. The GO modification to the low-cost fabrics enhances the binding of anti-EpCAM antibodies, resulting in 10–25% increase of capture efficiency compared to the surface without GO (anti-EpCAM antibodies directly onto the fabric sheets), while achieving high purity by isolating only 50–300 leukocytes in 1 mL of human blood. We investigated CTCs in ten human blood samples and successfully isolated 4–42 CTCs/mL from cancer patients, while none of cancerous cells were found among healthy donors. This remarkable results show the feasibility of GO-functionalized fabric sheet layers to be used in various CTC-based clinical applications, with high sensitivity and selectivity.



http://ift.tt/2kQIWvH

Modulation of Language Switching by Cue Timing: Implications for Models of Bilingual Language Control.

Author: Khateb, Asaid; Shamshoum, Rana; Prior, Anat

DOI: 10.1037/xlm0000382

Publication Date: POST AUTHOR CORRECTIONS, 16 February 2017

http://ift.tt/2m6botK

Is the Internet a Suitable Patient Resource for Information on Common Radiological Investigations?

Publication date: Available online 17 February 2017
Source:Academic Radiology
Author(s): Dermot J. Bowden, Lee-Chien Yap, Declan G. Sheppard
Rationale and Objective:This study aimed to assess the quality of Internet information about common radiological investigations.Materials and MethodsFour search engines (Google, Bing, Yahoo, and Duckduckgo) were searched using the terms "X-ray," "cat scan," "MRI," "ultrasound," and "pet scan." The first 10 webpage results returned for each search term were recorded, and their quality and readability were analyzed by two independent reviewers (DJB and LCY), with discrepancies resolved by consensus. Analysis of information quality was conducted using validated instruments for the assessment of health-care information (DISCERN score is a multi-domain tool for assessment of health-care information quality by health-care professionals and laypeople (max 80 points)) and readability (Flesch-Kincaid and SMOG or Simple Measure of Gobbledygook scores). The search result pages were further classified into categories as follows: commercial, academic (educational/institutional), and news/magazine. Several organizations offer website accreditation for health-care information, and accreditation is recognized by the presence of a hallmark or logo on the website. The presence of any valid accreditation marks on each website was recorded. Mean scores between groups were compared for significance using the Student t test.ResultsA total of 200 webpages returned (108 unique website addresses). The average DISCERN score was <50 points for all modalities and search engines. No significant difference was seen in readability between modalities or between search engines. Websites carrying validated accreditation marks were associated with higher average DISCERN scores: X-ray (39.36 vs 25.35), computed tomography (45.45 vs 31.33), and ultrasound (40.91 vs 27.62) (P < .01). Academic/government institutions produced material with higher DISCERN scores: X-ray (40.06 vs 22.23), magnetic resonance imaging (44.69 vs 29), ultrasound (46 vs 31.91), and positron emission tomography (45.93 vs 38.31) (P < .01). Commercial websites produced material with lower mean DISCERN scores: X-ray (17.25 vs 31.69), magnetic resonance imaging (20.8 vs 40.1), ultrasound (24.11 vs 42.35), and positron emission tomography (24.5 vs 44.45) (P < .01).ConclusionsAlthough readability is adequate, the overall quality of radiology-related health-care information on the Internet is poor. High-quality online resources should be identified so that patients may avoid the use of poor-quality information derived from general search engine queries.



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Phase II study of bevacizumab and irinotecan as second-line therapy for patients with metastatic colorectal cancer previously treated with fluoropyrimidines, oxaliplatin, and bevacizumab

Abstract

Purpose

Fluorouracil and folinic acid with irinotecan (FOLFIRI) plus bevacizumab (BV) is widely used as second-line chemotherapy for patients with metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidines, oxaliplatin, and BV. FOLFIRI requires a CV catheter and an infusion pump, which are inconvenient for patients. Sufficient data are not available for characterizing the effectiveness of fluoropyrimidines beyond first disease progression. In this study, we evaluated the efficacy and safety of irinotecan (CPT-11) plus BV as second-line therapy.

Methods

Patients with mCRC previously treated with at least four courses of a fluoropyrimidine, oxaliplatin, and BV were designated to receive 150 mg/m² of CPT-11 and 10 mg/kg of BV every 2 weeks as second-line therapy. The primary endpoint was progression-free survival (PFS), and secondary endpoints included response rate (RR), overall survival (OS), and adverse events.

Results

Thirty patients from six institutes were enrolled from March 2011 to January 2014. The median PFS was 5.7 months (95% CI 4.2–7.3 months), and the RR was 6.7% (range 0.8–22.1%). Grades 3–4 adverse events included leucopenia (36.7%), neutropenia (50%), thrombocytopenia (26.7%), anemia (30%), diarrhea (3.3%), anorexia (6.7%), and hypertension (3.3%). Relative dose intensities were 94.5 and 96.3% for CPT-11 and BV, respectively. The median OS was 11.8 months (6.3 months—not reached).

Conclusions

Administration of CPT-11 plus BV to patients with mCRC achieved comparable efficacies with relatively lower toxicities compared with the results of previous studies using FOLFIRI plus BV as second-line therapy. The dose intensity of CPT-11 was judged as satisfactory.

Clinical trial information

UMIN000005228

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Characterization of phospholipid nitroxidation by LC-MS in biomimetic models and in H9c2 Myoblast using a lipidomic approach

Publication date: Available online 17 February 2017
Source:Free Radical Biology and Medicine
Author(s): Tânia Melo, Pedro Domingues, Teresa M. Ribeiro-Rodrigues, Henrique Girão, Marcela A. Segundo, M.Rosário M. Domingues
Under nitroxidative stress conditions, lipids are prone to be modified by reaction with reactive nitrogen species (RNS) and different modifications were reported to occur in fatty acids. However, in the case of phospholipids (PL) studied under nitroxidative stress conditions, only nitroalkene derivatives of phosphatidylcholine (PC) and phosphatidylethanolamine (PE), were reported when using both in vitro biomimetic conditions and in vivo model system of type 1 diabetes mellitus. Therefore, in order to further explore other nitroxidative modifications of PL, a biomimetic model of nitroxidation combined with liquid chromatography mass spectrometry (MS) and MS/MS approaches were used to characterize the nitrated and nitroxidized derivatives of PCs and PEs. Single and multiple nitrated derivatives of phospholipids (PLs) such as nitroso and dinitroso, nitro, dinitro, and nitronitroso derivatives, together with nitroxidized derivatives were identified. Further, the specific MS/MS fragmentation pathways of these products were studied. Product ions arising from loss of HNO and HNO2, from the combined loss of HNO (or HNO2) and polar head groups, [NOn-FA+On+H]⁺ and [NOn-FA+On-H]^- (n=1–2) product ions corresponding to the modified fatty acyl chains were observed, depending on each modification.The knowledge obtained from the study of the MS/MS fragmentation pattern has allowed us to identify nitrated PCs, including NO2-PC, (NO2)2-PCs, (NO2)(NO)-PC, NO-PC; nitrated PEs, NO2-PEs; and nitroxidized PCs, (NO2)(2O)-PC in H9c2 cells under starvation, but not under ischemia or control conditions. The physiological relevance of this nitrated and nitroxidized PCs and PEs species observed exclusively in cardiomyoblast cells (H9c2) under starvation is still unknown but deserves to be explored.



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The role of mitochondria in cardiac development and protection

Publication date: Available online 17 February 2017
Source:Free Radical Biology and Medicine
Author(s): Jaakko L. Pohjoismäki, Steffi Goffart
Mitochondria are essential for the development as well as maintenance of the myocardium, the most energy consuming tissue in the human body. Mitochondria are not only a source of ATP energy but also generators of reactive oxygen species (ROS), that cause oxidative damage, but also regulate physiological processes such as the switch from hyperplastic to hypertrophic growth after birth. As excess ROS production and oxidative damage are associated with cardiac pathology, it is not surprising that much of the research focused on the deleterious aspects of free radicals. However, cardiomyocytes are naturally highly adapted against repeating oxidative insults, with evidence suggesting that moderate and acute ROS exposure has beneficial consequences for mitochondrial maintenance and cardiac health. Antioxidant defenses, mitochondrial quality control, mtDNA maintenance mechanisms as well as mitochondrial fusion and fission improve mitochondrial function and cardiomyocyte survival under stress conditions. As these adaptive processes can be induced, promoting mitohormesis or mitochondrial biogenesis using controlled ROS exposure could provide a promising strategy to increase cardiomyocyte survival and prevent pathological remodeling of the myocardium.



