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Πέμπτη, 18 Ιανουαρίου 2018

Diagnostic Value of Dual-input Computed Tomography Perfusion on Detecting Bronchial-Pulmonary Artery Fistula in Tuberculosis Patients with Massive Hemoptysis

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Publication date: Available online 19 January 2018
Source:Academic Radiology
Author(s): Haixian Qu, Maoqiang Wang, Zhijun Wang, Guokun Ao, Xiaodong Yuan, Qiang Li, Zepeng Ma, Qianru Xu, Jieyu Yan, Yanhua Bai
Rationale and ObjectivesThis prospective study aimed to evaluate the diagnostic performance of dual-input computed tomography perfusion technique (DI-CTP) in identifying the bronchial-pulmonary artery fistula in patients tuberculosis with massive hemoptysis.Material and MethodsTwenty patients with tuberculosis with massive hemoptysis were enrolled from January 2015 to December 2015. The association between DI-CTP parameters and the diagnostic outcomes of digital subtraction angiography was assessed. Diagnostic efficacy of DI-CTP was evaluated by receiver operating curve (ROC) analyses using the diagnostic outcomes of digital subtraction angiography, which is the gold standard for identifying bronchial-pulmonary artery fistula.ResultsCompared to lung segments with normal blood flow (n = 304), those with bronchial-pulmonary artery fistula (n = 164) had a reduced pulmonary flow value, perfusion index (PI) value, and an elevated bronchial artery (BF) value in the DI-CTP scan, which was further confirmed by multivariate logistic regression. ROC analysis showed that PI and bronchial artery has an excellent diagnostic performance (both area under the ROC curve > 0.9, P < .001) and high sensitivity and specificity (from 0.79 to 0.95 at the optimal cutoff). PI has the best diagnostic performance, with an overall diagnostic accuracy of 0.91.ConclusionsDI-CTP scan possesses the diagnostic value for detecting bronchial-pulmonary artery fistula in patients with tuberculosis with massive hemoptysis, providing an alternative diagnostic method.



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Breast Imaging of Transgender Individuals: A Review

Abstract

Purpose

This review will inform radiologists about the evidence base regarding radiographic imaging for transgender individuals and considerations for providing culturally sensitive care for this population.

Findings

Transgender individuals are increasingly referred for both screening and diagnostic breast imaging. It is important that the clinic environment is welcoming, the medical staff utilize accepted terminology and patients are able to designate their gender and personal history to ensure appropriate care. Hormone and surgical treatments used for transition by many transgender women and men may change the approach to imaging.

Summary

Although not yet evidence-based, screening mammography is currently suggested for transgender women with risk factors, including those receiving hormone treatment over 5 years. The risk for breast cancer in transgender individuals is still being defined.



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Accuracy of the Compressed Sensing Accelerated 3D-FLAIR Sequence for the Detection of MS Plaques at 3T [ADULT BRAIN]

BACKGROUND AND PURPOSE:

The use of 3D FLAIR improves the detection of brain lesions in MS patients, but requires long acquisition times. Compressed sensing reduces acquisition time by using the sparsity of MR images to randomly undersample the k-space. Our aim was to compare the image quality and diagnostic performance of 3D-FLAIR with and without compressed sensing for the detection of multiple sclerosis lesions at 3T.

MATERIALS AND METHODS:

Twenty-three patients with relapsing-remitting MS underwent both conventional 3D-FLAIR and compressed sensing 3D-FLAIR on a 3T scanner (reduction in scan time 1 minute 25 seconds, 27%; compressed sensing factor of 1.3). Two blinded readers independently evaluated both conventional and compressed sensing FLAIR for image quality (SNR and contrast-to-noise ratio) and the number of MS lesions visible in the periventricular, intra-juxtacortical, infratentorial, and optic nerve regions. The volume of white matter lesions was measured with automatic postprocessing segmentation software for each FLAIR sequence.

RESULTS:

Image quality and the number of MS lesions detected by the readers were similar between the 2 FLAIR acquisitions (P = .74 and P = .094, respectively). Almost perfect agreement was found between both FLAIR acquisitions for total MS lesion count (Lin concordance correlation coefficient = 0.99). Agreement between conventional and compressed sensing FLAIR was almost perfect for periventricular and infratentorial lesions and substantial for intrajuxtacortical and optic nerve lesions. Postprocessing with the segmentation software did not reveal a significant difference between conventional and compressed sensing FLAIR in total MS lesion volume (P = .63) or the number of MS lesions (P = .15).

CONCLUSIONS:

With a compressed sensing factor of 1.3, 3D-FLAIR is 27% faster and preserves diagnostic performance for the detection of MS plaques at 3T.



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Resting-State Functional MRI: Everything That Nonexperts Have Always Wanted to Know [REVIEW ARTICLE]

SUMMARY:

Resting-state fMRI was first described by Biswal et al in 1995 and has since then been widely used in both healthy subjects and patients with various neurologic, neurosurgical, and psychiatric disorders. As opposed to paradigm- or task-based functional MR imaging, resting-state fMRI does not require subjects to perform any specific task. The low-frequency oscillations of the resting-state fMRI signal have been shown to relate to the spontaneous neural activity. There are many ways to analyze resting-state fMRI data. In this review article, we will briefly describe a few of these and highlight the advantages and limitations of each. This description is to facilitate the adoption and use of resting-state fMRI in the clinical setting, helping neuroradiologists become familiar with these techniques and applying them for the care of patients with neurologic and psychiatric diseases.



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Cerebral Mitochondrial Microangiopathy Leads to Leukoencephalopathy in Mitochondrial Neurogastrointestinal Encephalopathy [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Mitochondrial neurogastrointestinal encephalopathy is a rare disorder due to recessive mutations in the thymidine phosphorylase gene, encoding thymidine phosphorylase protein required for mitochondrial DNA replication. Clinical manifestations include gastrointestinal dysmotility and diffuse asymptomatic leukoencephalopathy. This study aimed to elucidate the mechanisms underlying brain leukoencephalopathy in patients with mitochondrial neurogastrointestinal encephalopathy by correlating multimodal neuroradiologic features to postmortem pathology.

MATERIALS AND METHODS:

Seven patients underwent brain MR imaging, including single-voxel proton MR spectroscopy and diffusion imaging. Absolute concentrations of metabolites calculated by acquiring unsuppressed water spectra at multiple TEs, along with diffusion metrics based on the tensor model, were compared with those of healthy controls using unpaired t tests in multiple white matters regions. Brain postmortem histologic, immunohistochemical, and molecular analyses were performed in 1 patient.

RESULTS:

All patients showed bilateral and nearly symmetric cerebral white matter hyperintensities on T2-weighted images, extending to the cerebellar white matter and brain stem in 4. White matter, N-acetylaspartate, creatine, and choline concentrations were significantly reduced compared with those in controls, with a prominent increase in the radial water diffusivity component. At postmortem examination, severe fibrosis of brain vessel smooth muscle was evident, along with mitochondrial DNA replication depletion in brain and vascular smooth-muscle and endothelial cells, without neuronal loss, myelin damage, or gliosis. Prominent periependymal cytochrome C oxidase deficiency was also observed.

CONCLUSIONS:

Vascular functional and histologic alterations account for leukoencephalopathy in mitochondrial neurogastrointestinal encephalopathy. Thymidine toxicity and mitochondrial DNA replication depletion may induce microangiopathy and blood-brain-barrier dysfunction, leading to increased water content in the white matter. Periependymal cytochrome C oxidase deficiency could explain prominent periventricular impairment.



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Review of the Imaging Features of Benign Osteoporotic and Malignant Vertebral Compression Fractures [REVIEW ARTICLE]

SUMMARY:

Vertebral compression fractures are very common, especially in the elderly. Benign osteoporotic and malignant vertebral compression fractures have extremely different management and prognostic implications. Although there is an overlap in appearances, characteristic imaging features can aid in the distinction between these 2 types of compression fractures. The aim of this review is to characterize the imaging features of benign and malignant vertebral compression fractures seen with CT, PET, SPECT, and MR imaging.



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Development of High Signal Intensity within the Globus Pallidus and Dentate Nucleus following Multiple Administrations of Gadobenate Dimeglumine [PATIENT SAFETY]

BACKGROUND AND PURPOSE:

Previous studies have evaluated various gadolinium based contrast agents and their association with gadolinium retention, however, there is a discrepancy in the literature concerning the linear agent gadobenate dimeglumine. Our aim was to determine whether an association exists between the administration of gadobenate dimeglumine and the development of intrinsic T1-weighted signal in the dentate nucleus and globus pallidus.

MATERIALS AND METHODS:

In this single-center, retrospective study, the signal intensity of the globus pallidus, dentate nucleus, thalamus, and middle cerebellar peduncle was measured on unenhanced T1-weighted images in 29 adult patients who had undergone multiple contrast MRIs using exclusively gadobenate dimeglumine (mean, 10.1 ± 3.23 doses; range, 6–18 doses). Two neuroradiologists, blinded to the number of prior gadolinium-based contrast agent administrations, separately placed ROIs within the globi pallidi, thalami, dentate nuclei, and middle cerebellar peduncles on the last MR imaging examinations. The correlations between the globus pallidus:thalamus and the dentate nucleus:middle cerebellar peduncle signal intensity ratios with the number of gadolinium-based contrast agent administrations and cumulative dose were tested with either 1-tailed Pearson or Spearman correlations. A priori, P < .05 was considered statistically significant.

RESULTS:

Both the globus pallidus:thalamus and dentate nucleus:middle cerebellar peduncle ratios showed significant correlation with the number of gadolinium-based contrast agent administrations (r = 0.39, P = .017, and r = 0.58, P = .001, respectively). Additionally, the globus pallidus:thalamus and dentate nucleus:middle cerebellar peduncle ratios showed significant correlation with the cumulative dose of gadobenate dimeglumine (r = 0.48, P = .004, and r = 0.43, P = .009, respectively). Dentate nucleus hyperintensity was qualitatively present on the last MR imaging in 79.3%–86.2% of patients and in all patients who had received >10 doses.

CONCLUSIONS:

At high cumulative doses (commonly experienced by patients, for example, with neoplastic disease), gadobenate dimeglumine is associated with an increase in the globus pallidus:thalamus and dentate nucleus:middle cerebellar peduncles signal intensity ratios.



