Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

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Σάββατο 24 Μαρτίου 2018

Prevalence and molecular characterization of Staphylococcus aureus from human stool samples.

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Prevalence and molecular characterization of Staphylococcus aureus from human stool samples.

Antimicrob Resist Infect Control. 2018;7:42

Authors: Kates AE, Thapaliya D, Smith TC, Chorazy ML

Abstract
Background: To determine the prevalence of intestinal S. aureus colonization of patients at a large teaching hospital and determine the molecular characteristics of the identified strains. The second objective of this research was to determine risk factors associated with S. aureus intestinal colonization.
Methods: A cross-sectional study of 781 specimens from inpatients and outpatients at the University of Iowa Hospitals and Clinics Clinical Microbiology Laboratory was conducted. S. aureus was identified using traditional culture methodologies. Methicillin-resistance was determined via PCR of the mecA gene. PVL PCR, spa typing, and antimicrobial sensitivity testing were also done. A nested case-control study was done on a subset of patients with all colonized patients defined as cases and non-colonized controls. Medical record abstractions were done to identify risk factors for intestinal colonization in the nested study.
Results: Out of 625 patients included in the final study, 58 were positive for S. aureus (9.3%). One isolate was positive for the PVL gene. A high number of isolates were resistant to multiple antibiotics including oxacillin (43.1%), erythromycin (51.7%), and levofloxacin (41.4%). All isolates were susceptible to vancomycin, daptomycin, linezolid, and quinupristin-dalfopristin. In the nested study, having a disease or condition of the gastrointestinal tract significantly increased the odds of intestinal colonization (OR: 1.96, 95% CI: 1.04-3.7; aOR: 13.9, 95% CI: 1.67-115.7). No other variables were significantly associated with increased odds of colonization.
Conclusions: S. aureus was identified from the stool of patients at the University of Iowa Hospitals and Clinics, with a large number of those isolates being resistant to antibiotics and may serve a reservoir for subsequent infections as well as asymptomatic transmission.

PMID: 29568515 [PubMed - in process]



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Large herbivores affect forest ecosystem functions by altering the structure of dung beetle communities

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Publication date: April 2018
Source:Acta Oecologica, Volume 88
Author(s): Taichi Iida, Masashi Soga, Shinsuke Koike
Dramatic increases in populations of large mammalian herbivores have become a major ecological issue, particularly in the northern hemisphere, due to their substantial impacts on both animal and plant communities through processes such as grazing, browsing, and trampling. However, little is known about the consequences of these population explosions on ecosystem functions. Here, we experimentally investigated how the population density of sika deer (Cervus nippon) in temperate deciduous forest areas in Japan affected the decomposition of mammal dung by dung beetles, which is a key process in forest ecosystems. We measured a range of environmental variables (e.g., vegetation cover, soil hardness) and the dung decomposition rate, measured as the amount of deer dung decomposed during one week, and sampled dung beetles at 16 study sites with three different deer densities (high/intermediate/low). We then used structural equation modeling to investigate the relationships between deer density, environmental variables, the biomass of dung beetles (classified into small or large species), and the dung decomposition rate. We found that the biomass of small species increased with increasing deer density, whereas that of large species was not related to deer density. Furthermore, the dung decomposition rate was positively related to the biomass of small species but unrelated to that of large species. Overall, our results showed that an increase in deer density affects the decomposition rate of mammal dung by changing the structure of dung beetle communities (i.e., increasing the number of small dung beetles). Such an understanding of how increases in large herbivore populations affect ecosystem functions is important for accurately evaluating the ecological consequences of their overabundance and ultimately managing their populations appropriately.



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Dose escalation for prostate stereotactic ablative radiotherapy (SABR): Late outcomes from two prospective clinical trials

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Publication date: Available online 24 March 2018
Source:Radiotherapy and Oncology
Author(s): Yasir Alayed, Patrick Cheung, Geordi Pang, Alexandre Mamedov, Laura D'Alimonte, Andrea Deabreu, Kristina Commisso, Angela Commisso, Liang Zhang, Harvey C. Quon, Hima Bindu Musunuru, Joelle Helou, D. Andrew Loblaw
PurposeOptimal prostate SABR dose-fractionation is unknown. This study compares long-term outcomes from two prospective trials.MethodsStudy1 patients had low-risk PCa and received 35 Gy/5. Study2 patients had low/intermediate-risk PCa and received 40 Gy/5. Biochemical failure (BF) was defined as nadir + 2.Results114 patients were included (study1, n = 84; study2, n = 30). Median follow-up was 9.6 years and 6.9 years. Median nPSA was 0.4 and 0.1 ng/ml. Nine patients had BF (8 in study1, 1 in study2); two were managed with ADT and four had local salvage. The BF rate was 2.5% and 12.8% at 5 and 10 years for study1 and 3.3% at 5 years for study 2. BF probability was 0% if PSA <0.4 at 4 years, and 20.5% at 10 years if PSA ≥0.4 (p = 0.02). Nine patients died, none of PCa. No patient has metastases or castrate-resistance. At 10 years, OS and CSS were 90.4% (p = 0.25) and 100%.ConclusionsDose-escalated prostate SABR was associated with lower nPSAs but no difference in BF, OS, CSS or MFS. PSA <0.4 at 4 years was a predictor of biochemical control. Half of patients with BF were successfully salvaged. Given that this is a favorable-risk cohort, longer follow-up will be needed to see if the lower nPSA translates into lower BF rates.



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Boosting the LTP-like plasticity effect of intermittent theta-burst stimulation using gamma transcranial alternating current stimulation

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Publication date: Available online 24 March 2018
Source:Brain Stimulation
Author(s): Andrea Guerra, Antonio Suppa, Matteo Bologna, Valentina D'Onofrio, Edoardo Bianchini, Peter Brown, Vincenzo Di Lazzaro, Alfredo Berardelli
BackgroundTranscranial Alternating Current Stimulation (tACS) consists in delivering electric current to the brain using an oscillatory pattern that may entrain the rhythmic activity of cortical neurons. When delivered at gamma frequency, tACS modulates motor performance and GABA-A-ergic interneuron activity.ObjectiveSince interneuronal discharges play a crucial role in brain plasticity phenomena, here we co-stimulated the primary motor cortex (M1) in healthy subjects by means of tACS during intermittent theta-burst stimulation (iTBS), a transcranial magnetic stimulation paradigm known to induce long-term potentiation (LTP)-like plasticity.MethodsWe measured and compared motor evoked potentials before and after gamma, beta and sham tACS-iTBS. While we delivered gamma-tACS, we also measured short-interval intracortical inhibition (SICI) to detect any changes in GABA-A-ergic neurotransmission.ResultsGamma, but not beta and sham tACS, significantly boosted and prolonged the iTBS-induced after-effects. Interestingly, the extent of the gamma tACS-iTBS after-effects correlated directly with SICI changes.ConclusionsOverall, our findings point to a link between gamma oscillations, interneuronal GABA-A-ergic activity and LTP-like plasticity in the human M1. Gamma tACS-iTBS co-stimulation might represent a new strategy to enhance and prolong responses to plasticity-inducing protocols, thereby lending itself to future applications in the neurorehabilitation setting.



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Environmental asbestos exposure and mesothelioma cases in Bari, Apulia region, southern Italy: a national interest site for land reclamation

Abstract

Asbestos is an environmental carcinogen, and asbestos-related diseases are a global-scale public health issue. We report three cases (one male and two females) of pleural malignant mesothelioma (PMM) caused by environmental asbestos exposure reported by the Apulia Regional Operating Centre (COR) to the National Mesothelioma Registry (ReNaM). The patients revealed no history of asbestos exposure even after detailed assessment. The environmental (neighborhood) asbestos exposure for each of the three cases was due to both the residential history of the subjects and their workplace, close to a military barracks, at a distance of between 45 and 100 m. Moreover, in addition to this new source of pollution, an asbestos cement factory was located in the urban area of Bari municipality, in the Apulia region, southern Italy. Environmental-residential/neighborhood asbestos exposure in the city of Bari, a contaminated area classified as a site of national concern for land reclamation, is discussed also with reference to the military barracks.



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Characteristics of arsenic in humic substances extracted from natural organic sediments

Abstract

The stability and dispersion of naturally occurring As have been receiving increasing attention, because As is toxic and its contamination is a widespread problem in many countries. This study investigated As fractionation and speciation in organic sediments collected from different depositional settings to elucidate the existence of stable As in humic substances. Eleven organic sediment samples were collected from marine and terrestrial alluvial regions in Hokkaido prefecture, Japan, and the chemical fraction of As and species of humic substances were identified by sequential extraction. In addition, stable As bound in organic matter was evaluated by FT-IR spectroscopy. The As fraction mainly comprised inorganic substances, especially sulfur, iron, and manganese, and terrestrial sediments (lacustrine and inland deposits) were rich in sulfides and Fe and Al (hydr)oxides. When the residual fraction was excluded, the organic fraction of As was higher in seawater sediments than in terrestrial sediments. Among humic substances, cellulose, humic acid, and hydrophilic fulvic acid were clearly associated with As accumulation, and As speciation showed that the As was of organic origin. Cellulose, an organic compound of plant origin, was abundant in As=S and As (III)=O bonds, and As accumulation was higher in sulfur-rich peat sediments, corresponding with the physiological activities of As in plants. Hydrophilic fulvic acid and humic acid in these sediments, originating from small animals and microorganisms in addition to plants, denote higher As contents and abound in As (III, V)=C and C–H, CH3 bonds even in sulfur-rich sediments. The methylated As bonds reflect the ecological transition of organisms.



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Fine particulate matter (PM 2.5 ) in a compost facility: heavy metal contaminations and health risk assessment, Tehran, Iran

Abstract

The aim of this study was to evaluate the concentration of PM2.5 particles, potential sources, and determination of health risk assessment of heavy metals in various parts of composting facilities of Tehran's Kahrizak. A total of 60 PM2.5 particle samples were collected every 3 days from January to March 2016. To analyze the heavy metals, inductively coupled plasma atomic emission spectroscopy (ICP-AES) was applied. SEM-EDX analysis indicated that metals of Al, Si, Mg, Na, Au, S, Ca, K, and Co were dominant in the structure of particles. The concentration of PM2.5 was found to be the highest in the final processing site (c), followed by primary processing site (a) and the aerated site (b). The mean concentrations of Al and Fe in all sampling sites of a, b, and c were 7.46 ± 2.73, 1.48 ± 0.59, 24.30 ± 8.23 μg/m3 and 4.97 ± 2.83, 1.33 ± 0.48, 16.48 ± 7.36, respectively. The enrichment factor order of the trace elements was as follows: Cd > As > Pb > Zn > Cu > V > Cr > Ni > Mn > Fe > Al, with the highest EF value exceeding 10,000 for Cd at the a site. For all sampling sites in composting facilities, the cancer risk was more than > 1 × 10−4 as posed by the total of five carcinogenic metals (Pb, Cr, As, Ni, and Cd), indicating that risk factors were not negligible.