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Serotonin disturbs colon epithelial tolerance of commensal E. coli by increasing NOX-2-derived superoxide

Publication date: Available online 17 February 2017
Source:Free Radical Biology and Medicine
Author(s): Suhrid Banskota, Sushil Chandra Regmi, Jaya Gautam, Pallavi Gurung, Yu-Jeong Lee, Sae Kwang Ku, Jin-Hyung Lee, Jintae Lee, Hyeun Wook Chang, Sang Joon Park, Jung-Ae Kim
Adherent-invasive E. coli colonization and Toll-like receptor (TLR) expression are increased in the gut of inflammatory bowel disease (IBD) patients. However, the underlying mechanism of such changes has not been determined. In the current study, it was examined whether gut serotonin (5-hydroxytryptamine, 5-HT) can induce adherent-invasive E. coli colonization and increase TLR expression. In a co-culture system, commensal E. coli strain (BW25113, BW) adhered minimally to colon epithelial cells, but this was significantly enhanced by 5-HT to the level of a pathogenic strain (EDL933). Without inducing bacterial virulence, such as, biofilm formation, 5-HT enhanced BW-induced signaling in colon epithelial cells, that is, NADPH oxidase (NOX)-dependent superoxide production, the up-regulations of IL-8, TLR2, TLR4, and ICAM-1, and the down-regulations of E-cadherin and claudin-2. In a manner commensurate with these gene modulations, BW induced an increase in NF-κB and a decrease in GATA reporter signals in colon epithelial cells. However, 5-HT-enhanced BW adhesion and colon epithelial responses were blocked by knock-down of NOX2, TLR2, or TLR4. In normal mice, 5-HT induced the invasion of BW into gut submucosa, and the observed molecular changes were similar to those observed in vitro, except for significant increases in TNFα and IL-1β, and resulted in death. In dextran sulfate sodium-induced colitis mice (an IBD disease model), in which colonic 5-HT levels were markedly elevated, BW administration induced death in along with large amount of BW invasion into colon submucosa, and time to death was negatively related to the amount of BW injected. Taken together, our results demonstrate that 5-HT induces the invasion of commensal E. coli into gut submucosa by amplifying commensal bacteria-induced epithelial signaling (superoxide production and the inductions of NOX2 and TLR2/TLR4). The authors suggest that these changes may constitute the molecular basis for the pathogenesis of IBD.

Graphical abstract

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Electrochemical monitoring of biointeraction by graphene-based material modified pencil graphite electrode

Publication date: 15 June 2017
Source:Biosensors and Bioelectronics, Volume 92
Author(s): Ece Eksin, Erhan Zor, Arzum Erdem, Haluk Bingol
Recently, the low-cost effective biosensing systems based on advanced nanomaterials have received a key attention for development of novel assays for rapid and sequence-specific nucleic acid detection. The electrochemical biosensor based on reduced graphene oxide (rGO) modified disposable pencil graphite electrodes (PGEs) were developed herein for electrochemical monitoring of DNA, and also for monitoring of biointeraction occurred between anticancer drug, Daunorubicin (DNR), and DNA. First, rGO was synthesized chemically and characterized by using UV–Vis, TGA, FT-IR, Raman Spectroscopy and SEM techniques. Then, the quantity of rGO assembling onto the surface of PGE by passive adsorption was optimized. The electrochemical behavior of rGO–PGEs was examined by cyclic voltammetry (CV). rGO-PGEs were then utilized for electrochemical monitoring of surface-confined interaction between DNR and DNA using differential pulse voltammetry (DPV) technique. Additionally, voltammetric results were complemented with electrochemical impedance spectroscopy (EIS) technique. Electrochemical monitoring of DNR and DNA was resulted with satisfying detection limits 0.55µM and 2.71µg/mL, respectively.

Graphical abstract

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Immunorecognition magnetic supports for the development of an electrochemical immunoassay for azaspiracid detection in mussels

Publication date: 15 June 2017
Source:Biosensors and Bioelectronics, Volume 92
Author(s): Sandra Leonardo, Maria Rambla-Alegre, Ingunn A. Samdal, Christopher O. Miles, Jane Kilcoyne, Jorge Diogène, Ciara K. O'Sullivan, Mònica Campàs
As azaspiracids (AZAs) are being reported from the coastal waters of an increasing number of countries on a global scale, the need for rapid, simple and cost-effective methods to detect these marine toxins and protect seafood consumers' health is becoming evident. A magnetic bead (MB)-based direct immunoassay for the detection of AZAs, using protein G-coated MBs as supports for antibody immobilisation and peroxidase-labelled AZA as a tracer is detailed. A colorimetric approach was first developed to optimise the experimental parameters and establish the cross-reactivity factors for AZA-1–10. The subsequent combination of the immunorecognition MBs with 8-electrode arrays enabled the multiplexed electrochemical detection of AZAs. Naturally-contaminated mussel samples were analysed and the results obtained showed an excellent correlation with LC-MS/MS analysis. The MB-based immunoassay facilitated the quantification of a wide range of AZA concentrations (120–2875μg AZA-1 equiv./kg), with a limit of detection (63μg AZA-1 equiv./kg) below the European regulatory threshold, using a protocol that requires very few steps and a short analysis time (~ 15min). The simplicity, cost-effectiveness, rapidity, robustness, selectivity and precision of the assay provide a valuable tool for the detection of all regulated AZAs and other toxic AZA analogues, suitable for end users in the field of food safety.



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Clinical outcomes and prognostic factors of patients with advanced mesothelioma treated in a phase I clinical trials unit

Publication date: April 2017
Source:European Journal of Cancer, Volume 75
Author(s): Dionysis Papadatos-Pastos, Desam Roda, Maria Jose De Miguel Luken, Ann Petruckevitch, Awais Jalil, Marta Capelan, Vasiliki Michalarea, Joao Lima, Nikolaos Diamantis, Jaishree Bhosle, L. Rhoda Molife, Udai Banerji, Johann S. de Bono, Sanjay Popat, Mary E.R. O'Brien, Timothy A. Yap
BackgroundWe have previously reported a prognostic score for patients in phase I trials in the Drug Development Unit, treated at the Royal Marsden Hospital (RPS). The RPS is an objective tool used in patient selection for phase I trials based on albumin, number of disease sites and LDH. Patients with mesothelioma are often selected for phase I trials as the disease remains localised for long periods of time. We have now reviewed the clinical outcomes of patients with relapsed malignant mesothelioma (MM) and propose a specific mesothelioma prognostic score (m-RPS) that can help identify patients who are most likely to benefit from early referral.MethodsPatients who participated in 38 phase I trials between September 2003 and November 2015 were included in the analysis. Efficacy was assessed by response rate, median overall survival (OS) and progression-free survival (PFS). Univariate (UVA) and multivariate analyses (MVA) were carried out to develop the m-RPS.ResultsA total of 65 patients with advanced MM were included in this retrospective study. The PFS was 2.5 months (95% confidence interval [CI] 2.0–3.1 months) and OS was 8 months (95% CI 5.6–9.8 months). A total of four (6%) patients had RECIST partial responses, whereas 26 (40%) patients had RECIST stable disease >3 months. The m-RPS was developed comprising of three different prognostic factors: a neutrophil: lymphocyte ratio greater than 3, the presence of more than two disease sites (including lymph nodes as a single site of disease) and albumin levels less than 35 from the MVA. Patients each received a score of 1 for the presence of each factor. Patients in group A (m-RPS 0–1; n = 35) had a median OS of 13.4 months (95% CI 8.5–21.6), whereas those in group B (m-RPS 2–3; n = 30) had a median OS of 4.0 months (95% CI 2.9–7.1, P < 0.0001). A total of 56 (86%) patients experienced G1-2 toxicities, whereas reversible G3-4 toxicities were observed in 18 (28%) patients. Only 10 (15%) patients discontinued phase I trials due to toxicity.ConclusionsPhase I clinical trial therapies were well tolerated with early signals of antitumour activity in advanced MM patients. The m-RPS is a useful tool to assess MM patient suitability for phase I trials and should now be prospectively validated.



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Ipilimumab alone or in combination with nivolumab after progression on anti-PD-1 therapy in advanced melanoma

Publication date: April 2017
Source:European Journal of Cancer, Volume 75
Author(s): Lisa Zimmer, Susmitha Apuri, Zeynep Eroglu, Lisa A. Kottschade, Andrea Forschner, Ralf Gutzmer, Max Schlaak, Lucie Heinzerling, Angela M. Krackhardt, Carmen Loquai, Svetomir N. Markovic, Richard W. Joseph, Kelly Markey, Jochen S. Utikal, Carsten Weishaupt, Simone M. Goldinger, Vernon K. Sondak, Jonathan S. Zager, Dirk Schadendorf, Nikhil I. Khushalani
BackgroundThe anti-programmed cell death-1 (PD-1) inhibitors pembrolizumab and nivolumab alone or in combination with ipilimumab have shown improved objective response rates and progression-free survival compared to ipilimumab only in advanced melanoma patients. Anti-PD-1 therapy demonstrated nearly equal clinical efficacy in patients who had progressed after ipilimumab or were treatment-naïve. However, only limited evidence exists regarding the efficacy of ipilimumab alone or in combination with nivolumab after treatment failure to anti-PD-therapy.Patients and methodsA multicenter retrospective study in advanced melanoma patients who were treated with nivolumab (1 or 3 mg/kg) and ipilimumab (1 mg or 3 mg/kg) or ipilimumab (3 mg/kg) alone after treatment failure to anti-PD-1 therapy was performed. Patient, tumour, pre- and post-treatment characteristics were analysed.ResultsIn total, 47 patients were treated with ipilimumab (ipi-group) and 37 patients with ipilimumab and nivolumab (combination-group) after treatment failure to anti-PD-1 therapy. Overall response rates for the ipi- and the combination-group were 16% and 21%, respectively. Disease control rate was 42% for the ipi-group and 33% for the combination-group. One-year overall survival rates for the ipi- and the combination-group were 54% and 55%, respectively.ConclusionsIpilimumab should be considered as a viable treatment option for patients with failure to prior anti-PD-1 therapy, including those with progressive disease as best response to prior anti-PD-1. In contrast, the combination of ipilimumab and nivolumab appears significantly less effective in this setting compared to treatment-naïve patients.