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T2 Relaxometry MRI Predicts Cerebral Palsy in Preterm Infants [PEDIATRICS]

BACKGROUND AND PURPOSE:

T2-relaxometry brain MR imaging enables objective measurement of brain maturation based on the water-macromolecule ratio in white matter, but the outcome correlation is not established in preterm infants. Our study aimed to predict neurodevelopment with T2-relaxation values of brain MR imaging among preterm infants.

MATERIALS AND METHODS:

From January 1, 2012, to May 31, 2015, preterm infants who underwent both T2-relaxometry brain MR imaging and neurodevelopmental follow-up were retrospectively reviewed. T2-relaxation values were measured over the periventricular white matter, including sections through the frontal horns, midbody of the lateral ventricles, and centrum semiovale. Periventricular T2 relaxometry in relation to corrected age was analyzed with restricted cubic spline regression. Prediction of cerebral palsy was examined with the receiver operating characteristic curve.

RESULTS:

Thirty-eight preterm infants were enrolled for analysis. Twenty patients (52.6%) had neurodevelopmental abnormalities, including 8 (21%) with developmental delay without cerebral palsy and 12 (31.6%) with cerebral palsy. The periventricular T2-relaxation values in relation to age were curvilinear in preterm infants with normal development, linear in those with developmental delay without cerebral palsy, and flat in those with cerebral palsy. When MR imaging was performed at >1 month corrected age, cerebral palsy could be predicted with T2 relaxometry of the periventricular white matter on sections through the midbody of the lateral ventricles (area under the receiver operating characteristic curve = 0.738; cutoff value of >217.4 with 63.6% sensitivity and 100.0% specificity).

CONCLUSIONS:

T2-relaxometry brain MR imaging could provide prognostic prediction of neurodevelopmental outcomes in premature infants. Age-dependent and area-selective interpretation in preterm brains should be emphasized.



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Iodine Extravasation Quantification on Dual-Energy CT of the Brain Performed after Mechanical Thrombectomy for Acute Ischemic Stroke Can Predict Hemorrhagic Complications [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Intracerebral hemorrhage represents a potentially severe complication of revascularization of acute ischemic stroke. The aim of our study was to assess the capability of iodine extravasation quantification on dual-energy CT performed immediately after mechanical thrombectomy to predict hemorrhagic complications.

MATERIALS AND METHODS:

Because this was a retrospective study, the need for informed consent was waived. Eighty-five consecutive patients who underwent brain dual-energy CT immediately after mechanical thrombectomy for acute ischemic stroke between August 2013 and January 2017 were included. Two radiologists independently evaluated dual-energy CT images for the presence of parenchymal hyperdensity, iodine extravasation, and hemorrhage. Maximum iodine concentration was measured. Follow-up CT examinations performed until patient discharge were reviewed for intracerebral hemorrhage development. The correlation between dual-energy CT parameters and intracerebral hemorrhage development was analyzed by the Mann-Whitney U test and Fisher exact test. Receiver operating characteristic curves were generated for continuous variables.

RESULTS:

Thirteen of 85 patients (15.3%) developed hemorrhage. On postoperative dual-energy CT, parenchymal hyperdensities and iodine extravasation were present in 100% of the patients who developed intracerebral hemorrhage and in 56.3% of the patients who did not (P = .002 for both). Signs of bleeding were present in 35.7% of the patients who developed intracerebral hemorrhage and in none of the patients who did not (P < .001). Median maximum iodine concentration was 2.63 mg/mL in the patients who developed intracerebral hemorrhage and 1.4 mg/mL in the patients who did not (P < .001). Maximum iodine concentration showed an area under the curve of 0.89 for identifying patients developing intracerebral hemorrhage.

CONCLUSIONS:

The presence of parenchymal hyperdensity with a maximum iodine concentration of >1.35 mg/mL may identify patients developing intracerebral hemorrhage with 100% sensitivity and 67.6% specificity.



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The effects of sediment transport on temporal variation in radiocesium concentrations in very shallow water off the southern coast of Fukushima, Japan

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Publication date: April 2018
Source:Journal of Environmental Radioactivity, Volumes 184–185
Author(s): Akira Matsumoto, Hiroshi Myouse, Hisayuki Arakawa, Ken Higuchi, Naoto Hirakawa, Yoshiaki Morioka, Takuji Mizuno
We studied the very shallow coastal water off Iwaki City, Fukushima Prefecture, and investigated: (1) temporal variation in 137Cs concentrations; (2) particle-size distribution of sediments; and (3) the effect on variation by waves, component-fractionated concentration of radiocesium and mineral composition at three sampling stations (Yotsukura, Ena rocky reef and Ena sandy station). There was a decline in 137Cs concentrations in sediment samples at all sampling stations between 425 and 1173 days after the accident. All stations had fluctuations in 137Cs concentrations between 425 and 800 days. At Ena sandy station and Ena rocky reef stations the declines in 137Cs concentrations slowed from about 800 days after the accident. Fluctuations in particle median diameters were seen, as well as in 137Cs concentrations. At Yotsukura, where the fluctuation in median diameter was small, a constant decrease in 137Cs concentrations was observed. We considered that bioturbation may contribute the constant decrease. At Ena sandy station, where the fluctuation of the median diameter was large, the fluctuation in 137Cs concentrations was also large. The movement of sediments was evaluated by the Shields parameter, and results indicated that at any station where the sediment was moved more frequently, the fluctuation in 137Cs concentrations was also large. The highly contaminated small particles moved from our stations due to wave action between 425 and 800 days after the accident. The remaining relatively large particles might contribute to the slowing down in reduction of 137Cs concentrations from 800 days after the accident. However, the 137Cs concentrations in sediments in very shallow water off the southern coast of Fukushima may continue to decline over time.



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High-resolution 129I bomb peak profile in an ice core from SE-Dome site, Greenland

Publication date: April 2018
Source:Journal of Environmental Radioactivity, Volumes 184–185
Author(s): Angel T. Bautista, Yasuto Miyake, Hiroyuki Matsuzaki, Yoshinori Iizuka, Kazuho Horiuchi
129I in natural archives, such as ice cores, can be used as a proxy for human nuclear activities, age marker, and environmental tracer. Currently, there is only one published record of 129I in ice core (i.e., from Fiescherhorn Glacier, Swiss Alps) and its limited time resolution (1–2 years) prevents the full use of 129I for the mentioned applications. Here we show 129I concentrations in an ice core from SE-Dome, Greenland, covering years 1956–1976 at a time resolution of ∼6 months, the most detailed record to date. Results revealed 129I bomb peaks in years 1959, 1962, and 1963, associated to tests performed by the former Soviet Union, one year prior, in its Novaya Zemlya test site. All 129I bomb peaks were observed in winter (1958.9, 1962.1, and 1963.0), while tritium bomb peaks, another prominent radionuclide associated with nuclear bomb testing, were observed in spring or summer (1959.3, and 1963.6; Iizuka et al., 2017). These results indicate that 129I bomb peaks can be used as annual and seasonal age markers for these years. Furthermore, we found that 129I recorded nuclear fuel reprocessing signals and that these can be potentially used to correct timing of estimated 129I releases during years 1964–1976. Comparisons with other published records of 129I in natural archives showed that 129I can be used as common age marker and tracer for different types of records. Most notably, the 1963 129I bomb peak can be used as common age marker for ice and coral cores, providing the means to reconcile age models and associated trends from the polar and tropical regions, respectively.

Graphical abstract

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Experience of on-site disposal of production uranium-graphite nuclear reactor

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Publication date: April 2018
Source:Journal of Environmental Radioactivity, Volumes 184–185
Author(s): Alexander O. Pavliuk, Sergey G. Kotlyarevskiy, Evgeny V. Bespala, Elena V. Zakharova, Vyacheslav M. Ermolaev, Anna G. Volkova
The paper reported the experience gained in the course of decommissioning EI-2 Production Uranium-Graphite Nuclear Reactor. EI-2 was a production Uranium-Graphite Nuclear Reactor located on the Production and Demonstration Center for Uranium-Graphite Reactors JSC (PDC UGR JSC) site of Seversk City, Tomsk Region, Russia. EI-2 commenced its operation in 1958, and was shut down on December 28, 1990, having operated for the period of 33 years all together. The extra pure grade graphite for the moderator, water for the coolant, and uranium metal for the fuel were used in the reactor. During the operation nitrogen gas was passed through the graphite stack of the reactor. In the process of decommissioning the PDC UGR JSC site the cavities in the reactor space were filled with clay-based materials. A specific composite barrier material based on clays and minerals of Siberian Region was developed for the purpose. Numerical modeling demonstrated the developed clay composite would make efficient geological barriers preventing release of radionuclides into the environment.



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Comparisons between a new point kernel-based scheme and the infinite plane source assumption method for radiation calculation of deposited airborne radionuclides from nuclear power plants

Publication date: April 2018
Source:Journal of Environmental Radioactivity, Volumes 184–185
Author(s): Xiaole Zhang, George Efthimiou, Yan Wang, Meng Huang
Radiation from the deposited radionuclides is indispensable information for environmental impact assessment of nuclear power plants and emergency management during nuclear accidents. Ground shine estimation is related to multiple physical processes, including atmospheric dispersion, deposition, soil and air radiation shielding. It still remains unclear that whether the normally adopted "infinite plane" source assumption for the ground shine calculation is accurate enough, especially for the area with highly heterogeneous deposition distribution near the release point. In this study, a new ground shine calculation scheme, which accounts for both the spatial deposition distribution and the properties of air and soil layers, is developed based on point kernel method. Two sets of "detector-centered" grids are proposed and optimized for both the deposition and radiation calculations to better simulate the results measured by the detectors, which will be beneficial for the applications such as source term estimation. The evaluation against the available data of Monte Carlo methods in the literature indicates that the errors of the new scheme are within 5% for the key radionuclides in nuclear accidents. The comparisons between the new scheme and "infinite plane" assumption indicate that the assumption is tenable (relative errors within 20%) for the area located 1 km away from the release source. Within 1 km range, the assumption mainly causes errors for wet deposition and the errors are independent of rain intensities. The results suggest that the new scheme should be adopted if the detectors are within 1 km from the source under the stable atmosphere (classes E and F), or the detectors are within 500 m under slightly unstable (class C) or neutral (class D) atmosphere. Otherwise, the infinite plane assumption is reasonable since the relative errors induced by this assumption are within 20%. The results here are only based on theoretical investigations. They should be further thoroughly evaluated with real measurements in the future.

