Αρχειοθήκη ιστολογίου

Τετάρτη 1 Ιουνίου 2016

Influences of −482C>T and 3238G>C polymorphisms of the Apolipoprotein C3 gene on prevalence of metabolic syndrome

Abstract

Apolipoprotein C3 (ApoC3) plays a regulatory role in triglyceride (TG) metabolism. The higher level of TG can be a cause in pathogenesis of the vascular diseases or metabolic syndrome (MetS). In this study, we examined the associations of ApoC3 polymorphisms (−482C>T rs2854117 and 3238G>C rs5128) with Korean MetS patients. A total of 835 subjects were investigated, including 320 patients with MetS and 515 healthy subjects. The genotype analysis of the ApoC3 polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism methods. Of the two polymorphisms studied, we observed a significant difference in the −482C>T polymorphism between the MetS and control groups. The TT genotype of the −482C>T polymorphism was associated with increased risk for MetS, compared with the controls (OR 1.627, 95 % CI 1.075–2.463, P = 0.021). The association was female-specific. No associations were found for the risk of MetS in the 3238G>C polymorphism. Haplotypes composed of two polymorphisms, however, were associated with MetS susceptibility in only male group. The 3238G>C polymorphism was significantly associated with TG levels (P = 0.013). Our data suggest that the ApoC3 −482C>T polymorphism is associated with increased MetS susceptibility in the Korean population.



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Topical treatment with a two component gel releasing nitric oxide cures C57BL/6 mice from cutaneous leishmaniasis caused by Leishmania major



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NHE1-expression at wound margins increases time-dependently during physiological healing



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Frontal Fibrosing Alopecia: A disease fascinating for the researcher, disappointing for the clinician and distressing for the patient

Abstract

In just two decades since it was first described, FFA has gone from being a newly described disease entity to what is today considered by many dermatologists the most common clinical presentation of a primary scarring alopecia (1).

This article is protected by copyright. All rights reserved.



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Commentary on the Diagnostic Utility of Non-invasive Imaging Devices for Field Cancerization

Abstract

In this issue of Experimental Dermatology, Marneffe and collegues present a practical algorithmic guide to differentiating actinic keratosis (AK) from normal skin and squamous cell carcinoma (SCC) using high-definition optical coherence tomography (HD-OCT), outlining steps and markers to guide both novice and more experienced skin cancer experts (1).

This article is protected by copyright. All rights reserved.



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7 things you should and should not spend your first paycheck on

You've finally made it. You've passed your program, you've landed a job, and you are starting to feel financially secure. There is no doubt about it – when you get your first, hard-earned paycheck, it's exciting. That's why it's easy to put the cart before the horse when it comes to spending.

It's important to assess your new financial situation before you start splurging on items. Keep yourself in check and start your career path with smart financial decisions. Here's a list of dos and don'ts every one new to EMS should pay attention to.

1. Should: Do nothing out of your financial normal. Use your first few paychecks to observe how they work out with your already established bills. You may also be surprised about how much taxes or benefits cut into your paycheck. Jot down how much you have left after living your pre-career lifestyle: paying rent, your car payment and other ancillary fees. When you get into a rhythm of how much you are typically spending vs. how much you are making, you'll see how much discretionary income you actually have. The number may be smaller than you anticipated.

2. Should not: Immediately buy a new car. Maybe you've had your eye on a new SUV, or you're just looking for something practical to get around in. Either way, it's important to assess how much you can actually get away with spending before locking yourself into a car payment. You might also make unexpected observations – perhaps you're burning more gas on your commute than you thought, which could change your buying decision altogether.

3. Should: Spend on interest-accruing items you haven't had money to cover. Let's say you haven't had the ability to start chipping away at your student loans, a car payment or your credit card debt. You've gone this long without worrying about them, so it may be easy to take your first paycheck and put it toward something fun. The longer you resist debts, the more interest you're accruing – meaning the more you'll be paying in the long run. If you have a bit of padding this month, try to use some of it on your outstanding debt.

4. Should not: Get a credit card right away. You may have abstained from signing up for a credit card before your steady career paycheck, but now that you have regular money coming in, credit cards seem less scary. While credit cards are a great tool, especially if you haven't established a credit score, it's smart to hold off on getting one until you're comfortable with your new pay increase. Don't tempt yourself to live outside your means with a larger paycheck and an extra credit line.

5. Should: Start putting extra savings into a retirement account. It may seem odd to start thinking about retirement when you've only just begun your career, but ask any veteran paramedic – pensions aren't what they used to be. The younger you are when you start saving for retirement, the happier you'll be once you hang up the uniform.

6. Should not: Buy a vacation. Now is not the time to start taking paid vacation or dipping into your early savings. Although veterans at your station may scoff at the idea of taking a vacation at all, someday you will have the opportunity to treat yourself to a nice getaway – just not immediately. It's bad for your wallet and your reputation.

7. Should: Put a few pennies into an emergency fund. Getting surprised by car trouble, health issues or any other money obstacle that may come your way is never fun. Having some cash stashed away can take the sting out of these occurrences. Most experts agree that your emergency fund should equal three to six months' worth of living expenses.

We'll look the other way if you start these "should and should nots" after you buy yourself one decent meal. Congratulate yourself on the new job and a major accomplishment you've earned for yourself. Here's to a long – and fiscally responsible – journey in EMS .