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Risk of oesophageal adenocarcinoma in individuals with Barrett's oesophagus

Publication date: April 2017
Source:European Journal of Cancer, Volume 75
Author(s): Dag Holmberg, Eivind Ness-Jensen, Fredrik Mattsson, Hashem B. El-Serag, Jesper Lagergren
IntroductionRecent studies have indicated a lower incidence rate of oesophageal adenocarcinoma (OAC) in individuals with Barrett's oesophagus (BO) than most earlier studies. Our objective was to assess the risk of OAC in a Swedish unselected cohort of individuals with BO.MethodsThis population-based cohort study included all Swedish residents diagnosed with BO in 2006–2013, identified through the Swedish Patient Registry. The cohort members were followed from the date of first BO diagnosis until the first occurrence of OAC, high-grade dysplasia (HGD), death, emigration or end of study period. The main outcome was incidence rates with 95% confidence intervals (CIs) of OAC.ResultsAmong 7932 participants with BO and 18,415 person-years of follow-up, the overall incidence of OAC was 1.47 (95% CI 0.91–2.02) per 1000 person-years. When stratified into follow-up periods after BO diagnosis, the incidence rate of OAC was 15.53 (4.77–26.29) from 7 to 30 d, 4.10 (0.82–7.38) from 31 to 100 d, 1.87 (0.00–3.99) from 101 d to 6 months, 1.44 (0.18–2.70) from >6 months to 1 year, 0.94 (0.36–1.53) from >1 year to 3 years and 2.17 (1.14–3.21) from >3 years to the end of follow-up. The median follow-up time was 2.13 person-years.ConclusionThis population-based study indicates that OAC is primarily diagnosed during the first months following an initial diagnosis of BO. This could justify a changed surveillance strategy of BO with a repeated thorough endoscopy shortly after initial BO diagnosis to identify prevalent early OAC or HGD.



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Enhancer of zeste homologue 2 plays an important role in neuroblastoma cell survival independent of its histone methyltransferase activity

Publication date: April 2017
Source:European Journal of Cancer, Volume 75
Author(s): Laurel T. Bate-Eya, Hinco J. Gierman, Marli E. Ebus, Jan Koster, Huib N. Caron, Rogier Versteeg, M. Emmy M. Dolman, Jan J. Molenaar
Neuroblastoma is predominantly characterised by chromosomal rearrangements. Next to V-Myc Avian Myelocytomatosis Viral Oncogene Neuroblastoma Derived Homolog (MYCN) amplification, chromosome 7 and 17q gains are frequently observed. We identified a neuroblastoma patient with a regional 7q36 gain, encompassing the enhancer of zeste homologue 2 (EZH2) gene. EZH2 is the histone methyltransferase of lysine 27 of histone H3 (H3K27me3) that forms the catalytic subunit of the polycomb repressive complex 2. H3K27me3 is commonly associated with the silencing of genes involved in cellular processes such as cell cycle regulation, cellular differentiation and cancer. High EZH2 expression correlated with poor prognosis and overall survival independent of MYCN amplification status. Unexpectedly, treatment of 3 EZH2-high expressing neuroblastoma cell lines (IMR32, CHP134 and NMB), with EZH2-specific inhibitors (GSK126 and EPZ6438) resulted in only a slight G1 arrest, despite maximum histone methyltransferase activity inhibition. Furthermore, colony formation in cell lines treated with the inhibitors was reduced only at concentrations much higher than necessary for complete inhibition of EZH2 histone methyltransferase activity. Knockdown of the complete protein with three independent shRNAs resulted in a strong apoptotic response and decreased cyclin D1 levels. This apoptotic response could be rescued by overexpressing EZH2ΔSET, a truncated form of wild-type EZH2 lacking the SET transactivation domain necessary for histone methyltransferase activity. Our findings suggest that high EZH2 expression, at least in neuroblastoma, has a survival function independent of its methyltransferase activity. This important finding highlights the need for studies on EZH2 beyond its methyltransferase function and the requirement for compounds that will target EZH2 as a complete protein.



http://ift.tt/2kyd030

Low Osmolality and Shear Stress during Liposuction Impair Cell Viability in Autologous Fat Grafting

Liposuction and subsequent autologous fat grafting have become essential techniques for fat augmentation in plastic surgery. However, standard harvesting techniques that ensure survival of adipocytes and stromal vascular fraction (SVF) cells and thus preserve the transplanted fat volume are lacking. In particular, the effect of different parameters of the tumescent solution has not been studied in this context. We hypothesized that the osmolality of the tumescent solution could have a significant effect on the survival of adipocytes and SVF cells.

http://ift.tt/2lU9kc5

Cartilage Suspension using a Poly (lactic-co-glycolic) Acid System

This study aims to determine whether a bar-like implant made of poly lactic-co-glycolic acid (PLGA) could be used for cartilage suspension, and whether the implant would be suitable for rhinoplasty.

http://ift.tt/2m5X8kx

Preoperative asymmetry is a risk factor for reoperation in involutional blepharoptosis

Patients with involutional blepharoptosis sometimes require reoperation because of functional or aesthetic reasons after the primary operation. Few studies have analyzed risk factors for reoperation in such cases.

http://ift.tt/2lU49c4

Lateral Thigh Perforator Flap for Breast Reconstruction: Computed Tomographic Angiography Analysis and Clinical Series

While abdominally based flaps remain the first choice for autologous breast reconstruction, alternative donor sites are necessary when the abdomen is unavailable. Abdominal donor site suitability is determined, at times, based on DIEP-protocol computed tomographic angiography (CTA) results. CTA also provides information about the pelvis/upper thigh that can be used to evaluate suitability of other donor sites. The purpose of this study was to examine the utility of DIEP-protocol CTA in the assessment of a lateral thigh perforator flap (LTP).

http://ift.tt/2m5KwtY

Structural biomechanics of the craniomaxillofacial skeleton under maximal masticatory loading: inferences and critical analysis based on a validated computational model

The trend towards optimizing stabilization of the craniomaxillofacial skeleton (CMFS) with the minimum amount of fixation required to achieve union, and away from maximizing rigidity, requires a quantitative understanding of craniomaxillofacial biomechanics. This study uses computational modeling to quantify the structural biomechanics of the CMFS under maximal physiologic masticatory loading.

http://ift.tt/2lU48VC

Microvascular Surgery in the Congenital Cardiac Patient: A Case Series Exploring Feasibility and Practical Applications

Pediatric congenital heart disease patients are at risk for vascular injuries during surgical procedures or when the arterial system is accessed for monitoring or diagnostic studies. Our treatment of emergent situations in this patient population using microvascular techniques shows the feasibility of such techniques.

http://ift.tt/2m5H2HF

Indocyanine green applications in plastic surgery: a review of the literature

Using IndoCyanine Green (ICG) near-infrared fluorescence as a dye to assess tissue vascularisation is now well standardized. The aim of this literature review was to review and resume the most recent recommendations for ICG use in its plastic surgery applications.

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Orbicularis oculi muscle tightening for involutional entropion

To describe a novel technique for involutional entropion (IE) correction and to present a retrospective case study.

http://ift.tt/2m5LPcg

Combined Submuscular Tissue Expansion And Anterior Components Separation Technique For Abdominal Wall Reconstruction: Long-Term Outcomes Analysis

We report long-term outcomes analysis of twelve patients undergoing two-stage abdominal wall reconstruction using combined submuscular tissue expansion (TE) and anterior components separation (CS) technique.

http://ift.tt/2lU6vHY

Scarring of the C8-T1 roots with partial avulsion in situ in total obstetric brachial plexus palsy

Abstract

Background

Primary exploration of the brachial plexus in infants with obstetric palsy may reveal scarring of the lower roots with evidence of partial avulsion-in-situ. As we have been treating this lesion by neurolysis only, we aimed to investigate the recovery of hand function following such approach.

Methods

A series of 14 cases of total obstetric palsy with with evidence of partial avulsion-in-situ of the lower roots were included. All lesions were treated by neurolysis only (with no neurotization of the lower roots). Management of the injured upper roots was done by neurotization. Recovery was assessed as per our motor grading system.

Results

After a minimum follow-up of 4 years, hand functional recovery was considered good in 7 patients and excellent in the remaining 7 patients.

Conclusions

We highlight the scarring of lower roots with evidence of partial avulsion-in situ in obstetric palsy. We also document that neurolysis is an acceptable approach to such lesions.

Level of Evidence: Level IV, therapeutic study.