Graphical abstract

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Evaluation of abundance of artificial radionuclides in food products in South Korea and sources

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Publication date: April 2018
Source:Journal of Environmental Radioactivity, Volumes 184–185
Author(s): S.H. Lee, J.S. Oh, K.B. Lee, J.M. Lee, S.H. Hwang, M.K. Lee, E.H. Kwon, C.S. Kim, I.H. Choi, I.Y. Yeo, J.Y. Yoon, J.M. Im
Food samples are collected nationwide from January 2016 to February 2017 and their contents of artificial radionuclides are measured to address the growing concerns regarding the radioactive contamination of food products in Korea. Specifically, 900 food samples are collected for this study and their contents of representative artificial radionuclides 134Cs, 137Cs, 239,240Pu, and 90Sr are analyzed. The analysis shows that the activity concentrations of 137Cs in fish range from minimum detectable activity (MDA) to 340 mBq/kg of fresh weight. The concentration factor (CF) determined for 137Cs as a measure of its bioavailability is calculated to be ca. 74 and found to be very similar to that (100) recommended by the International Atomic Energy Agency. With an MDA of <0.221 mBq/kg, the results reveal that 239,240Pu values in fish are below the MDA. The activity concentrations of 137Cs and 90Sr are lower than the MDA in both shellfish and seaweed, while the activity concentrations of 239,240Pu in shellfish range from 0.26 to 2.18 mBq/kg, and for seaweed samples range from 2.07 to 3.38 mBq/kg. The atom ratios of 240Pu/239Pu in shellfish caught at the Korean coast vary from 0.209 to 0.237, with a mean of 0.227. The higher 240Pu/239Pu atom ratio determined in shellfish is thought to be caused by the plutonium transported from the Pacific Proving Grounds rather than other sources such as the Fukushima nuclear power plant accident. The activity concentrations of 137Cs in mushrooms are found to vary from 1.0 to 21.4 Bq/kg, with the highest concentrations observed in the Oak (shiitake) and Sarcodon asparatus. 134Cs is detected in three mushroom specimens collected from Jeju Island and about 3–3.6% of 137Cs present in the wild mushrooms native to the Jeju Island are introduced as a result of the Fukushima nuclear plant accident. The annual effective doses of 137Cs received through consumption of mushrooms and fish are 2.0 × 10−4 mSv yr−1 and 3.9 × 10−5 mSv yr−1, and those values are negligible compared to the annual effective doses limit of 1 mSv yr−1.



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Soil-to-plant transfer factors of natural radionuclides (226Ra and 40K) in selected Thai medicinal plants

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Publication date: April 2018
Source:Journal of Environmental Radioactivity, Volumes 184–185
Author(s): Kiadtisak Saenboonruang, Endu Phonchanthuek, Kamonkhuan Prasandee
A soil-to-plant transfer factor (TF) is an important parameter that could be used to estimate radionuclides levels in medicinal plants. This work reports concentrations of natural radionuclides (226Ra and 40K) and TFs in six Thai medicinal plants grown in central Thailand using an HPGe gamma ray spectrometer. Either root, leaf, or flower parts of each medicinal plant were selected for use in the investigation according to their practical uses in traditional medicine. The results showed that due to K being essential in plants, 40K had higher arithmetic means of activity concentrations and geometric means of TFs (geometric standard deviations in parentheses) of 610 ± 260 Bq kg−1 dry weight (DW) and 2.0 (1.4), respectively, than 226Ra, which had the activity concentrations and TFs of 4.8 ± 2.6 Bq kg−1 DW and 0.17 (1.8), respectively. The results also showed that the leaves of medicinal plants had higher activity concentrations and TFs than root and flower parts, probably due to higher metabolic activities in leaves. Furthermore, there was good agreement between the results from the current work and other similar reports on medicinal plants. The information obtained from this work could strengthen knowledge of natural radionuclides in plants and particularly increase available TF data on Thai medicinal plants.



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Source identification of uranium-containing materials at mine legacy sites in Portugal

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Publication date: March 2018
Source:Journal of Environmental Radioactivity, Volume 183
Author(s): A.C. Keatley, P.G. Martin, K.R. Hallam, O.D. Payton, R. Awbery, F. Carvalho, J.M. Oliveira, L. Silva, M. Malta, T.B. Scott
Whilst prior nuclear forensic studies have focused on identifying signatures to distinguish between different uranium deposit types, this paper focuses on providing a scientific basis for source identification of materials from different uranium mine sites within a single region, which can then be potentially used within nuclear forensics. A number of different tools, including gamma spectrometry, alpha spectrometry, mineralogy and major and minor elemental analysis, have been utilised to determine the provenance of uranium mineral samples collected at eight mine sites, located within three different uranium provinces, in Portugal. A radiation survey was initially conducted by foot and/or unmanned aerial vehicle at each site to assist sample collection. The results from each mine site were then compared to determine if individual mine sites could be distinguished based on characteristic elemental and isotopic signatures. Gamma and alpha spectrometry were used to differentiate between samples from different sites and also give an indication of past milling and mining activities. Ore samples from the different mine sites were found to be very similar in terms of gangue and uranium mineralogy. However, rarer minerals or specific impurity elements, such as calcium and copper, did permit some separation of the sites examined. In addition, classification rates using linear discriminant analysis were comparable to those in the literature.



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Acknowledgements to reviewers



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A well-circumscribed lobulated tumor on the hard palatal mucosa in a child.

Related Articles

A well-circumscribed lobulated tumor on the hard palatal mucosa in a child.

Oral Surg Oral Med Oral Pathol Oral Radiol. 2017 Dec 11;:

Authors: Salcines A, Woo SB, Noonan V, Mansfield MJ, Li CC

PMID: 29337189 [PubMed - as supplied by publisher]



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Preoperative evaluation of cochlear implantation through the round window membrane in the facial recess using high-resolution computed tomography.

Preoperative evaluation of cochlear implantation through the round window membrane in the facial recess using high-resolution computed tomography.

Surg Radiol Anat. 2018 Jan 16;:

Authors: Xie LH, Tang J, Miao WJ, Tang XL, Li H, Tang AZ

Abstract
PURPOSE: We evaluated the risk of cochlear implantation through the round window membrane in the facial recess through a preoperative analysis of the angle between the facial nerve-round window and the cranial midline using high-resolution temporal bone CT.
METHODS: Temporal bone CT films of 176 patients with profound sensorineural hearing loss at our hospital from 2013 to 2015 were reviewed. The preoperative temporal bone CT scans of the patients were retrospectively analysed. The vertical distance (d value) from the leading edge of the facial nerve to the posterior wall of the external auditory canal and the angle (α value) between the line from the leading edge of the facial nerve to the midpoint of the round window membrane and the median sagittal line on the round window membrane plane were measured. Based on intraoperative observation, the round window membrane was divided into complete round window membrane exposure (group A), partial exposure (group B), and unexposed (group C) groups, and statistical analysis was performed.
RESULTS: The α value could be effectively measured for all 176 patients (62.60 ± 7.12), and the d value could be effectively measured for 95 cases (5.53 ± 1.00). An analysis of the correlation between the α and d values of these 95 cases found a negative correlation. Of the 176 cases, one-way analysis of variance (ANOVA) showed that the differences among the groups were significant [P = 0.000 (< 0.05)].
CONCLUSION: The angle (α value) between the line connecting the leading edge of the facial nerve to the midpoint of the round window and the median sagittal line measured in preoperative CT scans was associated with the difficulty of intraoperatively exposing the round window membrane. When the α value was larger than a certain degree, the difficulty of exposing the round window membrane was increased. In such cases, the surgeon should fully expose the round window membrane during surgery, which could result decrease the likelihood of complications.

PMID: 29340754 [PubMed - as supplied by publisher]



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Treatment outcome and prognostic factors for adult patients with medulloblastoma: The Rare Cancer Network (RCN) experience

The optimal treatment for adults with newly diagnosed medulloblastoma (MB) has not been defined. We report a large series of cases from the Rare Cancer Network.

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A simple clinical method for predicting the benefit of prone vs. supine positioning in reducing heart exposure during left breast radiotherapy

The benefit of reduced radiation heart exposure in the prone vs. supine position individually differs. In this prospective cohort study, the goal was to develop a simple method for the operation of a validated model for the prediction of preferable treatment position during left breast radiotherapy.

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Ototoxicity and cochlear sparing in children with medulloblastoma: Proton vs. photon radiotherapy

To compare ototoxicity rates between medulloblastoma patients treated with protons vs. photons.

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Risk of Pelvic Inflammatory Disease in Relation to Chlamydia and Gonorrhea Testing, Repeat Testing, and Positivity: A Population-Based Cohort Study

Abstract
Background
There is uncertainty around whether the risks of pelvic inflammatory disease (PID) differ following Chlamydia trachomatis (chlamydia) and Neisseria gonorrhoeae (gonorrhea) infection. We quantified the risk of PID associated with chlamydia and gonorrhea infection and subsequent repeat infections in a whole-population cohort.
Methods
A cohort of 315123 Western Australian women, born during 1974–1995, was probabilistically linked to chlamydia and gonorrhea testing records and to hospitalizations and emergency department presentations for PID from 2002 to 2013. Time-updated survival analysis was used to investigate the association between chlamydia and gonorrhea testing, and positivity, and risk of PID.
Results
Over 3199135 person-years, 120748 women had pathology test records for both chlamydia and gonorrhea, 10745 chlamydia only, and 653 gonorrhea only. Among those tested, 16778 (12.8%) had ≥1 positive chlamydia test, 3195 (2.6%) ≥1 positive gonorrhea test, and 1874 (1.6%) were positive for both. There were 4819 PID presentations (2222 hospitalizations, 2597 emergency presentations). Adjusting for age, Aboriginality, year of follow-up, health area, and socioeconomic status, compared to women negative for chlamydia and gonorrhea, the relative risk (adjusted incidence rate ratio) of PID was 4.29 (95% confidence interval [CI], 3.66–5.03) in women who were both chlamydia and gonorrhea positive; 4.54 (95% CI, 3.87–5.33) in those only gonorrhea positive; and 1.77 (95% CI, 1.61–1.94) in those only chlamydia positive.
Conclusions
Gonorrhea infection conferred a substantially higher risk than chlamydia of hospitalization or emergency department presentation for PID. The emergence of gonorrhea antimicrobial resistance may have a serious impact on rates of PID and its associated reproductive health sequelae.

