Αρχειοθήκη ιστολογίου

Πέμπτη 28 Ιανουαρίου 2016

Translational-circular scanning for magneto-acoustic tomography with current injection

Magneto-acoustic tomography with current injection involves using electrical impedance imaging technology. To explore the potential applications in imaging biological tissue and enhance image quality, a new sc...

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Evaluation of a newly developed piezo actuator-driven pulsed water jet system for liver resection in a surviving swine animal model

Preservation of the hepatic vessels while dividing the parenchyma is key to achieving safe liver resection in a timely manner. In this study, we assessed the feasibility of a newly developed, piezo actuator-d...

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Effects of extremely low frequency pulsed magnetic fields on diabetic nephropathy in streptozotocin-treated rats

Extremely low frequency pulsed magnetic fields (ELFPMF) have been shown to induce Faraday currents and measurable effects on biological systems. A kind of very high frequency electromagnetic field was reported...

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Robust detection of heartbeats using association models from blood pressure and EEG signals

The heartbeat is fundamental cardiac activity which is straightforwardly detected with a variety of measurement techniques for analyzing physiological signals. Unfortunately, unexpected noise or contaminated s...

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Shape-based reconstruction of dynamic fluorescent yield with a level set method

Fluorescence molecular tomography (FMT) is an optical imaging technique that reveals biological processes within small animals through non-invasively reconstructing the distributions of fluorescent agents. The...

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A Review on Potential Mechanisms of Terminalia chebula in Alzheimer’s Disease

The current management of Alzheimer's disease (AD) focuses on acetylcholinesterase inhibitors (AChEIs) and NMDA receptor antagonists, although outcomes are not completely favorable. Hence, novel agents found in herbal plants are gaining attention as possible therapeutic alternatives. The Terminalia chebula (Family: Combretaceae) is a medicinal plant with a wide spectrum of medicinal properties and is reported to contain various biochemicals such as hydrolysable tannins, phenolic compounds, and flavonoids, so it may prove to be a good therapeutic alternative. In this research, we reviewed published scientific literature found in various databases: PubMed, Science Direct, Scopus, Web of Science, Scirus, and Google Scholar, with the keywords: T. chebula, AD, neuroprotection, medicinal plant, antioxidant, ellagitannin, gallotannin, gallic acid, chebulagic acid, and chebulinic acid. This review shows that T. chebula extracts and its constituents have AChEI and antioxidant and anti-inflammatory effects, all of which are currently relevant to the treatment of Alzheimer's disease.

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Engage, Inspire and Enthrall - John Zorn en de avant garde



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Interval: Hélène Gelèns versus de tijd.



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Dichters van het nieuwe millennium Nederlandse en Vlaamse poëzie in de 21e eeuw



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'Practice what you Teach': from the classroom to the boardroom



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Treatment of necrotizing fasciitis using negative pressure wound therapy in a puppy

A two-month-old German shepherd dog was presented with anorexia, lethargy and left hind limb lameness associated with swelling of the thigh. Clinical findings combined with cytology led to the presumptive diagnosis of necrotizing fasciitis (NF). Extensive debridement was performed and silver-foam-based negative pressure wound therapy (NPWT) was applied. During the first 48 hours, a negative pressure of -75 mmHg was used. Evaluation of the wound demonstrated no progression of necrosis and a moderate amount of granulation tissue formation. A new dress- ing was placed and a second 48-hour cycle of NPWT was initiated at -125 mmHg. At removal, a healthy wound bed was observed and surgical closure was performed. The prompt implementation of NPWT following surgical debridement led to accelerated wound healing without progression of necrosis in this case of canine NF. Negative pressure wound therapy could become an integral part of the management strategy of canine NF, improving the prognosis of this life-threatening disease.

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Another voice in the region? i24 news: multilingual mediascapes and representations of the Middle East



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'On n'entre point dans les raisons de cette grande tuerie': Bajazet ou la représentation d'une catastrophe orientale



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Verdraaid leven. Over Handleiding voor poetsvrouwen van Lucia Berlin



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Evaluation of Heating and Shearing on the Viscoelastic Properties of Calcium Hydroxyapatite Used in Injection Laryngoplasty.

Evaluation of Heating and Shearing on the Viscoelastic Properties of Calcium Hydroxyapatite Used in Injection Laryngoplasty.

Otolaryngol Head Neck Surg. 2016 Jan 26;

Authors: Mahboubi H, Mohraz A, Verma SP

Abstract
OBJECTIVE: To compare the viscoelastic properties of calcium hydroxyapatite (CaHA) to carboxymethylcellulose (CMC) injectables used for injection laryngoplasty and determine if they are affected by heating and shearing.
STUDY DESIGN: Experimental.
SETTING: University laboratory.
SUBJECTS AND METHODS: Vocal fold injection laryngoplasty with CaHA is oftentimes challenging due to the amount of pressure necessary to push the injectate through a needle. Anecdotal techniques, such as heating the product, have been suggested to facilitate injection. The viscoelastic properties of CaHA and CMC were measured with a rheometer. The effects of heating and shearing on sample viscoelasticity were recorded.
RESULTS: CaHA was 9.5 times more viscous than CMC (43,100 vs 4540 Pa·s). Heating temporarily decreased the viscosity of CaHA by 32%. However, it also caused the viscosity to subsequently increase after time. Shearing of CaHA reduced its viscosity by 26%. Heating and shearing together temporarily reduced the viscosity of CaHA by 52%.
CONCLUSION: A combination of heating and shearing had a more profound effect than heating or shearing alone on the viscosity of CaHA, potentially making it easier to inject temporarily. Long-term and in vivo studies are required to further analyze the effect of heating and shearing on CaHA injectables.

PMID: 26814211 [PubMed - as supplied by publisher]



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Variable Findings for Drug-Induced Sleep Endoscopy in Obstructive Sleep Apnea with Propofol versus Dexmedetomidine.

Variable Findings for Drug-Induced Sleep Endoscopy in Obstructive Sleep Apnea with Propofol versus Dexmedetomidine.