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Suitable flow pattern increases the removal efficiency of nitrogen in gravity sewers: a suitable anoxic and aerobic environment in biofilms

Abstract

The sewers have the function of carbon removal, which has been proven. But if the effect of nitrogen removal can be enhanced at the same time of carbon removal, it can lay a foundation for the realization of "sewer's working as a reactor." This paper investigated the effects of shear stress and C/N ratio on nitrogen removal through biofilms on the sewer inner wall and nitrogen transfer. The main conclusions are as follows: (1) nitrogen could be partially removed in sewers after a series of reactions; (2) the anaerobic, anoxic, aerobic environment and some bacteria related to nitrogen metabolism, which exist in the biofilm, promote the nitrification and denitrification; (3) a total of 722 functional genes involved in nitrogen metabolism were detected in the biofilm (C/N ratio of 10, shear stress of 1.4 Pa), accounting for 0.67% of all genes, and the functional genes related to denitrification were dominant.

Graphical abstract



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Texas Hill Country ENT Symposium Scheduled for April 2018

Mark your calendars for the McGovern Medical School Department of Otorhinolaryngology-Head and Neck Surgery's two-day CME meeting in the Texas... Read the full article...

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Remote sensing of on-road vehicle emissions: Mechanism, applications and a case study from Hong Kong

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Publication date: June 2018
Source:Atmospheric Environment, Volume 182
Author(s): Yuhan Huang, Bruce Organ, John L. Zhou, Nic C. Surawski, Guang Hong, Edward F.C. Chan, Yat Shing Yam
Vehicle emissions are a major contributor to air pollution in cities and have serious health impacts to their inhabitants. On-road remote sensing is an effective and economic tool to monitor and control vehicle emissions. In this review, the mechanism, accuracy, advantages and limitations of remote sensing were introduced. Then the applications and major findings of remote sensing were critically reviewed. It was revealed that the emission distribution of on-road vehicles was highly skewed so that the dirtiest 10% vehicles accounted for over half of the total fleet emissions. Such findings highlighted the importance and effectiveness of using remote sensing for in situ identification of high-emitting vehicles for further inspection and maintenance programs. However, the accuracy and number of vehicles affected by screening programs were greatly dependent on the screening criteria. Remote sensing studies showed that the emissions of gasoline and diesel vehicles were significantly reduced in recent years, with the exception of NOx emissions of diesel vehicles in spite of greatly tightened automotive emission regulations. Thirdly, the experience and issues of using remote sensing for identifying high-emitting vehicles in Hong Kong (where remote sensing is a legislative instrument for enforcement purposes) were reported. That was followed by the first time ever identification and discussion of the issue of frequent false detection of diesel high-emitters using remote sensing. Finally, the challenges and future research directions of on-road remote sensing were elaborated.



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Branchial Cleft Cyst Resection: A Pediatric Patient Benefits from Texas Medical Center Expertise and the Convenience of Follow-up ENT Care in Southeast Houston

When J. Caleb Simmons, MD, started medical school, he thought he might be a pediatrician. Today as an otolaryngologist, nearly... Read the full article...

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Determination of respirable-sized crystalline silica in different ambient environments in the United Kingdom with a mobile high flow rate sampler utilising porous foams to achieve the required particle size selection

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Publication date: June 2018
Source:Atmospheric Environment, Volume 182
Author(s): Peter Stacey, Andrew Thorpe, Paul Roberts, Owen Butler
Inhalation of respirable crystalline silica (RCS) can cause diseases including silicosis and cancer. Levels of RCS close to an emission source are measured but little is known about the wider ambient exposure from industry emissions or natural sources. The aim of this work is to report the RCS concentrations obtained from a variety of ambient environments using a new mobile respirable (PM4) sampler. A mobile battery powered high flow rate (52 L min−1) sampler was developed and evaluated for particulate aerosol sampling employing foams to select the respirable particle size fraction. Sampling was conducted in the United Kingdom at site boundaries surrounding seven urban construction and demolition and five sand quarry sites. These are compared with data from twelve urban aerosol samples and from repeat measurements from a base line study at a single rural site. The 50% particle size penetration (d50) through the foam was 4.3 μm. Over 85% of predict bias values were with ±10% of the respirable convention, which is based on a log normal curve. Results for RCS from all construction and quarry activities are generally low with a 95 th percentile of 11 μg m−3. Eighty percent of results were less than the health benchmark value of 3 μg m−3 used in some states in America for ambient concentrations. The power cutting of brick and the largest demolition activities gave the highest construction levels. Measured urban background RCS levels were typically below 0.3 μg m−3 and the median RCS level, at a rural background location, was 0.02 μg m−3. These reported ambient RCS concentrations may provide useful baseline values to assess the wider impact of fugitive, RCS containing, dust emissions into the wider environment.



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Dr. Michael Byrd Named 2017 Physician of the Year at Memorial Hermann Southeast Hospital

Otolaryngologist Michael Byrd, MD, has been recognized as 2017 Physician of the Year at Memorial Hermann Southeast Hospital, a 274-bed... Read the full article...

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2017 Lone Star Rhinology Course Recap

More than 80 physicians participated in Lone Star Rhinology 2017, an intensive two-day CME program dedicated to the study of... Read the full article...

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Evaluation of cellular effects of fine particulate matter from combustion of solid fuels used for indoor heating on the Navajo Nation using a stratified oxidative stress response model

Publication date: June 2018
Source:Atmospheric Environment, Volume 182
Author(s): Ning Li, Wyatt M. Champion, Jemal Imam, Damansher Sidhu, Joseph R. Salazar, Brian J. Majestic, Lupita D. Montoya
Communities in the Navajo Nation face public health burdens caused in part by the combustion of wood and coal for indoor heating using stoves that are old or in disrepair. Wood and coal combustion emits particulate matter (PM) with aerodynamic diameter < 2.5 μm (PM2.5), which can reach deep in the lung and cause injuries. Currently, there is little information about the health effects of wood and coal combustion-derived PM2.5 on Navajo Nation residents. This study tested the hypothesis that PM2.5 generated from solid fuel combustion in stoves commonly used by Navajo residents would induce stratified oxidative stress responses ranging from activation of antioxidant defense to inflammation and cell death in mouse macrophages (RAW 264.7). PM2.5 emitted from burning Ponderosa Pine (PP) and Utah Juniper (UJ) wood and Black Mesa (BM) and Fruitland (FR) coal in a stove representative of those widely used by Navajo residents were collected, and their aqueous suspensions used for cellular exposure. PM from combustion of wood had significantly more elemental carbon (EC) (15%) and soluble Ni (0.0029%) than the samples from coal combustion (EC: 3%; Ni: 0.0019%) and was also a stronger activator of antioxidant enzyme heme oxygenase-1 (11-fold increase vs. control) than that from coal (5-fold increase). Only PM from PP-wood (12-fold) and BM-coal (3-fold) increased the release of inflammatory cytokine tumor necrosis factor alpha. Among all samples, PP-wood consistently had the strongest oxidative stress and inflammatory effects. PM components, i.e. low-volatility organic carbon, EC, Cu, Ni and K were positively correlated with the cellular responses. Results showed that, at the concentrations tested, emissions from all fuels did not have significant cytotoxicity. These findings suggest that PM2.5 emitted from combustion of wood and coal commonly used by Navajo residents may negatively impact the health of this community.

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Characteristics of atmospheric ammonia and its relationship with vehicle emissions in a megacity in China

Publication date: June 2018
Source:Atmospheric Environment, Volume 182
Author(s): Ruyu Wang, Xingnan Ye, Yuxuan Liu, Haowen Li, Xin Yang, Jianmin Chen, Wei Gao, Zi Yin
Atmospheric ammonia plays an important role in haze formation in East China. In this study, long-term measurements of NH3 concentrations were implemented at urban, suburban, and tunnel sites in Shanghai, the largest city in East China. The average monthly ammonia concentrations at the urban site varied from 3.7 ppb to 14.5 ppb and exhibited the highest levels in summer and lowest levels in winter, indicating that the biological emissions and agriculture in the surrounding areas are important contributors. The suburban NH3 levels were significantly higher in autumn compared to those at the urban site, indicating the important contribution of agricultural activities. Regardless of the season, the difference of NH3 concentrations between the tunnel and urban sites remained almost constant. On average, the tunnel NH3 level was three times higher than that of the nearby urban site, indicating strong vehicle NH3 emissions in the tunnel. The tunnel NH3 levels on weekdays were comparable to those on weekends, a result that was in agreement with the daily average traffic volume. It was estimated that the vehicle emissions contributed 12.6–24.6% of the atmospheric NH3 in the urban area and 3.8–7.5% for the whole area of Shanghai. Our results suggest that vehicle NH3 emissions should be considered, although agricultural emissions are still more important for mitigating severe haze pollution during wintertime in the megacities of China.

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Endoplasmic Reticular–Mitochondrial Contactology: Structure and Signaling Functions

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Publication date: Available online 24 March 2018
Source:Trends in Cell Biology
Author(s): György Csordás, David Weaver, György Hajnóczky
Interorganellar contacts are increasingly recognized as central to the control of cellular behavior. These contacts, which typically involve a small fraction of the endomembrane surface, are local communication hubs that resemble synapses. We propose the term contactology to denote the analysis of interorganellar contacts. Endoplasmic reticulum (ER) contacts with mitochondria were recognized several decades ago; major roles in ion and lipid transfer, signaling, and membrane dynamics have been established, while others continue to emerge. The functional diversity of ER–mitochondrial (ER-mito) contacts is mirrored in their structural heterogeneity, with subspecialization likely supported by multiple, different linker-forming protein structures. The nanoscale size of the contacts has made studying their structure, function, and dynamics difficult. This review focuses on the structure of the ER–mito contacts, methods for studying them, and the roles of contacts in Ca2+ and reactive oxygen species (ROS) signaling.



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Modulating ion channel function with antibodies and nanobodies

Catelijne Stortelers | Carolina Pinto-Espinoza | Diane Van Hoorick | Friedrich Koch-Nolte

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High performance of 3D porous graphene/lignin/sodium alginate composite for adsorption of Cd(II) and Pb(II)

Abstract

A novel adsorbent, three-dimensional porous graphene/lignin/sodium alginate nanocomposite (denoted as 3D PG/L/SA) was fabricated by hydrothermal polymerization of lignin and sodium alginate in the presence of graphene oxide (GO) in an aqueous system. Fourier transform infrared spectra, thermo-gravimetric analysis, scanning electron microscopy, and X-ray photoelectron spectroscopy were employed to characterize the morphology and structure of this novel functional PG/L/SA nanocomposite. A series of adsorption experiments for cleanup of Cd(II) and Pb(II) were conducted to investigate the effects of lignin and sodium alginate on the graphene structure. It was found that PG/L/SA showed a significant increase in adsorption capacity contrast to porous graphene (PG). The as-prepared material achieved the adsorption capacity for Cd(II) and Pb(II) of 79.88 and 226.24 mg/g, respectively. Meanwhile, the adsorption process matched well with the Langmuir isotherm model and the pseudo-second-order kinetic model. Studies were also conducted to demonstrate the applicability of the sorbent to the removal of heavy metal ions from metal smelting wastewater.



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Engineering T cells for adoptive therapy: outsmarting the tumor

Publication date: April 2018
Source:Current Opinion in Immunology, Volume 51
Author(s): Andre Kunert, Reno Debets
Adoptive transfer of T cells gene-engineered with antigen-specific receptors, whether it be chimeric antigen receptors (CARs) or T cell receptors (TCRs), has proven its feasibility and therapeutic potential in the treatment of tumors. Despite clinical successes, the majority of patients experiences no or non-sustainable clearance of solid tumors, which is attributed to local T cell evasive mechanisms. A rapidly expanding understanding of molecular and cellular events that contribute to a reduction in numbers and/or activation of intra-tumor T cells has facilitated the development of gene-engineering strategies, enabling T cells to counter immune tolerance. Here, we present an overview of gene-engineering approaches and considerations to improve tumor-selectivity and effectiveness of adoptively transferred T cells.