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Cost-effectiveness of Bezlotoxumab Compared With Placebo for the Prevention of Recurrent Clostridium difficile Infection

Abstract
Background
Clostridium difficile infection (CDI) is the most commonly recognized cause of recurrent diarrhea. Bezlotoxumab, administered concurrently with antibiotics directed against C. difficile (standard of care [SoC]), has been shown to reduce the recurrence of CDI, compared with SoC alone. This study aimed to assess the cost-effectiveness of bezlotoxumab administered concurrently with SoC, compared with SoC alone, in subgroups of patients at risk of recurrence of CDI.
Methods
A computer-based Markov health state transition model was designed to track the natural history of patients infected with CDI. A cohort of patients entered the model with either a mild/moderate or severe CDI episode, and were treated with SoC antibiotics together with either bezlotoxumab or placebo. The cohort was followed over a lifetime horizon, and costs and utilities for the various health states were used to estimate incremental cost-effectiveness ratios (ICERs). Both deterministic and probabilistic sensitivity analyses were used to test the robustness of the results.
Results
The cost-effectiveness model showed that, compared with placebo, bezlotoxumab was associated with 0.12 quality-adjusted life-years (QALYs) gained and was cost-effective in preventing CDI recurrences in the entire trial population, with an ICER of $19824/QALY gained. Compared with placebo, bezlotoxumab was also cost-effective in the subgroups of patients aged ≥65 years (ICER of $15298/QALY), immunocompromised patients (ICER of $12597/QALY), and patients with severe CDI (ICER of $21430/QALY).
Conclusions
Model-based results demonstrated that bezlotoxumab was cost-effective in the prevention of recurrent CDI compared with placebo, among patients receiving SoC antibiotics for treatment of CDI.

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Genomic Investigation of a Putative Endoscope-Associated Carbapenem-Resistant Enterobacter cloacae Outbreak Reveals a Wide Diversity of Circulating Strains and Resistance Mutations

Abstract
A genomic epidemiologic investigation of a putative carbapenem-resistant Enterobacter cloacae outbreak revealed few plausible instances of nosocomial transmission, highlighting instead the frequent importation of E. cloacae into our hospital. Searching for genetic determinants of carbapenem resistance demonstrated that most resistance is due to convergent mutations in phylogenetically diverse E. cloacae.

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The Influence of Reported Penicillin Allergy

prophylaxisantibioticsurgical site infectionsallergyvancomycin

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The Impact of a Reported Penicillin Allergy on Surgical Site Infection Risk

Abstract
Background
A reported penicillin allergy may compromise receipt of recommended antibiotic prophylaxis intended to prevent surgical site infections (SSIs). Most patients with a reported penicillin allergy are not allergic. We determined the impact of a reported penicillin allergy on the development of SSIs.
Methods
In this retrospective cohort study of Massachusetts General Hospital hip arthroplasty, knee arthroplasty, hysterectomy, colon surgery, and coronary artery bypass grafting patients from 2010 to 2014, we compared patients with and without a reported penicillin allergy. The primary outcome was an SSI, as defined by the Centers for Disease Control and Prevention’s National Healthcare Safety Network. The secondary outcome was perioperative antibiotic use.
Results
Of 8385 patients who underwent 9004 procedures, 922 (11%) reported a penicillin allergy, and 241 (2.7%) had an SSI. In multivariable logistic regression, patients reporting a penicillin allergy had increased odds (adjusted odds ratio, 1.51; 95% confidence interval, 1.02–2.22) of SSI. Penicillin allergy reporters were administered less cefazolin (12% vs 92%; P < .001) and more clindamycin (49% vs 3%; P < .001), vancomycin (35% vs 3%; P < .001), and gentamicin (24% vs 3%; P < .001) compared with those without a reported penicillin allergy. The increased SSI risk was entirely mediated by the patients’ receipt of an alternative perioperative antibiotic; between 112 and 124 patients with reported penicillin allergy would need allergy evaluation to prevent 1 SSI.
Conclusions
Patients with a reported penicillin allergy had a 50% increased odds of SSI, attributable to the receipt of second-line perioperative antibiotics. Clarification of penicillin allergies as part of routine preoperative care may decrease SSI risk.

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A 12-Year Follow-up on the Long-Term Effectiveness of the Quadrivalent Human Papillomavirus Vaccine in 4 Nordic Countries

Abstract
Background
The long-term effectiveness of the quadrivalent human papillomavirus (qHPV) vaccine was assessed by monitoring the combined incidence of cervical intraepithelial neoplasia (CIN2, CIN3), adenocarcinoma in situ (AIS), and cervical cancer related to HPV16 or HPV18.
Methods
Women from Nordic countries of Denmark, Iceland, Norway, and Sweden who received a 3-dose regimen of the qHPV vaccine in the beginning of FUTURE II (Females United to Unilaterally Reduce Endo/Ectocervical Disease; V501-015, base study NCT00092534) are followed through different national registries. Effectiveness analyses were conducted approximately 2 years following completion of the base study and occur approximately every 2 years thereafter for 10 years (ie, 14 years from day 1 of the base study). Vaccine effectiveness against HPV16/18-related CIN2 or worse (CIN2+) was estimated by comparing the observed incidence with the expected incidence of CIN2+ in an unvaccinated cohort using historical registry data.
Results
In the per-protocol population (2084 women) analysis of effectiveness after the first 12 years, there were no breakthrough cases of HPV16/18 CIN2+ after 9437 person- years of follow-up. Statistical power was sufficient to conclude that qHPV vaccine effectiveness remains above 90% for at least 10 years. The number of person-years during the follow-up interval of 10–12 years is continuing to accrue and shows a trend toward continuing effectiveness of the vaccine during that period.
Conclusion
The qHPV vaccine shows continued protection in women through at least 10 years, with a trend for continued protection through 12 years of follow-up.
Clinical Trials Registration
NCT00092534.
Study Identification
V501-015

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Antimicrobial Resistance Gene Acquisition and Depletion Following Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection

Abstract
Fecal microbiota transplantation (FMT) may be a novel approach to eliminate multidrug-resistant bacteria from the gut and to prevent future infections. Using whole metagenome sequencing data from 8 FMT donor–recipient pairs, we identified 37 and 95 antimicrobial resistance genes that were acquired by or removed from FMT recipients, respectively.

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Comparison of a Novel Human Rabies Monoclonal Antibody to Human Rabies Immunoglobulin for Postexposure Prophylaxis: A Phase 2/3, Randomized, Single-Blind, Noninferiority, Controlled Study

Abstract
Background
Lack of access to rabies immunoglobulin (RIG) contributes to high rabies mortality. A recombinant human monoclonal antibody (SII RMAb) was tested in a postexposure prophylaxis (PEP) regimen in comparison with a human RIG (HRIG)–containing PEP regimen.
Methods
This was a phase 2/3, randomized, single-blind, noninferiority study conducted in 200 participants with World Health Organization category III suspected rabies exposures. Participants received either SII RMAb or HRIG (1:1 ratio) in wounds and, if required, intramuscularly on day 0, along with 5 doses of rabies vaccine intramuscualarly on days 0, 3, 7, 14 and 28. The primary endpoint was the ratio of the day 14 geometric mean concentration (GMC) of rabies virus neutralizing activity (RVNA) as measured by rapid fluorescent focus inhibition test for SII RMAb recipients relative to HRIG recipients.
Results
One hundred ninety-nine participants received SII RMAb (n = 101) or HRIG (n = 98) and at least 1 dose of vaccine. The day 14 GMC ratio of RVNA for the SII RMAb group relative to the HRIG group was 4.23 (96.9018% confidence interval [CI], 2.59–6.94) with a GMC of of 24.90 IU/mL (95% CI, 18.94–32.74) for SII RMAb recipients and 5.88 IU/mL (95% CI, 4.11–8.41) for HRIG recipients. The majority of local injection site and systemic adverse reactions reported from both groups were mild to moderate in severity.
Conclusions
A PEP regimen containing SII RMAb was safe and demonstrated noninferiority to HRIG PEP in RVNA production. The novel monoclonal potentially offers a safe and potent alternative for the passive component of PEP and could significantly improve the management of bites from suspected rabid animals.
Clincical Trials Registration
CTRI/2012/05/002709.

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Epidemiology and Antimicrobial Resistance Characteristics of the Sequence Type 131-H30 Subclone Among Extraintestinal Escherichia coli Collected From US Children

Abstract
Background
Escherichia coli sequence type (ST) 131-H30 is a globally important pathogen implicated in rising rates of multidrug resistance among E. coli causing extraintestinal infections. Previous studies have focused on adults, leaving the epidemiology of H30 among children undefined.
Methods
We used clinical data and isolates from a case-control study of extended-spectrum cephalosporin-resistant E. coli conducted at 4 US children’s hospitals to estimate the burden and identify host correlates of infection with H30. H30 isolates were identified using 2-locus genotyping; host correlates were examined using log-binomial regression models stratified by extended-spectrum cephalosporin resistance status.
Results
A total of 339 extended-spectrum cephalosporin-resistant and 1008 extended-spectrum cephalosporin-susceptible E. coli isolates were available for analyses. The estimated period prevalence of H30 was 5.3% among all extraintestinal E. coli isolates (95% confidence interval [CI], 4.6%–7.1%); H30 made up 43.3% (81/187) of extended-spectrum β-lactamase (ESBL)–producing isolates in this study. Host correlates of infection with H30 differed by extended-spectrum cephalosporin resistance status: Among resistant isolates, age ≤5 years was positively associated with H30 infection (relative risk [RR], 1.83 [95% CI, 1.19–2.83]); among susceptible isolates, age ≤5 years was negatively associated with H30 (RR, 0.48 [95% CI, .27–.87]), while presence of an underlying medical condition was positively associated (RR, 4.49 [95% CI, 2.43–8.31]).
Conclusions
ST131-H30 is less common among extraintestinal E. coli collected from children compared to reported estimates among adults, possibly reflecting infrequent fluoroquinolone use in pediatrics; however, it is similarly dominant among ESBL-producing isolates. The H30 subclone appears to disproportionately affect young children relative to other extended-spectrum cephalosporin-resistant E. coli.