Otolaryngol Head Neck Surg. 2016 Jan 26;

Authors: Capasso R, Rosa T, Tsou DY, Nekhendzy V, Drover D, Collins J, Zaghi S, Camacho M

Abstract
OBJECTIVE: To compare VOTE classification findings (velum, oropharyngeal-lateral walls, tongue base, and epiglottis) for drug-induced sleep endoscopy (DISE) among patients with obstructive sleep apnea (OSA) using 2 sedation protocols.
STUDY DESIGN: Case series with chart review.
SETTING: Single tertiary institution.
SUBJECTS: Patients with OSA who underwent DISE.
METHODS: A total of 216 patients underwent DISE between November 23, 2011, and May 1, 2015. DISE findings based on VOTE classification were compared between patients receiving the propofol- and dexmedetomidine-based sedation protocols.
RESULTS: Patients with OSA (N = 216; age, 44.3 ± 11.7 years; body mass index, 27.9 ± 4.8 kg/m(2)) underwent DISE with intravenous administration of propofol (n = 52) or dexmedetomidine (n = 164). There were no statistically significant differences between the 2 groups in baseline apnea-hypopnea index, oxygen desaturation index, Mallampati score, tonsil size, Epworth Sleepiness Scale score, peripheral oxygen saturation nadir, age, sex, or body mass index. Patients in the propofol group had a significantly increased likelihood of demonstrating complete tongue base obstruction (75%, 39 of 52) versus partial or no obstruction (25%, 13 of 52) in the anterior-posterior dimension, as compared with the dexmedetomidine group (complete obstruction: 42.7%, 70 of 164; partial or no obstruction: 57.3%, 94 of 164; odds ratio: 4.0; 95% confidence interval: 2.0-8.1; P = .0001). Obstruction of other airway subsites was not significantly different.
CONCLUSION: Use of propofol versus dexmedetomidine to induce sedation may have a significant effect on the pattern of upper airway obstruction observed during DISE. Randomized prospective studies are indicated to confirm these initial findings.

PMID: 26814208 [PubMed - as supplied by publisher]



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A Not So Lucky Penny.

A Not So Lucky Penny.

Otolaryngol Head Neck Surg. 2016 Jan 26;

Authors: Hiebert JC, Baranano CF

PMID: 26814207 [PubMed - as supplied by publisher]



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Transoral Surgical Anatomy and Clinical Considerations of Lateral Oropharyngeal Wall, Parapharyngeal Space, and Tongue Base.

Transoral Surgical Anatomy and Clinical Considerations of Lateral Oropharyngeal Wall, Parapharyngeal Space, and Tongue Base.

Otolaryngol Head Neck Surg. 2016 Jan 26;

Authors: Gun R, Durmus K, Kucur C, Carrau RL, Ozer E

Abstract
OBJECTIVE: With the emergence of transoral robotic approaches, head and neck surgeons are faced with an unfamiliar inside-out head and neck anatomy. This study was performed to describe key anatomic landmarks and surgical considerations of transoral robotic resection of the lateral oropharyngeal wall, the parapharyngeal space, and the base of the tongue.
STUDY DESIGN: Descriptive transoral anatomic study.
SETTING: Academic anatomy laboratory and tertiary academic hospital.
SUBJECTS AND METHODS: Transoral dissections of the lateral pharyngeal wall, base of tongue, and parapharyngeal space were performed in 5 vascular silicone-injected cadavers to illustrate anatomic landmarks from the inside-out perspective. Lateral neck dissections were also performed to better appreciate the anatomic structures and to be more familiar with intraoperative anatomy.
RESULTS: The neurovascular and muscular structures located in parapharyngeal space, lateral oropharyngeal wall, and base of tongue were described. Surgical significance of key anatomic landmarks was emphasized with high-quality illustrations.
CONCLUSION: A thorough understanding of transoral anatomy is crucial to perform transoral robotic surgery safely and efficiently. To understand inside-out anatomy of base of tongue, lateral oropharyngeal wall, and parapharyngeal space, cadaveric dissection is highly beneficial and may help to shorten the learning curve for transoral robotic dissections.

PMID: 26814206 [PubMed - as supplied by publisher]



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Cerebrospinal fluid leakage from the umbilicus: Case report and literature review.

Cerebrospinal fluid leakage from the umbilicus: Case report and literature review.

Int J Surg Case Rep. 2016 Jan 8;20:60-62

Authors: Dolas I, Apaydin HO, Yucetas SC, Ucar MD, Kilinc S, Ucler N

Abstract
INTRODUCTION: Shunt catheters within the peritoneal cavity have migrated through and perforated almost all the intra-abdominal hollow viscera. An umbilical cerebrospinal fluid fistula following a ventriculoperitoneal shunt is an extremely rare complication.
CASE PRESENTATION: We report a 8-month-old infant who presented with leak of clear fluid from the umbilicus, seven months after a ventriculoperitoneal shunt operation. We could not see distal tip of the shunt on examination. After the operation, the patient's follow-up was uneventful.
DISCUSSION: The direct effect of CSF and VP shunt, such as chronic irrigation, silicon allergy, foreign body reaction, may cause sterile inflammation on the abdominal structures and this inflammation may soften tissue and cause CFS leakage and VP shunt extrusion.
CONCLUSION: If the distal tip detected on umbilical region, these patients should be examined frequently for umbilical shunt pathologies, especially infants.

PMID: 26814999 [PubMed - as supplied by publisher]



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News and Views-March 2016.

News and Views-March 2016.

Nucl Med Commun. 2016 Mar;37(3):331-332

Authors:

PMID: 26815636 [PubMed - as supplied by publisher]



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The biodistribution of the radiolabeled kinds of choline in male patients, assessed by PET/CT.

The biodistribution of the radiolabeled kinds of choline in male patients, assessed by PET/CT.

Nucl Med Commun. 2016 Mar;37(3):329-330

Authors: Calabria F, Schillaci O

PMID: 26815635 [PubMed - as supplied by publisher]



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Comparison of 18F-FDG PET/CT scan and 99mTc-MDP bone scintigraphy in detecting bone metastasis in head and neck tumors.

Comparison of 18F-FDG PET/CT scan and 99mTc-MDP bone scintigraphy in detecting bone metastasis in head and neck tumors.

Nucl Med Commun. 2016 Jan 25;

Authors: Al-Bulushi NK, Abouzied ME

Abstract
PURPOSE: The aim of this study was to evaluate the efficacy of fluorine-18 fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) compared with bone scan in detecting bone metastases in patients with head and neck cancer.
MATERIALS AND METHODS: A total of 319 patients with head and neck cancer were identified in our database who had undergone F-FDG PET/CT, from January 2006 until June 2007. Of them 156 patients (age range 15-100 years) met our inclusion criteria - namely, biopsy-proven head and neck cancer, and bone scan and F-FDG PET/CT within 30 days. Comparison was made on a lesion-by-lesion analysis. MRI, multidetector CT, and the clinical course of the patients were our references.
RESULTS: F-FDG PET/CT identified (n=213) bone lesions in 18 patients, in addition to distant metastases in solid organs such as the liver and lung, lymphadenopathy above and below the diaphragm, and adrenal glands in 12 patients. However, bone scan identified (n=198) 16 patients. Bone scan missed two patients with confirmed bone metastases by means of biopsy in one patient and radiologically in the second. F-FDG PET/CT showed true-positive results in 18 patients, whereas bone scan showed true-positive results in 16 patients. F-FDG PET/CT showed true-negative results in 138 patients, whereas bone scan showed true-negative results in 134 patients. F-FDG PET/CT showed no false-positive or false-negative results. However, bone scan had two false-positive and two false-negative results. The overall sensitivity, specificity, and accuracy was 100% for F-FDG PET/CT and 88, 98, and 96%, respectively, for bone scan.
CONCLUSION: F-FDG PET/CT is superior to Tc-methylene diphosphonate bone scan in detecting bone metastases in head and neck cancer.