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Chemokines and cancer: new immune checkpoints for cancer therapy

Publication date: April 2018
Source:Current Opinion in Immunology, Volume 51
Author(s): Nathan Karin
The current review focuses on two chemokine–chemokine receptor interactions: CXCL10–CXCR3 and CCL1–CCR8. We show that CXCL10 acts on CD4+ and CD8+ T cells to enhance anti-tumor immunity, and explore the translational perspectives of these findings. As for CCR8 very recently, we identified a novel subset of CCR8+CD4+FOXp3+ regulatory T cells (Treg) that are major drivers of immune regulation. We observed that one of the four CCR8 ligands, CCL1, produced by these cells, potentiates their suppressive activity via induction of CCR8, FOXp3, CD39, Granzyme-B, and IL-10 in a positive feedback mechanism, making them master drivers of immune regulation. Collectively, this suggests blocking the CCR8–CCL1 interaction, alone or combined with other immune checkpoint inhibitors, as an approach to treat malignant diseases.

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Diffuse Gastric Ganglioneuromatosis: Novel Presentation of PTEN Hamartoma Syndrome—Case Report and Review of Gastric Ganglioneuromatous Proliferations and a Novel PTEN Gene Mutation

Gastrointestinal ganglioneuromatous proliferations are rare, most often found in the colon, and are three types: polypoid ganglioneuromas, ganglioneuromatous polyposis, and diffuse ganglioneuromatosis. We present a case of diffuse ganglioneuromatosis in the posterior gastric wall in a nine-year-old female. To our knowledge, this is the first reported case of diffuse ganglioneuromatosis located in the stomach. Only six cases of gastric ganglioneuromatous proliferations have previously been reported, two in English and none were diffuse ganglioneuromatosis. A diagnosis of diffuse ganglioneuromatosis is relevant for patient care because, unlike sporadic polypoid ganglioneuromas or ganglioneuromatous polyposis, most are syndromic. Diffuse ganglioneuromatosis is commonly associated with neurofibromatosis type 1, multiple endocrine neoplasia type 2b, and Cowden Syndrome, one of the phenotypes of PTEN hamartoma tumor syndrome. The patient had the noted gastric diffuse ganglioneuromatosis, as well as other major and minor criteria for Cowden syndrome. Genetic testing revealed a novel frameshift mutation in the PTEN gene in the patient, her father, paternal aunt, and the aunt's son who is a paternal first cousin of the patient.

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Effect of Cathodal Transcranial Direct Current Stimulation on a Child with Involuntary Movement after Hypoxic Encephalopathy

The aim of the study was to investigate the effect of cathodal transcranial direct current stimulation to the supplementary motor area to inhibit involuntary movements of a child. An 8-year-old boy who developed hypoxic encephalopathy after asphyxia at the age of 2 had difficulty in remaining standing without support because of involuntary movements. He was instructed to remain standing with his plastic ankle-foot orthosis for 10 s at three time points by leaning forward with his forearms on a desk. He received cathodal or sham transcranial direct current stimulation to the supplementary motor area at 1 mA for 10 min. Involuntary movements during standing were measured using an accelerometer attached to his forehead. The low-frequency power of involuntary movements during cathodal transcranial direct current stimulation significantly decreased compared with that during sham stimulation. No adverse effects were observed. Involuntary movement reduction by cathodal stimulation to supplementary motor areas suggests that stimulations modulated the corticobasal ganglia motor circuit. Cathodal stimulation to supplementary motor areas may be effective for reducing involuntary movements and may be safely applied to children with movement disorders.

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LEC1 (NF-YB9) directly interacts with LEC2 to control gene expression in seed

Publication date: Available online 24 March 2018
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): C. Boulard, J. Thévenin, O. Tranquet, V. Laporte, L. Lepiniec, B. Dubreucq
The LAFL transcription factors LEC2, ABI3, FUS3 and LEC1 are master regulators of seed development. LEC2, ABI3 and FUS3 are closely related proteins that contain a B3-type DNA binding domain. We have previously shown that LEC1 (a NF-YB type protein) can increase LEC2 and ABI3 but not FUS3 activity. Interestingly, FUS3, LEC2 and ABI3 contain a B2 domain, the function of which remains elusive. We showed that LEC1 and LEC2 partially co-localised in the nucleus of developing embryos. By comparing protein sequences from various species, we identified within the B2 domains a set of highly conserved residues (i.e. TKxxARxxRxxAxxR). This domain directly interacts with LEC1 in yeast. Mutations of the conserved amino acids of the motif in the B2 domain abolished this interaction both in yeast and in moss protoplasts and did not alter the nuclear localisation of LEC2 in planta. Conversely, the mutations of key amino acids for the function of LEC1 in planta (D86K) prevented the interaction with LEC2. These results provide molecular evidences for the binding of LEC1 to B2-domain containing transcription factors, to form heteromers, involved in the control of gene expression.



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Quantitative structure–activity relationship for the partition coefficient of hydrophobic compounds between silicone oil and air

Abstract

The silicon oil-air partition coefficients (KSiO/A) of hydrophobic compounds are vital parameters for applying silicone oil as non-aqueous-phase liquid in partitioning bioreactors. Due to the limited number of KSiO/A values determined by experiment for hydrophobic compounds, there is an urgent need to model the KSiO/A values for unknown chemicals. In the present study, we developed a universal quantitative structure–activity relationship (QSAR) model using a sequential approach with macro-constitutional and micromolecular descriptors for silicone oil-air partition coefficients (KSiO/A) of hydrophobic compounds with large structural variance. The geometry optimization and vibrational frequencies of each chemical were calculated using the hybrid density functional theory at the B3LYP/6-311G** level. Several quantum chemical parameters that reflect various intermolecular interactions as well as hydrophobicity were selected to develop QSAR model. The result indicates that a regression model derived from logKSiO/A, the number of non-hydrogen atoms (#nonHatoms) and energy gap of ELUMO and EHOMO (ELUMOEHOMO) could explain the partitioning mechanism of hydrophobic compounds between silicone oil and air. The correlation coefficient R2 of the model is 0.922, and the internal and external validation coefficient, Q2LOO and Q2ext , are 0.91 and 0.89 respectively, implying that the model has satisfactory goodness-of-fit, robustness, and predictive ability and thus provides a robust predictive tool to estimate the logKSiO/A values for chemicals in application domain. The applicability domain of the model was visualized by the Williams plot.



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“Tumulus” stabilization of a total ossicular replacement prosthesis

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Publication date: Available online 24 March 2018
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): T. Mom, C. Caburet, N. Saroul, L. Gilain, M. Gersdorff
Functional failure of total ossicular replacement prostheses (TORP) is often due to secondary displacement, ranging from simple subluxation to prosthesis extrusion following recurrence of severe tympanic membrane retraction. Several surgical techniques have been proposed to stabilize a TORP, mostly using superimposed non-organic or resorbable heterologous materials. We describe a simple so-called "tumulus" surgical technique that limits prosthesis displacement and extrusion, regardless of the type of TORP, by using a few fragments of autologous cartilage that are always available and perfectly tolerated at no cost. Review of 31 cases treated by this technique did not reveal any cases of prosthesis displacement and only one case (3.2%) of prosthesis extrusion with audiometric results comparable to the best results reported in the literature.



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In-clinic secondary tracheoesophageal puncture and voice prosthesis placement in laryngectomees

Publication date: Available online 24 March 2018
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): E. Ricci, G. Riva, F. Dagna, E. Seglie, A.L. Cavalot
Secondary tracheoesophageal puncture (TEP) with voice prosthesis placement represents one of the possibility to restore vocal function after total laryngectomy. However, some patients have comorbidities that contraindicate general anesthesia. In our department, an in-clinic TEP procedure for retrograde voice prosthesis placement was developed. It allows the immediate placement of the prosthesis and the avoidance of the use of dilators. We described our technique with advantages and pitfalls. The Provox Vega Puncture Set was used. Our technique for in-clinic secondary TEP without general anesthesia or target controlled infusion was a safe and effective procedure. It allows the use of the traditional TEP set, with possibility of voice prosthesis placement after previous TEP closure.



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Discordance entre SaO2 – PaO2 : ne pas oublier les hémoglobinopathies

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Publication date: Available online 24 March 2018
Source:Revue des Maladies Respiratoires
Author(s): E. Virot, S. Hirschi, M. Oswald, T. Degot, M. Canuet, A.-C. Galoisy, L. Kiger, S. Pissard, R. Kessler
IntroductionPlusieurs paramètres clinico-biologiques permettent d'estimer la quantité d'oxygène disponible pour l'organisme. La saturation en oxygène mesurée à l'oxymètre de pouls (SpO2), la saturation artérielle en oxygène (SaO2) et la pression partielle artérielle en oxygène (PaO2) mesurées par gazométrie sont les plus utilisées.ObservationNous rapportons le cas d'une patiente hospitalisée pour bilan d'insuffisance respiratoire découverte dans un contexte de dyspnée d'effort chronique. La SpO2 était diminuée tout comme la SaO2 mesurée par gazométrie malgré une PaO2 dans les normes. La dissociation entre les valeurs de PaO2 et de SaO2 nous a permis d'aboutir au diagnostic d'hémoglobinopathie (hémoglobine Bassett).ConclusionLe diagnostic d'hémoglobinopathie est à évoquer devant une désaturation en oxygène avec bilan respiratoire et cardiologique sans anomalie. Il ne semble pas y avoir d'argument pour proposer à ces patients une oxygénothérapie en condition stable.IntroductionDifferent clinico-biological parameters are used to estimate the amount of oxygen available for the organism. Oxygen saturation measured with pulse oxymetry (SpO2), oxygen saturation of arterial blood (SaO2) and oxygen partial pressure of the arterial blood (PaO2) are the most commonly used.Case reportWe report the case of a patient admitted for investigation of respiratory failure in the context of chronic dyspnea of effort. SpO2 and SaO2 were decreased, though the PaO2 was normal. This mismatch between oxygen saturation and PaO2 led to the diagnosis of hemoglobinopathy (Bassett hemoglobin).ConclusionThe diagnosis of hemoglobinopathy should be considered in cases of oxygen desaturation with normal respiratory and cardiac investigations. There are no reasons to prescribe long-term oxygen to these patients.



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Monitoring cellular redox state under hypoxia using a fluorescent sensor based on eel fluorescent protein

Publication date: Available online 23 March 2018
Source:Free Radical Biology and Medicine
Author(s): Hanyang Hu, Aoxue Wang, Li Huang, Yejun Zou, Yanfang Gu, Xianjun Chen, Yuzheng Zhao, Yi Yang
Genetically encoded fluorescent sensors are widely used to visualize secondary messengers, metabolites and dynamic events in living cells. However, almost all of these sensors are based on Aequorea GFPs or GFP-like proteins, which do not correctly maturate and fluoresce under hypoxia or anoxic conditions, greatly limiting their application in biomedical research. Herein, we provide a novel strategy for design of sensors and report a series of thiol redox-sensitive sensor based on a recently discovered oxygen-independent fluorescent protein UnaG from Japanese eel. These redox sensors have large dynamic range, rapid responsiveness, a flexible "switch", and pH-independence, are particularly compatible with hypoxia conditions, and therefore represent a substantial improvement for live-cell redox measurement. We further demonstrated the versatility of these redox sensors, by simultaneously monitoring redox changes and hypoxia state in living cells, thereby proving its capability as a powerful and flexible tool for indexing multidimensional metabolism data in the context of physiological stressors and pathological states. These redox sensors are not only the first case of UnaG-based functional sensors, but also the first case of functional sensors based on non GFP-like proteins. Based on this strategy, more oxygen-independent biosensors could be developed, hence, provide new opportunities for bioimaging.