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Evidence of Sexually Transmitted Disease Testing Outside of Primary Human Immunodeficiency Virus Care for People Living With Human Immunodeficiency Virus in San Francisco, California

To the Editor—Using data from the Medical Monitoring Project (MMP), Mattson and colleagues found that a low proportion of sexually active adults in human immunodeficiency virus (HIV) care were screened for sexually transmitted diseases (STDs) in the prior 12 months in their primary care setting [1]. Sexually transmitted disease testing was far below recommended guidelines for sexually active persons living with HIV [2]. Reading this article encouraged us to examine our local MMP data to determine whether STD testing rates among MMP participants in San Francisco were similar and to examine whether the proportion of persons screened for STDs was underestimated because data collection in MMP was limited to medical chart abstraction from the participants’ place of primary HIV care. Mattson et al noted this restriction as a limitation of their study.

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Monitoring of Parasite Kinetics in Indian Post–Kala-azar Dermal Leishmaniasis

Abstract
Background
The potential reservoirs of leishmaniasis in South Asia include relapsed cases of visceral leishmaniasis (VL), patients with post–kala-azar dermal leishmaniasis (PKDL), and an asymptomatically infected population. Therefore, assessment of cure in terms of parasite clearance, early detection of PKDL, and asymptomatic VL are pivotal for ensuring elimination. This study aimed to monitor the efficacy of miltefosine and liposomal amphotericin B (LAmB) in PKDL based on parasite load.
Methods
Patients with PKDL were recruited from the dermatology outpatient departments or during active field surveys. Skin biopsies were collected at disease presentation, immediately at the end of treatment, and 6 months later. The presence of parasite DNA was assessed by internal transcribed spacer-1 polymerase chain reaction, and quantified by amplification of parasite kinetoplastid DNA.
Results
At disease presentation (n = 184), the median parasite load was 5229 (interquartile range [IQR], 896–50898)/μg genomic DNA (gDNA). Miltefosine cleared the parasites to <10 in the macular (n = 17) and polymorphic (n = 21) variants, and remained so up to 6 months later (<10 parasites). LAmB reduced the parasite burden substantially in macular (n = 34; 2128 [IQR, 544–5763]/µg gDNA) and polymorphic PKDL (n = 36; 2541 [IQR, 650–9073]/µg gDNA). Importantly, in patients who returned 6 months later (n = 38), a resurgence of parasites was evident, as the parasites increased to 5665 (IQR, 1840–17067)/µg gDNA.
Conclusions
This study established that quantifying parasite load is an effective approach for monitoring patients with PKDL, wherein miltefosine demonstrated near-total parasite clearance and resolution of symptoms. However, in cases treated with LAmB, the persistence of parasites suggested treatment inadequacy. This needs immediate redressal in view of the leishmaniasis elimination program targeted for 2020.

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Long-term Clinical Outcomes in Visceral Leishmaniasis/Human Immunodeficiency Virus–Coinfected Patients During and After Pentamidine Secondary Prophylaxis in Ethiopia: A Single-Arm Clinical Trial

Abstract
Background
We have conducted a single-arm trial evaluating monthly pentamidine secondary prophylaxis (PSP) to prevent visceral leishmaniasis (VL) relapse in Ethiopian human immunodeficiency virus–infected patients. Outcomes at 12 months of PSP have been previously reported, supporting PSP effectiveness and safety. However, remaining relapse-free after PSP discontinuation is vital. We now report outcomes and associated factors for a period of up to 2.5 years after initiating PSP, including 1-year follow-up after PSP discontinuation.
Methods
The trial had 3 phases: (1) 12 months of PSP; (2) a 6-month PSP extension period if CD4 count was ≤200 cells/μL at month 12; and (3) 12-month follow-up after stopping PSP. The probability of relapse and risk factors were calculated using Kaplan-Meier methods and Cox regression analysis.
Results
For the 74 patients included, final study outcomes were as follows: 39 (53%) relapse-free, 20 (27%) relapsed, 5 (7%) deaths, 10 (14%) lost to follow-up. The 2-year risk of relapse was 36.9% (95% confidence interval, 23.4%–55.0%) and was highest for those with a history of VL relapse and low baseline CD4 count. Forty-five patients were relapse-free and in follow-up at month 12 of PSP. This included 28 patients with month 12 CD4 counts >200 cells/µL, remaining relapse-free after PSP discontinuation. Among the 17 with month 12 CD4 count <200 cells/µL, 1 relapsed and 3 were lost during the PSP extension period. During 1-year post-PSP follow-up, 2 patients relapsed and 1 was lost to follow-up. No PSP-related serious adverse events were reported during the PSP-extension/post-PSP follow-up period.
Conclusions
It seems safe to discontinue PSP at month 12 CD4 counts of >200 cells/µL. The management of those failing to reach this level remains to be defined.
Clinical Trials Registration
NCT01360762.

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Hepatitis C Screening: From Modeling to Public Health Policy

decision-analytic modelingcost-effectiveness analysisdirect-acting antiviralsMarkov modelscreening guidelines

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Textbook of Global Health Anne-Emanuelle Birn, Yogan Pillay, and Timothy H. Holtz. Fourth edition. Oxford University Press, 2017. 674 pp. $85.00 (hardcover).

For those seeking a clinical introduction to diseases encountered internationally, this is not your book. For the thoughtful undergraduate or graduate student interested in understanding the complex political, social, and environmental drivers of health disparities worldwide, this is for you. In fact, this insightful, well-researched, comprehensive textbook should be required reading for anyone working in global health. The authors, renowned scholars and practitioners, cover a range of material from the local to the international level in low- and high-income countries alike. The first section covers the history of the field (commenting on significant events, policies, and other factors that have shaped health over the years), dominant ideologies, key governmental and nongovernmental organizations, measures and patterns of disease, and social determinants of health. The next section focuses on health economics, a comparison of healthcare systems in different countries, and the impact of crisis conditions (eg, war, terrorism) and environmental changes on health. The final chapters address ethical considerations for global health work and a way forward for the field.

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The influence of elevated hormone levels on physiologic accumulation of 68 Ga-DOTATOC

Abstract

Objective

PET/CT imaging with 68Ga-1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid-D-Phe1-Tyr3-octreotide (DOTATOC) is useful in patients with neuroendocrine tumors (NETs). Functioning NETs by definition secrete abnormal levels of hormones, causing clinical symptoms. It is known that physiologic accumulation can be seen in some organs, but it remains unknown whether elevated hormone levels can affect the physiologic accumulation pattern of 68Ga-DOTATOC. We aimed to investigate the influence of higher hormone levels on physiologic accumulation of 68Ga-DOTATOC.

Methods

A total of 167 patients with known or suspected NET lesions were enrolled in this study. The numbers of patients with elevations of ACTH, gastrin, insulin, and no elevation were 10, 25, 7, and 125, respectively. We compared the maximum standardized uptake value (SUVmax) in various organs of each group.

Results

In the group with elevated ACTH levels, SUVmax in the pituitary gland, the uncinate process of the pancreas and adrenal glands was lower than those in the group with no elevation (5.7 ± 1.9 vs. 8.4 ± 3.1, P = 0.015; 4.7 ± 3.5 vs. 6.4 ± 2.8, P = 0.037; 10.8 ± 4.8 vs. 13.9 ± 4.7, P = 0.020, respectively). There were no differences in physiologic uptake of 68Ga-DOTATOC in the thyroid gland, the pancreatic body, the liver, the spleen, the bowel, or the kidney.

Conclusions

In NET patients with elevated ACTH levels, physiologic uptake of 68Ga-DOTATOC in the pituitary gland, the uncinate process of the pancreas and adrenal glands was significantly decreased. Other organs were unaffected.



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ViLLE – collaborative education tool: Designing and utilizing an exercise-based learning environment

Abstract

Automatically assessed exercises with immediate feedback can be a powerful tool for enhancing the effectiveness of education. In this article, we discuss the design and implementation of a collaborative learning tool called ViLLE. The design is based on experiences gathered from a previously developed and thoroughly researched visualization tool. Based on our earlier results and current educational theories, we developed four design principles upon which ViLLE is constructed. ViLLE includes various different exercise types which were designed to assist in the learning of computer science, mathematics and other subjects. It also supports different learning and teaching methods, such as pair programming and peer review. To justify the development of a new environment, we present four diverse case studies where ViLLE was utilized successfully: programming education, high school matriculation exam, elementary school mathematics and student counseling at university level. The results obtained from the studies seem to confirm that ViLLE can be used effectively to enhance student motivation and to improve student performance in various heterogeneous educational setups.



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Genes, Vol. 9, Pages 43: Isoform Sequencing and State-of-Art Applications for Unravelling Complexity of Plant Transcriptomes

Genes, Vol. 9, Pages 43: Isoform Sequencing and State-of-Art Applications for Unravelling Complexity of Plant Transcriptomes

Genes doi: 10.3390/genes9010043

Authors: Dong An Hieu Cao Changsheng Li Klaus Humbeck Wenqin Wang

Single-molecule real-time (SMRT) sequencing developed by PacBio, also called third-generation sequencing (TGS), offers longer reads than the second-generation sequencing (SGS). Given its ability to obtain full-length transcripts without assembly, isoform sequencing (Iso-Seq) of transcriptomes by PacBio is advantageous for genome annotation, identification of novel genes and isoforms, as well as the discovery of long non-coding RNA (lncRNA). In addition, Iso-Seq gives access to the direct detection of alternative splicing, alternative polyadenylation (APA), gene fusion, and DNA modifications. Such applications of Iso-Seq facilitate the understanding of gene structure, post-transcriptional regulatory networks, and subsequently proteomic diversity. In this review, we summarize its applications in plant transcriptome study, specifically pointing out challenges associated with each step in the experimental design and highlight the development of bioinformatic pipelines. We aim to provide the community with an integrative overview and a comprehensive guidance to Iso-Seq, and thus to promote its applications in plant research.



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Bibliometric analysis of a century of research on oral erythroplakia and leukoplakia

Abstract

Background

Oral squamous cell carcinoma is a major cause of cancer-associated morbidity and mortality and may develop from oral erythroplakia and leukoplakia (OEL), the most common oral potentially malignant lesions. Our objective was to provide a descriptive overview of the global research activity on OEL over the past decades.

