Longitudinal clinico-pathological data of the progression of oral mucosal melanoma–report of two cases and literature review

Publication date: Available online 28 December 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Paras B. Patel, John M. Wright, David R. Kang, Yi-Shing Lisa Cheng
Oral mucosal melanoma (OMM) is notorious for having a poor prognosis. Recognition of the early features of OMM by both clinicians and pathologists can play an important role in improving survival. Therefore, the purpose of this report is to increase awareness of the early features of OMM, by presenting two cases with longitudinal clinical and histopathological documentation showing progression of OMM from a deceptively bland pre-malignant (non-invasive) oral melanocytic lesion (POML). Analyzing the clinical and histopathological features of POML in our cases, and those in the literature, we found that the concerning features are: 1) clinically, a pigmented lesion violating the ABCDE criteria or showing multiple recurrences; and 2) histologically, a melanocytic proliferation, in either a lentiginous or pagetoid pattern with or without cellular atypia. Making a diagnosis of POML prospectively is often challenging. Increasing awareness of the clinical and histopathological features, and complete surgical excision of POML is emphasized.



from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2C6HrpF

BTB/POZ domain-containing protein 7 is inversely associated with fibronectin expression in salivary adenoid cystic carcinoma

Publication date: Available online 28 December 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Yunxia Liu, Jiwu Song, Jun Zhang, Liu Yang, Zongxia Liu, Xuxia Wang
ObjectiveThis study was aimed to investigate the relationship between BTB/POZ domain-containing protein 7 (BTBD7) and fibronectin (FN) expression in salivary adenoid cystic carcinoma (SACC) and the function of BTBD7 in proliferation, migration and invasion of SACC cells.MethodsThe BTBD7 and FN expression in SACC and non-tumor salivary tissues as well as SACC cells were characterized by immunohistochemistry and immunofluorescence. The effect of BTBD7 silencing on the proliferation, migration and invasion of SACC-LM cells were determined by wound healing and transwell invasion assays.ResultsThe percentages of SACC with positive BTBD7 expression were significantly higher than that of those with FN expression. BTBD7 silencing significantly increased the relative levels of FN expression and inhibited the proliferation, migration and invasion of SACC-LM cells.ConclusionsThe data indicated that BTBD7 was inversely associated with FN expression in SACC. BTBD7 may inhibit FN expression, but promote proliferation, migration and invasion of SACC-LM cells. Hence, BTBD7 may be associated with metastasis and a new therapeutic target for intervention of SACC.



from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2BRATau

Osteonecrosis of the jaw unrelated to medication or radiotherapy

Publication date: Available online 28 December 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Yusuf Gadiwalla, Vinod Patel
Osteonecrosis of the jaw (ONJ) is an increasingly common condition primarily due to the rise of medication related osteonecrosis of the jaw (MRONJ) and osteoradionecrosis (ORN). Apart from MRONJ and ORN there remains a wide and varied range of rare causes and diseases that can lead to a clinical presentation of ONJ. This article aims to highlight alternatives causes of jaw necrosis following review of the literature to aid diagnosis and treatment planning for dental and head and neck specialities.



from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2C9p8A8

Oral lymphangiectasias and Crohn's disease: two case reports

Publication date: Available online 28 December 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Sheila Galvin, Stephen R. Flint, Mary E. Toner, Claire M. Healy, Kumara Ekanayake
Lymphangiectasias, or acquired lymphangiomas, are rare in the oral cavity, more typically occurring on the skin or genital area, and to our knowledge have not been reported previously in association with Crohn's disease. Lymphangiectasias can occur at any age and develop secondary to chronic obstruction of lymphatics. This differentiates them from congenital lymphangiomas which are congenital malformations of the lymphatic system. We present two cases of oral lymphangiectasias associated with Crohn's disease, one of which was treated successfully with cryotherapy.



from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2BUNWHW

Grading system to categorize breast MRI using BI-RADS 5th edition: a statistical study of non-mass enhancement descriptors in terms of probability of malignancy

Abstract

Purpose

To analyze the association of breast non-mass enhancement descriptors in the BI-RADS 5th edition with malignancy, and to establish a grading system and categorization of descriptors.

Materials and methods

This study was approved by our institutional review board. A total of 213 patients were enrolled. Breast MRI was performed with a 1.5-T MRI scanner using a 16-channel breast radiofrequency coil. Two radiologists determined internal enhancement and distribution of non-mass enhancement by consensus. Corresponding pathologic diagnoses were obtained by either biopsy or surgery. The probability of malignancy by descriptor was analyzed using Fisher's exact test and multivariate logistic regression analysis. The probability of malignancy by category was analyzed using Fisher's exact and multi-group comparison tests.

Results

One hundred seventy-eight lesions were malignant. Multivariate model analysis showed that internal enhancement (homogeneous vs others, p < 0.001, heterogeneous and clumped vs clustered ring, p = 0.003) and distribution (focal and linear vs segmental, p < 0.001) were the significant explanatory variables. The descriptors were classified into three grades of suspicion, and the categorization (3, 4A, 4B, 4C, and 5) by sum-up grades showed an incremental increase in the probability of malignancy (p < 0.0001).