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Arginase-1 is frequently positive in hepatoid adenocarcinomas

Publication date: September 2016
Source:Human Pathology, Volume 55
Author(s): Vishal S. Chandan, Sejal S. Shah, Michael S. Torbenson, Tsung-Teh Wu
Hepatoid adenocarcinoma is a rare extrahepatic tumor, which shows morphological and immunohistochemical similarities to hepatocellular carcinoma (HCC). Hence, hepatoid adenocarcinoma can cause diagnostic confusion with HCC. Arginase-1 immunostain has been recently shown to be an excellent marker of normal hepatocytes and is a sensitive and specific marker for HCC. However, the expression of Arginase-1 in hepatoid adenocarcinoma has not been evaluated in detail. Eight cases of hepatoid adenocarcinoma were immunostained with Arginase-1, Hepar-1, Glypican-3, CK7, CK20, CK19, polyclonal carcinoembryonic antigen, ɑ-fetoprotein, CDX2, and TTF-1. Albumin in situ hybridization was performed in 4 cases. All 8 cases were positive for Hepar-1. Arginase-1 was positive in 5 (62.5%) of 8 cases; 2 of these cases showed diffuse staining, while 3 showed patchy staining. Glypican-3, CK7 and ɑ-fetoprotein were each positive in 4 (50%) of 8 cases. CK19 was positive in 3 (37.5%) of 8 cases. polyclonal carcinoembryonic antigen showed canalicular staining in 3 (37.5%) of 8 cases and albumin in situ hybridization was positive in 3 (75%) of 4 cases. CDX2 was positive in 2 (25%) of 8 cases, both arising from the stomach. CK20 was positive in 1 (12.5%) of 8 case while TTF-1 was negative in all cases. Hepatoid adenocarcinoma has a similar immunostaining profile as HCC. Arginase-1 expression is common (62.5%) in hepatoid adenocarcinoma and hence it is not useful in distinguishing HCC from hepatoid adenocarcinoma.



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Novel t(1;3)(q21,p21) translocation in a basal cell adenocarcinoma of the parotid gland: potential association with tumorigenesis

Publication date: August 2016
Source:Human Pathology, Volume 54
Author(s): Karan Saluja, Pulivarthi H. Rao, Jeffery N. Myers, Adel K. El-Naggar
We report a rare translocation involving chromosomes 1q23 and 3p21 regions in a basaloid salivary carcinoma. Our case together with a previously reported instance of translocation involving chromosome 1q 21-24 region defines a specific chromosomal segment that may house a gene associated with the development of a subset of basaloid salivary tumors.



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Elevated integrin α6β4 expression is associated with venous invasion and decreased overall survival in non–small cell lung cancer

Publication date: August 2016
Source:Human Pathology, Volume 54
Author(s): Rachel L. Stewart, Dava West, Chi Wang, Heidi L. Weiss, Tamas Gal, Eric B. Durbin, William O'Connor, Min Chen, Kathleen L. O'Connor
Lung cancer carries a poor prognosis and is the most common cause of cancer-related death worldwide. The integrin α6β4, a laminin receptor, promotes carcinoma progression in part by cooperating with various growth factor receptors to facilitate invasion and metastasis. In carcinoma cells with mutant TP53, the integrin α6β4 promotes cell survival. TP53 mutations and integrin α6β4 overexpression co-occur in many aggressive malignancies. Because of the high frequency of TP53 mutations in lung squamous cell carcinoma (SCC), we sought to investigate the association of integrin β4 expression with clinicopathologic features and survival in non–small cell lung cancer (NSCLC). We constructed a lung cancer tissue microarray and stained sections for integrin β4 subunit expression using immunohistochemistry. We found that integrin β4 expression is elevated in SCC compared with adenocarcinoma (P<.0001), which was confirmed in external gene expression data sets (P<.0001). We also determined that integrin β4 overexpression associates with the presence of venous invasion (P=.0048) and with reduced overall patient survival (hazard ratio, 1.46; 95% confidence interval, 1.01-2.09; P=.0422). Elevated integrin β4 expression was also shown to associate with reduced overall survival in lung cancer gene expression data sets (hazard ratio, 1.49; 95% confidence interval, 1.31-1.69; P<.0001). Using cBioPortal, we generated a network map demonstrating the 50 most highly altered genes neighboring ITGB4 in SCC, which included laminins, collagens, CD151, genes in the EGFR and PI3K pathways, and other known signaling partners. In conclusion, we demonstrate that integrin β4 is overexpressed in NSCLC where it is an adverse prognostic marker.



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Role of Environmental Factors on Resuming Valued Activities Poststroke: A Systematic Review of Qualitative and Quantitative Findings

Publication date: June 2016
Source:Archives of Physical Medicine and Rehabilitation, Volume 97, Issue 6
Author(s): Sandra Jellema, Rob van der Sande, Suzanne van Hees, Jana Zajec, Esther M. Steultjens, Maria W. Nijhuis-van der Sanden
ObjectiveTo investigate how reengagement in valued activities poststroke is influenced by environmental factors.Data SourcesPubMed, CINAHL, and PsycINFO were searched to June 2015 using multiple search terms for stroke, activities, disability, and home and community environments, with the following constraints: English, humans, and adults.Study SelectionStudies were included that contained data on how reengagement in valued activities of community-dwelling stroke survivors was influenced by the environment. Two reviewers independently selected the studies. The search yielded 3726 records; 39 studies were eventually included.Data ExtractionFindings were extracted from qualitative, quantitative, and mixed-design studies. Two reviewers independently assessed study quality using the Oxford Critical Appraisal Skills Programme lists and independently extracted results.Data SynthesisThematic analysis was conducted on qualitative data, revealing 9 themes related to the iterative nature of the process of reengagement and the associated environmental factors. During the process of reengagement, environmental factors interact with personal and disease-related factors in a gradual process of shaping or abandoning valued activities. The sociocultural context in this case determines what activities are valued and can be resumed by stroke survivors. Social support; activity opportunities and obligations; familiar and accessible environments; resources and reminders; and a step-by-step return facilitate stroke survivors to explore, adapt, resume, and maintain their activities. Social support is helpful at all stages of the process and particularly is important in case stroke survivors are fearful to explore their activity possibilities. The quantitative data identified largely endorsed these findings. No quantitative data were found in respect to the iterative nature of the process, familiar environments, or accessibility.ConclusionsReengagement in valued activities is a gradual process. In each stage of the process, several environmental factors play a role. During rehabilitation, professionals should pay attention to the role physical and social environmental factors have in reengagement poststroke and find ways to optimize stroke survivors' environments.



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Sacrificing the buccal branch of the facial nerve during parotidectomy

Abstract

Background

The need for and consequence of sacrificing the buccal branch of the facial nerve during parotidectomy is unknown. We sought to determine the indication, frequency, and functional outcome of buccal branch sacrifice.

Methods

We conducted a prospective study of all cases of parotidectomy at a tertiary referral center.