Methods

We performed a systematic bibliometric analysis of articles and reviews on OEL up to December 31st 2016 using the SCOPUS database. Contribution of each country was analyzed by density equalizing mapping (DEMP). The overall scientific productivity was analyzed for each journal and country

Results

A total of 5,098 published items (articles or reviews) were identified. They are expected to double by 2040, with an expected number of 400 items per year. Only 4% of all research on oral oncology is focused on OEL. Together with the increasing number of publications since 1980s, an increasing number of international collaborative studies were observed. Journal of Oral Pathology and Medicine and Oral Oncology are the leading journals in terms of number of published items. The US, India and the UK were the most prolific countries in terms of publications over time

Conclusions

We identified the leading journals as well as the leading authors and countries contributing to the research on OEL. International collaborative studies in the field are to be encouraged in order to refine strategies of oral cancer prevention.

This article is protected by copyright. All rights reserved.



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Gelatin- hydroxyapatite- calcium sulphate based biomaterial for long term sustained delivery of bone morphogenic protein-2 and zoledronic acid for increased bone formation: In-vitro and in-vivo carrier properties

Publication date: 28 February 2018
Source:Journal of Controlled Release, Volume 272
Author(s): Deepak Bushan Raina, David Larsson, Filip Mrkonjic, Hanna Isaksson, Ashok Kumar, Lars Lidgren, Magnus Tägil
In this study, a novel macroporous composite biomaterial consisting of gelatin-hydroxyapatite-calcium sulphate for delivery of bone morphogenic protein-2 (rhBMP-2) and zoledronic acid (ZA) has been developed. The biomaterial scaffold has a porous structure and functionalization of the scaffold with rhBMP-2 induces osteogenic differentiation of MC3T3-e1 cells seen by a significant increase in biochemical and genetic markers of osteoblastic differentiation. In-vivo muscle pouch experiments showed higher mineralization using scaffold+rhBMP-2 when compared to an approved absorbable collagen sponge (ACS)+rhBMP-2 as verified by micro-CT. Co-delivery of rhBMP-2+ZA via the novel scaffold enabled a reduction in the effective rhBMP-2 doses. The presence of tartrate resistant acid phosphatase staining in the rhBMP-2 group indicates osteoclastic resorption, which could be stalled by adding ZA, which by speculation could explain the net increase in mineralization. The new scaffold allowed for slow release of rhBMP-2 in-vitro (3.3±0.1%) after 4weeks. Using single photon emission computed tomography (SPECT), the release kinetics of 125I–rhBMP-2 in-vivo was followed for 4weeks and a total of 65.3±15.2% 125I–rhBMP-2 was released from the scaffolds. In-vitro 14C–ZA release curve shows an initial burst release on day 1 (8.8±0.7%) followed by a slow release during the following 4weeks (13±0.1%). In-vivo, an initial release of 43.2±7.6% of 14C–ZA was detected after 1day, after which the scaffold retained the remaining ZA during 4-weeks. Taken together, our results show that the developed biomaterial is an efficient carrier for spatio-temporal delivery of rhBMP-2 and ZA leading to increased bone formation compared to commercially available carrier for rhBMP-2.

Graphical abstract

image


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Molecular phylogenetics of Boulengerula (Amphibia: Gymnophiona: Caeciliidae) and implications for taxonomy, biogeography and conservation

Phylogenetic relationships of the East African caeciliid Boulengerula were reconstructed using 12S, 16S and cytb mitochondrial gene sequences for 32 samples from Kenya and Tanzania. The generally well-supported and resolved phylogeny displayed the following relationships among the five nominate species sampled: (B. boulengeri ((B. taitanus, B. niedeni),(B. changamwensis, B. uluguruensis))). This resolution supports a formerly proposed bipartition of the genus, and differs significantly from previous, morphological phylogenies. Our analyses identified genetic differences between several mtDNA clades that potentially represent undescribed species. If substantiated, the necessary taxonomic revision will have implications for conservation assessments that depend to an important extent upon sizes of distributions. Overall, there is a positive correlation between genetic and geographic distance among and within the main clades. The two lowland, coastal individuals sampled are nested within primarily montane clades. Dating analyses suggest some temporally congruent divergences in Boulengerula, but other divergences happened at different times and over a long period, perhaps extending back to the Oligocene/Eocene. Our results for Boulengerula suggest a role for relative long-term environmental stability in the origins of the Eastern Arc Mountains biodiversity hotspot.

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The systematics of Boulengerula fischeri (Amphibia: Gymnophiona: Caeciliidae) based on morphological and molecular data

Eight new specimens are reported for the caecilian amphibian Boulengerula fischeri, a species known in detail previously only from its holotype collected in 1987. The new material was collected at the type locality in Rwanda in 2009, and is used to expand and refine the morphological characterization of the species. Mitochondrial and nuclear gene sequences were used to assess the phylogenetic position of B. fischeri in the context of a recent molecular phylogeny of six of the seven other species of Boulengerula (from Kenya and Tanzania). Among nominal species, only B. denhardti remains to be included in molecular phylogenetic studies of Boulengerula. Boulengerula is recovered as monophyletic, with either B. fischeri or (more probably) B. boulengeri sister to all other sampled species. There are at least three deep lineages within Boulengerula: (1) B. boulengeri, (2) B. fischeri, and (3) all other Eastern Arc Mountain and Coastal Forest species from Kenya and Tanzania. The status of Afrocaecilia, a genus erected by Taylor in 1968 to contain all Boulengerula except B. boulengeri, is not yet resolved.

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Composition of bacterial and archaeal communities in freshwater sediments with different contamination levels (Lake Geneva, Switzerland)

The aim of this study was to compare the composition of bacterial and archaeal communities in contaminated sediments (Vidy Bay) with uncontaminated sediments (Ouchy area) of Lake Geneva using 16S rRNA clone libraries. Sediments of both sites were analysed for physicochemical characteristics including porewater composition, organic carbon, and heavy metals. Results show high concentrations of contaminants in sediments from Vidy. Particularly, high contents of fresh organic matter and nutrients led to intense mineralisation, which was dominated by sulphate-reduction and methanogenesis. The bacterial diversity in Vidy sediments was significantly different from the communities in the uncontaminated sediments. Phylogenetic analysis revealed a large proportion of Betaproteobacteria clones in Vidy sediments related to Dechloromonas sp., a group of dechlorinating and contaminant degrading bacteria. Deltaproteobacteria, including clones related to sulphate-reducing bacteria and Fe(III)-reducing bacteria (Geobacter sp.) were also more abundant in the contaminated sediments. The archaeal communities consisted essentially of methanogenic Euryarchaeota, mainly found in the contaminated sediments rich in organic matter. Multiple factor analysis revealed that the microbial community composition and the environmental variables were correlated at the two sites, which suggests that in addition to environmental parameters, pollution may be one of the factors affecting microbial community structure. Research highlights ► Vidy Bay (Lake Geneva) heavily contaminated with organic and inorganic pollutants. ► Microbial composition significantly different between polluted and non-polluted sediments. ► Microbial diversity affected by nutrients, organic matter and degree of pollution. ► Large proportion of clones from Vidy sediments related to Dechloromonas sp.

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Intrinsic biodegradation potential of aromatic hydrocarbons in an alluvial aquifer - Potentials and limits of signature metabolite analysis and two stable isotope-based techniques

Three independent techniques were used to assess the biodegradation of monoaromatic hydrocarbons and low-molecular weight polyaromatic hydrocarbons in the alluvial aquifer at the site of a former cokery (Flémalle, Belgium). Firstly, a stable carbon isotope-based field method allowed quantifying biodegradation of monoaromatic compounds in situ and confirmed the degradation of naphthalene. No evidence could be deduced from stable isotope shifts for the intrinsic biodegradation of larger molecules such as methylnaphthalenes or acenaphthene. Secondly, using signature metabolite analysis, various intermediates of the anaerobic degradation of (poly-) aromatic and heterocyclic compounds were identified. The discovery of a novel metabolite of acenaphthene in groundwater samples permitted deeper insights into the anaerobic biodegradation of almost persistent environmental contaminants. A third method, microcosm incubations with 13C-labeled compounds under in situ-like conditions, complemented techniques one and two by providing quantitative information on contaminant biodegradation independent of molecule size and sorption properties. Thanks to stable isotope labels, the sensitivity of this method was much higher compared to classical microcosm studies. The 13C-microcosm approach allowed the determination of first-order rate constants for 13C-labeled benzene, naphthalene, or acenaphthene even in cases when degradation activities were only small. The plausibility of the third method was checked by comparing 13C-microcosm-derived rates to field-derived rates of the first approach. Further advantage of the use of 13C-labels in microcosms is that novel metabolites can be linked more easily to specific mother compounds even in complex systems. This was achieved using alluvial sediments where 13C-acenaphthyl methylsuccinate was identified as transformation product of the anaerobic degradation of acenaphthene.

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Citizen science reveals unexpected continental-scale evolutionary change in a model organism

Organisms provide some of the most sensitive indicators of climate change and evolutionary responses are becoming apparent in species with short generation times. Large datasets on genetic polymorphism that can provide an historical benchmark against which to test for recent evolutionary responses are very rare, but an exception is found in the brown-lipped banded snail (Cepaea nemoralis). This species is sensitive to its thermal environment and exhibits several polymorphisms of shell colour and banding pattern affecting shell albedo in the majority of populations within its native range in Europe. We tested for evolutionary changes in shell albedo that might have been driven by the warming of the climate in Europe over the last half century by compiling an historical dataset for 6,515 native populations of C. nemoralis and comparing this with new data on nearly 3,000 populations. The new data were sampled mainly in 2009 through the Evolution MegaLab, a citizen science project that engaged thousands of volunteers in 15 countries throughout Europe in the biggest such exercise ever undertaken. A known geographic cline in the frequency of the colour phenotype with the highest albedo (yellow) was shown to have persisted and a difference in colour frequency between woodland and more open habitats was confirmed, but there was no general increase in the frequency of yellow shells. This may have been because snails adapted to a warming climate through behavioural thermoregulation. By contrast, we detected an unexpected decrease in the frequency of Unbanded shells and an increase in the Mid-banded morph. Neither of these evolutionary changes appears to be a direct response to climate change, indicating that the influence of other selective agents, possibly related to changing predation pressure and habitat change with effects on micro-climate

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Vaccines, Vol. 6, Pages 7: Development of Zika Virus Vaccines

Vaccines, Vol. 6, Pages 7: Development of Zika Virus Vaccines

Vaccines doi: 10.3390/vaccines6010007

Authors: Huda Makhluf Sujan Shresta

Zika virus (ZIKV) is a mosquito-borne flavivirus that emerged as a global threat following the most recent outbreak in Brazil in 2015. ZIKV infection of pregnant women is associated with fetal abnormalities such as microcephaly, and infection of adults can lead to Guillain–Barré syndrome, an autoimmune disease characterized by neurological deficits. Although there are currently licensed vaccines for other flaviviruses, there remains an urgent need for preventative vaccines against ZIKV infection. Herein we describe the current efforts to accelerate the development of ZIKV vaccines using various platforms, including live attenuated virus, inactivated virus, DNA and RNA, viral vectors, and in silico-predicted immunogenic viral epitopes. Many of these approaches have leveraged lessons learned from past experience with Dengue and other flavivirus vaccines.