PMID: 26813992 [PubMed - as supplied by publisher]



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The role of 18F-FDG PET/CT in the follow-up of well-differentiated thyroid cancer with negative thyroglobulin but positive and/or elevated antithyroglobulin antibody.

The role of 18F-FDG PET/CT in the follow-up of well-differentiated thyroid cancer with negative thyroglobulin but positive and/or elevated antithyroglobulin antibody.

Nucl Med Commun. 2016 Jan 25;

Authors: Liu Y

Abstract
Thyroglobulin measurement is the most sensitive and important indicator of persistent and/or recurrent disease in the follow-up of well-differentiated thyroid cancer (DTC) after total thyroidectomy and radioiodine ablation therapy. However, positive or elevated thyroglobulin autoantibody (TgAb) interferes with the accurate measurement of serum thyroglobulin and may mask the presence of a recurrent and/or metastatic disease. It was reported that persistently positive TgAb could be viewed as evidence of the continued presence of functional thyroid cells, either benign or malignant, and elevated TgAb might indicate the recurrent and/or metastatic disease and could be used as an alternative of the tumor marker for DTC. However, the clinical application and usefulness of TgAb for the follow-up of DTC are uncertain. Imaging studies such as the neck ultrasound and whole-body radioiodine are still used widely for the detection of the lesions. Although it is not used routinely in DTC, limited clinical observations showed that fluorine-18-fluorodeoxyglucose (F-FDG) PET/computed tomography could be an additive valuable imaging modality in the detection of recurrent and/or metastatic disease in these patients, with promising sensitivity and specificity. A negative F-FDG PET/computed tomography result was associated with the absence of active disease and disappearing TgAb over time, and F-FDG-avid residual/recurrent/metastatic lesions were associated with aggressive disease, poor outcome, and persistently increased TgAb levels.

PMID: 26813991 [PubMed - as supplied by publisher]



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Clinical relevance of 18F-FDG-negative osteoblastic metastatic bone lesions noted on PET/CT in breast cancer patients.

Clinical relevance of 18F-FDG-negative osteoblastic metastatic bone lesions noted on PET/CT in breast cancer patients.

Nucl Med Commun. 2016 Jan 25;

Authors: Al-Muqbel KM, Yaghan RJ, Al-Omari MH, Rousan LA, Dagher NM, Al Bashir S

Abstract
PURPOSE: Our study aims to assess the clinical relevance of fluorine-18 fluorodeoxyglucose (F-FDG) negative osteoblastic metastatic bone lesions noted on PET/computed tomography (CT) in breast cancer patients.
PATIENTS AND METHODS: The medical records of breast cancer patients were reviewed retrospectively from January 2012 until April 2015. We included the patients who had metastatic bone disease evaluated by F-FDG-PET/CT. Group 1 included patients with newly diagnosed metastatic bone disease at the time of imaging and group 2 included patients with a history of treated metastatic bone disease at the time of imaging. Functional and structural bone abnormality was monitored on F-FDG-PET/CT scans.
RESULTS: Fifty-three patients, median age 47.1 years (range 27-80 years), were included. Group 1 included 35 patients. Of those, 88% had predominantly F-FDG-avid osteolytic and mixed lesions (destructive pattern). Complete response was noted in 65% of the patients after treatment, evidenced by disappearance of bony focal activity with partial or total ossification of most osteolytic lesions converting into mixed and 'secondary' osteoblastic lesions. In addition, more ossified lesions were noted in some patients whose lesions were left untreated for long time (aged lesions). The remaining 12% of group 1 patients had pure 'primary' osteoblastic lesions (nondestructive pattern), which started small and expanded with time and tend to be F-FDG-negative. Group 2 included 18 patients who had predominantly mixed and 'secondary' osteoblastic lesions.
CONCLUSION: We described two types of osteoblastic metastatic bone lesions in breast cancer patients: 'primary' and 'secondary'. 'Secondary' lesions (88%) are totally ossified (healed) osteolytic lesions and are almost always F-FDG-negative on PET/CT. These lesions are of no clinical importance. Healing is potentially seen after treatment or if the lesions are left untreated for a long time (aged lesions). 'Primary' lesions (12%) are seen without previous bone destruction and tend to be F-FDG-negative, although they contain tumor cells. Hence, sequential CT is more helpful than sequential FDG-PET in following 'primary' lesions.

PMID: 26813990 [PubMed - as supplied by publisher]



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Individualized 131I-mIBG therapy in the management of refractory and relapsed neuroblastoma.

Individualized 131I-mIBG therapy in the management of refractory and relapsed neuroblastoma.

Nucl Med Commun. 2016 Jan 25;

Authors: George SL, Falzone N, Chittenden S, Kirk SJ, Lancaster D, Vaidya SJ, Mandeville H, Saran F, Pearson AD, Du Y, Meller ST, Denis-Bacelar AM, Flux GD

Abstract
OBJECTIVE: Iodine-131-labelled meta-iodobenzylguanidine (I-mIBG) therapy is an established treatment modality for relapsed/refractory neuroblastoma, most frequently administered according to fixed or weight-based criteria. We evaluate response and toxicity following a dosimetry-based, individualized approach.
MATERIALS AND METHODS: A review of 44 treatments in 25 patients treated with I-mIBG therapy was performed. Patients received I-mIBG therapy following relapse (n=9), in refractory disease (n=12), or with surgically unresectable disease despite conventional treatment (n=4). Treatment schedule (including mIBG dose and number of administrations) was individualized according to the clinical status of the patient and dosimetry data from either a tracer study or previous administrations. Three-dimensional tumour dosimetry was also performed for eight patients.
RESULTS: The mean administered activity was 11089±7222 MBq and the mean whole-body dose for a single administration was 1.79±0.57 Gy. Tumour-absorbed doses varied considerably (3.70±3.37 mGy/MBq). CTCAE grade 3/4 neutropenia was documented following 82% treatments and grade 3/4 thrombocytopenia following 71% treatments. Further acute toxicity was found in 49% of patients. All acute toxicities resolved with appropriate therapy. The overall response rate was 58% (complete or partial response), with a further 29% of patients having stable disease.
CONCLUSION: A highly personalized approach combining patient-specific dosimetry and clinical judgement enables delivery of high activities that can be tolerated by patients, particularly with stem cell support. We report excellent response rates and acceptable toxicity following individualized I-mIBG therapy.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://ift.tt/1hexVwJ.

PMID: 26813989 [PubMed - as supplied by publisher]



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Accuracy of PET/MR image coregistration of cervical lesions.

Accuracy of PET/MR image coregistration of cervical lesions.