Results

Of 100 consecutive cases of parotidectomy, the buccal branch was sacrificed in 23 cases. This subgroup was more likely to have anterior or deep lesions (p < .001), retrograde facial nerve dissection (p = .037), and immediate postoperative upper and lower facial weakness (p = .051 and .002, respectively). However, if the temporozygomatic and cervicomandibular branches were anatomically preserved, full facial (including buccal) function was restored.

Conclusion

Deep or anterior lesions may warrant sacrifice of the buccal branch for adequate access and excision. However, this does not result in long-term impairment of facial function. © 2016 Wiley Periodicals, Inc. Head Neck, 2016



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Adverse effect of smoking on prognosis in human papillomavirus-associated oropharyngeal carcinoma

Abstract

Background

The purpose of this retrospective study was to identify prognostic factors in a cohort of patients with oropharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT).

Methods

Medical records of 142 patients treated with (chemo)radiotherapy between September 2005 and September 2011 were reviewed and the human papillomavirus (HPV) status was determined by polymerase chain reaction (PCR) analysis. Potential prognostic factors for 3-year locoregional control and overall survival (OS) were evaluated.

Results

HPV-positive patients (n = 82) had locoregional control and OS of 78% and 79%, respectively. Significant prognostic factors on multivariate analysis were smoking (p = .03) for locoregional control and OS, and comorbidity (p = .04) for OS. Further stratification was done according to smoking behavior in HPV-positive patients. Locoregional control in current smokers was 67% compared to 86% in never smokers and former smokers, respectively (p = .02).

Conclusion

Smoking was the only modifiable prognostic factor in HPV-positive patients. Therefore, active stop-smoking programs must be integrated in the routine management of patients to maximize treatment results. © 2016 Wiley Periodicals, Inc. Head Neck, 2016



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Oncologic outcomes of patients with positive margins after laser cordectomy for T1 and T2 glottic squamous cell carcinoma

Abstract

Background

The oncologic impact of surgical margins after transoral laser microsurgery (TLM) for T1 and T2 glottic carcinoma is controversial. The purpose of this study was to assess the prognostic value of margin status in terms of local control.

Methods

Records of 266 patients treated from 1990 to 2013 were evaluated. Patients with previous cordectomy or without preoperative CT scan were excluded from the study.

Results

A total 110 patients (85 T1a, 8 T1b, and 17 T2) were enrolled. A local recurrence was observed in 23 patients. Five-year disease-free survival was significantly impaired in patients with positive margins (p = .009) and in patients with deep involvement of the vocal muscle (p = .004).

Conclusion

The present study shows that invaded margin is a factor of poor local control even though laser vaporization was systematically applied after resection. In case of deep vocal fold involvement, TLM should be extended beyond the vocal muscle to improve local control. © 2016 Wiley Periodicals, Inc. Head Neck, 2016



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ReActiv8 Implantable Muscle Stimulator for Treating Chronic Lower Back Pain EU Cleared

ReActiv8

Mainstay Medical, a company based in Ireland, received European approval and is launching in Germany its ReActiv8 neurostimulator. The device is designed to address chronic lower back pain, but it works rather differently than common spinal stimulators that mask electric pain signals moving up the nerves.

Instead the ReActiv8 stimulates the multifidus muscle that runs along the spine and is key in stabilizing the joints within. The control of this muscle is often damaged due to injury to the back and spinal joints end up flexing too much, causing pain.

As the name implies, the ReActiv8 stimulator reactivates this muscle during patient controlled therapy sessions. These can be done at home with the ability to set how much stimulation is received.

The company will be initially introducing the technology in Germany with a follow-up study to be part of that process. In the U.S. we'll have to wait for a proper clinical trial.

Here's a promo video from Mainstay Medical explaining the technology behind the ReActiv8:

Product page: ReActiv8…

Via: Mainstay Medical…

The post ReActiv8 Implantable Muscle Stimulator for Treating Chronic Lower Back Pain EU Cleared appeared first on Medgadget.

Medgadget?d=yIl2AUoC8zA Medgadget?d=qj6IDK7rITs Medgadget?i=fiitfNrlhZg:0hUD2Q5YEQE:gIN9


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Molecular Imaging of Small Animals

This article reviews Molecular Imaging of Small Animals by H. Zaidi
 
Instrumentation and Applications. Editor: . , Heidelberg, NY, 2014. 760 pp. Price: $239.00. ISBN: 978-1-4939-0893-6 (hardcover).


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Imaging in Nuclear Medicine

This article reviews Imaging in Nuclear Medicine
 
Editors. A. Giussani and C. Hoeschen , Heidelberg, NY, 2013. Hardcover 237 pp. Price: $139.00. ISBN: 978-3-642-31414-8 eBook Price: $109.00. ISBN: 978-3-642-31415-5.


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Erratum: “Coverage-based treatment planning to accommodate deformable organ variations in prostate cancer treatment” [Med. Phys. 41(10), 101705 (14pp.) (2014)]



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Guidelines by the AAPM and GEC-ESTRO on the use of innovative brachytherapy devices and applications: Report of Task Group 167

Although a multicenter, Phase III, prospective, randomized trial is the gold standard for evidence-based medicine, it is rarely used in the evaluation of innovative devices because of many practical and ethical reasons. It is usually sufficient to compare the dose distributions and dose rates for determining the equivalence of the innovative treatment modality to an existing one. Thus, quantitative evaluation of the dosimetric characteristics of innovative radiotherapy devices or applications is a critical part in which physicists should be actively involved. The physicist's role, along with physician colleagues, in this process is highlighted for innovative brachytherapy devices and applications and includes evaluation of (1) dosimetric considerations for clinical implementation (including calibrations, dose calculations, and radiobiological aspects) to comply with existing societal dosimetric prerequisites for sources in routine clinical use, (2) risks and benefits from a regulatory and safety perspective, and (3) resource assessment and preparedness. Further, it is suggested that any developed calibration methods be traceable to a primary standards dosimetry laboratory (PSDL) such as the National Institute of Standards and Technology in the U.S. or to other PSDLs located elsewhere such as in Europe. Clinical users should follow standards as approved by their country's regulatory agencies that approved such a brachytherapy device. Integration of this system into the medical source calibration infrastructure of secondary standard dosimetry laboratories such as the Accredited Dosimetry Calibration Laboratories in the U.S. is encouraged before a source is introduced into widespread routine clinical use. The American Association of Physicists in Medicine and the Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology (GEC-ESTRO) have developed guidelines for the safe and consistent application of brachytherapy using innovative devices and applications. The current report covers regulatory approvals, calibration, dose calculations, radiobiological issues, and overall safety concerns that should be addressed during the commissioning stage preceding clinical use. These guidelines are based on review of requirements of the U.S. Nuclear Regulatory Commission, U.S. Department of Transportation, International Electrotechnical Commission Medical Electrical Equipment Standard 60601, U.S. Food and Drug Administration, European Commission for CE Marking (Conformité Européenne), and institutional review boards and radiation safety committees.