Conclusion

The three-grade criteria and categorization by sum-up grades of descriptors appear valid for non-mass enhancement.

from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2zJXnYY

MR Imaging Criteria for the Detection of Nasopharyngeal Carcinoma: Discrimination of Early-Stage Primary Tumors from Benign Hyperplasia [HEAD & NECK]

BACKGROUND AND PURPOSE:

MR imaging can detect nasopharyngeal carcinoma that is hidden from endoscopic view, but for accurate detection carcinoma confined within the nasopharynx (stage T1) must be distinguished from benign hyperplasia of the nasopharynx. This study aimed to document the MR imaging features of stage T1 nasopharyngeal carcinoma and to attempt to identify features distinguishing it from benign hyperplasia.

MATERIALS AND METHODS:

MR images of 189 patients with nasopharyngeal carcinoma confined to the nasopharynx and those of 144 patients with benign hyperplasia were reviewed and compared in this retrospective study. The center, volume, size asymmetry (maximum percentage difference in area between the right and left nasopharyngeal halves), signal intensity asymmetry, deep mucosal white line (greater contrast enhancement along the deep tumor margin), and absence/distortion of the adenoidal septa were evaluated. Differences were assessed with logistic regression and the ² test.

RESULTS:

The nasopharyngeal carcinoma center was lateral, central, or diffuse in 134/189 (70.9%), 25/189 (13.2%), and 30/189 (15.9%) cases, respectively. Nasopharyngeal carcinomas involving the walls showed that a deep mucosal white line was present in 180/183 (98.4%), with a focal loss of this line in 153/180 (85%) cases. Adenoidal septa were absent or distorted in 111/111 (100%) nasopharyngeal carcinomas involving the adenoid. Compared with benign hyperplasia, nasopharyngeal carcinoma had a significantly greater volume, size asymmetry, signal asymmetry, focal loss of the deep mucosal white line, and absence/distortion of the adenoidal septa (P < .001). Although size asymmetry was the most accurate criterion (89.5%) for nasopharyngeal carcinoma detection, use of this parameter alone would have missed 11.9% of early-stage T1 nasopharyngeal carcinomas.

CONCLUSIONS:

MR imaging features can help distinguish stage T1 nasopharyngeal carcinoma from benign hyperplasia in most cases.

from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2EcdZvV

Clinical and Radiologic Characteristics of Deep Lumbosacral Dural Arteriovenous Fistulas [SPINE]

BACKGROUND AND PURPOSE:

Spinal dural arteriovenous fistulas located in the deep lumbosacral region are rare and the most difficult to diagnose among spinal dural arteriovenous fistulas located elsewhere in the spinal dura. Specific clinical and radiologic features of these fistulas are still inadequately reported and are the subject of this study.

MATERIALS AND METHODS:

We retrospectively evaluated all data of patients with spinal dural arteriovenous fistulas treated and/or diagnosed in our institution between 1990 and 2017. Twenty patients with deep lumbosacral spinal dural arteriovenous fistulas were included in this study.

RESULTS:

The most common neurologic findings at the time of admission were paraparesis (85%), sphincter dysfunction (70%), and sensory disturbances (20%). Medullary T2 hyperintensity and contrast enhancement were present in most cases. The filum vein and/or lumbar veins were dilated in 19/20 (95%) patients. Time-resolved contrast-enhanced dynamic MRA indicated a spinal dural arteriovenous fistula at or below the L5 vertebral level in 7/8 (88%) patients who received time-resolved contrast-enhanced dynamic MRA before DSA. A bilateral arterial supply of the fistula was detected via DSA in 5 (25%) patients.

CONCLUSIONS:

Clinical symptoms caused by deep lumbosacral spinal dural arteriovenous fistulas are comparable with those of spinal dural arteriovenous fistulas at other locations. Medullary congestion in association with an enlargement of the filum vein or other lumbar radicular veins is a characteristic finding in these patients. Spinal time-resolved contrast-enhanced dynamic MRA facilitates the detection of the drainage vein and helps to localize deep lumbosacral-located fistulas with a high sensitivity before DSA. Definite detection of these fistulas remains challenging and requires sufficient visualization of the fistula-supplying arteries and draining veins by conventional spinal angiography.

from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2pMHQb8

Cervical Cord Atrophy and Long-Term Disease Progression in Patients with Primary-Progressive Multiple Sclerosis [SPINE]

BACKGROUND AND PURPOSE:

Cervical cord atrophy has been associated with clinical disability in multiple sclerosis and is proposed as an outcome measure of neurodegeneration. The aim of this study was to quantify the development of cervical cord atrophy and to evaluate its association with disability progression in patients with primary-progressive multiple sclerosis.

MATERIALS AND METHODS:

Thirty-one patients with primary-progressive multiple sclerosis underwent 1.5T brain and spinal cord MR imaging at baseline and 6–7 years later. The cervical spinal cord from C1 to C5 was segmented to evaluate the normalized overall cross-sectional area and the cross-sectional area of C2–C3, C3–C4, and C4–C5. The annualized rates of normalized cross-sectional area loss were also evaluated. To estimate clinical progression, we determined the Expanded Disability Status Scale score at baseline and at 2 and 14 years after baseline to compute the normalized area under the curve of the Expanded Disability Status Scale and the Expanded Disability Status Scale changes from baseline to the follow-up time points. Associations between the cord cross-sectional area and brain MR imaging and clinical measures were also investigated. Finally, the value of all these measures for predicting long-term disability was evaluated.