Nucl Med Commun. 2016 Jan 25;

Authors: Zhang S, Xin J, Sun H, Ma J, Ma Q, Guo Q, Zhao X

Abstract
PURPOSE: This study aimed to evaluate the accuracy of sequential whole-body PET/MR image coregistration of cervical lesions.
MATERIALS AND METHODS: Twenty-five patients with cervical carcinomas underwent fluorine-18 fluorodeoxyglucose PET/MR before radiotherapy. MR-volumes of interest (VOIs), PET-VOIs, and apparent diffusion coefficient (ADC)-VOIs were outlined manually on T2-weighted MR images, PET images, and ADC maps. The difference between the lesion centers on PET and MR was determined by calculating the distance of the respective geometric center of gravity. In addition, the tumor volume contour differences were assessed using the dice similarity coefficient for PET and ADC. Results were analyzed by mean±SD and a two-sample t-test.
RESULTS: The mean values of the center of gravity mismatch were relatively higher with lesions between PET and ADC (5.79±1.70 mm) than that between PET and MR-T2 (5.22±1.97 mm; P=0.304). Tumor location overlap difference between MR-T2 and PET images (0.64±0.13) was larger than that between ADC and PET (0.56±0.14; P=0.054). The average differences between the centers of lesions on PET and T2-weighted images were 6.25±1.91, 5.24±2.17, and 4.30±1.30 mm for MR-VOI less than 14, 14-62, and at least 62 ml. The average differences between the center of lesions on PET and ADC were 5.97±1.48, 5.43±1.40, and 5.78±2.75 mm, respectively. Image registration tended to be slightly less accurate in the smaller lesions than in the larger lesions (P>0.05). The average overlaps were 0.51±0.13, 0.63±0.10, and 0.76±0.03 between the T2-weighted image and PET, respectively. The average overlaps were 0.44±0.14, 0.58±0.11, and 0.66±0.04 between the ADC and PET, respectively. Larger tumors had a higher degree of overlap compared with small tumors (P<0.05).
CONCLUSION: Image coregistration of cervical lesions is usually accurate in sequential whole-body PET/MR. The accuracy of image registration between MR-T2 and PET was larger than that between ADC and PET. Image registration tended to be more accurate in the larger lesions.

PMID: 26813988 [PubMed - as supplied by publisher]



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Do We Pay Enough Attention to Culture Conditions in Context of Perinatal Outcome after In Vitro Fertilization? Up-to-Date Literature Review

Adverse perinatal outcomes in singleton IVF pregnancies have been most often explained by parental underlying diseases and so far laboratory conditions during embryo culture are still not explored well. The following review discusses the current state of knowledge on the influence of IVF laboratory procedures on the possible perinatal outcome. The role of improved media for human embryo culture is unquestionable. Addition of certain components to culture media and their effect on embryo survival and implantation rates have been taken into consideration recently and studied on animal model. Impact of media on perinatal outcome in IVF offspring has also been studied. It has been discovered that epigenetic changes and neonatal birth weight are probably associated with the use of specific culture media, as is the relation between placental size and its influence on perinatal outcome. There are still questions in the discussion about duration of embryo culture (cleavage stage versus blastocyst transfer). Some of the IVF methods, such as in vitro maturation of oocytes and freezing/thawing procedures, also require well-powered randomized controlled trials in order to define their exact impact on perinatal outcome. Constant further research is needed to assess the impact of laboratory environment on fetal and postnatal development.

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The Impact of Biopsy on Human Embryo Developmental Potential during Preimplantation Genetic Diagnosis

Preimplantation Genetic Diagnosis and Screening (PGD/PGS) for monogenic diseases and/or numerical/structural chromosomal abnormalities is a tool for embryo testing aimed at identifying nonaffected and/or euploid embryos in a cohort produced during an IVF cycle. A critical aspect of this technology is the potential detrimental effect that the biopsy itself can have upon the embryo. Different embryo biopsy strategies have been proposed. Cleavage stage blastomere biopsy still represents the most commonly used method in Europe nowadays, although this approach has been shown to have a negative impact on embryo viability and implantation potential. Polar body biopsy has been proposed as an alternative to embryo biopsy especially for aneuploidy testing. However, to date no sufficiently powered study has clarified the impact of this procedure on embryo reproductive competence. Blastocyst stage biopsy represents nowadays the safest approach not to impact embryo implantation potential. For this reason, as well as for the evidences of a higher consistency of the molecular analysis when performed on trophectoderm cells, blastocyst biopsy implementation is gradually increasing worldwide. The aim of this review is to present the evidences published to date on the impact of the biopsy at different stages of preimplantation development upon human embryos reproductive potential.

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Potential Diagnostic and Prognostic Biomarkers of Epigenetic Drift within the Cardiovascular Compartment

Biomarkers encompass a wide range of different measurable indicators, representing a tangible link to physiological changes occurring within the body. Accessibility, sensitivity, and specificity are significant factors in biomarker suitability. New biomarkers continue to be discovered, and questions over appropriate selection and assessment of their usefulness remain. If traditional markers of inflammation are not sufficiently robust in their specificity, then perhaps alternative means of detection may provide more information. Epigenetic drift (epigenetic modifications as they occur as a direct function with age), and its ancillary elements, including platelets, secreted microvesicles (MVs), and microRNA (miRNA), may hold enormous predictive potential. The majority of epigenetic drift observed in blood is independent of variations in blood cell composition, addressing concerns affecting traditional blood-based biomarker efficacy. MVs are found in plasma and other biological fluids in healthy individuals. Altered MV/miRNA profiles may also be found in individuals with various diseases. Platelets are also highly reflective of physiological and lifestyle changes, making them extremely sensitive biomarkers of human health. Platelets release increased levels of MVs in response to various stimuli and under a plethora of disease states, which demonstrate a functional effect on other cell types.

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Current Investigational Drugs for the Treatment of Attention-Deficit/Hyperactivity Disorder.

Current Investigational Drugs for the Treatment of Attention-Deficit/Hyperactivity Disorder.

Expert Opin Investig Drugs. 2016 Jan 27;

Authors: Childress A, Tran C

Abstract
INTRODUCTION: Symptoms of attention-deficit/hyperactivity disorder (ADHD) were first described more than 100 years ago. It is a common neurobehavioral disorder that begins in childhood and often persists into adulthood. Treatment for ADHD has been available since Bradley first prescribed amphetamines for hyperkinetic boys more than 70 years ago. Although multiple effective medications for the treatment of ADHD are on the market, all have limitations. Stimulants are controlled substances and may not be effective or tolerable for all patients. The non-stimulants are not as effective as stimulants and have their own side effect profiles. Areas Covered: In this review, the limitations of currently available medications including methylphenidates, amphetamines, atomoxetine, extended-release guanfacine and extended-release clonidine are considered and drugs in development for the treatment of ADHD are examined. Although the main focus is on phase I and II trials, drugs which may soon be marketed are also discussed. Expert opinion: Multiple drugs are currently in development, with several targeting novel receptors originally identified using animal models. Since ADHD appears to be complex disorder associated with multiple genes, these models have often not predicted effectiveness in humans. Until there is a better understanding of the genetics of ADHD, drug development will remain challenging.