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A concept for classification of optimal breathing pattern for use in radiotherapy tracking, based on respiratory tumor kinematics and minimum jerk analysis

Purpose:

During radiotherapy, maintaining the patient in a relaxed and comfortable state helps ensure respiratory regularity and reproducibility, thereby supports accurate respiratory tracking/gating treatment. Criteria to evaluate respiratory naturalness, regularity, and phase robustness are therefore needed to aid for the treatment system numerically and medical observers visually. This study introduces a new concept of respiratory tumor kinematics that describes the trajectory of tumor motion with respiration, leading to the minimum jerk theory. Using this theory, this study proposes novel respiratory criteria for respiratory naturalness, regularity, and phase robustness.

Methods:

According to respiratory tumor kinematics, tumor motion follows the minimum curvature/jerk trajectory in 4D spacetime. Using this theory, the following three respiratory criteria are proposed: (1) respiratory naturalness , the residual sum of the squared difference between the normalized average free respiratory wave (single inhalation/exhalation averaged over each 10 phases) and the normalized minimum jerk theoretical respiratory wave; (2) respiratory regularity , the cumulative jerk squared cost function sampling every 0.2 s with a peak adjustment coefficient, 16; and (3) respiratory phase robustness (L Δ), a second-order partial differential in the respiratory position for regarded C j16 as the respiratory position function. To verify these respiratory criteria, values obtained from CyberKnife tracking marker log data for 15 patients were compared with regard to the correlation error between the correlation model and the imaged tumor position, as well as with the number of remodels. The C j16 growth curve was also compared between 15 patients and 15 healthy volunteers.

Results:

In the 15 patients, data with Us C j16(60 s) Us values (less respiratory naturalness) and higher C j16(60 s) values (less respiratory regularity) demonstrated more than 3 mm average/5 mm maximum correlation errors and an increased number of remodels. The data for the 15 patients and 15 volunteers demonstrated that the C j16 growth curve over 120 s from the start of sampling indicated patient-specific respiratory trends and that the distribution of L Δ clearly showed the respiratory phase shift. In 22 of 30 subjects, the degree of change in the Cj growth curve trends from 60 to 120 s was 22% ± 13% (average ± SD). In contrast, the residual data observed when C j16 > 1000 showed minimum and mean changes of 91% and 180%, respectively.

Conclusions:

The authors developed and verified novel respiratory criteria for respiratory naturalness, regularity, and phase robustness obtained using respiratory tumor kinematics and minimum jerk analysis. These criteria should be useful in monitoring respiratory trends on a real-time basis during treatment, as well as in selecting optimal breathing for tracking/gating radiation treatment and defining numerical goals for respiratory training/gating.



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Conformal image-guided microbeam radiation therapy at the ESRF biomedical beamline ID17

Purpose:

Upcoming veterinary trials in microbeam radiation therapy (MRT) demand for more advanced irradiation techniques than in preclinical research with small animals. The treatment of deep-seated tumors in cats and dogs with MRT requires sophisticated irradiation geometries from multiple ports, which impose further efforts to spare the normal tissue surrounding the target.

Methods:

This work presents the development and benchmarking of a precise patient alignment protocol for MRT at the biomedical beamline ID17 of the European Synchrotron Radiation Facility (ESRF). The positioning of the patient prior to irradiation is verified by taking x-ray projection images from different angles.

Results:

Using four external fiducial markers of 1.7  mm diameter and computed tomography-based treatment planning, a target alignment error of less than 2  mm can be achieved with an angular deviation of less than 2. Minor improvements on the protocol and the use of smaller markers indicate that even a precision better than 1  mm is technically feasible. Detailed investigations concerning the imaging dose lead to the conclusion that doses for skull radiographs lie in the same range as dose reference levels for human head radiographs. A currently used online dose monitor for MRT has been proven to give reliable results for the imaging beam.

Conclusions:

The ESRF biomedical beamline ID17 is technically ready to apply conformal image-guided MRT from multiple ports to large animals during future veterinary trials.



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Quantitative IR microscopy and spectromics open the way to 3D digital pathology

Currently, only mass-spectrometry (MS) microscopy brings a quantitative analysis of chemical contents of tissue samples in 3D. Here, the reconstruction of a 3D quantitative chemical images of a biological tissue by FTIR spectro-microscopy is reported. An automated curve-fitting method is developed to extract all intense absorption bands constituting IR spectra. This innovation benefits from three critical features: (1) the correction of raw IR spectra to make them quantitatively comparable; (2) the automated and iterative data treatment allowing to transfer the IR-absorption spectrum into a IR-band spectrum; (3) the reconstruction of an 3D IR-band matrix (x, y, z for voxel position and a 4th dimension with all IR-band parameters). Spectromics, which is a new method for exploiting spectral data for tissue metadata reconstruction, is proposed to further translate the related chemical information in 3D, as biochemical and anatomical tissue parameters. An example is given with oxidative stress distribution and the reconstruction of blood vessels in tissues. The requirements of IR microscopy instrumentation to propose 3D digital histology as a clinical routine technology is briefly discussed.

Thumbnail image of graphical abstract

The reconstruction of a 3D quantitative chemical image of a biological tissue by FTIR spectro-microscopy is reported. An automated curve-fitting method is developed to extract all intense absorption bands constituting IR spectra. Spectromics, which is a new method for exploiting spectral data for tissue metadata reconstruction, is proposed to further translate the related chemical information in 3D, as biochemical and anatomical tissue parameters. The requirements of IR microscopy instrumentation to propose 3D digital histology as a clinical routine technology is briefly discussed.