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Plant-microbial association in petroleum and gas exploration sites in the state of Assam, north-east India—significance for bioremediation

Abstract

The state of Assam in north-east India gained popularity in Asia because of discovery of oil. Pollution due to petroleum and gas exploration is a serious problem in Assam. Oil and gas exploration by various agencies in Assam resulted in soil pollution due to hydrocarbons (HCs) and heavy metals (HMs). Bioremediation gained considerable significance in addressing petroleum hydrocarbon polluted sites in various parts of the world. In this investigation, we have observed 15 species of plants belonging to grass growing on the contaminated soils. Among 15 species of grasses, 10 species with high important value index (IVI) were found to be better adapted. The highest IVI is exhibited by Axonopus compressus (21.41), and this grass can be identified as key ecological tool in the rehabilitation of the degraded site. But no definite correlation between the IVI and the biomass of the various grass existed in the study sites. Chemical study of rhizosphere (RS) and non-rhizosphere (NRS) soil of these grasses revealed both aromatic and aliphatic compounds (M.W. 178–456). Four-ring pyrene was detected in NRS soil but not in RS soil. Microbiological study of RS and NRS soil showed high colony-forming unit (CFU) of HC-degrading microbes in RS compared to NRS. The increased microbial catabolism in RS soil established the fact that pyrene is transformed to aliphatic compounds. Metals in RS soil ranged from (in mg kg⁻¹) 222.6 to 267.3 (Cr), 854 to 956 (Pb) and 180 to 247 (Ni), but despite the very high total metal concentration in RS and NRS soil, the CaCl₂-extracted metals were relatively low in RS soil (1.04 for Cr, 0.56 for Pb, 0.35 for Ni). Plants with the highest uptake of metals were Leersia hexandra (36.43 mg Cr kg⁻¹) and Kyllinga brevifolia (67.73 mg Pb kg⁻¹ and 40.24 mg Ni kg⁻¹). These plant species could be potentially exploited for biomonitoring and bioremediation. Out of 15 plant species, 8 of them have high percentages of cellulose, crude fibres, lignin and holocellulose (14–16%). The explored species thus qualify as energy crops since they have high bioproductivity and are more resilient and adaptable in HM/HC-contaminated sites.

http://ift.tt/2kI1NIn

Removal mechanisms for extremely high-level fluoroquinolone antibiotics in pharmaceutical wastewater treatment plants

Abstract

Pharmaceutical wastewater treatment plants (PWWTPs) receive industrial effluents from the plant that contain extremely high levels of antibiotics and are regarded as one of the major sources of antibiotics in the environment. Two PWWTPs have been selected in Zhejiang Province, China, to assess the removal mechanisms of fluoroquinolone antibiotics (FQs). PWWTP A uses activated sludge with biocarriers in a moving bed biofilm reactor in anoxic and aerobic units, and PWWTP B uses biological units under anaerobic, aerobic, and anoxic conditions. The wastewater samples and solid samples (sludge and suspended solid matter) were analyzed using solid-phase extraction and ultra-performance liquid chromatography-mass spectrometry. Ofloxacin (OFX) was detected in each stage of PWWTP A, and enrofloxacin and ciprofloxacin were detected in PWWTP B. The concentrations of FQs ranged from 0.32 μg/L to 5.7 mg/L. Although the FQs were largely removed in the biological units (94.5 to 99.9%), large amounts were still discharged in the final effluent (up to 88.0 ± 7.0 μg/L) and dewatered sludge (up to 0.85 ± 0.24 mg/kg). Mass balance analyses of samples from PWWTP A indicated that biodegradation (93.8%) was the major mechanism responsible for the removal of OFX, whereas the contribution of sorption by sludge (0.79%) was less significant, deviating from the findings of most similar studies. Using linear analysis and correlation analysis, we found that the log₁₀ values of the FQ concentration in the sludge were positively related with the log₁₀ values of the equilibrium concentration in water (C _w ). These relationships can be described by a Freundlich-like equation. However, these relationships were negative when the C _w values were high. Our preliminary explanation is that the equilibrium C _w plays an important role in controlling the sorption behavior of FQs in activated sludge.

http://ift.tt/2lsDYZ8

Hydropower reservoirs: cytotoxic and genotoxic assessment using the Allium cepa root model

Abstract

Hydropower offers a reliable source of electricity in several countries, and Brazil supplies its energy needs almost entirely through hydropower plants. Nevertheless, hydropower plants comprise large buildings and water reservoirs and dams, resulting in huge ecological disruptions. Here, we analyzed the impact of four hydropower reservoirs construction in metals and pesticides incidence and the cytotoxic and genotoxic potential of sediment elutriate of rivers from southern Brazil. Our analyses have evidenced the elevated incidence of different metals (lead, iron, cadmium, and chrome) and pesticides (methyl parathion, atrazine, and 2,4-dichlorophenoxyacetic acid). We showed that Allium cepa exposed to sediment elutriates did not change the seed germination rate and mitotic index. However, roots from Allium cepa exposed to reservoirs sediment elutriates showed increased occurrence of chromosomal aberrations and nuclear abnormalities. Therefore, the results obtained in our study indicate that sediment from reservoirs present elevated concentration of metals and pesticides and a significant genotoxic potential. Taken together, our data support that hydropower reservoirs represent an environmental scenario that could impact surrounding wildlife and population.

http://ift.tt/2kI7cyZ

Responses of soil methanogens, methanotrophs, and methane fluxes to land-use conversion and fertilization in a hilly red soil region of southern China

Abstract

Changes in land-uses and fertilization are important factors regulating methane (CH₄) emissions from paddy soils. However, the responses of soil CH₄ emissions to these factors and the underlying mechanisms remain unclear. The objective of this study was to explore the effects of land-use conversion from paddies to orchards and fertilization on soil CH₄ fluxes, and the abundance and community compositions of methanogens and methanotrophs. Soil CH₄ fluxes were quantified by static chamber and gas chromatography technology. Abundance and community structures of methanogens and methanotrophs (based on mcrA and pmoA genes, respectively) were determined by quantitative real-time PCR (qPCR), and terminal restriction fragment length polymorphism (TRFLP), cloning and sequence analysis, respectively. Results showed that land-use conversion from paddies to orchards dramatically decreased soil CH₄ fluxes, whereas fertilization did not distinctly affect soil CH₄ fluxes. Furthermore, abundance of methanogens and methanotrophs were decreased after converting paddies to orchards. Fertilization decreased the abundance of these microorganisms, but the values were not statistically significant. Moreover, land-use conversion had fatal effects on some members of the methanogenic archaea (Methanoregula and Methanosaeta), increased type II methanotrophs (Methylocystis and Methylosinus), and decreased type I methanotrophs (Methylobacter and Methylococcus). However, fertilization could only significantly affect type I methanotrophs in the orchard plots. In addition, CH₄ fluxes from paddy soils were positively correlated with soil dissolved organic carbon contents and methanogens abundance, whereas CH₄ fluxes in orchard plots were negatively related to methanotroph abundance. Therefore, our results suggested that land-use conversion from paddies to orchards could change the abundance and community compositions of methanogens and methanotrophs, and ultimately alter the soil CH₄ fluxes. Overall, our study shed insight on the underlying mechanisms of how land-use conversion from paddies to orchards decreased CH₄ emissions.

http://ift.tt/2lsDCBT

Management of brain metastasized non-small cell lung cancer (NSCLC) - from local treatment to new systemic therapies

Publication date: Available online 17 February 2017
Source:Cancer Treatment Reviews
Author(s): G. Tsakonas, L. De Petris, S. Ekman
Lung cancer has the highest frequency of brain dissemination compared to all other solid tumours. Classical treatment options such as brain irradiation have started to be questioned due to lack of survival benefit and risk for severe side effects. Oncogenic driven tumours have the highest frequency of brain dissemination among NSCLC patients and available targeted therapies have shown activity both intra- and extracranially, with an acceptable toxicity profile. The recent approval of immune checkpoint inhibitors for the treatment of NSCLC has complicated treatment selection even more. Data regarding efficacy of immune therapy in the CNS are limited, though promising, and data from larger cohorts are eagerly expected.The purpose of this review is to summarize all available treatment options for brain metastatic NSCLC with an emphasis on oncogenic driven tumours. Treatment selection for brain metastasized NSCLC patients is challenging because of the detrimental effect of potential treatment related CNS side effects in patients' quality of life. Clinical decision making should be done in an individualised way, taking both clinical and molecular factors into consideration.



http://ift.tt/2lgeewX

Imaging performance in guiding response to neoadjuvant therapy according to breast cancer subtypes: A systematic literature review

Publication date: Available online 17 February 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Melanie A. Lindenberg, Anna Miquel-Cases, Valesca P. Retèl, Gabe S. Sonke, Jelle Wesseling, Marcel P.M. Stokkel, Wim H. van Harten
Monitoring therapeutic response to neoadjuvant chemotherapy(NAC) is likely to improve NAC effectiveness in breast cancer(BC). Imaging performance seems to vary per tumour subtype(by ER and HER2 status), therefore we performed a systematic review on subtype specific imaging performance in monitoring NAC in BC.Studies examining imaging performance in predicting pathologic complete response(pCR) during NAC in BC subtypes were selected. Per study, negative- and positive predictive value, sensitivity(se) and specificity(sp), AUC and accuracy were derived.Fifteen/106 articles were included. Inter-study variability was revealed in: monitoring interval, response and pCR definitions. In ER-positive/HER2-negative BC, ¹⁸F-FDG-PET/CT showed se/sp of 38%-89%/74%-100%, MRI showed se/sp of 35%-37%/87%-89%. In triple negative BC, ¹⁸F-FDG-PET/CT showed se/sp of 0%-79%/95%-100%. ¹⁸F-FDG-PET/CT showed in ER-positive/HER2-positive BC se/sp of 59%/80% and in ER-negative/HER2-positive 27%/88%.Evidence on imaging performance in monitoring NAC according BC subtypes is lacking. Consensus should be reached in: definitions of pCR, response and monitoring interval before starting well-designed studies.