RESULTS:

Some normalized cross-sectional area measurements showed moderate correlations with the normalized area under the curve of the Expanded Disability Status Scale, ranging from –0.439 to –0.359 (P < .05). Moreover, the annualized rate of the normalized mean cross-sectional area loss and the baseline Expanded Disability Status Scale were independent predictors of long-term disability progression.

CONCLUSIONS:

These data indicate that development of cervical cord atrophy is associated with progression of disability and is predictive of this event in patients with primary-progressive MS.

from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2E7tCVr

Cerebrovascular Manifestations of Neurosarcoidosis: An Underrecognized Aspect of the Imaging Spectrum [REVIEW ARTICLE]

SUMMARY:

Involvement of the central nervous system by sarcoidosis, also referred to as neurosarcoidosis, is seen clinically in about 5% of patients with systemic disease. CNS involvement most frequently affects the leptomeninges and cranial nerves, though the ventricular system, brain parenchyma, and pachymeninges may also be involved. Even though the involvement of the intracranial vascular structures is well-known on postmortem studies, there is scant literature on imaging manifestations secondary to the vessel wall involvement, being confined mostly to isolated case reports and small series. The authors present a review of various cerebrovascular manifestations of neurosarcoidosis, along with a brief synopsis of the existing literature.

from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2pSMwMK

Spinal Arteriovenous Vascular Malformations in Patients with Neural Tube Defects [SPINE]

BACKGROUND AND PURPOSE:

Neural tube defects, such as tethered cord, intradural lipoma, or myelomeningocele may coexist with spinal vascular malformations. The coexistence of these 2 rare entities is suggestive of a causal relationship between them, which may lead to further understanding of their pathogenesis. We present a series of 6 patients with epidural spinal arteriovenous fistulas associated with neural tube defects.

MATERIALS AND METHODS:

We retrieved cases of spinal vascular malformations associated with neural tube defects seen at our institution. The clinical presentation, MR imaging/MRA and angiographic imaging, treatment outcomes, and long-term neurologic outcomes were analyzed. Descriptive statistical analyses are reported.

RESULTS:

Six patients with epidural arteriovenous fistulas and neural tube defects were included in this study. The mean age at presentation was 42 years, and the most common presenting symptoms were lower extremity weakness followed by sensory disturbances and bladder/bowel dysfunction. In most cases (5/6), the fistulas were located at the sacral level. All cases were fed by the lateral sacral artery (6/6). Four patients had prior spine surgery, but the fistula was in the operative bed in 2 cases. All fistulas were extradural with secondary intradural venous drainage. Five patients underwent transarterial embolization with Onyx, and 1 patient had a treatment-related complication.

CONCLUSIONS:

It is conceivable that there is a pathophysiologic link between neural tube defects and development of spinal vascular malformations. Delayed neurologic deterioration or high conus signal in a patient with a neural tube defect should suggest the possibility of such an association.

from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2Eb6Z2u

Noninvasive Assessment of Intracranial Pressure Status in Idiopathic Intracranial Hypertension Using Displacement Encoding with Stimulated Echoes (DENSE) MRI: A Prospective Patient Study with Contemporaneous CSF Pressure Correlation [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Intracranial pressure is estimated invasively by using lumbar puncture with CSF opening pressure measurement. This study evaluated displacement encoding with stimulated echoes (DENSE), an MR imaging technique highly sensitive to brain motion, as a noninvasive means of assessing intracranial pressure status.

MATERIALS AND METHODS:

Nine patients with suspected elevated intracranial pressure and 9 healthy control subjects were included in this prospective study. Controls underwent DENSE MR imaging through the midsagittal brain. Patients underwent DENSE MR imaging followed immediately by lumbar puncture with opening pressure measurement, CSF removal, closing pressure measurement, and immediate repeat DENSE MR imaging. Phase-reconstructed images were processed producing displacement maps, and pontine displacement was calculated. Patient data were analyzed to determine the effects of measured pressure on pontine displacement. Patient and control data were analyzed to assess the effects of clinical status (pre–lumbar puncture, post–lumbar puncture, or control) on pontine displacement.

RESULTS:

Patients demonstrated imaging findings suggesting chronically elevated intracranial pressure, whereas healthy control volunteers demonstrated no imaging abnormalities. All patients had elevated opening pressure (median, 36.0 cm water), decreased by the removal of CSF to a median closing pressure of 17.0 cm water. Patients pre–lumbar puncture had significantly smaller pontine displacement than they did post–lumbar puncture after CSF pressure reduction (P = .001) and compared with controls (P = .01). Post–lumbar puncture patients had statistically similar pontine displacements to controls. Measured CSF pressure in patients pre– and post–lumbar puncture correlated significantly with pontine displacement (r = 0.49; P = .04).

CONCLUSIONS:

This study establishes a relationship between pontine displacement from DENSE MR imaging and measured pressure obtained contemporaneously by lumbar puncture, providing a method to noninvasively assess intracranial pressure status in idiopathic intracranial hypertension.

from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2pRiQQ1

Patterns of bone tracer uptake on SPECT-CT in symptomatic and asymptomatic patients with primary total hip arthroplasty

Abstract

Purpose

The primary purpose of this study was to compare bone tracer uptake (BTU) on SPECT/CT in symptomatic and asymptomatic total hip arthroplasty (THA) and identify a possible relationship between BTU patterns and patient's symptoms. The secondary purpose was to investigate if the fixation methods (cemented versus uncemented) lead to different BTU patterns.