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Effect of photodynamic therapy for the treatment of halitosis in adolescents – a controlled, microbiological, clinical trial

Halitosis can exert a negative influence on the social relations of adolescents and affect one's self-image. The aim of this study was to evaluate the clinical and microbiological effect of antimicrobial photodynamic therapy (aPDT) on halitosis in adolescents. Forty-six individuals aged 12 to 19 years were randomly allocated: Group 1 – treatment with photodynamic therapy; Group 2 – treatment with a tongue scraper and Group 3 – treatment with a tongue scraper and photodynamic therapy. The count of bacterial colony-forming units per milliliter was used for the microbiological analysis. Statistical analysis involved the Kruskal–Wallis test followed by the Student–Newman–Keuls test. ANOVA was used for the determination of colony-forming units after treatment. The level of significance for all statistical tests was 5% (p < 0.05). After treatment, a statistically significant reduction in total volatile sulfur compounds was found in all groups (p < 0.001), with the largest reduction (median: 0) found in Group 3 (tongue scraper and photodynamic therapy). Moreover, a statistically significant difference was found between treatment with aPDT and a tongue scraper alone (p < 0.001). The present findings demonstrate an option for the treatment of halitosis in adolescents, with an immediate effect and without the mechanical aggression to the toungue.

Thumbnail image of graphical abstract

Halitosis can affect the social life and bring a lot of embarrassment to anyone who has this condition, especially by teenagers who are in a phase of social acceptance, it is mainly caused by degradation of organic substrates by anaerobic bacteria present in the dorsum of the tongue. This study aimed to propose a new approach to treatment for halitosis using antimicrobial photodynamic therapy, due to the high efficiency of this therapy when used in other dental treatments, and few studies submitted for this purpose. As a result it was possible to observe an immediate result in the reduction of halitosis.



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Front Cover: In situ non-destructive measurement of biofilm thickness and topology in an interferometric optical microscope (J. Biophotonics 6/2016)

Thumbnail image of graphical abstract

The cover picture shows a biofilm imaged using a new technique that utilizes white light interferometry (WLI). WLI is an established surface metrology technique that has not been previously used to image biofilms and we present the first images of biofilm growth using this nondestructive method. WLI produces a 3D topographical map of the biofilm with nanometer vertical resolution that will enable detailed studies of biofilm features and growth rates.

Further details can be found in the article by Curtis Larimer et al. on pp. 656–666.



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Contents: J. Biophotonics 6/2016



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Issue Information: J. Biophotonics 6/2016

No abstract is available for this article.



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Back Cover: Observation of an improved healing process in superficial skin wounds after irradiation with a blue-LED haemostatic device (J. Biophotonics 6/2016)

Thumbnail image of graphical abstract

Graphic composition representing thermographic images taken during EMOLED treatment of a superficial skin wound (middle), surrounded by multiphoton (top) and confocal fluorescence (bottom) images of a superficial skin wound treated with EMOLED (left) and untreated (right).

Further details can be found in the article by Riccardo Cicchi et al. on pp. 645–655.



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Implications of using whole genome sequencing to test unselected populations for high risk breast cancer genes: a modelling study

Abstract

Background

The decision to test for high risk breast cancer gene mutations is traditionally based on risk scores derived from age, family and personal cancer history. Next generation sequencing technologies such as whole genome sequencing (WGS) make wider population testing more feasible. In the UK's 100,000 Genomes Project, mutations in 16 genes including BRCA1 and BRCA2 are to be actively sought regardless of clinical presentation. The implications of deploying this approach at scale for patients and clinical services are unclear. In this study we aimed to model the effect of using WGS to test an unselected UK population for high risk BRCA1 and BRCA2 gene variants to inform the debate around approaches to secondary genomic findings.

Methods

We modelled the test performance of WGS for identifying pathogenic BRCA1 and BRCA2 mutations in an unselected hypothetical population of 100,000 UK women, using published literature to derive model input parameters. We calculated analytic and clinical validity, described potential health outcomes and highlighted current areas of uncertainty. We also performed a sensitivity analysis in which we re-ran the model 100,000 times to investigate the effect of varying input parameters.

Results

In our models WGS was predicted to identify correctly 93 pathogenic BRCA1 mutations and 151 BRCA2 mutations in 120 and 200 women respectively, resulting in an analytic sensitivity of 75.5-77.5 %. Of 244 women with identified pathogenic mutations, we estimated that 132 (range 121–198) would develop breast cancer, so could potentially be helped by intervention. We also predicted that breast cancer would occur in 41 women (range 36–62) incorrectly identified with no pathogenic mutations and in 12,460 women without BRCA1 or BRCA2 mutations. There was considerable uncertainty about the penetrance of mutations in people without a family history of disease and the appropriate threshold of absolute disease risk for clinical action, which impacts on judgements about the clinical utility of intervention.

Conclusions

This simple model demonstrates the need for robust processes to support the testing for secondary genomic findings in unselected populations that acknowledge levels of uncertainty about the clinical validity and clinical utility of testing positive for a cancer risk gene.



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Fibrinogen and base excess levels as predictive markers of the need for massive blood transfusion after blunt trauma

Abstract

Background

Assessment blood consumption and trauma-associated severe hemorrhage scores are useful for predicting the need for massive transfusion (MT) in severe trauma patients. However, fibrinogen (Fbg) and base excess (BE) levels might also be useful indicators for the need for MT. We evaluated the accuracy of prediction for MT of the scoring system vs. Fbg and BE.

Methods

The subjects of this retrospective single center observational study were patients with injury severity score ≥16 trauma, divided into a non-MT group and an MT group. We compared variables, including the scoring system (comprising vital signs and focused assessment with sonography for trauma; FAST) and Fbg between the groups. We then performed a multiple logistic regression modeling and a receiver operating characteristic analysis to clarify which value was the most useful predictive indicator for MT.

Results

There were 114 patients in the non-MT group and 39 in the MT group. The level of Fbg and BE were independent predictors of MT. The area under the curve values for Fbg and BE were 0.765 and 0.845, respectively, and the optimal cutoff values of Fbg and BE were 211 mg/dL and −1.4, respectively.