PMID: 26814173 [PubMed - as supplied by publisher]



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Detection of an early adult T-cell leukemia-lymphoma clone in lymph nodes with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma involvement

Publication date: Available online 27 January 2016
Source:Cancer Genetics
Author(s): Masahito Tokunaga, Noriaki Yoshida, Nobuaki Nakano, Ayumu Kubota, Shogo Takeuchi, Yoshifusa Takatsuka, Masao Seto, Atae Utsunomiya
A 58-year old man was admitted to our hospital with systemic lymphadenopathy and was diagnosed with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (ALCL) by lymph node biopsy. Although he was a human T-cell leukemia virus type I (HTLV-1) carrier, Southern blot analysis of the lymph node did not show monoclonal integration of HTLV-1 provirus deoxyribonucleic acid (DNA). He achieved complete remission after chemotherapy and subsequently, autologous peripheral blood stem cell transplantation (auto-PBSCT) was performed. Fifteen months after the auto-PBSCT, abnormal lymphocytes in the peripheral blood gradually increased. Southern blot analysis revealed monoclonal integration of HTLV-1 provirus DNA and monoclonal rearrangement of TRB. He was diagnosed with chronic type adult T-cell leukemia-lymphoma (ATL), which immediately progressed to the acute type. He died of tumor progression despite intensive chemotherapy. We analyzed genomic alterations of the ALCL and ATL cells using array comparative genomic hybridization. We found that the genomic alteration pattern differed between the two diseases. T-cell receptor clonality analysis using polymerase chain reaction (PCR) showed that the T-cell clone of the ATL was present in the lymph nodes with ALCL involvement, but not in peripheral blood. This finding suggests that lymph nodes can serve as a niche for ATL development.



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How to evaluate sexual health in cancer patients: development of the EORTC sexual health questionnaire for cancer patients.

How to evaluate sexual health in cancer patients: development of the EORTC sexual health questionnaire for cancer patients.

Transl Androl Urol. 2015 Apr;4(2):95-102

Authors: Nagele E, Den Oudsten B, Greimel E, EORTC Quality of Life Group

Abstract
BACKGROUND: The aim of the study is to describe the development of a comprehensive European Organisation for Research and Treatment of Cancer (EORTC) questionnaire to assess sexual health of female and male cancer patients and for cancer survivors.
METHODS: According to the EORTC guidelines, the development of an EORTC sexual health questionnaire is typically organised in four phases. The first phases comprise a literature search following interviews with patient and health care professionals (HCPs) (phase 1) and the operationalization into items (phase 2). The translation process is formally conducted according to the EORTC QLG Translation guidelines with a rigorous forward-backward procedure supported by native speakers.
RESULTS: Studies on sexuality in oncology patients which were identified by a literature search predominantly focused on issues of activity, experiences of sexual dysfunction, and satisfaction with sexual functioning. The literature review identified themes beyond these aspects. In total 53 potentially relevant issues were presented to 107 patients and 83 HCPs, different evaluations were found.
CONCLUSIONS: A questionnaire that includes physical, psychological, and social aspects of sexuality of cancer survivors will be needed. Pre-testing and validation of the questionnaire will be done in future (phases 3 and 4). Divergent ratings of patients and professionals should be further investigated.

PMID: 26816816 [PubMed - as supplied by publisher]



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Attitude and practice of brachytherapy in India: a study based on the survey amongst attendees of Annual Meeting of Indian Brachytherapy Society.

Attitude and practice of brachytherapy in India: a study based on the survey amongst attendees of Annual Meeting of Indian Brachytherapy Society.

J Contemp Brachytherapy. 2015 Dec;7(6):462-468

Authors: Gandhi AK, Sharma DN, Julka PK, Rath GK

Abstract
PURPOSE: We performed a survey amongst attendees of the 4(th) Annual Meeting of Indian Brachytherapy Society to study the patterns of brachytherapy practice and attitude towards brachytherapy use.
MATERIAL AND METHODS: A 19-point questionnaire was designed and e-mailed to the attendees immediately after the conference. Descriptive analysis of the responses were done and satisfaction index was used as a tool for evaluation of the program effectiveness. Binomial test was used to assess the difference between distributions of responses and Mann-Whitney U test was used to assess the correlation between responses. P value (2-tailed) of < 0.05 was taken significant for all statistical analysis.
RESULTS: Of a total of 202 attendees, 90 responded to the survey (response rate: 44.5%). Seventy-two percent belonged to an academic institute while 28% belonged to non-academic institutes. Eighty-six percent were radiation oncologists and 10% were medical physicists. Eighty-nine percent respondents used high-dose-rate, 14% - pulse-dose-rate, and 13% used low-dose-rate brachytherapy facility. Orthogonal X-rays, computed tomography, and magnetic resonance imaging was used for brachytherapy planning by 56%, 69%, and 14%, respectively. Ninety-three percent of them thought that lack of training is a hurdle in practicing brachytherapy and 92% opined that brachytherapy dedicated meetings can change their perception about brachytherapy. Seventy percent respondents admitted to make some changes in their practice patterns after attending this meeting. Ninety-seven percent of them would like to attend future meetings and 98% felt the need to include live workshops, hands on demonstrations, and video presentations in the scientific programme.
CONCLUSIONS: The survey highlights a positive attitude towards increasing brachytherapy use, and may serve as an important guiding tool in designing teaching and training programmes; thus overcoming the hurdles in successful and widespread use of a quality brachytherapy programme at radiotherapy centers.

PMID: 26816503 [PubMed - as supplied by publisher]



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Reliability and day-to-day variability of peak fat oxidation during treadmill ergometry.

Reliability and day-to-day variability of peak fat oxidation during treadmill ergometry.

J Int Soc Sports Nutr. 2016;13:4

Authors: De Souza Silveira R, Carlsohn A, Langen G, Mayer F, Scharhag-Rosenberger F