Methods

A total of 58 THAs, 31 symptomatic (group S) and 27 asymptomatic (group AS), were prospectively collected and retrospectively analyzed. All symptomatic patients underwent standardized detailed history, clinical examination, radiographs and 99mTc-HDP SPECT/CT. BTU in SPECT/CT was quantified in three dimensions and anatomically localized in a scheme of quadrants and levels using a customized previously validated software. T tests were used on both quadrants and levels inside and between groups. A Pearson correlation was performed for BTU within the quadrants. An area under receiver operating characteristic curves was drawn in order to find a BTU value that could differentiate the two groups. Within the groups, patients with cemented and uncemented stems were compared for influences on BTU intensity.

Results

The causes of pain were identified in 61% of the patients. The most common problem was aseptic loosening (n = 12). In group AS, levels 1, 2 and 5 had similar BTUs. BTUs in these levels were significantly higher than in level 3, 4 and 6. In group S, no significant differences were seen in terms of BTU in level 1–5. However, BTU here was significantly higher than at level 6 (p < 0.001). In both groups, level 1, the superior, had a significantly higher BTU than level 2 (group AS p < 0.01, group S p < 0.05). Comparing the BTU of the two groups among levels, significant differences were found for level 4, level 5 and the entire stem areas (p < 0.05). The ROC curve calculated on the whole stem allowed identification of a BTU ratio of 3.1 that separated the 92.6% patients of group AS with BTU < 3.1 from the 54.8% of patients of group S with a BTU ≥ 3.1. With regards to the fixation technique, only the BTU at the level 6 in group S presented a significant difference between cemented and uncemented stems (p < 0.05).

Conclusions

Higher BTU levels significantly correlated with symptoms, but a normal BTU could not exclude a specific pathology after THA. A threshold of BTU in SPECT/CT was identified to distinguish between symptomatic and asymptomatic patients after THA.

from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2DpVUJQ

Correction to: 18F-NaF PET/CT: EANM procedure guidelines for bone imaging

Abstract

The original version of this article unfortunately contained an error. The name and affiliation of "Frédéric Paycha" needs to be corrected. Given in this article is the correct author name and affiliation.

from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2Ce0FGX

Validation of the mIBG skeletal SIOPEN scoring method in two independent high-risk neuroblastoma populations: the SIOPEN/HR-NBL1 and COG-A3973 trials

Abstract

Background

Validation of the prognostic value of the SIOPEN mIBG skeletal scoring system in two independent stage 4, mIBG avid, high-risk neuroblastoma populations.

Results

The semi-quantitative SIOPEN score evaluates skeletal meta-iodobenzylguanidine (mIBG) uptake on a 0–6 scale in 12 anatomical regions. Evaluable mIBG scans from 216 COG-A3973 and 341 SIOPEN/HR-NBL1 trial patients were reviewed pre- and post-induction chemotherapy. The prognostic value of skeletal scores for 5-year event free survival (5 yr.-EFS) was tested in the source and validation cohorts. At diagnosis, both cohorts showed a gradual non-linear increase in risk with cumulative scores. Several approaches were explored to test the relationship between score and EFS. Ultimately, a cutoff score of ≤3 was the most useful predictor across trials. A SIOPEN score ≤ 3 pre-induction was found in 15% SIOPEN patients and in 22% of COG patients and increased post-induction to 60% in SIOPEN patients and to 73% in COG patients. Baseline 5 yr.-EFS rates in the SIOPEN/HR-NBL1 cohort for scores ≤3 were 47% ± 7% versus 26% ± 3% for higher scores at diagnosis (p < 0.007) and 36% ± 4% versus 14% ± 4% (p < 0.001) for scores obtained post-induction. The COG-A3973 showed 5 yr.-EFS rates for scores ≤3 of 51% ± 7% versus 34% ± 4% for higher scores (p < 0.001) at diagnosis and 43% ± 5% versus 16% ± 6% (p = 0.004) for post-induction scores. Hazard ratios (HR) significantly favoured patients with scores ≤3 after adjustment for age and MYCN-amplification. Optimal outcomes were recorded in patients who achieved complete skeletal response.

Conclusions

Validation in two independent cohorts confirms the prognostic value of the SIOPEN skeletal score. In particular, patients with an absolute SIOPEN score > 3 after induction have very poor outcomes and should be considered for alternative therapeutic strategies.

from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2DpVN0S

Correction to: Peptide receptor radionuclide therapy (PRRT) in European Neuroendocrine Tumour Society (ENETS) grade 3 (G3) neuroendocrine neoplasia (NEN) - a single-institution retrospective analysis

Abstract

On page 4 of the original version of this article, the text "Eight (29%) of the patients had significant FDG-avid disease (i.e. with intensity above liver parenchyma) prior to treatment" needs to be corrected.

from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2CeYaE1

Quantitative 18 F-DOPA PET/CT in pheochromocytoma: the relationship between tumor secretion and its biochemical phenotype

Abstract

Introduction

¹⁸F-FDOPA illustrates the properties of uptake and storage of catecholamines in pheochromocytomas (PHEOs). Until now, the relationship between ¹⁸F-FDOPA quantitative parameters and a PHEO secretory profile has not been specifically evaluated.