http://ift.tt/2lsioUz

Stage-I small cell lung cancer: A new potential option for sterotactic ablative radiation therapy? A review of literature

Publication date: Available online 17 February 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Filippo Alongi, Stefano Arcangeli, Berardino De Bari, Niccolò Giaj-Levra, Alba Fiorentino, Rosario Mazzola, Marco Trovò
Small cell lung cancer (SCLC) is relative rare histology in lung cancer patients. The standard treatment, in patients with an intra-thoracic disease, is represented by the use of concurrent chemo-radiotherapy; while patients with early SCLC stage, surgical resection could be recommended. Stereotactic body radiotherapy (SBRT) is a recently introduced technique allowing the delivery of very high radiation doses to limited target volumes and it is considered the standard approach in the treatment of not operable stage I Non Small-Cell Lung Cancer (NSCLC). The successful role option of SBRT in early NSCLC in terms of local control and toxicity profile opened the issue in the use of this approach in early stage small cell lung cancer (SCLC). Aim of this review is to discuss the current literature in the safety and efficacy of SBRT in the treatment of patients with stage I SCLC.



http://ift.tt/2kHTuw1

Interferon Induced Thrombotic Microangiopathy (TMA): Analysis and Concise Review

Publication date: Available online 17 February 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Ajay Kundra, Jen Chin Wang
Interferon (IFN) has been associated with development of thrombotic microangiopathy including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). We reviewed literature from the earliest reported association in 1993, to July 2016 and found 68 cases. Analysis of this data shows: (1) Mean age at diagnosis was 47 years old (95% CI, 44-50). (2) Majority of cases were seen where IFN was used for the treatment of chronic myelogenous leukemia (CML), multiple sclerosis (MS), chronic hepatitis C virus infection (HCV) and one case each for hairy cell leukemia (HCL) and Sezary syndrome. (3) There were no cases reported for polycythemia vera (PV) or malignant lymphoma. (4) Sex distribution was nearly equivalent with the exception in patients with multiple sclerosis where there was female predominance (12 of 16 with reported data). (5) For pooled analysis, the average duration of treatment with IFN before TMA was diagnosed was 40.4 months. (6) Comparative analysis showed that patients with MS required the highest cumulative dose exposure before developing TMA (MS 68.6 months, CML 35.5 months, HCV 30.4 months). (7) Cases of confirmed TTP (where A disintegrin and Metalloprotease with thrombospondin type 1 motif 13: ADAMTS 13 level was measured) showed presence of an inhibitor. (8) In all cases of confirmed TTP, moderate to severe thrombocytopenia was a striking clinical feature at presentation while this was not a consistent finding in all other cases of TMA. (9) Outcome analysis revealed complete remission in 27, (40%) persistent chronic kidney disease (CKD) in 28 (42%) and fatality in 12 patients (18%). (10) Treatment with corticosteroids, plasma exchange, and, rituximab resulted in durable responses.



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Preparation and identification of some metal complexes with new heterocyclic azo dye ligand 2-[2−- (1- Hydroxy -4- Chloro phenyl) azo ]- imidazole and their spectral and thermal studies

Publication date: 5 June 2017
Source:Journal of Molecular Structure, Volume 1137
Author(s): Khalid Al-Adilee, Hussein A.K. Kyhoiesh
The preparation and spectral identification of metal complexes for Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II) ions with new heterocyclic azo dye as ligand 2-[2⁻- (1- Hydroxy - 4- Chloro phenyl) azo ]- imidazole (HClPAI) were prepared by reacting adizonium chloride salt solution of 2-amino -4- chloro phenol with imidazole in alkaline ethanolic solution. Azo dye ligand and their metal complexes have been characterized by analytical data, ¹H NMR, Mass spectrum, Infrared, Electronic spectral data, XRD, SEM, thermal analysis (TG-DSC-DTG), magnetic susceptibility and molar conductance. The elemental analysis of the metal complexes confirm the stoichiometry of the type [M(L)2] Cl where M = Cr(III), Fe(III), Co(II) and [M(L)2] where M = Mn(II), Ni(II), Cu(II), Zn(II), Cd(II), Hg(II) and L = azo dye ligand. Molar conductance measurements for prepared metal complexes showed 1:1 electrolyte for Cr(III), Fe(III) and Co(III) ions and non-electrolyte the rest metal complexes. The data show that the azo dye ligand behaves a tridentate and coordinates to the metal ion via nitrogen atom of azo group which is the farthest of imidazole molecule, nitrogen atom of azomethine group of heterocyclic imidazole ring and phenolic oxygen. Octahedral environment is suggested for all metal complexes.



http://ift.tt/2lsENSk

Using isotope dilution assays to understand speciation changes in Cd, Zn, Pb and Fe in a soil model system under simulated flooding conditions

Publication date: 1 June 2017
Source:Geoderma, Volume 295
Author(s): M. Izquierdo, A.M. Tye, S.R. Chenery
Flooded soils are systems with complex chemistry and understanding the mechanisms that control the mobility and bioavailability of metals in these soils is important for their management. This work uses stable metal multi-element isotopic dilution combined with sequential extraction assays to help understand the changes in solid and solution speciation of Cd, Fe, Pb and Zn in a contaminated soil following submergence. However, it is necessary to ensure that the isotopic dilution principles, originally developed for aerobic soils, are not compromised; in particular due to the presence of non-labile colloids in the solution phase. In particular, no studies examining the validity of these assays in systems where rapid pH and Eh changes are occurring due to fermentation reactions have been published. Thus sucrose (0.42% and 1.26% added C) was used as a carbon source to stimulate bacterial mediated fermentation reactions allowing changes in Cd, Zn, Fe and Pb isotopic exchangeability, speciation and solution chemistry to be examined after 10, 20 and 42days of submergence. Without the addition of added C, submergence for 42days only produced minor changes in the speciation of the metals in solid or solution phases. However, the presence of easily labile carbon produced significant responses depending on the quantity of C added. Assessments of whether fermentation products caused over-estimation of the isotopically exchangeable pool of metals (E-values) were made by measuring concentrations with and without a resin purification step. Results showed generally good agreement over a pH range of 4–7 for Pb, Cd, Zn and Fe and demonstrate that fermentation by-products do not induce the formation of non-exchangeable metal colloids. E-value concentrations were compared with fractions extracted using a modified Tessier sequential extraction. With no carbonate phases present in the soils, the E-values for Cd, Zn, Fe and Pb compared favourably with the concentrations of metal present in the combined solution, exchangeable and specifically adsorbed fractions. This provided additional evidence that the conditions for the isotopic dilution assays were not violated as these fractions should be isotopically exchangeable. Combining results from the different treatments and stages of the reduction process, strong pH dependence was found for the isotopically exchangeable and the solution pools of Cd, Zn and Pb.



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Very High Prevalence of Frozen Shoulder in Patients with Type 1 Diabetes of More than 45 Years’ Duration. The Dialong Shoulder Study

Publication date: Available online 17 February 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Niels Gunnar Juel, Jens Ivar Brox, Cathrine Brunborg, Kristine Bech Holte, Tore Julsrud Berg
ObjectiveTo compare the prevalence of shoulder disorders and self-reported shoulder disability in patients with long-term type 1 diabetes mellitus and diabetes-free controls and explore the association between the long-term glycemic burden and shoulder disability in the diabetes group.DesignA cross-sectional study of shoulder diagnoses with 30 years' historical data on glycemic burden in the diabetes patients.SettingQuestionnaires, interviews and medical records were collected at the Norwegian Diabetics Center (NDC). A clinical examination and shoulder x-rays were performed at Oslo university hospital.ParticipantsIn 2015 136 patients attended NDC with type 1 diabetes since 1970 or earlier. All subjects were invited and 105 patients were included. 102 patients (50% women), mean age 61.9 years and 73 diabetes-free controls (55% women), mean age 62.5 years completed the study.InterventionsNot applicable.Main Outcome MeasuresShoulder diagnoses decided through clinical examination according to scientific diagnostic criteria.ResultsFrozen shoulder was diagnosed in 60 (59%) patients with diabetes and 0 controls with a lifetime prevalence of 76% in the diabetes group versus 14% in controls. Diabetes patients had higher disability, QuickDASH score (SD) 23.0 (19.9) than controls 8.9 (12.0), with a mean difference (95% CI) of -14.2 (–19.3 to -9.0) points, P < .001. We found an association between chronic hyperglycemia and QuickDASH score, with a 6.16 point increase in QuickDASH per unit increase in HbA1c, P = .014.ConclusionsThe point prevalence of frozen shoulder in patients with long-lasting type 1 diabetes was 59% and the lifetime prevalence was 76%. The diabetes group had more shoulder disability than controls. The historical HbA1c level was associated with increased shoulder disability.