Abstract
BACKGROUND: Exercising at intensities where fat oxidation rates are high has been shown to induce metabolic benefits in recreational and health-oriented sportsmen. The exercise intensity (Fatpeak) eliciting peak fat oxidation rates is therefore of particular interest when aiming to prescribe exercise for the purpose of fat oxidation and related metabolic effects. Although running and walking are feasible and popular among the target population, no reliable protocols are available to assess Fatpeak as well as its actual velocity (VPFO) during treadmill ergometry. Our purpose was therefore, to assess the reliability and day-to-day variability of VPFO and Fatpeak during treadmill ergometry running.
METHODS: Sixteen recreational athletes (f = 7, m = 9; 25 ± 3 y; 1.76 ± 0.09 m; 68.3 ± 13.7 kg; 23.1 ± 2.9 kg/m(2)) performed 2 different running protocols on 3 different days with standardized nutrition the day before testing. At day 1, peak oxygen uptake (VO2peak) and the velocities at the aerobic threshold (VLT) and respiratory exchange ratio (RER) of 1.00 (VRER) were assessed. At days 2 and 3, subjects ran an identical submaximal incremental test (Fat-peak test) composed of a 10 min warm-up (70 % VLT) followed by 5 stages of 6 min with equal increments (stage 1 = VLT, stage 5 = VRER). Breath-by-breath gas exchange data was measured continuously and used to determine fat oxidation rates. A third order polynomial function was used to identify VPFO and subsequently Fatpeak. The reproducibility and variability of variables was verified with an intraclass correlation coefficient (ICC), Pearson's correlation coefficient, coefficient of variation (CV) and the mean differences (bias) ± 95 % limits of agreement (LoA).
RESULTS: ICC, Pearson's correlation and CV for VPFO and Fatpeak were 0.98, 0.97, 5.0 %; and 0.90, 0.81, 7.0 %, respectively. Bias ± 95 % LoA was -0.3 ± 0.9 km/h for VPFO and -2 ± 8 % of VO2peak for Fatpeak.
CONCLUSION: In summary, relative and absolute reliability indicators for VPFO and Fatpeak were found to be excellent. The observed LoA may now serve as a basis for future training prescriptions, although fat oxidation rates at prolonged exercise bouts at this intensity still need to be investigated.

PMID: 26816497 [PubMed - as supplied by publisher]



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High expression of matrix metalloproteinases: MMP-2 and MMP-9 predicts poor survival outcome in colorectal carcinoma.

High expression of matrix metalloproteinases: MMP-2 and MMP-9 predicts poor survival outcome in colorectal carcinoma.

Future Oncol. 2016 Feb;12(3):323-331

Authors: Salem N, Kamal I, Al-Maghrabi J, Abuzenadah A, Peer-Zada AA, Qari Y, Al-Ahwal M, Al-Qahtani M, Buhmeida A

Abstract
AIM: To evaluate the expression pattern of matrix metalloproteinases (MMPs); MMP-2, MMP-7 and MMP-9 in colorectal cancer (CRC) and determine its prognostic potential.
PATIENTS & METHODS: CRC samples of 127 patients were studied. Protein expressions of MMP-2, -7 and -9 were analyzed by immunohistochemistry and association with clinicopathological variables was statistically analyzed.
RESULTS: Overexpressions of MMP-2 and MMP-9 correlated with poor outcome as evaluated by univariate Kaplan-Meier for disease-free survival (p = 0.04, p = 0.0001) and disease-specific survival (p = 0.01, p = 0.01), respectively. Cox analysis of MMP-2 and -9 were significant independent predictors of disease-free survival (p = 0.006, p = 0.018) and disease-specific survival (p = 0.004, p = 0.049), respectively.
CONCLUSION: MMPs expression patterns provide useful prognostic information in CRC, while predicting the patients at high risk for recurrent disease.

PMID: 26814712 [PubMed - as supplied by publisher]



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Gene-expression profiling of localized prostate cancer: still miles to go before we sleep.

Gene-expression profiling of localized prostate cancer: still miles to go before we sleep.

Future Oncol. 2016 Feb;12(3):273-276

Authors: Garzotto M, Kopp RP

PMID: 26814711 [PubMed - as supplied by publisher]



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Infectious Complications in Children With Acute Myeloid Leukemia and Down Syndrome: Analysis of the Prospective Multicenter Trial AML-BFM 2004.

Infectious Complications in Children With Acute Myeloid Leukemia and Down Syndrome: Analysis of the Prospective Multicenter Trial AML-BFM 2004.

Pediatr Blood Cancer. 2016 Jan 27;

Authors: Hassler A, Bochennek K, Gilfert J, Perner C, Schöning S, Creutzig U, Reinhardt D, Lehrnbecher T

Abstract
BACKGROUND: Children with acute myeloid leukemia (AML) and Down syndrome have high survival rates with intensity-reduced chemotherapeutic regimens, although the optimal balance between dose intensity and treatment toxicity has not been determined. We, therefore, characterized infectious complications in children with AML and Down syndrome treated according to AML-BFM 2004 study (ClinicalTrials.gov NCT00111345; amended 2006 for Down syndrome with reduced intensity).
PROCEDURE: Data on infectious complications were gathered from the medical records in the hospital where the patient was treated. Infectious complications were categorized as fever without identifiable source (FUO), or as microbiologically or clinically documented infections.
RESULTS: A total of 157 infections occurred in 61 patients (60.5% FUO, 9.6% and 29.9% clinically and microbiologically documented infections, respectively). Almost 90% of the pathogens isolated from the bloodstream were Gram-positive bacteria, and approximately half of them were viridans group streptococci. All seven microbiologically documented episodes of pneumonia were caused by viruses. Infection-related mortality was 4.9%, and all three patients died due to viral infection.
CONCLUSIONS: Our data demonstrate that a reduced-intensity chemotherapeutic regimen in children with AML and Down syndrome is still associated with high morbidity. Although no patient died due to bacteria or fungi, viruses were responsible for all lethal events. Future studies, therefore, have to focus on the impact of viruses on morbidity and mortality of patients with AML and Down syndrome.

PMID: 26814618 [PubMed - as supplied by publisher]



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Core principles of sexual health treatments in cancer for men.

Core principles of sexual health treatments in cancer for men.

Curr Opin Support Palliat Care. 2016 Mar;10(1):38-43

Authors: Matthew A

Abstract
PURPOSE OF REVIEW: The considerable prevalence of sexual health problems in men after cancer treatment coupled with the severity of impact and challenges to successful intervention make sexual dysfunction one of the most substantial health-related quality of life burdens in all of cancer survivorship. Surgeries, radiation therapies, and nontreatment (e.g., active surveillance) variously result in physical disfigurement, pain, and disruptions in physiological, psychological, and relational functioning. Although biomedical and psychological interventions have independently shown benefit, long-term, effective treatment for sexual dysfunction remains elusive.
RECENT FINDINGS: Recognizing the complex nature of men's sexual health in an oncology setting, there is a trend toward the adoption of a biopsychosocial orientation that emphasizes the active participation of the partner, and a broad-spectrum medical, psychological, and social approach. Intervention research to date provides good insight into the potential active ingredients of successful sexual rehabilitation programming.
SUMMARY: Combining a biopsychosocial approach with these active intervention elements forecasts an optimistic future for men's sexual rehabilitation programming within oncology. However, significant gaps remain in our understanding of patient experience and appropriate sexual health intervention for gay men and men of diverse race and culture.

PMID: 26814146 [PubMed - in process]



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Premalignancy in Prostate Cancer: Rethinking What we Know.

Premalignancy in Prostate Cancer: Rethinking What we Know.