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Intron-retained transcripts of the spinal muscular atrophy genes, SMN1 and SMN2

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Publication date: Available online 23 March 2018
Source:Brain and Development
Author(s): Nur Imma Fatimah Harahap, Emma Tabe Eko Niba, Mawaddah Ar Rochmah, Yogik Onky Silvana Wijaya, Toshio Saito, Kayoko Saito, Hiroyuki Awano, Ichiro Morioka, Kazumoto Iijima, Poh San Lai, Masafumi Matsuo, Hisahide Nishio, Masakazu Shinohara
BackgroundThe SMN genes, SMN1 and SMN2, are highly homologous genes which are related to the development or clinical severity of spinal muscular atrophy. Some alternative splicing patterns of the SMN genes have been well documented. In 2007, an SMN1 transcript with a full sequence of intron 3 was reported as the first intron-retained SMN transcript.MethodsIntron-retained SMN transcripts in various cells and tissues were studied using reverse transcription (RT)-PCR. HeLa cells were used for subcellular localization of the transcripts and protein expression analysis with Western blotting.ResultsTwo intron-retained SMN transcripts were detected, which contain full sequences of intron 2b or intron 3. These transcripts were produced from SMN1 and SMN2, and ubiquitously expressed in human cells and tissues. Western blotting analysis showed no proteins derived from the intron-retained transcripts. Fractionation analysis showed that these intron-retained transcripts were localized mainly in the nucleus. Contrary to our expectation, the intron-retained transcript levels decreased during the treatment of cycloheximide, an inhibitor of nonsense-mediated decay (NMD), suggesting that they were not targets of NMD.ConclusionIntron 2b-retained SMN transcript and intron3-retained SMN transcript were ubiquitously expressed in human cells and tissues. The intron-retained transcripts were mainly localized in the nucleus and decreased through non-NMD pathway.



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Neuroplasticity: the Other Side of the Coin

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Publication date: Available online 23 March 2018
Source:Pediatric Neurology
Author(s): Ria Pal, Jorina Elbers




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The art of imagination

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Publication date: Available online 24 March 2018
Source:Cortex
Author(s): Susan Aldworth
Scientific studies of visual imagery, well represented in this Special Issue, tend to focus on our capacity to 'see' things in the mind's eye in their absence. Yet the visual imagination, as described and used by practising artists, is a much richer and more complex ability, cultivated by artistic training, strongly linked to personality and emotion and often exercised in the act of creation rather than a passive 'visualising'. This Viewpoint complements the scientific studies represented here by reporting the thoughts and views of a number of artists on their own experience of visual imagination and is illustrated by a series of works that exemplify the output of the author's.



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Discriminability of numerosity-evoked fMRI activity patterns in human intra-parietal cortex reflects behavioral numerical acuity

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Publication date: Available online 23 March 2018
Source:Cortex
Author(s): G. Lasne, M. Piazza, S. Dehaene, A. Kleinschmidt, E. Eger
Areas of the primate intraparietal cortex have been identified as an important substrate of numerical cognition. In human fMRI studies, activity patterns in these and other areas have allowed researchers to read out the numerosity a subject is viewing, but the relation of such decodable information with behavioral numerical proficiency remains unknown.Here, we estimated the precision of behavioral numerosity discrimination (internal Weber fraction) in twelve adult subjects based on psychophysical testing in a delayed numerosity comparison task outside the scanner. FMRI data were then recorded during a similar task, to obtain the accuracy with which the same sample numerosities could be read out from evoked brain activity patterns, as a measure of the precision of the neuronal representation. Sample numerosities were decodable in both early visual and intra-parietal cortex with approximately equal accuracy on average. In parietal cortex, smaller numerosities were better discriminated than larger numerosities of the same ratio, paralleling smaller behavioral Weber fractions for smaller numerosities. Furthermore, in parietal but not early visual cortex, fMRI decoding performance was correlated with behavioral number discrimination acuity across subjects (subjects with a more precise behavioral Weber fraction measured prior to scanning showed greater discriminability of fMRI activity patterns in intraparietal cortex, and more specifically, the right LIP region).These results suggest a crucial role for intra-parietal cortex in supporting a numerical representation which is explicitly read out for numerical decisions and behavior.



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Characterization of rat primary trigeminal satellite glial cells and associated extracellular vesicles under normal and inflammatory conditions

Publication date: Available online 23 March 2018
Source:Journal of Proteomics
Author(s): Hye Sook Han Vinterhøj, Allan Stensballe, Meg Duroux, Parisa Gazerani
Satellite glial cells (SGCs) in sensory ganglia contribute to the pathogenesis of chronic pain, potentially through mediating extracellular or paracrine signaling. Recently, extracellular vesicles (EVs) in the form of exosomes have been found to play an important role in cell-cell communication. However, their release from SGCs and extent in modulating pain remain unknown. An in vitro cell platform using fresh primary SGCs was used to characterize the shed vesicles by size and proteomic profiling following activation of SGCs by lipopolysaccharide (LPS), simulating neurogenic inflammation in vivo. Results demonstrated that SGCs shed vesicles in the size range of exosomes (>150 nm) but with altered protein expression upon LPS-activation. Proteomic profiling of SGCs-shed EVs showed that a number of proteins were differentially regulated upon LPS stimulation such as junction plakoglobin and myosin 9 that are proposed as novel biomarkers of SGCs activation under inflammatory conditions. Findings from this study highlight the utility of using fresh primary SGC cultures as a model to further investigate EVs under normal and inflammatory conditions.SignificanceThis study demonstrated that1. Primary SGCs do express the phenotypic marker.2. One ng/mL LPS is sufficient enough to activate SGCs in vitro without any form of toxicity.3. SGCs shed a population of extracellular vesicles in the exosomal size range and the identified proteins have a potential effect on SGCs morphology upon activation by LPS.4. Myosin-9 was identified as a possible novel marker of LPS-activated SGCs in fresh primary SGCs that can be applicable for inflammatory pain conditions.



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Evaluation of some effects on plant metabolism through proteins and enzymes in transgenic and non-transgenic soybeans after cultivation with silver nanoparticles

Publication date: Available online 24 March 2018
Source:Journal of Proteomics
Author(s): Rodrigo Moretto Galazzi, Cícero Alves Lopes Júnior, Tatiani Breneli de Lima, Fábio Cesar Gozzo, Marco Aurélio Zezzi Arruda
To evaluate the effects of silver nanoparticles (AgNP) exposition, transgenic (through gene cp4EPSPS) and non-isogenic non-transgenic soybeans were cultivated in the presence or absence of AgNP or silver nitrate (AgNO3) at 50 mg/kg of silver. Physiological aspects of the plants including mass production and development of roots, proteomics such as protein amount and differential proteins, enzymes and lipid peroxidation were determined after exposition. The mass production of non-transgenic plants treated with AgNP or AgNO3 was decreased by 25 and 19%, respectively, on their mass based, while for transgenic soybean this effect was observed for AgNP cultivation only. Fifty-nine proteins were identified from the differentially abundant spots by two-dimensional difference gel electrophoresis and nano-electrospray ionization liquid chromatography coupled tandem mass spectrometry. Identified species as ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO), ATP synthase, superoxide dismutase (SOD), related to plant metabolism were less abundant for the cultivation with either AgNP and AgNO3 than the control. Finally, this work demonstrated significant correlation as evidenced by changes in lipid peroxidation content and catalase activity, which were a result of exposure to either AgNP or AgNO3 cultivations. Further, necrotic areas in the basal part of the stems and damage or chlorotic areas were found in the leaves.SignificanceOnce nanoparticles have been employed for several applications in recent years and they can be released in the environmental matrices, this study highlights proteomic and enzymatic alterations in transgenic and non-transgenic soybeans, an important crop, after cultivation with silver nanoparticles. Such strategy employing proteomic and enzymatic approaches to evaluate soybeans exposed to silver nanoparticles has not yet been reported. Therefore, the results obtained in this study can.

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A matter of ingredients

Publication date: Available online 24 March 2018
Source:Journal of Proteomics
Author(s): Ingrid Miller, Elisabetta Gianazza, Ivano Eberini

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Molecular signatures of medullary thyroid carcinoma by matrix-assisted laser desorption/ionisation mass spectrometry imaging

Publication date: Available online 24 March 2018
Source:Journal of Proteomics
Author(s): Andrew Smith, Manuel Galli, Isabella Piga, Vanna Denti, Martina Stella, Clizia Chinello, Nicola Fusco, Davide Leni, Marco Manzoni, Gaia Roversi, Mattia Garancini, Angela Ida Pincelli, Vincenzo Cimino, Giulia Capitoli, Fulvio Magni, Fabio Pagni
The main aim of the study was to assess the feasibility of matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) in the pathological investigation of Medullary Thyroid Carcinoma (MTC).Formalin-fixed paraffin-embedded (FFPE) samples from seven MTC patients were analysed by MALDI-MSI in order to detect proteomic alterations within tumour lesions and to define the molecular profiles of specific findings, such as amyloid deposition and C cell hyperplasia (CCH). nLC-ESI MS/MS was employed for the identification of amyloid components and to select alternative proteomic markers of MTC pathogenesis.Results highlighted the potential of MALDI-MSI to confirm the classic immunohistochemical methods employed for the diagnosis of MTC, with good sensitivity and specificity. Intratumoural amyloid components were also detected and identified, and were characterised by calcitonin, apolipoprotein E, apolipoprotein IV, and vitronectin. The tryptic peptide profiles representative of MTC and CCH were distinctly different, with four alternative markers for MTC being detected; K1C18, and three histones (H2A, H3C, and H4). Finally, a further 115 proteins were identified through the nLC-ESI-MS/MS analysis alone, with moesin, veriscan, and lumican being selected due to their potential involvement in MTC pathogenesis.This approach represents a complimentary strategy that could be employed to detect new proteomic markers of MTC.Statement of significanceMedullary thyroid carcinoma (MTC) is a rare endocrine malignancy that originates from the parafollicular C-cells of the thyroid. The diagnosis is typically established using a combination of fine-needle aspiration biopsy (FNAB) of a suspicious nodule along with the demonstrable elevation of serum biomarkers, such as calcitonin and carcinoembryonic antigen (CEA). Unfortunately, this combination is often associated with a high degree of false-positive results and this can lead to misdiagnosis and avoidable total thyroidectomy.The current study presents the potential role of MALDI-MSI in the search for new proteomic markers of MTC with diagnostic and prognostic significance. MALDI-MSI was capable of detecting the classic immunohistochemical markers employed for the diagnosis of MTC, with good sensitivity and specificity. Furthermore, the complementary combination of MALDI-MSI and nLC-ESI-MS/MS analysis, using a single tissue section, enabled further potential markers to be identified and their spatial localisation visualised within tumoural regions. Such findings could be a valuable starting point for further studies focused on confirming the data presented here using thyroid FNABs, with the final objective being to provide complimentary assistance for the detection of MTC during the pre-operative phase.