Materials and methods

Fifty-six patients (56% females, median age: 47.5 yrs) with non-metastatic PHEO, evaluated by ¹⁸F-FDOPA PET/CT, were included in this retrospective study. Forty-five patients had negative genetic testing (80.4%); five patients (8.9%) had RET, two patients (3.6%) had SDHB, two had SDHD (3.6%), one patient (1.8%) had NF1, and one patient had a VHL (1.8%) mutation. Correlation between ¹⁸F-FDOPA metabolic parameters (tumor SUVmax, tumor SUVmean, tumor SUVmax/liver SUVmax, MTV 42%, total lesion uptake), urinary metanephrines (MNs), and plasma chromogranin A (CgA) were evaluated.

Results

All patients had positive ¹⁸F-FDOPA PET/CT. On univariate analysis, there was a strong correlation between all metabolic parameters and urinary MNs and plasma chromogranin A (CgA). The highest correlations were observed between total lesion (TL) uptake and the value of urinary MNs regardless of their nature (p = 8.10⁻¹⁵ and r = 0.80) and between MTV 42% and plasma CgA levels (p = 2.10⁻⁹, r = 0.74). On multivariate analysis, the correlation of uptake parameters and CgA levels did not persist further due to the relation of CgA and tumor diameter. A correlation between TL uptake and the normetanephrine/metanephrine ratio (NMN/MN) was also found, a finding that was in accordance with in vitro studies, which were found to have a higher catecholamine content in epinephrine producing PHEOs.

Conclusion

This retrospective study shows a correlation between ¹⁸F-FDOPA uptake, especially using TL uptake, urinary MNs, and a PHEO biochemical phenotype. This illustrates that beyond its localization value, ¹⁸F-FDOPA PET further enables PHEO characterization at a specific metabolic level.

from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2DpVGT0

Repeatability of tumour hypoxia imaging using [ 18 F]EF5 PET/CT in head and neck cancer

Abstract

Purpose

Hypoxia contributes to radiotherapy resistance and more aggressive behaviour of several types of cancer. This study was designed to evaluate the repeatability of intratumour uptake of the hypoxia tracer [¹⁸F]EF5 in paired PET/CT scans.

Methods

Ten patients with newly diagnosed head and neck cancer (HNC) received three static PET/CT scans before chemoradiotherapy: two with [¹⁸F]EF5 a median of 7 days apart and one with [¹⁸F]FDG. Metabolically active primary tumour volumes were defined in [¹⁸F]FDG images and transferred to co-registered [¹⁸F]EF5 images for repeatability analysis. A tumour-to-muscle uptake ratio (TMR) of 1.5 at 3 h from injection of [¹⁸F]EF5 was used as a threshold representing hypoxic tissue.

Results

In 10 paired [¹⁸F]EF5 PET/CT image sets, SUVmean, SUVmax, and TMR showed a good correlation with the intraclass correlation coefficients of 0.81, 0.85, and 0.87, respectively. The relative coefficients of repeatability for these parameters were 15%, 17%, and 10%, respectively. Fractional hypoxic volumes of the tumours in the repeated scans had a high correlation using the Spearman rank correlation test (r = 0.94). In a voxel-by-voxel TMR analysis between the repeated scans, the mean of Pearson correlation coefficients of individual patients was 0.65. The mean (± SD) difference of TMR in the pooled data set was 0.03 ± 0.20.

Conclusion

Pretreatment [¹⁸F]EF5 PET/CT within one week shows high repeatability and is feasible for the guiding of hypoxia-targeted treatment interventions in HNC.

from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2ChjUiR

Klaus Bohndorf, Mark Anderson, Mark Davies, Herwig Imhof, Klaus Woertler: Imaging of bones and joints. A concise, multimodality approach

from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2DpWuqX

Invited editorial for the paper by Silvoniemi et al. “Repeatability of tumor hypoxia imaging using [ 18 F]EF5 PET/CT in head and neck cancer.” in this issue of EJNMMI

from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2CeYgvn

All that glitters is not gold - new reconstruction methods using Deauville criteria for patient reporting

from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2DnKVAu

Added value of dedicated axillary hybrid 18F-FDG PET/MRI for improved axillary nodal staging in clinically node-positive breast cancer patients: a feasibility study

Abstract

Purpose

To investigate the feasibility and potential added value of dedicated axillary 18F-FDG hybrid PET/MRI, compared to standard imaging modalities (i.e. ultrasound [US], MRI and PET/CT), for axillary nodal staging in clinically node-positive breast cancer.

Methods

Twelve patients with clinically node-positive breast cancer underwent axillary US and dedicated axillary hybrid 18F-FDG PET/MRI. Nine of the 12 patients also underwent whole-body PET/CT. Maximum standardized uptake values (SUVmax) were measured for the primary breast tumor and the most FDG-avid axillary lymph node. A positive axillary lymph node on dedicated axillary hybrid PET/MRI was defined as a moderate to very intense FDG-avid lymph node. The diagnostic performance of dedicated axillary hybrid PET/MRI was calculated by comparing quantitative and its qualitative measurements to results of axillary US, MRI and PET/CT. The number of suspicious axillary lymph nodes was subdivided as follows: N0 (0 nodes), N1 (1–3 nodes), N2 (4–9 nodes) and N3 (≥ 10 nodes).