Cancer Prev Res (Phila). 2016 Jan 26;

Authors: De Marzo AM, Haffner MC, Lotan TL, Yegnasubramanian S, Nelson WG

Abstract
High-grade prostatic intra-epithelial neoplasia (PIN) has been accepted as the main precursor lesion to invasive adenocarcinoma of the prostate, and this is likely to be the case. However, in an unknown number of cases, lesions fulfilling the diagnostic criteria for high-grade PIN may actually represent intra-acinar or intra-ductal spread of invasive carcinoma. Intriguingly, this possibility would not contradict many of the findings of previous epidemiological studies linking high-grade PIN to carcinoma or molecular pathological studies showing similar genomic (e.g. TMPRSS2-ERG gene fusion) as well as epigenomic and molecular phenotypic alterations between high-grade PIN and carcinoma. Also, this possibility would be consistent with previous anatomic studies in prostate specimens linking high-grade PIN and carcinoma in autopsy and other whole prostate specimens. In addition, if some cases meeting morphologic criteria for PIN actually represent intra-acinar spread of invasive carcinoma, this could be an important potential confounder of the interpretation of past clinical trials enrolling patients presumed to be without carcinoma, who are at high risk of invasive carcinoma. Thus, in order to reduce possible bias in future study/trial designs, novel molecular pathology approaches are needed to decipher when an apparent PIN lesion may be intra-acinar/intra-ductal spread of an invasive cancer and when it truly represents a precursor state. Similar approaches are needed for lesions known as intraductal carcinoma to facilitate better classification of them as true intra-ductal/acinar spread on one hand, or as precursor high-grade PIN (cribriform type) on the other hand, a number of such molecular approaches are already showing excellent promise.

PMID: 26813971 [PubMed - as supplied by publisher]



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Imaging Surrogates of Infiltration Obtained Via Multiparametric Imaging Pattern Analysis Predict Subsequent Location of Recurrence of Glioblastoma.

Imaging Surrogates of Infiltration Obtained Via Multiparametric Imaging Pattern Analysis Predict Subsequent Location of Recurrence of Glioblastoma.

Neurosurgery. 2016 Jan 19;

Authors: Akbari H, Macyszyn L, Da X, Bilello M, Wolf RL, Martinez-Lage M, Biros G, Alonso-Basanta M, OʼRourke DM, Davatzikos C

Abstract
BACKGROUND: Glioblastoma is an aggressive and highly infiltrative brain cancer. Standard surgical resection is guided by enhancement on postcontrast T1-weighted (T1) magnetic resonance imaging, which is insufficient for delineating surrounding infiltrating tumor.
OBJECTIVE: To develop imaging biomarkers that delineate areas of tumor infiltration and predict early recurrence in peritumoral tissue. Such markers would enable intensive, yet targeted, surgery and radiotherapy, thereby potentially delaying recurrence and prolonging survival.
METHODS: Preoperative multiparametric magnetic resonance images (T1, T1-gadolinium, T2-weighted, T2-weighted fluid-attenuated inversion recovery, diffusion tensor imaging, and dynamic susceptibility contrast-enhanced magnetic resonance images) from 31 patients were combined using machine learning methods, thereby creating predictive spatial maps of infiltrated peritumoral tissue. Cross-validation was used in the retrospective cohort to achieve generalizable biomarkers. Subsequently, the imaging signatures learned from the retrospective study were used in a replication cohort of 34 new patients. Spatial maps representing the likelihood of tumor infiltration and future early recurrence were compared with regions of recurrence on postresection follow-up studies with pathology confirmation.
RESULTS: This technique produced predictions of early recurrence with a mean area under the curve of 0.84, sensitivity of 91%, specificity of 93%, and odds ratio estimates of 9.29 (99% confidence interval: 8.95-9.65) for tissue predicted to be heavily infiltrated in the replication study. Regions of tumor recurrence were found to have subtle, yet fairly distinctive multiparametric imaging signatures when analyzed quantitatively by pattern analysis and machine learning.
CONCLUSION: Visually imperceptible imaging patterns discovered via multiparametric pattern analysis methods were found to estimate the extent of infiltration and location of future tumor recurrence, paving the way for improved targeted treatment.
ABBREVIATIONS: UC, area under the curveBBB, blood-brain barrierDSC, dynamic susceptibility contrast-enhancedDTI, diffusion tensor imagingFLAIR, fluid-attenuated inversion recoveryPC, principal componentROI, region of interestT1, T1-weightedT2, T2-weighted.

PMID: 26813856 [PubMed - as supplied by publisher]



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Functional analysis of androgen receptor mutations that confer anti-androgen resistance identified in circulating cell-free DNA from prostate cancer patients.

Functional analysis of androgen receptor mutations that confer anti-androgen resistance identified in circulating cell-free DNA from prostate cancer patients.

Genome Biol. 2016;17(1):10

Authors: Lallous N, Volik SV, Awrey S, Leblanc E, Tse R, Murillo J, Singh K, Azad AA, Wyatt AW, LeBihan S, Chi KN, Gleave ME, Rennie PS, Collins CC, Cherkasov A

Abstract
BACKGROUND: The androgen receptor (AR) is a pivotal drug target for the treatment of prostate cancer, including its lethal castration-resistant (CRPC) form. All current non-steroidal AR antagonists, such as hydroxyflutamide, bicalutamide, and enzalutamide, target the androgen binding site of the receptor, competing with endogenous androgenic steroids. Several AR mutations in this binding site have been associated with poor prognosis and resistance to conventional prostate cancer drugs. In order to develop an effective CRPC therapy, it is crucial to understand the effects of these mutations on the functionality of the AR and its ability to interact with endogenous steroids and conventional AR inhibitors.
RESULTS: We previously utilized circulating cell-free DNA (cfDNA) sequencing technology to examine the AR gene for the presence of mutations in CRPC patients. By modifying our sequencing and data analysis approaches, we identify four additional single AR mutations and five mutation combinations associated with CRPC. Importantly, we conduct experimental functionalization of all the AR mutations identified by the current and previous cfDNA sequencing to reveal novel gain-of-function scenarios. Finally, we evaluate the effect of a novel class of AR inhibitors targeting the binding function 3 (BF3) site on the activity of CRPC-associated AR mutants.
CONCLUSIONS: This work demonstrates the feasibility of a prognostic and/or diagnostic platform combining the direct identification of AR mutants from patients' serum, and the functional characterization of these mutants in order to provide personalized recommendations regarding the best future therapy.

PMID: 26813233 [PubMed - in process]



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Systematic identification of genes with a cancer-testis expression pattern in 19 cancer types.

Systematic identification of genes with a cancer-testis expression pattern in 19 cancer types.