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Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis: The HYPRESS Randomized Clinical Trial

Publication date: March 2017
Source:The Journal of Emergency Medicine, Volume 52, Issue 3
Author(s): John Michael Rague




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An Unusual Cause of Abdominal Pain

Publication date: March 2017
Source:The Journal of Emergency Medicine, Volume 52, Issue 3
Author(s): Seyedhossein Seyedhosseini Davarani, Hadi Mirfazaelian




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Issue Highlights

Publication date: March 2017
Source:The Journal of Emergency Medicine, Volume 52, Issue 3





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US Emergency Department Visits for Outpatient Adverse Drug Events, 2013-2014

Publication date: March 2017
Source:The Journal of Emergency Medicine, Volume 52, Issue 3
Author(s): Benjamin Li




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Contents

Publication date: March 2017
Source:The Journal of Emergency Medicine, Volume 52, Issue 3





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American Academy of Emergency Medicine

Publication date: March 2017
Source:The Journal of Emergency Medicine, Volume 52, Issue 3





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Partial Contents of Volume 52, Number 4

Publication date: March 2017
Source:The Journal of Emergency Medicine, Volume 52, Issue 3





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Epidemiology of Sports-Related Eye Injuries in the United States

Publication date: March 2017
Source:The Journal of Emergency Medicine, Volume 52, Issue 3
Author(s): Alexa Camarena-Michel




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Editorial Board

Publication date: March 2017
Source:The Journal of Emergency Medicine, Volume 52, Issue 3





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Association of Persistent Postconcussive Symptoms With Pediatric Quality of Life

Publication date: March 2017
Source:The Journal of Emergency Medicine, Volume 52, Issue 3
Author(s): Alexa Camarena-Michel




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Lung Ultrasound as First-Line Examination for the Diagnosis of Community-Acquired Pneumonia in Children

Publication date: March 2017
Source:The Journal of Emergency Medicine, Volume 52, Issue 3
Author(s): Stephanie Diebold




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Association Between Serum Calcium Level and Extent of Bleeding in Patients with Intracerebral Hemorrhage

Publication date: March 2017
Source:The Journal of Emergency Medicine, Volume 52, Issue 3
Author(s): Benjamin Li




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Concerns Over Accuracy of Record-High Ethylene Glycol Level

Publication date: March 2017
Source:The Journal of Emergency Medicine, Volume 52, Issue 3
Author(s): Paul Hamilton, Jennifer Hamilton




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Association Between Early Participation in Physical Activity Following Acute Concussion and Persistent Postconcussive Symptoms in Children and Adolescents

Publication date: March 2017
Source:The Journal of Emergency Medicine, Volume 52, Issue 3
Author(s): John Michael Rague




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Smaller Introducer Sheaths for REBOA May Be Associated With Fewer Complications

Publication date: March 2017
Source:The Journal of Emergency Medicine, Volume 52, Issue 3
Author(s): John Michael Rague




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Azithromycin for Acute Exacerbations of Asthma: The AZALEA Randomized Clinical Trial

Publication date: March 2017
Source:The Journal of Emergency Medicine, Volume 52, Issue 3
Author(s): Alexa Camarena-Michel




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Calcific Tendonitis of the Longus Colli: An Uncommon but Benign Cause of Throat Pain that Closely Mimics Retropharyngeal Abscess

Publication date: March 2017
Source:The Journal of Emergency Medicine, Volume 52, Issue 3
Author(s): Nathan Zapolsky, Michael Heller, Mark Felberbaum, Jeremy Rose, Eric Steinberg




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Unintentional Pediatric Exposures to Marijuana in Colorado, 2009-1015

Publication date: March 2017
Source:The Journal of Emergency Medicine, Volume 52, Issue 3
Author(s): Stephanie Diebold




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Hypothermia for Neuroprotection in Convulsive Status Epilepticus

Publication date: March 2017
Source:The Journal of Emergency Medicine, Volume 52, Issue 3
Author(s): Stephanie Diebold




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Shortened Antimicrobial Treatment for Acute Otitis Media in Young Children

Publication date: March 2017
Source:The Journal of Emergency Medicine, Volume 52, Issue 3
Author(s): Benjamin Li




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Vehicle type affects filling of fractional laser-ablated channels imaged by optical coherence tomography

Abstract

Ablative fractional laser (AFXL) is an emerging method that enhances topical drug delivery. Penetrating the skin in microscopic, vertical channels, termed microscopic treatment zones (MTZs), the fractional technique circumvents the skin barrier and allows increased uptake of topically applied drugs. This study aims to elucidate the impact of vehicle type on the filling of MTZs from application of liquid, gel, and cream vehicles. Ex vivo pig skin was exposed to 10,600 nm fractional CO₂ laser at 5% density, 120 μm beam diameter, and fluences of 40 and 80 mJ/microbeam (mJ/mb). Six repetitions were performed for each of six interventions (2 fluences and 3 vehicle types, n = 36). MTZ dimensions and filling by vehicle type were evaluated by optical coherence tomography, using blue tissue dye as a contrast-enhancing agent. Outcome measure was degree of MTZ filling assessed as percentages of empty, partially filled, and completely filled MTZs (108–127 MTZs/intervention analyzed) and evaluated statistically using Kruskal-Wallis and Dunn's tests. MTZs reached mid-dermal levels of 225 μm (40 mJ/mb) and 375 μm (80 mJ/mb) penetration depths (p < 0.0001). Filling of MTZs depended on type of applied vehicle. At 80 mJ/mb, liquid (67% completely filled, p < 0.01) and gel (60%, p < 0.05) formulations filled MTZs significantly better than cream formulation (31%). At 40 mJ/mb, liquid and gel formulations filled 90% (p < 0.05) and 77% (p > 0.05) of MTZs completely versus 55% for cream formulation. Thus, filling was overall greater for more superficial MTZs. In conclusion, vehicle type affects filling of MTZs, which may be of importance for AFXL-assisted drug delivery.

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Stereotactic Radiosurgery and Fractionated Stereotactic Radiotherapy for the Treatment of Uveal Melanoma

Publication date: Available online 17 February 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Gozde Yazici, Hayyam Kiratli, Gokhan Ozyigit, Sezin Yuce Sari, Mustafa Cengiz, Bercin Tarlan, Burce Ozgen Mocan, Faruk Zorlu
PurposeTo evaluate treatment results of stereotactic radiosurgery or fractionated stereotactic radiotherapy (SRS/FSRT) for uveal melanoma.Methods and MaterialsWe retrospectively evaluated 181 patients with 182 uveal melanomas receiving SRS/FSRT between 2007 and 2013. Treatment was administered via the CyberKnife® (Accuray Inc., Sunnyvale, CA, USA).ResultsAccording to Collaborative Ocular Melanoma Study criteria, tumor size was small in 1%, medium in 49.5%, and large in 49.5% of the patients. Seventy-one tumors received <45 Gy and 111 received ≥45 Gy. Median follow-up time was 24 months. Complete and partial response was observed in 8 and 104 eyes, respectively. The rate of 5-year overall survival (OS) was 98%, disease-free survival (DFS) 57%, local recurrence-free survival (LRFS) 73%, distant metastasis-free survival (DMFS) 69%, and enucleation-free survival (EFS) 73%. There was a significant correlation between tumor size and DFS, SRS/FSRT dose and EFS; and both were prognostic for LRFS. Enucleation was performed in 41 eyes due to progression in 26 and complications in 11.ConclusionsThe radiotherapy dose is of great importance for local control and eye retention; the best treatment outcome was achieved using ≥45 Gy in 3 fractions.

Teaser

The results of stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) in uveal melanoma was retrospectively evaluated. It was found that with doses of ≥45 Gy in 3 fractions higher tumor control rates are achieved. Two-year EFS rate was 73% for all, and 69% for large tumors, respectively.