Results

According to dedicated axillary hybrid PET/MRI findings, seven patients were diagnosed with N1, four with N2 and one with N3. With regard to mean SUVmax, there was no significant difference in the primary tumor (9.0 [±5.0] vs. 8.6 [±5.7], p = 0.678) or the most FDG-avid axillary lymph node (7.8 [±5.3] vs. 7.7 [±4.3], p = 0.767) between dedicated axillary PET/MRI and PET/CT. Compared to standard imaging modalities, dedicated axillary hybrid PET/MRI resulted in changes in nodal status as follows: 40% compared to US, 75% compared to T2-weighted MRI, 40% compared to contrast-enhanced MRI, and 22% compared to PET/CT.

Conclusions

Adding dedicated axillary 18F-FDG hybrid PET/MRI to diagnostic work-up may improve the diagnostic performance of axillary nodal staging in clinically node-positive breast cancer patients.

from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2CenEBz

Delayed response after repeated 177 Lu-PSMA-617 radioligand therapy in patients with metastatic castration resistant prostate cancer

Abstract

Purpose

Radioligand therapy (RLT) using Lutetium-177 labeled PSMA-617 (Lu-PSMA) ligand is a new therapeutic option for salvage therapy in heavily pretreated patients with metastatic castration resistant prostate cancer. The aim of this retrospective study was to analyze response in patients receiving 3 cycles of Lu-PSMA.

Methods

Seventy-one patients (median age: 72 years; range 44–87) received 3 cycles of RLT with Lu-PSMA (mean administered activity: 6.016 ± 0.543 GBq) every 8 weeks. Response was evaluated using serum PSA levels and a PSA decline ≥50% was considered as biochemical response. Additionally, any PSA decline after the first cycle was evaluated for further therapy effects after the second and third cycle.

Results

A total of 213 cycles were performed in 71 patients. Data for response and adverse events were available for all patients. A PSA decline ≥50% and some PSA decline occurred in 56% and 66% of the patients. Of 30 patients with a PSA response after the first cycle, 28 remained responders and 12/41 of non-responders responded to further therapy cycles.

Conclusion

RLT with Lu-177-PSMA-617 shows respectable response rates. In this retrospective analysis, a relevant number of patients showed a delayed response, even if they did not respond to the first cycle of the therapy.

from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2DoJh1k

The role of interim FDG PET-CT after induction chemotherapy as a predictor of concurrent chemoradiotherapy efficacy and prognosis for head and neck cancer

Abstract

Purpose

Induction chemotherapy (ICT) with docetaxel, cisplatin, and 5-fluorouracil (TPF) followed by concurrent chemoradiotherapy (CCRT) has the advantages of organ preservation and systemic control in head and neck cancer (HNC). Early prediction of CCRT efficacy may help identify patients who will benefit more from surgery than from CCRT. We investigated the role of interim 18-fluoro-2-deoxy-glucose positron emission tomography computed tomography (FDG PET-CT) after ICT to predict the efficacy of CCRT and clinical outcomes.

Methods

Tumor responses were retrospectively reviewed after CCRT based on the Response Evaluation Criteria in Solid Tumors. FDG PET-CT imaging was performed before and after three cycles of TPF. We examined the associations between the metabolic response (percentage decrease in the maximum standardized uptake value [SUVmax] and total metabolic tumor volume [MTV]) after ICT and complete response (CR) to CCRT, progression-free survival (PFS), and overall survival (OS).

Results

We studied 43 HNC patients with a median follow-up of 32.7 months. Lymph node (LN) SUVmax and total MTV decreases from baseline after ICT were greater in patients with a CR to CCRT than in non-CR patients (LN SUVmax, 88.8% vs. 62.5%, respectively; total MTV, 99.7% vs. 89.9%, respectively). Decreases in total MTV ≥ 78% and LN SUVmax ≥73% after ICT predicted CR to CCRT and longer OS and PFS.

Conclusions

Using interim FDG PET-CT to measure SUVmax and total MTV after three cycles of ICT may be a useful technique for identifying HNC patients who will benefit from CCRT and predicting survival outcomes.

from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2CfL1L2

A score combining baseline neutrophilia and primary tumor SUV peak measured from FDG PET is associated with outcome in locally advanced cervical cancer

Abstract

Purpose

We investigated whether a score combining baseline neutrophilia and a PET biomarker could predict outcome in patients with locally advanced cervical cancer (LACC).

Methods

Patients homogeneously treated with definitive chemoradiation plus image-guided adaptive brachytherapy (IGABT) between 2006 and 2013 were analyzed retrospectively. We divided patients into two groups depending on the PET device used: a training set (TS) and a validation set (VS). Primary tumors were semi-automatically delineated on PET images, and 11 radiomics features were calculated (LIFEx software). A PET radiomic index was selected using the time-dependent area under the curve (td-AUC) for 3-year local control (LC). We defined the neutrophil SUV grade (NSG = 0, 1 or 2) score as the number of risk factors among (i) neutrophilia (neutrophil count >7 G/L) and (ii) high risk defined from the PET radiomic index. The NSG prognostic value was evaluated for LC and overall survival (OS).