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Association between third molar and mandibular angle fracture: a systematic review and Meta-analysis

The aim of this study was to investigate the risk of mandibular angle fracture associated with the presence of a mandibular third molar and its position when the mandibular fracture occurs.

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Nutrient and Antinutrient Compositions and Heavy Metal Uptake and Accumulation in S. nigrum Cultivated on Different Soil Types

Solanum nigrum cultivated on different soil texture types, sandy clay loam, silty clay loam, clay loam, loam, and control soils, were evaluated for proximate compositions, antinutrients, vitamins, and mineral composition with plant age using standard analytical methods. Accumulation of trace elements using translocation factor was studied to determine their toxic levels in plant tissues. Data were analysed by ANOVA and results expressed as means and standard deviation. Ash content, crude fibre, protein, alkaloid, phytate, and saponin ranged between 11.4 and 12%, 19.24 and 19.95%, 34.23 and 38.98, 42.08 and 45.76 mg/ml, 0.84 and 1.17%, and 94.10 and 97.00%, respectively. Vitamins A, C, and B were present in high quantity. Macro- and micronutrients recorded showed that S. nigrum is a potential reservoir of minerals. Accumulation of micronutrients was observed to be the highest at the flowering stage between the 4th and 5th weeks after transplanting. Plants cultivated on clay loam, silty clay loam, and loam soils accumulated elevated nutritional compositions and abundant antinutrients. However, the accumulated trace metals in the plants are within the recommended safe levels. All nutrient values are in the recommended requirements for daily consumption.

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Multistability Analysis and Function Projective Synchronization in Relay Coupled Oscillators

Regions of stability phases discovered in a general class of Genesio−Tesi chaotic oscillators are proposed. In a relatively large region of two-parameter space, the system has coexisting point attractors and limit cycles. The variation of two parameters is used to characterize the multistability by plotting the isospike diagrams for two nonsymmetric initial conditions. The parameters window in which the jerk system exhibits the unusual and striking feature of multiple attractors (e.g., coexistence of six disconnected periodic chaotic attractors and three-point attraction) is investigated. The second aspect of this study presents the synchronization of systems that act as mediators between two dynamical units that, in turn, show function projective synchronization (FPS) with each other. These are the so-called relay systems. In a wide range of operating parameters; this setup leads to synchronization between the outer circuits, while the relaying element remains unsynchronized. The results show that the coupled systems can achieve function projective synchronization in a determined time despite the unpredictability of the scaling function. In the coupling path, the outer dynamical systems show finite-time synchronization of their outputs, that is, displaying the same dynamics at exactly the same moment. Further, this effect is rather general and it has a wide range of applications where sustained oscillations should be retained for proper functioning of the systems.

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Qualitative Analysis of Primary Fingerprint Pattern in Different Blood Group and Gender in Nepalese

Dermatoglyphics, the study of epidermal ridges on palm, sole, and digits, is considered as most effective and reliable evidence of identification. The fingerprints were studied in 300 Nepalese of known blood groups of different ages and classified into primary patterns and then analyzed statistically. In both sexes, incidence of loops was highest in ABO blood group and Rh +ve blood types, followed by whorls and arches, while the incidence of whorls was highest followed by loops and arches in Rh −ve blood types. Loops were higher in all blood groups except “A –ve” and “B –ve” where whorls were predominant. The fingerprint pattern in Rh blood types of blood group “A” was statistically significant while in others it was insignificant. In middle and little finger, loops were higher whereas in ring finger whorls were higher in all blood groups. Whorls were higher in thumb and index finger except in blood group “O” where loops were predominant. This study concludes that distribution of primary pattern of fingerprint is not related to gender and blood group but is related to individual digits.

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Association between Sleep Apnea Hypopnea Syndrome and the Risk of Atrial Fibrillation: A Meta-Analysis of Cohort Study

Numerous reports have been done to seek the relationship between sleep apnea hypopnea syndrome (SAHS) and the risk of atrial fibrillation (AF). However, definite conclusion has not yet been fully established. We examined whether SAHS increases AF incidence in common population and summarized all existing studies in a meta-analysis. We summarized the current studies by searching related database for potential papers of the association between SAHS and the risk of AF. Studies that reported original data or relative risks (RRs) with 95% confidence intervals (CIs) for the associations were included. Sensitivity analyses were performed by omitting each study iteratively and publication bias was detected by Begg’s tests. Eight eligible studies met the inclusion criteria. Fixed effects meta-analysis showed that SAHS increased AF risk in the common population (RR = 1.70, 95% CI: 1.53–1.89, , ). There was a significant association between mild SAHS and the risk of AF (RR = 1.52, 95% CI: 1.28–1.79, , ), moderate SAHS (RR = 1.88, 95% CI: 1.55–2.27, , ), and severe SAHS (RR = 2.16, 95% CI: 1.78–2.62, , ). The results suggest that sleep apnea hypopnea syndrome could increase the risk of AF, and the higher the severity of SAHS, the higher risk of atrial fibrillation.

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HIT Solar Cells with N-Type Low-Cost Metallurgical Si

A conversion efficiency of 20.23% of heterojunction with intrinsic thin layer (HIT) solar cell on 156 mm × 156 mm metallurgical Si wafer has been obtained. Applying AFORS-HET software simulation, HIT solar cell with metallurgical Si was investigated with regard to impurity concentration, compensation level, and their impacts on cell performance. It is known that a small amount of impurity in metallurgical Si materials is not harmful to solar cell properties.

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Placenta and Placental Derivatives in Regenerative Therapies: Experimental Studies, History, and Prospects

Placental structures, capable to persist in a genetically foreign organism, are a natural model of allogeneic engraftment carrying a number of distinctive properties. In this review, the main features of the placenta and its derivatives such as structure, cellular composition, immunological and endocrine aspects, and the ability to invasion and deportation are discussed. These features are considered from a perspective that determines the placental material as a unique source for regenerative cell therapies and a lesson for immunological tolerance. A historical overview of clinical applications of placental extracts, cells, and tissue components is described. Empirically accumulated data are summarized and compared with modern research. Furthermore, we define scopes and outlooks of application of placental cells and tissues in the rapidly progressing field of regenerative medicine.

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Primary Pancreatic Burkitt’s Lymphoma: A Case Report and Review of the Literature

Primary pancreatic lymphoma (PPL) is of very rare occurrence as an extra nodal site of Non-Hodgkin’s lymphoma (NHL). It represents less than 1% of NHL. Out of which Burkitt lymphoma of pancreas is of a rare presentation. It usually occurs in children and presenting in adults is uncommon. The prevalence of pancreatic Burkitt lymphoma is not known as the incidence is significantly low. Clinical features of PPL are predominantly nonspecific and can become difficult with associated inflammation of pancreas. Differentiation of lymphoma to adenocarcinoma is important as chemotherapy is the main stay of treatment in lymphoma. We report a case of 68-year-old female who presented with nonspecific symptoms and was found to have obstructive jaundice secondary to pancreatic head neoplasm which was proved to be pancreatic Burkitt lymphoma which is a rare presentation.

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Homogenate Extraction of Crocins from Saffron Optimized by Response Surface Methodology

Saffron, which has many kinds of biological activities, has been widely used in medicine, cosmetics, food, and other fields of health promotion industries. Crocins are the main component of saffron (Crocus sativus L.). At present, most of the extraction methods for crocins require long time or special instruments to complete the process and some of them are not suitable for industrial production at present. In this article, homogenate extraction technology which is a convenient and efficient method was developed for crocins extraction from saffron. Firstly, the influences of extraction voltage, extraction time, ethanol concentration, and temperature on crocins yield were studied by single factor experiments; and then response surface methodology (RSM) was used to optimize levels of four variables based on the result of single factor experiments. Results showed that the optimum extraction process conditions for crocins were as follows: extraction voltage, 110 V; ethanol concentration, 70%; extraction temperature, 57°C; and extraction time, 40 s. Based on these conditions, the extraction yield of crocins can reach 22.76% which is higher than ultrasonic extraction method. Therefore, homogenate extraction is an effective way to extract crocins from saffron with higher extraction yield and shorter extraction time.

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Homogenate Extraction of Crocins from Saffron Optimized by Response Surface Methodology

Saffron, which has many kinds of biological activities, has been widely used in medicine, cosmetics, food, and other fields of health promotion industries. Crocins are the main component of saffron (Crocus sativus L.). At present, most of the extraction methods for crocins require long time or special instruments to complete the process and some of them are not suitable for industrial production at present. In this article, homogenate extraction technology which is a convenient and efficient method was developed for crocins extraction from saffron. Firstly, the influences of extraction voltage, extraction time, ethanol concentration, and temperature on crocins yield were studied by single factor experiments; and then response surface methodology (RSM) was used to optimize levels of four variables based on the result of single factor experiments. Results showed that the optimum extraction process conditions for crocins were as follows: extraction voltage, 110 V; ethanol concentration, 70%; extraction temperature, 57°C; and extraction time, 40 s. Based on these conditions, the extraction yield of crocins can reach 22.76% which is higher than ultrasonic extraction method. Therefore, homogenate extraction is an effective way to extract crocins from saffron with higher extraction yield and shorter extraction time.