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A novel super-resolution approach to time-resolved volumetric 4DMRI with high spatiotemporal resolution for multi-breathing cycle motion assessment

Publication date: Available online 17 February 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Guang Li, Jie Wei, Mo Kadbi, Jason Moody, August Sun, Shirong Zhang, Svetlana Markova, Kristen Zakian, Margie Hunt, Joseph O. Deasy
PurposeTo develop and evaluate a super-resolution approach to reconstruct time-resolved four-dimensional magnetic resonance imaging (TR-4DMRI) with a high spatiotemporal resolution for multi-breathing cycle motion assessment.Methods and MaterialsA super-resolution approach was developed to combine fast 3D cine MRI with low-resolution during free breathing (FB) and high-resolution 3D static MRI during breath hold (BH) using deformable image registration (DIR). A T1-weighted, turbo field echo sequence, coronal 3D cine acquisition, partial Fourier approximation, and SENSE parallel acceleration were employed. The same MRI pulse sequence, field of view, and acceleration techniques were applied in both FB and BH acquisitions; the intensity-based Demons DIR method was used. Under an IRB-approved protocol, seven volunteers were studied with 3D cine FB scan (voxel size:5x5x5mm³) at 2Hz for 40s and a 3D static BH scan (2x2x2mm³). To examine the image fidelity of 3D cine and super-resolution TR-4DMRI, a mobile gel phantom with multi-internal targets was scanned at three velocities and compared with the 3D static image. Image similarity among 3D cine, 4DMRI, and 3D static was evaluated visually using difference image and quantitatively using voxel intensity correlation and Dice index (phantom only). Multi-breathing-cycle waveforms were extracted and compared in both phantom and volunteer images using the 3D cine as the references.ResultsMild imaging artifacts were found in the 3D cine and TR-4DMRI of the mobile gel phantom with a Dice index of >0.95. Among seven volunteers, the super-resolution TR-4DMRI yielded high voxel-intensity correlation (0.92±0.05) and low voxel-intensity difference (<0.05). The detected motion differences between TR-4DMRI and 3D cine were -0.2±0.5mm (phantom) and -0.2±1.9mm (diaphragms).ConclusionSuper-resolution TR-4DMRI has been reconstructed with adequate temporal (2Hz) and spatial (2x2x2mm³) resolutions. Further TR-4DMRI characterization and improvement are necessary before clinical applications. Multi-breathing cycles can be examined, providing patient-specific breathing irregularities and motion statistics for future 4D radiotherapy.

Teaser

This study presents a super-resolution approach to achieve time-resolved 4DMRI over multi-breathing cycles with a clinically-adequate spatiotemporal resolution through deformable image registration from a high-resolution breath-hold 3D static image to low-resolution free-breathing 3D cine images. A mobile phantom and seven volunteer experiments were conducted to validate this new approach. This TR-4DMRI technique can image irregular motion without binning artifacts, show high soft-tissue contrast without radiation, and provide multi-breath motion statistics for future high-precision motion-compensated treatment planning.


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Role of levothyroxine and vitamin E supplementation in the treatment of oxidative stress-induced injury and apoptosis of myocardial cells in hypothyroid rats

Abstract

Objective

To explore the underlying mechanism and treatment of myocardial injury caused by hypothyroidism, we evaluated oxidative stress in serum and myocardial tissue of hypothyroid rats. The effect of levothyroxine (LT4) replacement therapy and vitamin E (VitE) supplementation on oxidative stress-induced injury and apoptosis of myocardial tissue is examined.

Methods

Male Sprague-Dawley rats were divided into five groups: normal control group, propylthiouracil group (PTU group), LT4 treatment group (PTU + LT4 group), vitamin E treatment group (PTU + VitE group), and combined treatment group (PTU + LT4 + VitE group). Superoxide dismutase (SOD) activity and malondialdehyde (MDA) expression in serum and myocardium were determined. Myocardial apoptosis index (AI) in each group was determined by TUNEL assay.

Results

SOD levels in serum were significantly increased in PTU + VitE and PTU + LT4 + Vit E groups, as compared to that in PTU and PTU + LT4 groups (P < 0.05). MDA levels in serum and myocardial tissue were significantly lower in PTU + LT4, PTU + VitE, and PTU + LT4 + VitE groups, as compared to that in the PTU group (P < 0.05). Myocardial apoptosis was significantly increased in PTU and PTU + VitE groups as compared to that in the normal control group (P < 0.05), while it was significantly lower in PTU + LT4 and PTU + LT4 + VitE groups, as compared to that in the PTU group (P < 0.05).

Conclusion

In this study, levothyroxine replacement therapy and vitamin E supplementation appeared to ameliorate myocardial apoptosis in hypothyroid rats, the mechanism of which appears to be related to improved thyroid function and reduced oxidative stress.

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Ultrasound-guided fine-needle aspiration biopsy of thyroid nodules in patients on oral anticoagulants

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Circulating microRNAs and diabetes mellitus: a novel tool for disease prediction, diagnosis, and staging?

Abstract

Diabetes is a complex, multifactorial group of metabolic diseases characterized by chronic hyperglycaemia due to pancreatic beta-cell dysfunction and/or loss. It is characterized by an asymptomatic and highly variable prodromic phase, which renders diabetes mellitus difficult to be predicted with sufficient accuracy. Despite several efforts in the identification and standardization of newly trustable. Biomarkers able to predict and follow-up diabetes and to specifically subtype its different forms, few of them have proven of clinical utility. Recently, a new class of endogenous non-coding small RNAs, namely microRNAs, have been indicated as putative biomarkers, being released by cells and tissues and found in a cell-free circulating form in many biological fluids, including serum and/or plasma. MicroRNAs have been initially identified as promising biomarkers in cancer, and nowadays their application has been extended to other diseases, including diabetes. Although an increasing number of studies focused on the evaluation of circulating microRNAs in diabetes, few reproducibly identified microRNAs as biomarkers for disease prediction or follow-up. Technological problems as well as the need to obtain highly standardized operating procedures and methods are still an issue in such research field. In this review, we comprehensively resume the main and most recent findings on circulating microRNAs, and their possible use as biomarkers to predict and follow-up diabetes and its complications, as well as the methodological challenges to standardize accurate operating procedures for their analysis.

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Erratum to: Effects of nutraceuticals on quality of life and sexual function of perimenopausal women

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Popliteal Artery Entrapment Syndrome in Children: Experience With Four Cases of Acute Ischaemia and Review of the Literature

Publication date: Available online 17 February 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): N. Settembre, Z. Bouziane, M.A. Bartoli, V. Nabokov, M. Venermo, P. Feugier, S. Malikov
ObjectivePopliteal artery entrapment syndrome (PAES) is an uncommon anatomical anomaly, frequently described in adults. The most common symptom is claudication. Acute limb ischaemia (ALI) in children is rare, but it may evolve and lead to limb loss or lifelong complications. Clinical and surgical experience of PAES in children is reported. Data from the literature are analysed in order to assess the severity of this disease and to identify the factors characterising the diagnosis and the outcome of treatment in paediatric patients.MethodsFour children (aged 7–16 years) were referred with ALI due to PAES. Among the 439 articles reporting cases of PAES, 55 patients under 18 years of age were the focus. The PAES cases were classified according to the Love and Whelan classification modified by Rich.ResultsData from 79 children (106 limbs, 27 bilateral PAES) were collected and analysed. Type I PAES was present in 41 (39%), Type II in 23 (22%), Type III in 24 (23%), Type IV in 12 (11%), and Type V in two (2%) limbs. A functional PAES was present in one patient bilaterally. In two cases, the type of PAES was not reported. Claudication occurred in 68 cases (64%), and ALI in 19 (18%). In 60 cases (57%), revascularisation with or without myotomy was required; myotomy alone was performed in 41 cases (39%).ConclusionsSymptomatic PAES in children should be considered a severe condition requiring urgent investigation in order to avoid any delays in the treatment. Early diagnosis and treatment are essential to prevent serious complications. The long-term outcomes of surgical treatment with the correction of the anatomical anomaly and vascular reconstruction are satisfactory with a low complication rate.



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Inorganic arsenic inhibits the nucleotide excision repair pathway and reduces the expression of XPC

Publication date: Available online 16 February 2017
Source:DNA Repair
Author(s): Nathaniel Holcomb, Mamta Goswami, Sung Gu Han, Tim Scott, John D'Orazio, David K. Orren, C.Gary Gairola, Isabel Mellon
Chronic exposure to arsenic, most often through contaminated drinking water, has been linked to several types of cancer in humans, including skin and lung cancer. However, the mechanisms underlying its role in causing cancer are not well understood. There is evidence that exposure to arsenic can enhance the carcinogenicity of UV light in inducing skin cancers and may enhance the carcinogenicity of tobacco smoke in inducing lung cancers. The nucleotide excision repair (NER) pathway removes different types of DNA damage including those produced by UV light and components of tobacco smoke. The aim of the present study was to investigate the effect of sodium arsenite on the NER pathway in human lung fibroblasts (IMR-90 cells) and primary mouse keratinocytes. To measure NER, we employed a slot-blot assay to quantify the introduction and removal of UV light-induced 6-4 photoproducts (6-4 PP) and cyclobutane pyrimidine dimers (CPDs). We find a concentration-dependent inhibition of the removal of 6-4 PPs and CPDs in both cell types treated with arsenite. Treatment of both cell types with arsenite resulted in a significant reduction in the abundance of XPC, a protein that is critical for DNA damage recognition in NER. The abundance of RNA expressed from several key NER genes was also significantly reduced by treatment of IMR-90 cells with arsenite. Finally, treatment of IMR-90 cells with MG-132 abrogated the reduction in XPC protein, suggesting an involvement of the proteasome in the reduction of XPC protein produced by treatment of cells with arsenic. The inhibition of NER by arsenic may reflect one mechanism underlying the role of arsenic exposure in enhancing cigarette smoke-induced lung carcinogenesis and UV light-induced skin cancer, and it may provide some insights into the emergence of arsenic trioxide as a chemotherapeutic agent.