Results

Data from 108 patients were analyzed. Estimated 3-year LC was 72% in the TS (n = 69) and 65% in the VS (n = 39). In the TS, SUV_peak was selected as the most LC-predictive biomarker (td-AUC = 0.75), and was independent from neutrophilia (p = 0.119). Neutrophilia (HR = 2.6), high-risk SUV_peak (SUV_peak > 10, HR = 4.4) and NSG = 2 (HR = 9.2) were associated with low probability of LC in TS. In multivariate analysis, NSG = 2 was independently associated with low probability of LC (HR = 7.5, p < 0.001) and OS (HR = 5.8, p = 0.001) in the TS. Results obtained in the VS (HR = 5.2 for OS and 3.5 for LC, p < 0.02) were promising.

Conclusion

This innovative scoring approach combining baseline neutrophilia and a PET biomarker provides an independent prognostic factor to consider for further clinical investigations.

from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2DohWfJ

Could 68 Ga-somatostatin analogues be an important alternative to 18 F-DOPA PET/CT in pediatrics?

from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2CeW4Ee

68 Ga-PSMA 11 ligand PET imaging in patients with biochemical recurrence after radical prostatectomy – diagnostic performance and impact on therapeutic decision-making

Abstract

Objective

To evaluate the diagnostic performance of [⁶⁸Ga]Ga-PSMA^HBED-CC conjugate 11 positron emission tomography (PSMA-PET) in the early detection of metastases in patients with biochemical recurrence (BCR) after radical prostatectomy (RP) for clinically non-metastatic prostate cancer, to compare it to CT/MRI alone and to assess its impact on further therapeutic decisions.

Material and methods

We retrospectively assessed 117 consecutive hormone-naïve BCR patients who had ⁶⁸Ga-PSMA 11 PET/CT (n = 46) or PET/MRI (n = 71) between May 2014 and January 2017. BCR was defined as two PSA rises above 0.2 ng/ml. Two dedicated uro-oncological imaging experts (radiology/nuclear medicine) reviewed separately all images. All results were presented in a blinded sequential fashion to a multidisciplinary tumorboard in order to assess the influence of PSMA-PET imaging on decision-making.

Results

The median time from RP to BCR was 36 months (IQR 16–72). Overall, 69 (59%) patients received postoperative radiotherapy. Median PSA level at the time of imaging was 1.04 ng/ml (IQR 0.58–1.87). PSMA-positive lesions were detected in 100 (85.5%) patients. Detection rates were 65% for a PSA value of 0.2 to <0.5 ng/ml, 85.7% for 0.5 to <1, 85.7% for 1 to <2 and 100% for ≥2. PSMA-positive lesions could be confirmed by either histology (16%), PSA decrease in metastasis-directed radiotherapy (45%) or additional information in diffusion-weighted imaging when PET/MRI was performed (18%) in 79% of patients. PSMA-PET detected lesions in 67 patients (57.3%) who had no suspicious correlates according to the RECIST 1.1 criteria on MRI or CT. PSMA-PET changed therapeutic decisions in 74.6% of these 67 patients (p < 0.001), with 86% of them being considered for metastases-directed therapies.

Conclusions

We confirm the high performance of PSMA-PET imaging for the detection of disease recurrence sites in patients with BCR after RP, even at relatively low PSA levels. Moreover, it adds significant information to standard CT/MRI, changing treatment strategies in a significant number of patients.

from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2DpOqXb

Texture analysis of high-resolution dedicated breast 18 F -FDG PET images correlates with immunohistochemical factors and subtype of breast cancer

Abstract

Purpose

This study aims to determine whether PET textural features measured with a new dedicated breast PET scanner reflect biological characteristics of breast tumors.

Methods

One hundred and thirty-nine breast tumors from 127 consecutive patients were included in this analysis. All of them underwent a ¹⁸F-FDG PET scan before treatment. Well-known PET quantitative parameters such as SUV _{m a x} , SUV _{m e a n} , metabolically active tumor volume (MATV) and total lesion glycolysis (TLG) were extracted. Together with these parameters, local, regional, and global heterogeneity descriptors, which included five textural features (TF), were computed. Immunohistochemical classification of breast cancer considered five subtypes: luminal A like (LA), luminal B like/HER2 − (LB −), luminal B like/HER2+ (LB+), HER2-positive-non-luminal (HER2pnl), and triple negative (TN). Associations between PET features and tumor characteristics were assessed using non-parametric hypothesis tests.

Results

Along with well-established associations, new correlations were found. HER2-positive tumors had significantly higher uptake (p < 0.001, AUCs > 0.70) and presented different global and regional heterogeneity (p = 0.002, p = 0.016, respectively, AUCs < 0.70). Nine out of ten analyzed features were significantly associated with immunohistochemical subtype. Uptake was lower for LA tumors (p < 0.001) with AUCs ranging from 0.71 to 0.88 for each subgroup comparison. Heterogeneity metrics were significantly associated when comparing LA and LB − (p < 0.01), being regional heterogeneity metrics more discriminative than any other parameter (AUC = 0.80 compared to AUC = 0.71 for SUV). LB+ and HER2pnl tumors also showed more regional heterogeneity than LA tumors (AUCs = 0.79 and 0.84, respectively). After comparison with whole-body PET studies, we observed an overall improvement in the classification ability of both non-heterogeneity metrics and textural features.