Conclusions

Fbg and BE levels can be used as an independent predictor for MT.



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Intracardiac metastasis of high-grade sarcoma of the neck causing right ventricular outflow obstruction

Description

A 71-year-old man with a medical history significant for high-grade pleomorphic undifferentiated soft tissue sarcoma of the neck and multiple lung metastases presented to the emergency room, with exertional dyspnoea. He was actively receiving palliative radiation at the time of presentation as his tumour was deemed untreatable by his oncologist. Physical examination revealed a cachectic man in mild respiratory distress, at rest. A firm, non-tender 8x8 cm mass was palpated in the suboccipital area of his neck. On auscultation, there were bilateral scattered rhonchi, but no crackles. Cardiovascular examination revealed a grade 3/6 ejection systolic murmur, heard loudest in the pulmonic area, which worsened on inspiration but did not radiate to other areas.

Chest X-ray displayed bilateral pleural effusions and multiple new metastatic lesions, as well as earlier metastatic lesions that were enlarged as compared to those seen on the patient's prior CT chest scans. The initial differential...



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Management of a patient with pericardial decompression syndrome and HOCM

A 44-year-old man, with a history of arterial hypertension, was referred with increasing shortness of breath due to a large pericardial effusion and imminent tamponade. Emergency ultrasound-guided pericardiocentesis resulted in the rapid withdrawal of 2760 cc of serous fluid. 3 hours later, the patient developed acute pulmonary oedema, which was successfully treated. Hypertrophic obstructive cardiomyopathy was later diagnosed and malignancy was excluded as a cause of the effusion. Clinicians performing pericardiocentesis need to be aware of pericardial decompression syndrome (PDS), a rare but serious complication. Although the underlying mechanisms causing PDS are not fully understood, patients with high left ventricular (LV) filling pressures are at particular risk. In other words: diastolic dysfunction of the LV is a risk factor for the occurrence of PDS.



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Sleep-dependent Memory Consolidation in the Epilepsy Monitoring Unit: a Pilot Study

Publication date: Available online 31 May 2016
Source:Clinical Neurophysiology
Author(s): Rani A. Sarkis, Javad Alam, Milena K. Pavlova, Barbara A. Dworetzky, Page B. Pennell, Robert Stickgold, Ellen J. Bubrick
ObjectiveWe sought to examine whether patients with focal epilepsy exhibit sleep dependent memory consolidation, whether memory retention rates correlated with particular aspects of sleep physiology, and how the process was affected by seizures.MethodsWe prospectively recruited patients with focal epilepsy and assessed declarative memory using a task consisting of 15 pairs of colored pictures on a 5 x 6 grid. Patients were tested 12 hours after training, once after 12 hours of wakefulness and once after 12 hours that included sleep. EMG chin electrodes were placed to enable sleep scoring. The number and density of sleep spindles were assessed using a wavelet-based algorithm.ResultsEleven patients were analyzed age 21-56 years. The percentage memory retention over 12 hours of wakefulness was 62.7%% and over 12 hours which included sleep 83.6% (p = 0.04). Performance on overnight testing correlated with the duration of slow wave sleep (SWS) (r=+0.63, p <0.05). Three patients had seizures during the day, and another 3 had nocturnal seizures. Day-time seizures did not affect retention rates, while those patients who had night time seizures had a drop in retention from an average of 92% to 60.5%.ConclusionsThere is evidence of sleep dependent memory consolidation in patients with epilepsy which mostly correlates with the amount of SWS. Our preliminary findings suggest that nocturnal seizures likely disrupt sleep dependent memory consolidation.SignificanceFindings highlightthe importance of SWS in sleep dependent memory consolidation and the adverse impact of nocturnal seizures on this process.



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Broadening substrate specificity of a chain-extending ketosynthase through a single active-site mutation

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC03501A, Communication
Annabel C Murphy, Hui Hong, Steven Vance, R. William Broadhurst, Peter Francis Leadlay
An in vitro model system based on a ketosynthase domain of the erythromycin polyketide synthase was used to probe the apparent substrate tolerance of ketosynthase domains of the mycolactone polyketide...
The content of this RSS Feed (c) The Royal Society of Chemistry


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Hepatobiliary Secretion Kinetics of Conjugated Bile Acids Measured in Pigs by 11C-Cholylsarcosine PET

The aim of this study was to develop a method for the quantification of hepatobiliary uptake and secretion of conjugated bile acids with PET and the 11C-labeled conjugated bile acid analog [N-methyl-11C]cholylsarcosine (11C-CSar). Methods: Six pigs (13 experiments) underwent dynamic 11C-CSar PET of the liver with simultaneous measurements of hepatic blood perfusion and 11C-CSar concentrations in arterial, portal, and hepatic venous blood. In 3 pigs (7 experiments), bile was collected from a catheter in the common hepatic duct. PET data were analyzed with a 2-tissue compartmental model with calculation of rate constants for the transport of 11C-CSar among blood, hepatocytes, and intra- and extrahepatic bile ducts. PET results were validated against invasive blood and bile measurements. Results: The directly measured rate of secretion of 11C-CSar into bile was equal to the rate of removal from blood at steady state. Accordingly, hepatocytes did not accumulate bile acids but simply facilitated the transport of bile acids from blood to bile against a measured concentration gradient of 4,000. The rate constant for the secretion of 11C-CSar from hepatocytes into bile in experiments with a catheter in the common hepatic duct was 25% of that in experiments without a catheter (P < 0.05); we interpreted this result to be mild cholestasis caused by the catheter. The catheter caused an increased backflux of 11C-CSar from hepatocytes to blood, and hepatic blood flow was 25% higher than in experiments without the catheter. The capacity for the overall transport of 11C-CSar from blood to bile, as quantified by intrinsic clearance, was significantly lower in experiments with the catheter than in those without the catheter (P < 0.001). PET and blood measurements correlated significantly (P < 0.05). Conclusion: The in vivo kinetics of hepatobiliary secretion of conjugated bile acids can now be determined by dynamic 11C-CSar PET.