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Drug repurposing screening identifies bortezomib and panobinostat as drugs targeting cancer associated fibroblasts (CAFs) by synergistic induction of apoptosis

Summary

Cancer associated fibroblasts (CAFs) are the most abundant components of cancer-microenvironment. They play important roles in cancer initiation, progression, and metastasis. In addition, CAFs can confer drug-resistance to cancer cells. Considering their pro-tumorigenic roles, it is recommended to remove CAFs to prevent cancer recurrence after chemotherapy. Despite their clinical significance, few anti-CAF drugs have been developed. The objective of this study was to find a drug that could suppress the viability of patient-derived CAFs through repurposed screening of 51 drugs that were in clinical trials or received FDA approval. As a result, bortezomib (BTZ), carfilzomib (CFZ), and panobinostat (PST) were identified as anti-CAF drug candidates. It was confirmed that BTZ and PST could decrease the viability of various patients derived CAFs through inducing of caspase-3 mediated apoptosis. Interestingly, combination therapy with BTZ and PST showed better efficacy of inhibiting CAFs than single treatment. The synergistic effect between BTZ and PST on viability of CAFs was observed both in vitro CAF culture and in vivo mouse model. Furthermore, combination therapy with BTZ/PST and conventional anticancer compound docetaxel strongly inhibited tumor growth in xenografts of mouse breast cancer cells with mouse CAFs. In conclusion, our present study revealed that BTZ and PST could significantly reduce the viability of CAFs. Therefore, a combination therapy with BTZ/PST and anticancer drugs might be considered as a new rational for the development of anticancer therapy.



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Hello, Goodbye!


Int Arch Allergy Immunol

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Dulling cancer therapy's double-edged sword

Researchers have discovered that killing cancer cells can actually have the unintended effect of fuelling the proliferation of residual, living cancer cells, ultimately leading to aggressive tumour progression. The findings of the multi-institutional...

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Researchers develop swallowable test to detect pre-cancerous Barrett's oesophagus

Investigators at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center have developed a simple, swallowable test for early detection of Barrett's oesophagus that offers promise for preventing deaths from...

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Modular gene enhancer promotes leukaemia and regulates effectiveness of chemotherapy

Every day, billions of new blood cells are generated in the bone marrow. The gene Myc is known to play an important role in this process, and is also known to play a role in cancer. Scientists from the German Cancer Research Center (DKFZ) and the...

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Tonsillectomy sparing transoral robot assisted styloidectomy

Eagle Syndrome can present with a variety of symptoms and be caused by an elongated styloid process or calcified stylohyoid ligament. Patients failing medical management of this disorder may be treated with surgical excision of the styloid process. In the literature, transoral and transcervical approach have both been described. Although transoral approaches typically begin with a tonsillectomy, tonsil-sparing approaches have also been utilized. With the advent of robotic surgery, the potential for a tonsillectomy sparing approach has become a feasible alternative, preventing the pain and morbidity associated with adult tonsillectomy while continuing to provide superior exposure and instrumentation.

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à Jour, Rechtsprechungsübersicht Strafrecht 3+4/17



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à jour Rechtsprechungsübersicht Strafrecht 1/17



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IJMS, Vol. 19, Pages 285: Double Heterozygosity for BRCA1 Pathogenic Variant and BRCA2 Polymorphic Stop Codon K3326X: A Case Report in a Southern Italian Family

IJMS, Vol. 19, Pages 285: Double Heterozygosity for BRCA1 Pathogenic Variant and BRCA2 Polymorphic Stop Codon K3326X: A Case Report in a Southern Italian Family

International Journal of Molecular Sciences doi: 10.3390/ijms19010285

Authors: Raffaele Palmirotta Domenica Lovero Luigia Stucci Erica Silvestris Davide Quaresmini Angela Cardascia Franco Silvestris

Here, we describe a patient with bilateral breast cancer and melanoma, and with a concomitant double variant, namely p.Gln563Ter in BRCA1 and p.Lys3326Ter in BRCA2. The BRCA2 p.Lys3326Ter (K3326X) (rs11571833) mutation identified in our patient is a debated substitution of thymidine for adenine which is currently regarded as benign polymorphism in main gene databases. Recent studies, however, describe this variant as associated with breast and ovarian tumors. Based on the observation of the cancer’s earliest age of onset in this subject, our purpose was to reevaluate this variant according to recent papers indicating a role of powerful modifier of the genetic penetrance. Genetic testing was performed in all consenting patient’s relatives, and in the collection of the clinical data particular attention was paid to the age of onset of the neoplasia. Following our observation that the our patient with double heterozygosis had an early age of onset for cancer similar to a few rare cases of double mutation for BRCA1 and BRCA2, we also performed an extensive review of the literature relative to patients carrying a double heterozygosity for both genes. In line with previous studies relative to the rare double heterozygosity in both BRCA1/2 genes, we found the earlier onset of breast cancer in our patient with both BRCA1/2 mutations with respect to other relatives carrying the single BRCA1 mutation. The presence of the second K3326X variant in our case induces a phenotype characterized by early onset of the neoplasia in a manner similar to the other cases of double heterozygosity previously described. Therefore, we suggest that during the genetic counseling, it should be recommendable to evaluate the presence of the K3326X variant in association with other pathogenic mutations.



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IJMS, Vol. 19, Pages 283: The Biological Role of Hyaluronan-Rich Oocyte-Cumulus Extracellular Matrix in Female Reproduction

IJMS, Vol. 19, Pages 283: The Biological Role of Hyaluronan-Rich Oocyte-Cumulus Extracellular Matrix in Female Reproduction

International Journal of Molecular Sciences doi: 10.3390/ijms19010283

Authors: Eva Nagyova

Fertilization of the mammalian oocyte requires interactions between spermatozoa and expanded cumulus extracellular matrix (ECM) that surrounds the oocyte. This review focuses on key molecules that play an important role in the formation of the cumulus ECM, generated by the oocyte-cumulus complex. In particular, the specific inhibitors (AG1478, lapatinib, indomethacin and MG132) and progesterone receptor antagonist (RU486) exerting their effects through the remodeling of the ECM of the cumulus cells surrounding the oocyte have been described. After gonadotropin stimulus, cumulus cells expand and form hyaluronan (HA)-rich cumulus ECM. In pigs, the proper structure of the cumulus ECM depends on the interaction between HA and serum-derived proteins of the inter-alpha-trypsin inhibitor (IαI) protein family. We have demonstrated the synthesis of HA by cumulus cells, and the presence of the IαI, tumor necrosis factor-alpha-induced protein 6 and pentraxin 3 in expanding oocyte-cumulus complexes (OCC). We have evaluated the covalent linkage of heavy chains of IαI proteins to HA, as the principal component of the expanded HA-rich cumulus ECM, in porcine OCC cultured in medium with specific inhibitors: AG1478 and lapatinib (both inhibitors of epidermal growth factor receptor tyrosine kinase activity); MG132 (a specific proteasomal inhibitor), indomethacin (cyclooxygenase inhibitor); and progesterone receptor antagonist (RU486). We have found that both RU486 and indomethacin does not disrupt the formation of the covalent linkage between the heavy chains of IαI to HA in the expanded OCC. In contrast, the inhibitors AG1478 and lapatinib prevent gonadotropin-induced cumulus expansion. Finally, the formation of oocyte-cumulus ECM relying on the covalent transfer of heavy chains of IαI molecules to HA has been inhibited in the presence of MG132.



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Total congenital sternal cleft isolated in a newborn of 20 days: Rare case

Sternal clefts are rare malformations that result from a failure of fusion of the sternal bars, which is normally done in the 9th week of intrauterine life in the cranio-caudal direction.

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Uncertain effect of preventative shoulder rehabilitation for patients who underwent total laryngectomy with neck dissection

Abstract

Introduction

Total laryngectomy (TL) with neck dissection (ND) is considered as crucial management for advanced-stage of laryngeal cancer. Shoulder dysfunction has long been recognized as a potential complication resulting from neck dissection. The aim of this study was to evaluate the effect of early prophylactic rehabilitation program in patients who underwent TL with ND.

Methods

A prospective, nonrandomized design was used. Seventy-six participants who underwent TL with ND were assigned into either an intervention or a control group. The control group received current standard care with no formal shoulder exercise provided, while the intervention group attended early preventive rehabilitation lasting 12 weeks. Participants were assessed at baseline, and at 3 and 6 months after surgery. Measured outcomes included shoulder function and patient-reported quality of life. General linear models with repeated measures were used to examine outcome changes in both groups over the designated assessment intervals.

Results

Improvement in shoulder function and patient-reported quality of life were both statistically significant over time, with no significant difference between control or intervention groups, indicating little or no benefit of preventative intervention on shoulder function outcomes. Analysis involving five subscales and the summary score of the quality of life questionnaire had only statistically significant improvement over time for both the control or intervention groups, except for physical well-being domain which had statistical significance both over time and between the control and intervention groups.

Conclusion

In this study, preventative exercise program initiated immediately after surgery had a limited impact on both shoulder function and perceived quality of life.



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Cosmetics, Vol. 5, Pages 13: Personal-Care Products Formulated with Natural Antioxidant Extracts

Cosmetics, Vol. 5, Pages 13: Personal-Care Products Formulated with Natural Antioxidant Extracts

Cosmetics doi: 10.3390/cosmetics5010013

Authors: Maria Soto María Parada Elena Falqué Herminia Domínguez

The objective of this study was to evaluate the potential use of some vegetal raw materials in personal-care products. Four ethanolic extracts (grape pomace, Pinus pinaster wood chips, Acacia dealbata flowers, and Lentinus edodes) were prepared and total phenolics, monomeric sugars, and antioxidant capacity were determined on alcoholic extracts. Six of the most important groups of cosmetics products (hand cream, body oil, shampoo, clay mask, body exfoliating cream, and skin cleanser) were formulated. Participants evaluated some sensory attributes and overall acceptance by a 10-point scale; the results showed differences among age-intervals, but not between males and females. The results confirmed that all extracts presented characteristics appropriate for their use in cosmetic formulations and their good acceptability by consumers into all cosmetic products. Texture/appearance, spreadability, and skin feeling are important attributes among consumer expectations, but odor and color were the primary drivers and helped differentiate the natural extracts added into all personal-care products.



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