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Specific killing of DNA damage-response deficient cells with inhibitors of poly(ADP-ribose) glycohydrolase

Publication date: Available online 17 February 2017
Source:DNA Repair
Author(s): Polly Gravells, Emma Grant, Kate M. Smith, Dominic I. James, Helen E. Bryant
Poly(ADP-ribosylation) of proteins following DNA damage is well studied and the use of poly(ADP-ribose) polymerase (PARP) inhibitors as therapeutic agents is an exciting prospect for the treatment of many cancers. Poly(ADP-ribose) glycohydrolase (PARG) has endo-and exoglycosidase activities which can cleave glycosidic bonds, rapidly reversing the action of PARP enzymes. Like addition of poly(ADP-ribose) (PAR) by PARP, removal of PAR by PARG is also thought to be required for repair of DNA strand breaks and for continued replication at perturbed forks. Here we use siRNA to show a synthetic lethal relationship between PARG and BRCA1, BRCA2, PALB2, FAM175A (ABRAXAS) and BARD1. In addition, we demonstrate that MCF7 cells depleted of these proteins are sensitive to Gallotannin and a novel and specific PARG inhibitor PDD00017273. We confirm that PARG inhibition increases endogenous DNA damage, stalls replication forks and increases homologous recombination, and propose that it is the lack of homologous recombination (HRR) proteins at PARG inhibitor-induced stalled replication forks that induces cell death. Interestingly not all genes that are synthetically lethal with PARP result in sensitivity to PARG inhibitors, suggesting that although there is overlap, the functions of PARP and PARG may not be completely identical. These data together add further evidence to the possibility that single treatment therapy with PARG inhibitors could be used for treatment of certain HRR deficient tumours and provide insight into the relationship between PARP, PARG and the processes of DNA repair.



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Gammagrafía hepatobiliar con 99mTc-mebrofenina en una paciente con fístula bilio-pleuro-bronquial

Publication date: Available online 17 February 2017
Source:Revista Española de Medicina Nuclear e Imagen Molecular
Author(s): V. Marín-Oyaga, K. Cohen-Castillo, C. Gutierrez-Villamil, S. Arevalo-Leal




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Carcinoma epidermoide primario de tiroides. Valoración inicial y control evolutivo mediante 18F-FDG PET/TC

Publication date: Available online 16 February 2017
Source:Revista Española de Medicina Nuclear e Imagen Molecular
Author(s): L. Caballero Gullón, E. Carmona González, A. Martínez Estévez, M.P. Gómez Camarero, J.J. Corral, I. Borrego Dorado
El carcinoma epidermoide primario de tiroides es una neoplasia muy poco frecuente, con comportamiento agresivo, de mal pronóstico, con pobre respuesta al tratamiento quimioterápico y radioterápico, y cuyo tratamiento de elección es la cirugía. Suele presentarse al diagnóstico como enfermedad extendida, como una tumefacción cervical que causa la mayoría de sus síntomas por invasión o metástasis locales. Su diagnóstico requiere excluir infiltración desde un tumor adyacente, afectación metastásica a distancia desde otro carcinoma epidermoide primario y realizar estudio inmunohistoquímico, el cual refleje el patrón característico de expresión de citoqueratinas. Presentamos el caso de un paciente de 53 años con antecedentes oncológicos de hepatocarcinoma, en el que durante el seguimiento se detecta una lesión cervical, caracterizada como hipermetabólica al realizar el estudio de extensión mediante tomografía por emisión de positrones con ¹⁸F-FDG (¹⁸F-FDG PET/TC). También presentamos el control evolutivo de dicha lesión mediante esta técnica y la utilidad de esta última.Squamous cell carcinoma of thyroid is an uncommon, very aggressive neoplasm, having a poor prognosis and poor response to chemotherapy and radiotherapy. Surgery is the initial treatment of choice, although it often presents as a widespread disease at the time of diagnosis, usually with cervical swelling that causes most of the symptoms due to local infiltration or metastasis. Local infiltration from adjacent tumour and metastatic disease needs to be excluded from other primary epidermoid carcinomas, in order to make a correct diagnosis. This also requires the typical cytokeratin pattern seen in histological studies. The case is presented of a 53 year-old man with a medical history of hepatocarcinoma, with a cervical hypermetabolic lesion detected in an ¹⁸F-FDG PET/CT performed to exclude widespread disease. The follow-up of this lesion with this technique and its usefulness is also described.



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18F-FDG-PET/CT guiding to diagnosis of neurosarcoidosis

Publication date: Available online 16 February 2017
Source:Revista Española de Medicina Nuclear e Imagen Molecular
Author(s): P. Guglielmo, C. Crivellaro, L. Marzorati, M. Patassini, S. Morzenti, C. Landoni




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Valor de la PET/TC cerebral con 18F-fluorocolina en la detección de recurrencias de neoplasias primarias del sistema nervioso central

Publication date: Available online 17 February 2017
Source:Revista Española de Medicina Nuclear e Imagen Molecular
Author(s): A. Montes, A. Fernández, V. Camacho, C. de Quintana, O. Gallego, J. Craven-Bartle, D. López, J. Molet, B. Gómez-Ansón, I. Carrió
ObjetivoEstudiar el impacto clínico en el manejo de los pacientes de la ¹⁸F-fluorocolina (¹⁸F-COL) en la recurrencia de neoplasias cerebrales primarias.Material y métodosSe estudió prospectivamente a 21 pacientes con sospecha de recidiva de neoplasia cerebral primaria mediante PET/TC cerebral con ¹⁸F-COL en uso compasivo. La distribución por patología de los pacientes estudiados fue: 3 astrocitomas grado ii, 3 astrocitomas grado iii, un oligodendroglioma grado ii, 3 oligodendrogliomas grado iii, un oligoastrocitoma grado iii, 4 glioblastomas multiformes, una gliomatosis cerebri y 5 meningiomas. Se consideraron positivos los estudios en los que había una captación visualmente significativa respecto al fondo del parénquima cerebral.ResultadosDiecisiete de los pacientes fueron positivos, comprobándose dicho resultado por histología (10 de ellos) o seguimiento clínico y por neuroimagen, sin hallarse falsos positivos o negativos. El índice target to backgroud ratio medio para los positivos fue de 8,02 y para los negativos de 0,94, lo que representa una diferencia significativa (p=0,003).ConclusiónLa PET/TC con ¹⁸F-COL presenta resultados alentadores en la valoración de pacientes con sospecha de recidiva.AimTo study the usefulness of ¹⁸F-fluorocholine (FCH) in detecting the recurrence of primary brain tumours.Material and methodsA prospective study was conducted on brain PET/CT with FCH for compassionate use in 21 patients with suspected recurrence of a primary brain tumour. The distribution by pathology was: three grade ii astrocytomas, three grade iii astrocytomas, one grade ii oligodendroglioma, three grade iii oligodendrogliomas, one grade iii oligoastrocytoma, four glioblastoma multiform, one gliomatosis cerebri, and five meningiomas. Studies in which there was a visually significant uptake in the brain parenchyma were classified as positive.ResultsA total of 17 patients were classified as positive, with the results being confirmed by histology (10 cases) or clinical follow-up and imaging, with no false positives or negatives. The mean SUVmax for positive patients was 8.02 and 0.94 for the negative ones, which was significantly different (P=.003)ConclusionPET/CT with FCH shows encouraging results in the evaluation of patients with suspected recurrence of primary brain neoplasms.



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Thermoresponsive Polymer-Modified Microfibers for Cell Separations

Publication date: Available online 17 February 2017
Source:Acta Biomaterialia
Author(s): Kenichi Nagase, Yoichi Sakurada, Satoru Onizuka, Takanori Iwata, Masayuki Yamato, Naoya Takeda, Teruo Okano
Thermoresponsive polymer-modified microfibers were prepared through electrospinning of poly(4-vinylbenzyl chloride) (PVBC) and subsequent surface-initiated atom transfer radical polymerization for grafting poly(N-isopropylacrylamide) (PIPAAm). Electrospinning conditions were optimized to produce large-diameter (20 μm) PVBC microfibers. The amount of PIPAAm grafted on the microfibers was controlled via the IPAAm monomer concentration. The microfibers exhibited thermally controlled cell separation by selective adhesion of normal human dermal fibroblasts in a mixed cell suspension that also contained human umbilical vein endothelial cells. In addition, adipose-derived stem cells (ADSCs) exhibited thermally modulated cell adhesion and detachment, while adhesion of other ADSC-related cells was low. Thus, ADSCs could be separated from a mixture of adipose tissue-derived cells simply by changing the temperature. Overall, the PIPAAm-modified microfibers are potentially applicable as temperature-modulated cell separation materials.Statement of SignificanceThermoresponsive poly(N-isopropylacrylamide) (PIPAAm) polymer-modified poly(4-vinylbenzyl chloride) (PVBC) microfibers were prepared via electrospinning of PVBC, followed by surface-initiated ATRP. They formed effective thermally-modulated cell separation materials with large surface areas. Cells adhered and extended along the modified microfibers; this was not observed on previously reported PIPAAm-modified flat substrates. The cellular adhesion enabled separation of fibroblast cells, as well as that of adipose-derived mesenchymal stem cells, from mixtures of similar cells. Thus, the temperature-controlled thermoresponsive microfibers would be potentially useful as cell separation materials.

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