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Czernin to Be New JNM Editor-in-Chief



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Impact of MR-Based Attenuation Correction on Neurologic PET Studies

Hybrid PET and MR scanners have become a reality in recent years, with the benefits of reduced radiation exposure, reduction of imaging time, and potential advantages in quantification. Appropriate attenuation correction remains a challenge. Biases in PET activity measurements were demonstrated using the current MR-based attenuation-correction technique. We aimed to investigate the impact of using a standard MR-based attenuation correction technique on the clinical and research utility of a PET/MR hybrid scanner for amyloid imaging. Methods: Florbetapir scans were obtained for 40 participants on a hybrid scanner with simultaneous MR acquisition. PET images were reconstructed using both MR- and CT-derived attenuation maps. Quantitative analysis was performed for both datasets to assess the impact of MR-based attenuation correction to absolute PET activity measurements as well as target-to-reference ratio (SUVR). Clinical assessment was also performed by a nuclear medicine physician to determine amyloid status based on the criteria in the Food and Drug Administration prescribing information for florbetapir. Results: MR-based attenuation correction led to underestimation of PET activity for most parts of the brain, with a small overestimation for deep brain regions. There was also an overestimation of SUVRs with cerebellar reference. SUVR measurements obtained from the 2 attenuation-correction methods were strongly correlated. Clinical assessment of amyloid status resulted in identical classification as positive or negative regardless of the attenuation-correction methods. Conclusion: MR-based attenuation correction causes biases in quantitative measurements. The biases may be accounted for by a linear model, although the spatial variation cannot be easily modeled. The quantitative differences, however, did not affect clinical assessment as positive or negative.



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CMS Part B Drug Models Challenged



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This Month in JNM



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Outstanding JNM Articles for 2015



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Intratumorally Injected 177Lu-Labeled Gold Nanoparticles: Gold Nanoseed Brachytherapy with Application for Neoadjuvant Treatment of Locally Advanced Breast Cancer

Improvements in the treatment of locally advanced breast cancer (LABC) are needed. Our objective was to study a radiation nanomedicine (gold nanoseeds) composed of 30-nm gold nanoparticles (AuNP) modified with polyethyleneglycol (PEG) chains linked to DOTA for complexing the β-particle emitter 177Lu and to panitumumab for targeting epidermal growth factor receptors (EGFR) (177Lu-T-AuNP) as a novel neoadjuvant brachytherapy for LABC. Nontargeted gold nanoseeds (177Lu-NT-AuNP) were constructed without panitumumab for comparison. Methods: 177Lu-T-AuNP or 177Lu-NT-AuNP was injected intratumorally in CD-1 athymic mice bearing subcutaneous EGFR-positive MDA-MB-468 human breast cancer tumors. Biodistribution and small-animal SPECT/CT imaging studies were performed to evaluate tumor and normal organ localization. A short-term (15 d) study was conducted to select the most effective amount of 177Lu-T-AuNP or 177Lu-NT-AuNP for treatment with long-term observation (90–120 d). Normal organ toxicities were assessed by monitoring body weight, blood cell counts, and serum alanine aminotransferase and creatinine. Radiation-absorbed doses in the tumor and normal organs were estimated by Monte Carlo N-Particle version 5.0 modeling. Results: Tumor radioactivity concentrations were high at 1 h after injection (>300–400 percentage injected dose per gram [%ID/g]) but decreased by 2–3-fold at 48 h after injection. Normal organ uptake was low (<0.5 %ID/g) except for the liver and spleen (<3 %ID/g), increasing by 2–5-fold at 48 h after injection. Treatment with 4.5 MBq (6 x 1011 AuNP) of 177Lu-T-AuNP or 177Lu-NT-AuNP arrested tumor growth over 90 d without normal organ toxicity, whereas tumors continued to grow in mice treated with unlabeled T-AuNP or 177Lu-labeled PEG polymer not linked to AuNP. Survival was prolonged up to 120 d in mice treated with 177Lu-T-AuNP or 177Lu-NT-AuNP. Radiation-absorbed doses to the tumor were 30 and 22 Gy for 177Lu-T-AuNP and 177Lu-NT-AuNP, respectively. Some tumor regions received high radiation doses (250–1,300 Gy). Normal organ doses were low (0.04–0.6 Gy). Conclusion: Gold nanoseeds injected intratumorally were highly effective for inhibiting the growth of breast cancer tumors in CD-1 athymic mice and caused no normal organ toxicity. These results are promising for their application for neoadjuvant brachytherapy of LABC. Because EGFR targeting was not required, the approach is broadly applicable to LABC with different phenotypes.



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Outstanding JNMT Articles for 2015



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Erratum



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FDA: CT and Electronic Medical Devices



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Impact of Training Method on the Robustness of the Visual Assessment of 18F-Florbetaben PET Scans: Results from a Phase-3 Study

Training for accurate image interpretation is essential for the clinical use of β-amyloid PET imaging, but the role of interpreter training and the accuracy of the algorithm for routine visual assessment of florbetaben PET scans are unclear. The aim of this study was to test the robustness of the visual assessment method for florbetaben scans, comparing efficacy readouts across different interpreters and training methods and against a histopathology standard of truth (SoT). Methods: Analysis was based on data from an international open-label, nonrandomized, multicenter phase-3 study in patients with or without dementia (ClinicalTrials.gov: NCT01020838). Florbetaben scans were assessed visually and quantitatively, and results were compared with amyloid plaque scores. For visual assessment, either in-person training (n = 3 expert interpreters) or an electronic training method (n = 5 naïve interpreters) was used. Brain samples from participants who died during the study were used to determine the histopathologic SoT using Bielschowsky silver staining (BSS) and immunohistochemistry for β-amyloid plaques. Results: Data were available from 82 patients who died and underwent postmortem histopathology. When visual assessment results were compared with BSS + immunohistochemistry as SoT, median sensitivity was 98.2% for the in-person–trained interpreters and 96.4% for the e-trained interpreters, and median specificity was 92.3% and 88.5%, respectively. Median accuracy was 95.1% and 91.5%, respectively. On the basis of BSS only as the SoT, median sensitivity was 98.1% and 96.2%, respectively; median specificity was 80.0% and 76.7%, respectively; and median accuracy was 91.5% and 86.6%, respectively. Interinterpreter agreement (Fleiss ) was excellent (0.89) for in-person–trained interpreters and very good (0.71) for e-trained interpreters. Median intrainterpreter agreement was 0.9 for both in-person–trained and e-trained interpreters. Visual and quantitative assessments were concordant in 88.9% of scans for in-person–trained interpreters and in 87.7% of scans for e-trained interpreters. Conclusion: Visual assessment of florbetaben images was robust in challenging scans from elderly end-of-life individuals. Sensitivity, specificity, and interinterpreter agreement were high, independent of expertise and training method. Visual assessment was accurate and reliable for detection of plaques using BSS and immunohistochemistry and well correlated with quantitative assessments.