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Loss of PD-L1 (SP-142) expression characterizes renal vein tumor thrombus microenvironment in clear cell renal cell carcinoma

Publication date: Available online 24 March 2018
Source:Annals of Diagnostic Pathology
Author(s): José I. López, Rafael Pulido, Charles H. Lawrie, Javier C. Angulo
Immunotherapy is a promising tool in the treatment of patients with advancer renal cancer, in particular the blockage of immune checkpoint inhibitors. Clear cell renal cell carcinoma is an example of heterogeneous neoplasm and this particular characteristic is responsible of many therapeutic failures so far. Since variations in the local microenvironment across a tumor may conditionate the effect of this new therapy, a deeper knowledge of this issue seems advisable for any treatment success. We have analyzed the PD-L1 (SP142) expression in three different areas in the tumor and in two areas in the renal vein/caval thrombi in 39 advanced clear cell renal cell carcinomas to determine the extent and potential clinical significance of this regional variability. A statistically significant decrease in PD-L1 expression has been detected between the main tumor and its thrombus faction (p < 0.0001). Also, we have observed a high variability in the PD-L1 positivity across the three different areas of the main tumor tested, with only three cases being uniformly positive in all tested areas. In conclusion, PD-L1 expression display a highly variable distribution in clear cell renal cell carcinomas and this particularity should be kept in mind when selecting the tumor samples to be tested for immunotherapy.



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Editorial Board

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Publication date: April 2018
Source:Microbiological Research, Volume 209





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Subterranean infestation by Holotrichia parallela larvae is associated with changes in the peanut (Arachis hypogaea L.) rhizosphere microbiome

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Publication date: Available online 23 March 2018
Source:Microbiological Research
Author(s): Li-Li Geng, Gao-Xiang Shao, Ben Raymond, Mei-Ling Wang, Xiao-Xiao Sun, Chang-Long Shu, Jie Zhang
Rhizosphere microorganisms contribute to the health and development of crops and these beneficial microbes are recruited to the root-zone when plants experience biotic/abiotic stress. The subterranean pests Holotrichia parallela cause severe crop loss in peanut (Arachis hypogaea L.) fields. Hypothesizing that infestation by H. parallela larva may influence the composition of rhizosphere microbial communities, deep sequencing of V3 and V4 hypervariable regions of 16S rRNA gene was used to characterize the rhizosphere bacteria of infested and uninfested peanuts. A total of 2,673,656 reads were generated and an average of 2,558 OTUs were obtained for each sample. Comparisons of rhizosphere bacterial community structure of peanuts with those infested by H. parallela larva revealed that the relative abundance of Proteobacteria and Bacteroidetes increased, while that of Actinobacteria decreased in the rhizosphere with infestation. A significant shift in bacterial communities was observed within 24 h after infestation by principal coordinate analysis. For the 332 genera identified in 24 h treatment, infestation of white grubs led to the significant changes of abundance of 67 genera. An increase in the Pseudomonas genus of infested-samples for 24 h was verified by real-time qPCR. Our results indicate H. parallela larvae infestation can quickly leads to the change of peanut rhizosphere microbiome and enrichment of specific bacterial species. But the effects were not persistent. This study provides the insight into the function of rhizosphere microbiome in the interaction between subterranean pests and crops.



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Neural synchronization deficits linked to cortical hyper-excitability and auditory hypersensitivity in fragile X syndrome.

https:--s3-service-broker-live-ddda94b7- https:--www.ncbi.nlm.nih.gov-corehtml-pm Related Articles

Neural synchronization deficits linked to cortical hyper-excitability and auditory hypersensitivity in fragile X syndrome.

Mol Autism. 2017;8:22

Authors: Ethridge LE, White SP, Mosconi MW, Wang J, Pedapati EV, Erickson CA, Byerly MJ, Sweeney JA

Abstract
BACKGROUND: Studies in the fmr1 KO mouse demonstrate hyper-excitability and increased high-frequency neuronal activity in sensory cortex. These abnormalities may contribute to prominent and distressing sensory hypersensitivities in patients with fragile X syndrome (FXS). The current study investigated functional properties of auditory cortex using a sensory entrainment task in FXS.
METHODS: EEG recordings were obtained from 17 adolescents and adults with FXS and 17 age- and sex-matched healthy controls. Participants heard an auditory chirp stimulus generated using a 1000-Hz tone that was amplitude modulated by a sinusoid linearly increasing in frequency from 0-100 Hz over 2 s.
RESULTS: Single trial time-frequency analyses revealed decreased gamma band phase-locking to the chirp stimulus in FXS, which was strongly coupled with broadband increases in gamma power. Abnormalities in gamma phase-locking and power were also associated with theta-gamma amplitude-amplitude coupling during the pre-stimulus period and with parent reports of heightened sensory sensitivities and social communication deficits.
CONCLUSIONS: This represents the first demonstration of neural entrainment alterations in FXS patients and suggests that fast-spiking interneurons regulating synchronous high-frequency neural activity have reduced functionality. This reduced ability to synchronize high-frequency neural activity was related to the total power of background gamma band activity. These observations extend findings from fmr1 KO models of FXS, characterize a core pathophysiological aspect of FXS, and may provide a translational biomarker strategy for evaluating promising therapeutics.

PMID: 28596820 [PubMed - indexed for MEDLINE]



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Phylogenetic relationship of a fossil macaque (Macaca cf. robusta) from the Korean Peninsula to extant species of macaques based on zygomaxillary morphology

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Publication date: June 2018
Source:Journal of Human Evolution, Volume 119
Author(s): Tsuyoshi Ito, Yung-jo Lee, Takeshi D. Nishimura, Mikiko Tanaka, Jong-yoon Woo, Masanaru Takai
Little is known about the biogeographical and evolutionary histories of macaques (Macaca spp.) in East Asia because the phylogenetic positions of fossil species remain unclear. Here we examined the zygomaxillary remains of a fossil macaque (M. cf. robusta) from the Durubong Cave Complex, South Korea, that dates back to the late Middle to Late Pleistocene, to infer its phylogenetic relationship to extant species. We took 195 fixed- and semi-landmarks from the zygomaxillary regions of the fossil specimen and from 147 specimens belonging to 14 extant species. We then conducted a generalized Procrustes analysis followed by a multivariate statistical analysis to evaluate the phenetic affinities of the fossil to the extant species and reconstructed the most parsimonious phylogenetic tree using a phylogenetic morphometric approach. We found that the fossil was most similar to Macaca fuscata (Japanese macaque) in the zygomaxillary morphospace although it was at the limit of the range of variation for this species. The second closest in the morphospace was the continental Macaca mulatta (rhesus macaque). Parsimonious reconstruction confirmed that the fossil was most closely related to M. fuscata, even after controlling for the effects of allometry. These findings suggest that in the late Middle to Late Pleistocene, close relatives of M. fuscata that looked like the extant species were distributed on the Korean Peninsula, where no species of macaques are found today. Thus, some morphological characteristics of M. fuscata may have developed before its ancestor dispersed into the Japanese archipelago.



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Toxicity evaluation of 4,4′-di-CDPS and 4,4′-di-CDE on green algae Scenedesmus obliquus : growth inhibition, change in pigment content, and oxidative stress

Abstract

Polychlorinated diphenyl sulfides and polychlorinated diphenyl ethers are two types of dioxin-like pollutants, which are prevalent in aquatic environments. However, to date, limited information is available regarding their toxicity to green algae. In this study, growth inhibition, effect on pigment content, and oxidative stress potentials of 4,4′-di-CDPS and 4,4′-di-CDE on green algae Scenedesmus obliquus were investigated. The results indicate that the EC50 values of 4,4′-di-CDPS after 24, 48, 72, and 96 h of exposure were 1.736, 1.172, 0.994, and 0.820 mg/L, while the corresponding values for 4,4′-di-CDE were 0.697, 1.087, 0.833, and 0.327 mg/L. As compared to the control group, most of the measured pigment content in algal cells significantly decreased after 96-h exposure to these two chemicals, suggesting their suppressive capability on the photosynthesis process in algal cells. Additionally, oxidative stress occurred as demonstrated by the significantly inhibited activities of the antioxidant enzymes (total superoxide dismutase (T-SOD), catalase (CAT), and glutathione peroxidase (GPx)), and high increases in malondialdehyde (MDA) content in all 4,4′-di-CDE-treated groups and some moderate-dose and high-dose treatments with 4,4′-di-CDPS. Acute toxicity tests and biochemical analysis showed that 4,4′-di-CDE was more toxic than 4,4′-di-CDPS on S. obliquus.



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Abass Alavi: A giant in Nuclear Medicine turns 80 and is still going strong!

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Abass Alavi: A giant in Nuclear Medicine turns 80 and is still going strong!

Hell J Nucl Med. 2017 Mar 20;:

Authors:

Abstract
Little was written in the stars above the city of Tabriz in Iran on March 15, 1938 indicating that a newborn citizen would immigrate to America and become a master of modern mo-lecular imaging with a sharp focus on 18F-FDG PET to the benefit of millions of people around the world. Nonetheless, that's what happened. A gifted boy who lost his farther early and grew up with his uneducated mother and two siblings in humble circumstances to become a premium student, nationally no. 1 in mathematics while in school, and later a medical doctor before he decided in 1966 to seek his fortune in the US. Here he started education in internal medicine, hematology and oncology, albeit found this unsatisfactory due to tradition and rote learning. He turned to radiology and nuclear medicine in a search for new knowledge and better methods to benefit patients and society, an attitude he had been taught from early childhood. The very same attitude has been the beacon for Alavi's activities throughout his professional life, instead of money, power and social status. He married into a highly academic environment. His wife, Jane Bradley Alavi, was a specialist in hematology and oncology and is still his life partner. They never had children, so their many students and the numerous medical doctors, physicists and other academics they coached became their family. While Jane Alavi retired some years ago, Abass Alavi continued his professional career and has no plans of retirement when he turns 80 on March 15, 2018 after 46 years in nuclear medicine at the University of Pennsylvania and with an admirable network of pupils and colleagues across all five continents. On the contrary, Alavi has probably never been busier, his scientific work goes on, his multinational scientific "family" steadily increases all over the world as does the appli-cation of PET in the shape of PET/CT or PET/MRI. Alavi's contributions to the scientific literature has more than doubled within the last decade making him one of the most cited researchers at the University of Pennsylvania with a production of more than 1,200 articles, a similar number of published abstracts and close to 58,000 citations according to Google Scholar, of which about 20,000 since 2012 when he was 74. This is just part of an amazing story. Having turned to nuclear medicine in 1971, Alavi entered into one of the World's most ingenious and productive medical research en-vironments comprising collaboration of experts in nuclear medicine (David Kuhl) and neurology (Martin Reivich) at Penn, and in physiology and pharmacology (Louis Sokoloff) at the NIH, all of whom contributed significantly to the development of PET. Focus was on cerebral research with beta-emitting 14C-labeled deoxyglucose for mapping regional cerebral glucose metabolism by means of autoradiography. Alavi became a junior member of this collaboration in which the idea of labeling deoxyglucose with a gamma-emitting isotope arose to allow in vivo examination of the normal and diseased human brain. They contacted Alfred Wolf at Brookhaven National Laboratory who had an interest in synthesizing positron-emitting compounds. He suggested labeling instead with 18F-FDG and in 1975 Wolf's group including Tatsuo Ido and Joanna Fowler succeeded in synthesizing 18F-FDG. In the meantime, investigators at Penn had developed high energy collimators for the Mark IV scanner to allow imaging with 18F-FDG, so in August 1976, two normal volunteers were the first to receive a dose of 18F-FDG for tomographic brain imaging showing concentration of 18F-FDG in the gray matter while in one volunteer a "whole-body" scan from the top of the scull to mid-thigh was also obtained. A year before, investigators at Washington University, i.e., Michel Ter-Pogossian in collaboration with Michael Phelps, Edward Hoffmann, and Nizar Mullani had developed what they termed a positron-emission transaxial tomograph for nuclear imaging, i.e. a machine which was the starting point of today's PET scanners. Alavi understood from the beginning the potential of PET and in particular 18F-FDG PET even if PET images at that time were blurry and difficult to interpret, a circum-stance which for a quarter of a century brought the method in poor standing in the minds of many. Alavi started as a brain researcher, but training in internal medicine, hematology, radiology and nuclear medicine broadened his scope and over the years there are few diseases and clinical specialties in which Alavi has not provided results obtained with molecular imaging. He was a pioneer in using iodine-123 in thyroid cancer, MIBG in pheochromocytoma, radiolabeled white blood cells in infection, and 99mTc for the detection of gastrointestinal bleeds, and together with his wife 18F-FDG PET for the demonstration of recurrent brain tumors. Thus, Alavi has contributed often very successfully by promoting new ideas and their implementation to achieve improved ways of examining a variety of medical disorders. Alavi has been accused of seeing 18F-FDG as the only useful PET tracer. In a way this is true. FDG became the dominant tracer and has remained so for over 40 years now. In his 2008 SNM Highlight Lecture, Henry N. Wagner, Jr. called FDG the "tracer molecule of the 20thth century". According to a recent forecast of the Global Nuclear Medicine Radioisotopes Market, the global 18F-FDG market is expected to grow from an estimated $1.233 billion in 2014 to $2.148 billion in 2019 and the vast majority of this growth is due to a continued increase in the use of 18F-FDG, indicating that this tracer may remain the tracer molecule of at least the first half of the 21st century. The world calls for more specific tracers than 18F-FDG, and like others Dr. Alavi has constantly been looking for these, but with time, it became apparent that our body holds few organ or disease specific targets, so that the concept of very specific disease-characterizing tracers is not as rosy as previously assumed. Thus, in cancer, genetic profiling has demonstrated that tumors are genetically often a mixture of cellular clones and that these are not necessarily also present in local, regional or remote metastases, meaning that ultra-specific PET tracers for cancer diagnosis and staging may be more a utopian vision than a realistic future possibility. This, together with inborn limitations of the PET technique has made Abass Alavi more prudent and hesitant toward reports of highly promising new PET tracers and an advocate of timely carefulness when using our limited financial resources. Teaching and education of talented young individuals is one of Alavi's main academic missions. Thus, with Gerald Mandell, MD, he established the Alavi-Mandell Award, presented for the first time at the SNM meeting in 1999 to a candidate selected from among all those in a given year who were trainees at the time their names appeared as first authors of papers in JNM. Together with his wife Jane, Alavi established the Bradley-Alavi Student Fellowship which was presented for the first time in 2001 and is given to the top students selected by the SNMMI Education and Research Foundation. Alavi himself is a recipient of multiple awards, including the Georg Charles de Hevesy Nuclear Pioneer Award (2004), the Benedict Cassen Prize for Research in Nuclear Medicine (2012), the Honorary Citizenship of his native town Tabriz (2015) and the Gold Medal of the National Institute for Medical Research Development, Tehran (2015). In addition, he has received the Honorary PhD Degree in Molecular Biology of the University of Shiraz (2007), and the Honorary Doctoral Degrees of the University of Bologna (2007), the University of the Sciences in Philadelphia (2008), the Medical University of Gdansk (2016), and the University of Southern Denmark (2016). Since January 2011, Alavi has been a frequent guest in the city of Odense, Denmark. Its University Hospital holds one of the biggest departments of nuclear medicine and PET in Northern Europe. From being behind, Denmark has become the country in the world with the highest relative number of PET/CT scanners and PET scans, i.e., an estimated 0.7 and 1000, respectively, per 100 000 inhabitants in 2017. At 17 consecutive interdisciplinary Abass Alavi Meetings in Odense, he has been inspirer and initiator of multi-disciplinary scientific projects that have resulted in more than 100 publications and as many scientific presentations. Abass Alavi personifies the polymath, a species rarely found today. He discusses and produces science in as diverse areas as brain, cardiovascular, and musculoskeletal diseases, inflammation, cancer and many more disorders that plague humanity, and he has a clear eye to make results clinically useful. Had the Noble Prize been awarded not only for single inventions but also for the cumulated contribution of an outstanding researcher to patients who suffer and mankind as a whole, Dr. Abass Alavi would be on top of the candidate list. What may such an experienced birthday-person foretell about the future? He would probably say that the gamma camera and SPET will be entirely substituted by PET, that skeletal metastases are bone marrow and not bone metastases and that all indirect methodologies for imaging of skeletal metastases, including bone scintigraphy and CT, will be replaced by PET imaging with 18F-FDG or more cancer specific tracers. Also that motion and partial volume correction will be satisfactorily dealt with to allow calculation of a global disease score representing the total burden of disease in the body, whether caused by cancer, atherosclerosis or other severe disorders, and that, thus, PET will take its lead position as the diagnostic imaging modality of the 21st century. It is hard to say how many of these predictions will come true while Dr. Alavi is still going strong. What is certain is that very few persons, if any, has contributed so significantly to the development and clinical implementation of PET imaging worldwide as have this 80 year old giant in modern nuclear and molecular medicine! Abass Alavi currently holds appointments as Professor and Director of Research Education in the Department of Radiology, Perelman School of Medicine, of the University of Pennsylvania and as Honorary Fellow of the International Society of Medical Olympicus Association in Greece.

PMID: 29550853 [PubMed - as supplied by publisher]



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Differentiated thyroid cancer and selenium supplements for protection of salivary glands from 131I treatment.

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Differentiated thyroid cancer and selenium supplements for protection of salivary glands from 131I treatment.

Hell J Nucl Med. 2017 Mar 20;:

Authors: Mazokopakis E

Abstract
Dear Editor, I read with great interest the article by Son et al about the radioprotective effect of selenium (Se) supplementation for the salivary glands from 131I treatment in patients with differentiated thyroid cancer (DTC). In this study, 8 patients received 300μg of Se (as inorganic sodium selenite; selenase®) orally for 10 days, 3 days before to 6 days after 131I treatment. On the occasion of the use of Se among these patients, I want with this letter to remind the differences among the prescribed Se supplements in clinical practice, such as the possible health consequences of Brazil nut consumption as another choice for the preparation of DTC patients for radioactive iodine (RAI) therapy. Selenium is an essential element with many pleiotropic effects that can be found in foods and supplements in organic form (as selenomethionine, selenocysteine, γ-glutamyl-Se-methylselenocysteine) or/and in inorganic form (as sodium selenate and sodium selenite). Selenium in multivitamin/multimineral supplements or in a stand-alone supplement is often available in the forms of L-selenomethionine, Se-enriched yeast (grown in a high-Se medium), mustard seed-derived Se, or as sodium selenite or sodium selenate. Because these two (organic and inorganic) forms of Se are absorbed and metabolized differently, it is very important for the physicians, when prescribe a Se supplement, to know the contained form of Se. Inorganic forms of Se are easily absorbed through the intestine but poorly retained. Once they reach the blood, inorganic Se is quickly filtered out by the kidneys and excreted in the urine. So, the consumption of supplements with inorganic forms of Se does not offer the maximum health benefits of the element. Conversely, Se-containing amino acids, such as selenomethionine and selenocysteine, are introduced directly into proteins, including muscle proteins. These organic proteins-bound Se (selenoproteins) are better retained, utilized, and incorporated by the human body. About 90% of the received selenomethionine is actually absorbed in the intestinal tract, and about half of that remains in the body. The higher degree of absorption of selenomethionine against selenite was described in a recently published systematic review and meta-analysis by Wichman et al. In this review, a significant decrease in serum thyroid peroxidase antibodies (TPO-Ab) levels was found among patients receiving 200μg selenomethionine, but not among those receiving 200μg sodium selenite. In another investigation, 10 groups of Se-replete subjects were randomly assigned to receive a placebo or either 200 or 400 or 600μg/day Se as selenomethionine, sodium selenite, or high-selenium yeast (in which an estimated 75% of Se was in the form of selenomethionine) for 16 weeks. Selenium bioavailability, based on urinary excretion, was greatest for selenomethionine and lowest for selenite. However, supplementation with any of these forms only affected plasma Se levels and not glutathione peroxidase activity or selenoprotein P concentration, suggesting that study participants were selenium replete before they began taking Se supplements. Because the absorption of selenite was approximately two-thirds of the absorption of selenomethionine in this study, we can assume that the daily dose of 300μg of sodium selenite in the study of Son et al corresponded to 200μg of selenomethionine which is the most frequently used dose in intervention trials. However, in our opinion, the prescription of supplements with organic forms of Se must be preferred, when required. It is also worth mentioning that the prescribed Se supplements should not contain iodine considering that for a successful RAI therapy after thyroidectomy, DTC patients must, not only increase their thyroid-stimulating hormone (TSH) levels, but also deplete the whole body iodine pool through a low-iodine diet (low-quality evidence). One of the richest known food sources of bioavailable Se, in the organic form of selenomethionine, are the Brazil nuts. Brazil nuts grow on massive tropical trees, the Bertholletia excelsa of the Lecythidaceae family, some reaching heights over 45m. The average Se content of each Brazil nut in most elemental analyses varies ranging from 2.7 to 11μg Se/g, and the average weight of each nut varies between 3 and 4 g. Their consumption can increase the likelihood of Se toxicity, regardless of the quantity of the nuts consumed, and thus is not be a safe dietary choice. Moreover, Brazil nuts may be infected externally by aflatoxins or can trigger allergic reactions in sensitive people. However, raw Brazil nuts don't contain iodine and thus their consumption would not undermine the dietary efforts of DTC patient in the framework of the required low-iodine diet. The consumption of 2-3 unshelled and raw (unsalted) Brazil nuts daily could be another choice for the post-thyroidectomy period up to 10 days after RAI therapy among DTC patients who do not want to receive supplements as source of Se. We must emphasize that some patients having DTC and also Hashimoto's thyroiditis may had previously received Se supplements or Brazil nuts for a long period of time before DTC was diagnosed and thyroidectomy had followed. In conclusion, the prescription of supplements with organic forms of Se must be preferred against of supplements with inorganic forms of Se among DTC patients for the protection of their salivary glands from 131I treatment and Brazil nuts could be another choice.

PMID: 29550852 [PubMed - as supplied by publisher]



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Andersson's lesion in ankylosing spondylitis diagnosed by 18F-FDG PET/CT.

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Andersson's lesion in ankylosing spondylitis diagnosed by 18F-FDG PET/CT.