Nat Commun. 2016;7:10499

Authors: Wang C, Gu Y, Zhang K, Xie K, Zhu M, Dai N, Jiang Y, Guo X, Liu M, Dai J, Wu L, Jin G, Ma H, Jiang T, Yin R, Xia Y, Liu L, Wang S, Shen B, Huo R, Wang Q, Xu L, Yang L, Huang X, Shen H, Sha J, Hu Z

Abstract
Cancer-testis (CT) genes represent the similarity between the processes of spermatogenesis and tumorigenesis. It is possible that their selective expression pattern can help identify driver genes in cancer. In this study, we integrate transcriptomics data from multiple databases and systematically identify 876 new CT genes in 19 cancer types. We explore their relationship with testis-specific regulatory elements. We propose that extremely highly expressed CT genes (EECTGs) are potential drivers activated through epigenetic mechanisms. We find mutually exclusive associations between EECTGs and somatic mutations in mutated genes, such as PIK3CA in breast cancer. We also provide evidence that promoter demethylation and close non-coding RNAs (namely, CT-ncRNAs) may be two mechanisms to reactivate EECTG gene expression. We show that the meiosis-related EECTG (MEIOB) and its nearby CT-ncRNA have a role in tumorigenesis in lung adenocarcinoma. Our findings provide methods for identifying epigenetic-driver genes of cancer, which could serve as targets of future cancer therapies.

PMID: 26813108 [PubMed - in process]



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Nausea and vomiting induced by gastrointestinal radiation therapy: current status and future directions.

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Nausea and vomiting induced by gastrointestinal radiation therapy: current status and future directions.

Curr Opin Support Palliat Care. 2015 Jun;9(2):182-8

Authors: Dennis K, Poon M, Chow E

Abstract
PURPOSE OF REVIEW: Radiation therapy-induced nausea and vomiting (RINV) are common and troublesome symptoms among patients receiving radiation therapy for gastrointestinal cancers. Their impact on function, quality of life and, ultimately, cancer control warrant a review of their incidence, underlying mechanisms, treatments and research themes.
RECENT FINDINGS: Research in RINV is underrepresented relative to that in chemotherapy-induced nausea and vomiting. The incidence of RINV among patients receiving modern day radiation therapy is questioned and supportive care practice patterns vary among radiation oncologists. Antiemetic guideline recommendations for prophylactic and rescue therapy are based solely on the anatomic region being irradiated and not other patient-related, radiation therapy-related, or organ-specific dosimetric factors that likely modulate the risk of RINV. Dosimetric predictors are likely the most attainable biomarker moving forward, but only early steps have been taken. The small bowel and stomach will be the best first candidates for study among patients with gastrointestinal cancers. Studies of the mechanisms underlying RINV are conspicuously lacking. A new generation of observational studies and therapeutic clinical trials is needed, and more attention must be given to the relative impact of nausea and vomiting on the function and quality of life among specific homogeneous patient populations.
SUMMARY: Optimal supportive care strategies for RINV following radiation therapy for gastrointestinal cancers are lacking, and will not be known until future research answers the many open questions regarding the mechanisms underlying RINV, the true incidence and impact of these symptoms among patients and the best way to predict and mitigate them.

PMID: 25872120 [PubMed - indexed for MEDLINE]



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Probiotics to prevent gastrointestinal toxicity from cancer therapy: an interpretive review and call to action.

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Probiotics to prevent gastrointestinal toxicity from cancer therapy: an interpretive review and call to action.

Curr Opin Support Palliat Care. 2015 Jun;9(2):157-62

Authors: Ciorba MA, Hallemeier CL, Stenson WF, Parikh PJ

Abstract
PURPOSE OF REVIEW: There is currently an unmet need for agents that can prevent the gastrointestinal toxicity (mucositis and enteritis) associated with chemotherapy and radiation therapy of abdominal and pelvic cancers. Herein we provide an overview of how manipulation of the gut microbiota by probiotic administration affects these gastrointestinal symptoms. We focus this review on published human trials and also provide suggestions on how the field can move forward.
RECENT FINDINGS: Several clinical trials of varying design, patient populations and probiotic products have been reported. Lactobacillus probiotics of adequate dosage demonstrate a potential to reduce gastrointestinal toxicity when administered prophylactically. Common study limitations prevent the widespread adoption of this practice at this point but are informative for rational design of future trials.
SUMMARY: No single probiotic strain or product has emerged from human clinical trials for this indication. Further human studies are required to address limitations in the current literature. Preclinical model data should be used to inform the rational design of these new clinical trials to adequately address this important question.

PMID: 25872116 [PubMed - indexed for MEDLINE]



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Adenoviral-mediated imaging of gene transfer using a somatostatin receptor-cytosine deaminase fusion protein.

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Adenoviral-mediated imaging of gene transfer using a somatostatin receptor-cytosine deaminase fusion protein.

Cancer Gene Ther. 2015 Mar;22(4):215-21

Authors: Lears KA, Parry JJ, Andrews R, Nguyen K, Wadas TJ, Rogers BE

Abstract
Suicide gene therapy is a process by which cells are administered a gene that encodes a protein capable of converting a nontoxic prodrug into an active toxin. Cytosine deaminase (CD) has been widely investigated as a means of suicide gene therapy owing to the enzyme's ability to convert the prodrug 5-fluorocytosine (5-FC) into the toxic compound 5-fluorouracil (5-FU). However, the extent of gene transfer is a limiting factor in predicting therapeutic outcome. The ability to monitor gene transfer, non-invasively, would strengthen the efficiency of therapy. In this regard, we have constructed and evaluated a replication-deficient adenovirus (Ad) containing the human somatostatin receptor subtype 2 (SSTR2) fused with a C-terminal yeast CD gene for the non-invasive monitoring of gene transfer and therapy. The resulting Ad (AdSSTR2-yCD) was evaluated in vitro in breast cancer cells to determine the function of the fusion protein. These studies demonstrated that both the SSTR2 and yCD were functional in binding assays, conversion assays and cytotoxicity assays. In vivo studies similarly demonstrated the functionality using conversion assays, biodistribution studies and small animal positron-emission tomography (PET) imaging studies. In conclusion, the fusion protein has been validated as useful for the non-invasive imaging of yCD expression and will be evaluated in the future for monitoring yCD-based therapy.

PMID: 25837665 [PubMed - indexed for MEDLINE]



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Psychological help-seeking and homeless adolescents.

Collins, P.M.; (2004) Psychological help-seeking and homeless adolescents. Doctoral thesis, University of London. Green open access

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Perspective Taking in Definite Reference Resolution

Zheng, X; (2015) Perspective Taking in Definite Reference Resolution. Doctoral thesis, UCL (University College London). Green open access

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Animal procurement in the Late Neolithic of the Yangtze River Basin: Integrating the fish remains into a case-study from Tianluoshan

Zhang, Y; (2015) Animal procurement in the Late Neolithic of the Yangtze River Basin: Integrating the fish remains into a case-study from Tianluoshan. Doctoral thesis, UCL (University College London).

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Structural studies of neuropilin-1

Yelland, TS; (2015) Structural studies of neuropilin-1. Doctoral thesis, UCL (University College London).

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An investigation of the stem cell potential of skeletal muscle satellite cells.

Collins, C.A.; (2004) An investigation of the stem cell potential of skeletal muscle satellite cells. Doctoral thesis, University of London. Green open access

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