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SNMMI Leadership Update: Challenges, Opportunities, and Accomplishments



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Pharmacokinetics of 99mTc-MAA- and 99mTc-HSA-Microspheres Used in Preradioembolization Dosimetry: Influence on the Liver-Lung Shunt

Perfusion scintigraphy using 99mTc-labeled albumin aggregates is mandatory before hepatic radioembolization with 90Y-microspheres. As part of a prospective trial, the intrahepatic and intrapulmonary stability of 2 albumin compounds, 99mTc-MAA (macroaggregated serum albumin [MAA]) and 99mTc-HSA (human serum albumin [HSA]), was assessed. Methods: In 24 patients with metastatic colorectal cancer, biodistribution (liver, lung) and liver–lung shunt (LLS) of both tracers (12 patients each) were assessed by sequential planar scintigraphy (1, 5, and 24 h after injection). Results: Liver uptake of both albumin compounds decreased differently. Although initial LLSs at 1 h after injection were similar in both groups, MAA-LLS increased significantly from 1 (3.9%) to 5 h (7.7%) and 24 h (9.9%) after injection, respectively. HSA-LLS did not change significantly (1 to 5 h), indicating a steady state of pulmonary and intrahepatic degradation. Conclusion: Compared with 99mTc-MAA-microspheres, 99mTc-HSA-microspheres are likely more resistant to degradation over time, allowing a reliable LLS determination even at later time points.



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Newsbriefs



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PET Imaging of Mitochondrial Complex I with 18F-BCPP-EF in the Brains of MPTP-Treated Monkeys

18F-BCPP-EF was applied to assess mitochondrial complex I (MC-I) activity in the brains of Parkinson disease model monkeys prepared by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and also presynaptic dopamine parameters. Methods: 11C-β-CFT for the dopamine transporter; 11C-3,4-dihydroxy-phenyl-L-alanine (β-11C-L-DOPA), L-6-18F-fluorodopa (18F-FDOPA), or 6-11C-methyl-m-tyrosine (11C-6MemTyr) for dopamine synthesis; or 2-tert-butyl-4-chrolo-5-{6-[2-(2-18F-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one (18F-BCPP-EF) for MC-I was intravenously injected into normal and MPTP monkeys in order to analyze their uptake in the striatum. Results: Significant reductions in presynaptic dopamine parameters and MC-I activity were detected in the striatum of MPTP monkeys. Correlations were observed between MC-I activity and dopamine transporter as well as between MC-I activity and dopamine synthesis in the striatum. The order of detectability of impaired MC-I activity was 11C-6MemTyr >> β-11C-L-DOPA > 18F-FDOPA. Conclusion: 18F-BCPP-EF has potential as a PET probe for the quantitative imaging of MC-I damage in the living brains of Parkinson disease model monkeys using PET.



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From the Literature



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Molecular Imaging and Quantitation of EphA2 Expression in Xenograft Models with 89Zr-DS-8895a

Subtype A2 of the erythropoietin-producing hepatocellular tyrosine kinase (EphA2) cell surface receptor is expressed in a range of epithelial cancers. This study evaluated the molecular imaging of EphA2 expression in vivo in mouse tumor models using SPECT/MR and PET/MR and a humanized anti-EphA2 antibody, DS-8895a. Methods: DS-8895a was labeled with 111In, 125I, and 89Zr and assessed for radiochemical purity, immunoreactivity (Lindmo analysis), antigen-binding affinity (Scatchard analysis), and serum stability in vitro. In vivo biodistribution, imaging, and pharmacokinetic studies were performed with SPECT/MR and PET/MR. A dose-escalation study was also performed to determine EphA2 receptor saturability through tissue and imaging quantitative analysis. Results: All conjugates demonstrated good serum stability and specific binding to EphA2-expressing cells in vitro. In vivo biodistribution studies showed high uptake of 111In-CHX-A''-DTPA-DS-8895a and 89Zr-Df-Bz-NCS-DS-8895a in EphA2-expressing xenograft models, with no specific uptake in normal tissues. In comparison, retention of 125I-DS-8895a in tumors was lower because of internalization of the radioconjugate and dehalogenation. These results were confirmed by SPECT/MR and PET/MR. EphA2 receptor saturation was observed at the 30 mg/kg dose. Conclusion: Molecular imaging of tumor uptake of DS-8895a allows noninvasive measurement of EphA2 expression in tumors in vivo and determination of receptor saturation. 89Zr-Df-Bz-NCS-DS-8895a is suited for human bioimaging trials on the basis of superior imaging characteristics and will inform DS-8895a dose assessment and patient response evaluation in clinical trials.



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Molecular Imaging of Ovarian Cancer

Ovarian cancer is the most lethal gynecologic malignancy and the fifth leading cause of cancer-related death in women. Over the past decade, medical imaging has played an increasingly valuable role in the diagnosis, staging, and treatment planning of the disease. In this "Focus on Molecular Imaging" review, we seek to provide a brief yet informative survey of the current state of the molecular imaging of ovarian cancer. The article is divided into sections according to modality, covering recent advances in the MR, PET, SPECT, ultrasound, and optical imaging of ovarian cancer. Although primary emphasis is given to clinical studies, preclinical investigations that are particularly innovative and promising are discussed as well. Ultimately, we are hopeful that the combination of technologic innovations, novel imaging probes, and further integration of imaging into clinical protocols will lead to significant improvements in the survival rate for ovarian cancer.



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