Hell J Nucl Med. 2018 Mar 20;:

Authors: Zhang Y, Li B, Yu H, Hou J, Shi H

Abstract
Ankylosing spondylitis (AS) is a form of arthritis that affects the spine, the sacroiliac joints, and sometimes the hips and shoulders. Andersson lesion (AL), was first described by Andersson in 1937 as a destructive vertebral body and discovertebral portion of the spine in AS. In this case, we report a 50 years old man with medical history of AS diagnosed AL by fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT).

PMID: 29550851 [PubMed - as supplied by publisher]



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Simultaneous pulmonary and inferior vena cava tumor thromboembolism secondary to retroperitoneal pleomorphic liposarcoma.

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Simultaneous pulmonary and inferior vena cava tumor thromboembolism secondary to retroperitoneal pleomorphic liposarcoma.

Hell J Nucl Med. 2018 Mar 20;:

Authors: Chen C, Jiang C, Li L

Abstract
Retroperitoneal pleomorphic liposarcoma (RPLS) is the least common but the most aggressive subtype of liposarcoma. We herein report a case of tumor embolism (TE) to the inferior vena cava (IVC) and pulmonary arteries in a 54 years old woman with RPLS. The case suggests that fusion fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) can accurately detect occult TE. It also illustrates the usefulness of computed tomography (CT) and high 18F-FDG uptake by PET/CT imaging for diagnosing such findings as filling defect in the veins and beaded pulmonary arteries as TE. To our knowledge, this is the first reported case of simultaneous pulmonary and inferior vena cava thromboembolism secondary to RPLS. And occult TE from RPLS has not been reported previously by 18F-FDG PET/CT.

PMID: 29550849 [PubMed - as supplied by publisher]



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123I-ioflupane SPET and 123I-MIBG in the diagnosis of Parkinson's disease and parkinsonian disorders and in the differential diagnosis between Alzheimer's and Lewy's bodies dementias.

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123I-ioflupane SPET and 123I-MIBG in the diagnosis of Parkinson's disease and parkinsonian disorders and in the differential diagnosis between Alzheimer's and Lewy's bodies dementias.

Hell J Nucl Med. 2018 Mar 20;:

Authors: Nuvoli S, Palumbo B, Malaspina S, Madeddu G, Spanu A

Abstract
Nuclear medicine procedures are widely used as "in vivo" biomarkers in a large number of brain diseases, especially in the diagnosis of Parkinson's disease (PD) and of parkinsonian disorders (pD). Furthermore, nuclear medicine is used in the differential diagnosis of dementias especially Alzheimer's disease (AD) and dementia with Lewy's bodies (LBD) which share many clinical symptoms and often LBD is misdiagnosed as AD. The differential diagnosis between these clinical entities is crucial for treatment since LBD also shares some clinical symptoms with parkinsonian disorders. We reviewed the most relevant papers that study the usefulness of both iodine-123-ioflupane studied by single photon emission tomography (123I-ioflupane SPET) and of 123I-metaiodobenzylguanidine (123I-MIBG) cardiac scintigraphy in the diagnosis of PD and pD and in the differential diagnosis between AD and LBD in order to contribute to the clinical practice of the diseases.

PMID: 29550847 [PubMed - as supplied by publisher]



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Is there an incremental value to use myocardial perfusion imaging with or without CT attenuation for the diagnosis of coronary artery disease? A study in Chinese patients.

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Is there an incremental value to use myocardial perfusion imaging with or without CT attenuation for the diagnosis of coronary artery disease? A study in Chinese patients.

Hell J Nucl Med. 2018 Mar 20;:

Authors: Xin WC, Shao XL, Wang YT, Wang JF, Wang XS, Yang L, Yang W, Zhang FF

Abstract
OBJECTIVE: To evaluate whether computed tomography attention correction (CTAC) has incremental diagnostic value for single photon emission tomography (SPET) myocardial perfusion imaging (MPI) for the detection of coronary artery disease (CAD) in Chinese patients.
SUBJECTS AND METHODS: This retrospective study consisted of 181 suspected CAD patients who underwent one-stop SPET examination by MPI combined with a CT scan. Two observers independently evaluated non-attenuation correction (NAC) and CTAC MPI images, and coronary angiography (CAG) results were used as reference standards. The diagnostic efficacies of the two methods were compared.
RESULTS: a) In the whole group, the sensitivity, specificity and accuracy for the detection of CAD were found to be 75.7%, 55.1% and 63.5% for NAC images and 52.7%, 86.9% and 72.9% for CTAC images, respectively; the areas under the receiver operating characteristic curves (AUC) were 0.654 and 0.698 (P>0.05). b) The accuracy of CTAC and the AUC were significantly higher than those for NAC in Chinese males. c) The accuracy of CTAC was also significantly increased for the right coronary artery (RCA) territory and in overweight patients (BMI≥24), although differences in the AUC were marginally insignificant.
CONCLUSION: Compared to NAC MPI, CTAC improved SPET MPI specificity but decreased sensitivity, leading to no obvious improvement in overall accuracy for the diagnosis of CAD in Chinese patients. However, CTAC might be of value in the subgroups of males and overweight patients and for the RCA territory. In routine clinical application, the integration of NAC and CTAC findings combined with CAD pre-test probability could improve MPI diagnostic performance.

PMID: 29550846 [PubMed - as supplied by publisher]



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Correlations between dual-phase 18F-FDG uptake and clinicopathologic and biological markers of breast cancer.

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Correlations between dual-phase 18F-FDG uptake and clinicopathologic and biological markers of breast cancer.

Hell J Nucl Med. 2018 Mar 20;:

Authors: Kaida H, Azuma K, Toh U, Kawahara A, Sadashima E, Hattori S, Akiba J, Tahara N, Rominger A, Ishii K, Murakami T, Ishibashi M

Abstract
OBJECTIVE: To assess the correlations between dual-phase fluorine-18 fluorodeoxyglucose (18F-FDG) uptake and clinicopathological and immunohistochemical prognostic factors in patients with surgically resected breast cancer.
SUBJECTS AND METHODS: We retrospectively analyzed the cases of 105 patients. We calculated the maximum standardized uptake value (SUVmax) at 85min (SUV1), SUVmax at 125min (SUV2) and the retention index [RI]. Spearman's rank correlation test, the Kruskal-Wallis test and receiver operating characteristic (ROC) analysis were performed to assess the association between 18F-FDG uptake and the clinicopathological and immunohistochemical factors: glucose transporter-1 (Glut-1), estrogen receptor alpha (ERα), ERβ, progesterone receptor (PR), human epidermal growth factor 2 (Her2), mammalian target of rapamycin (mTOR), and P70S6kinase (P70S6).
RESULTS: The SUV1 and SUV2 values were correlated with Glut-1, pathological tumor size, ERα negativity, and pathological stage (all P values were <0.05), but not with mTOR, P70S6, ERβ, PR, Her2 or other factors. The SUV1 and SUV2 in the triple negative subtype were significantly higher than those of the hormone receptor-positive subtype (P<0.05). The RI was associated with pathological tumor size alone. In the ROC analysis of Glut-1, the areas under the curve for SUV1 and SUV2 were significantly larger than that for RI (SUV1, p=0.032, SUV2, p=0.022).
CONCLUSION: Glucose transporter-1, estrogen receptor alpha negativity and nuclear grade might affect the high 18F-FDG uptake in breast cancer. The SUVmax might be more useful than the RI for predicting the Glut-1 expression and the aggressiveness of breast cancer.

PMID: 29550845 [PubMed - as supplied by publisher]



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18F-FDG PET/CT and ultrasonogrpahy in differentiated thyroid carcinoma patients with elevated serum levels of antithyroglobulin antibody, negative Tg and whole body 131I scan.

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18F-FDG PET/CT and ultrasonogrpahy in differentiated thyroid carcinoma patients with elevated serum levels of antithyroglobulin antibody, negative Tg and whole body 131I scan.

Hell J Nucl Med. 2018 Mar 20;:

Authors: Liu J, Liu B, Yu Y, Chao F, Liu Y, Han X

Abstract
OBJECTIVE: In the follow-up of patients with differentiated thyroid cancer (DTC), several patients had elevated serum levels of antithyroglobulin antibody (TgAb), undetectable serum thyroglobulin (Tg), and negative radioiodine whole body scan (131I-WBS). We describe the use of neck ultrasonography (US) and fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging in these patients to investigate this clinically challenging problem and propose treating.
SUBJECTS AND METHODS: A total of 49 DTC patients with elevated serum levels of TgAb (>115IU/mL), undetectable Tg and negative 131I-WBS were divided into two groups (positive and negative) according to the neck US findings. Differences in the rate of recurrence between the two groups were investigated. The diagnostic value of 18F-FDG PET/CT in these patients was evaluated.
RESULTS: Among the 49 patients, the rate of recurrence of patients with positive neck US was 50%, which was significantly higher than that of patients with negative neck US (17.24%; P=0.014). The sensitivity, specificity, and positive predictive values of 18F-FDG PET/CT imaging in diagnosing the clinical status of these patients were 93.33%, 70.59% and 58.33%, respectively. After the 18F-FDG PET/CT scan, clinical management was changed in 14 patients. Nine patients were operated and five underwent 131I ablation therapy.
CONCLUSION: In the 49 DTC patients with elevated serum levels of TgAb but negative findings in serum Tg and in 131I-WBS, neck US and 18F-FDG PET/CT imaging supported the clinical diagnosis and suggested subsequent treatment.

PMID: 29550843 [PubMed - as supplied by publisher]



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Tumoricidal effect and pain relief after concurrent therapy by strontium-89 chloride and zoledronic acid for bone metastases.

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Tumoricidal effect and pain relief after concurrent therapy by strontium-89 chloride and zoledronic acid for bone metastases.

Hell J Nucl Med. 2018 Mar 20;:

Authors: Baba K, Kaida H, Hattori C, Muraki K, Kugiyama T, Fujita H, Ishibashi M

Abstract
OBJECTIVE: The purpose of this study was to investigate the palliative and tumoricidal effects of concurrent therapy of strontium-89 chloride (89SrCl2) and zoledronic acid (ZA) for painful bone metastases.
SUBJECTS AND METHODS: Fifty-one patients with painful bone metastases prostate cancer (n=17), lung cancer (n=13), breast cancer (n=12), other cancers (n=9) were treated. Bone metastases was confirmed in all patients by technetium-99m hydroxymethylene diphosphonate (99mTc-HMDP) bone scintigraphy. The numeric rating scale (NRS) and performance status (PS) were used to assess the degree of pain and patients' physical condition. The extent of bone metastases was assessed with imaging modalities including CT, MRI and/or 99mTc bone scintigraphy before treatment and 2 or 3 months after.
RESULTS: The pain relief response of 89SrCl2 with ZA for bone metastases was 94% (48/51) from 1 to 3 months after treatment. The tumoricidal effect of concurrent therapy by 89SrCl2 with ZA for painful bone metastases was 8/22 as shown by imaging modalities and the rate of non-progressive disease (non-PD) was 19/22. Pain due to bone metastases assessed with the NRS was significantly improved (P<0.001) in many types of primary cancer, including prostate, breast and lung cancers.
CONCLUSION: Concurrent therapy of 89SrCl2 with ZA may offer not only pain relief, but also a tumoricidal effect for painful bone metastases.

PMID: 29550842 [PubMed - as supplied by publisher]



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Value of 18F-FDG PET/CT in discrimination between indolent and aggressive non-Hodgkin's lymphoma: A study of 328 patients.

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Value of 18F-FDG PET/CT in discrimination between indolent and aggressive non-Hodgkin's lymphoma: A study of 328 patients.

Hell J Nucl Med. 2018 Mar 20;:

Authors: Alobthani G, Romanov V, Isohashi K, Matsunaga K, Watabe T, Kato H, Tatsumi M, Shimosegawa E, Hatazawa J

Abstract
OBJECTIVE: Non-Hodgkin's lymphoma (NHL) cases with inconclusive biopsy findings are not infrequently referred for fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). We searched for maximum standardized uptake value (SUVmax) cut-off values that could discriminate between indolent and aggressive NHL in conventional non-time of flight (non-TOF) 18F-FDG PET/CT and TOF 18F-FDG PET/CT.
SUBJECTS AND METHODS: Retrospectively, 328 patients were selected by the following inclusion criteria: biopsy-proven NHL with no more than one histopathological type; new cases with less than 90 days between obtaining biopsy and 18F-FDG PET/CT scanning; recurrent cases with time interval more than six months since the last therapy with no history of transformation; and blood glucose less than 150mg/dL. Two hundred forty six (246) selected patients were scanned with non-TOF PET/CT, and 82 patients were scanned with TOF 18F-FDG PET/CT.
RESULTS: The SUVmax of NHL tends to be higher in TOF 18F-FDG PET/CT than non-TOF 18F-FDG PET/CT. New aggressive NHL had significantly higher SUVmax than new indolent NHL in both, non-TOF 18F-FDG PET/CT (13.6±7.7g/mL vs. 5.3±3.4g/mL, P<0.0001) and TOF 18F-FDG PET/CT (20.5±9.8g/mL vs. 6.6±4.7g/mL, P<0.0001). A receiver operating characteristic curve analysis for new cases in non-TOF 18F-FDG PET/CT (n=204), demonstrated SUVmax of 10g/mL as the most balanced cut-off between aggressive and indolent NHL, with the area under the curve (AUC) of 86%, specificity of 94%, and sensitivity of 71%. While SUVmax of 13g/mL was the most balanced cut-off for new cases in TOF 18F-FDG PET/CT (n=57), with AUC of 91%, specificity of 95.5%, and sensitivity of 77%.
CONCLUSION: Both SUVmax>10g/mL in non-TOF 18F-FDG PET/CT and >13g/mL in TOF 18F-FDG PET/CT were highly suggestive of an aggressive nature of NHL, while there was an overlap between indolent and aggressive NHL in the lower SUVmax levels.

PMID: 29550841 [PubMed - as supplied by publisher]



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Abass Alavi: A giant in Nuclear Medicine turns 80 and is still going strong!

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Abass Alavi: A giant in Nuclear Medicine turns 80 and is still going strong!

Hell J Nucl Med. 2017 Mar 20;:

Authors:

Abstract
Little was written in the stars above the city of Tabriz in Iran on March 15, 1938 indicating that a newborn citizen would immigrate to America and become a master of modern mo-lecular imaging with a sharp focus on 18F-FDG PET to the benefit of millions of people around the world. Nonetheless, that's what happened. A gifted boy who lost his farther early and grew up with his uneducated mother and two siblings in humble circumstances to become a premium student, nationally no. 1 in mathematics while in school, and later a medical doctor before he decided in 1966 to seek his fortune in the US. Here he started education in internal medicine, hematology and oncology, albeit found this unsatisfactory due to tradition and rote learning. He turned to radiology and nuclear medicine in a search for new knowledge and better methods to benefit patients and society, an attitude he had been taught from early childhood. The very same attitude has been the beacon for Alavi's activities throughout his professional life, instead of money, power and social status. He married into a highly academic environment. His wife, Jane Bradley Alavi, was a specialist in hematology and oncology and is still his life partner. They never had children, so their many students and the numerous medical doctors, physicists and other academics they coached became their family. While Jane Alavi retired some years ago, Abass Alavi continued his professional career and has no plans of retirement when he turns 80 on March 15, 2018 after 46 years in nuclear medicine at the University of Pennsylvania and with an admirable network of pupils and colleagues across all five continents. On the contrary, Alavi has probably never been busier, his scientific work goes on, his multinational scientific "family" steadily increases all over the world as does the appli-cation of PET in the shape of PET/CT or PET/MRI. Alavi's contributions to the scientific literature has more than doubled within the last decade making him one of the most cited researchers at the University of Pennsylvania with a production of more than 1,200 articles, a similar number of published abstracts and close to 58,000 citations according to Google Scholar, of which about 20,000 since 2012 when he was 74. This is just part of an amazing story. Having turned to nuclear medicine in 1971, Alavi entered into one of the World's most ingenious and productive medical research en-vironments comprising collaboration of experts in nuclear medicine (David Kuhl) and neurology (Martin Reivich) at Penn, and in physiology and pharmacology (Louis Sokoloff) at the NIH, all of whom contributed significantly to the development of PET. Focus was on cerebral research with beta-emitting 14C-labeled deoxyglucose for mapping regional cerebral glucose metabolism by means of autoradiography. Alavi became a junior member of this collaboration in which the idea of labeling deoxyglucose with a gamma-emitting isotope arose to allow in vivo examination of the normal and diseased human brain. They contacted Alfred Wolf at Brookhaven National Laboratory who had an interest in synthesizing positron-emitting compounds. He suggested labeling instead with 18F-FDG and in 1975 Wolf's group including Tatsuo Ido and Joanna Fowler succeeded in synthesizing 18F-FDG. In the meantime, investigators at Penn had developed high energy collimators for the Mark IV scanner to allow imaging with 18F-FDG, so in August 1976, two normal volunteers were the first to receive a dose of 18F-FDG for tomographic brain imaging showing concentration of 18F-FDG in the gray matter while in one volunteer a "whole-body" scan from the top of the scull to mid-thigh was also obtained. A year before, investigators at Washington University, i.e., Michel Ter-Pogossian in collaboration with Michael Phelps, Edward Hoffmann, and Nizar Mullani had developed what they termed a positron-emission transaxial tomograph for nuclear imaging, i.e. a machine which was the starting point of today's PET scanners. Alavi understood from the beginning the potential of PET and in particular 18F-FDG PET even if PET images at that time were blurry and difficult to interpret, a circum-stance which for a quarter of a century brought the method in poor standing in the minds of many. Alavi started as a brain researcher, but training in internal medicine, hematology, radiology and nuclear medicine broadened his scope and over the years there are few diseases and clinical specialties in which Alavi has not provided results obtained with molecular imaging. He was a pioneer in using iodine-123 in thyroid cancer, MIBG in pheochromocytoma, radiolabeled white blood cells in infection, and 99mTc for the detection of gastrointestinal bleeds, and together with his wife 18F-FDG PET for the demonstration of recurrent brain tumors. Thus, Alavi has contributed often very successfully by promoting new ideas and their implementation to achieve improved ways of examining a variety of medical disorders. Alavi has been accused of seeing 18F-FDG as the only useful PET tracer. In a way this is true. FDG became the dominant tracer and has remained so for over 40 years now. In his 2008 SNM Highlight Lecture, Henry N. Wagner, Jr. called FDG the "tracer molecule of the 20thth century". According to a recent forecast of the Global Nuclear Medicine Radioisotopes Market, the global 18F-FDG market is expected to grow from an estimated $1.233 billion in 2014 to $2.148 billion in 2019 and the vast majority of this growth is due to a continued increase in the use of 18F-FDG, indicating that this tracer may remain the tracer molecule of at least the first half of the 21st century. The world calls for more specific tracers than 18F-FDG, and like others Dr. Alavi has constantly been looking for these, but with time, it became apparent that our body holds few organ or disease specific targets, so that the concept of very specific disease-characterizing tracers is not as rosy as previously assumed. Thus, in cancer, genetic profiling has demonstrated that tumors are genetically often a mixture of cellular clones and that these are not necessarily also present in local, regional or remote metastases, meaning that ultra-specific PET tracers for cancer diagnosis and staging may be more a utopian vision than a realistic future possibility. This, together with inborn limitations of the PET technique has made Abass Alavi more prudent and hesitant toward reports of highly promising new PET tracers and an advocate of timely carefulness when using our limited financial resources. Teaching and education of talented young individuals is one of Alavi's main academic missions. Thus, with Gerald Mandell, MD, he established the Alavi-Mandell Award, presented for the first time at the SNM meeting in 1999 to a candidate selected from among all those in a given year who were trainees at the time their names appeared as first authors of papers in JNM. Together with his wife Jane, Alavi established the Bradley-Alavi Student Fellowship which was presented for the first time in 2001 and is given to the top students selected by the SNMMI Education and Research Foundation. Alavi himself is a recipient of multiple awards, including the Georg Charles de Hevesy Nuclear Pioneer Award (2004), the Benedict Cassen Prize for Research in Nuclear Medicine (2012), the Honorary Citizenship of his native town Tabriz (2015) and the Gold Medal of the National Institute for Medical Research Development, Tehran (2015). In addition, he has received the Honorary PhD Degree in Molecular Biology of the University of Shiraz (2007), and the Honorary Doctoral Degrees of the University of Bologna (2007), the University of the Sciences in Philadelphia (2008), the Medical University of Gdansk (2016), and the University of Southern Denmark (2016). Since January 2011, Alavi has been a frequent guest in the city of Odense, Denmark. Its University Hospital holds one of the biggest departments of nuclear medicine and PET in Northern Europe. From being behind, Denmark has become the country in the world with the highest relative number of PET/CT scanners and PET scans, i.e., an estimated 0.7 and 1000, respectively, per 100 000 inhabitants in 2017. At 17 consecutive interdisciplinary Abass Alavi Meetings in Odense, he has been inspirer and initiator of multi-disciplinary scientific projects that have resulted in more than 100 publications and as many scientific presentations. Abass Alavi personifies the polymath, a species rarely found today. He discusses and produces science in as diverse areas as brain, cardiovascular, and musculoskeletal diseases, inflammation, cancer and many more disorders that plague humanity, and he has a clear eye to make results clinically useful. Had the Noble Prize been awarded not only for single inventions but also for the cumulated contribution of an outstanding researcher to patients who suffer and mankind as a whole, Dr. Abass Alavi would be on top of the candidate list. What may such an experienced birthday-person foretell about the future? He would probably say that the gamma camera and SPET will be entirely substituted by PET, that skeletal metastases are bone marrow and not bone metastases and that all indirect methodologies for imaging of skeletal metastases, including bone scintigraphy and CT, will be replaced by PET imaging with 18F-FDG or more cancer specific tracers. Also that motion and partial volume correction will be satisfactorily dealt with to allow calculation of a global disease score representing the total burden of disease in the body, whether caused by cancer, atherosclerosis or other severe disorders, and that, thus, PET will take its lead position as the diagnostic imaging modality of the 21st century. It is hard to say how many of these predictions will come true while Dr. Alavi is still going strong. What is certain is that very few persons, if any, has contributed so significantly to the development and clinical implementation of PET imaging worldwide as have this 80 year old giant in modern nuclear and molecular medicine! Abass Alavi currently holds appointments as Professor and Director of Research Education in the Department of Radiology, Perelman School of Medicine, of the University of Pennsylvania and as Honorary Fellow of the International Society of Medical Olympicus Association in Greece.

PMID: 29550853 [PubMed - as supplied by publisher]



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