Conclusions

PET parameters extracted from high-resolution dedicated breast PET images showed new and stronger correlations with immunohistochemical factors and immunohistochemical subtype of breast cancer compared to whole-body PET.

from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2CfVVAx

Longitudinal clinico-pathological data of the progression of oral mucosal melanoma–report of two cases and literature review

Oral mucosal melanoma (OMM) is notorious for having a poor prognosis. Recognition of the early features of OMM by both clinicians and pathologists can play an important role in improving survival. Therefore, the purpose of this report is to increase awareness of the early features of OMM, by presenting two cases with longitudinal clinical and histopathological documentation showing progression of OMM from a deceptively bland pre-malignant (non-invasive) oral melanocytic lesion (POML). Analyzing the clinical and histopathological features of POML in our cases, and those in the literature, we found that the concerning features are: 1) clinically, a pigmented lesion violating the ABCDE criteria or showing multiple recurrences; and 2) histologically, a melanocytic proliferation, in either a lentiginous or pagetoid pattern with or without cellular atypia.

from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2lpa4Dh

Osteonecrosis of the jaw unrelated to medication or radiotherapy

Osteonecrosis of the jaw (ONJ) is an increasingly common condition primarily due to the rise of medication related osteonecrosis of the jaw (MRONJ) and osteoradionecrosis (ORN). Apart from MRONJ and ORN there remains a wide and varied range of rare causes and diseases that can lead to a clinical presentation of ONJ. This article aims to highlight alternatives causes of jaw necrosis following review of the literature to aid diagnosis and treatment planning for dental and head and neck specialities.

from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2ClU1OY

Oral lymphangiectasias and Crohn's disease: two case reports

Lymphangiectasias, or acquired lymphangiomas, are rare in the oral cavity, more typically occurring on the skin or genital area, and to our knowledge have not been reported previously in association with Crohn's disease. Lymphangiectasias can occur at any age and develop secondary to chronic obstruction of lymphatics. This differentiates them from congenital lymphangiomas which are congenital malformations of the lymphatic system. We present two cases of oral lymphangiectasias associated with Crohn's disease, one of which was treated successfully with cryotherapy.

from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2DtAkUE

BTB/POZ domain-containing protein 7 is inversely associated with fibronectin expression in salivary adenoid cystic carcinoma

This study was aimed to investigate the relationship between BTB/POZ domain-containing protein 7 (BTBD7) and fibronectin (FN) expression in salivary adenoid cystic carcinoma (SACC) and the function of BTBD7 in proliferation, migration and invasion of SACC cells.

from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2CiconL

CT ventilation imaging derived from breath hold CT exhibits good regional accuracy with Galligas PET

CT ventilation imaging (CTVI) derived from four dimensional CT (4DCT) has shown only moderate spatial accuracy in humans due to 4DCT image artefacts. Here we assess the accuracy of an improved CTVI using high quality exhale/inhale breath-hold CT (BHCT).

from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2E7yQk7

Ultrasonographic appearance of ulnar nerve at different points of elbow.

Publication date: Available online 28 December 2017
Source:European Journal of Radiology
Author(s): Daniele Coraci, Silvia Giovannini, Claudia Loreti, Luca Di Sante, Valter Santilli, Luca Padua




from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2Cek2Cd

Gas-induced susceptibility artefacts on diffusion-weighted MRI of the rectum at 1.5T – Effect of applying a micro-enema to improve image quality

Publication date: Available online 28 December 2017
Source:European Journal of Radiology
Author(s): Joost J.M. van Griethuysen, Elyse M. Bus, Michael Hauptmann, Max J. Lahaye, Monique Maas, Leon C. ter Beek, Geerard L. Beets, Frans C.H. Bakers, Regina G.H. Beets-Tan, Doenja M.J. Lambregts
PurposeAssess whether application of a micro-enema can reduce gas-induced susceptibility artefacts in Single-shot Echo Planar Imaging (EPI) Diffusion-weighted imaging of the rectum at 1.5T.Materials and MethodsRetrospective analysis of n = 50 rectal cancer patients who each underwent multiple DWI-MRIs (1.5T) from 2012-2016 as part of routine follow-up during a watch-and-wait approach after chemoradiotherapy. From March 2014 DWI-MRIs were routinely acquired after application of a preparatory micro-enema (Microlax^®;5 ml; self-administered shortly before acquisition); before March 2014 no bowel preparation was given. In total, 335 scans were scored by an experienced reader for the presence/severity of gas-artefacts (on b1000 DWI), ranging from 0 (no artefact) to 5 (severe artefact). A score ≥3 (moderate-severe) was considered a clinically relevant artefact. A random sample of 100 scans was re-assessed by a second independent reader to study inter-observer effects. Scores were compared between the scans performed without and with a preparatory micro-enema using univariable and multivariable logistic regression taking into account potential confounding factors (age/gender, acquisition parameters, MRI-hardware, rectoscopy prior to MRI).ResultsClinically relevant gas-artefacts were seen in 24.3% (no micro-enema) vs. 3.7% (micro-enema), odds ratios were 0.118 in univariable and 0.230 in multivariable regression (P = 0.0005 and 0.0291). Mean severity score (±SD) was 1.19 ± 1.71 (no-enema) vs 0.32 ± 0.77 (micro-enema), odds ratios were 0.321 (P < 0.0001) and 0.489 (P = 0.0461) in uni- and multivariable regression, respectively. Inter-observer agreement was excellent (κ0.85).ConclusionUse of a preparatory micro-enema shortly before rectal EPI-DWI examinations performed at 1.5T MRI significantly reduces both the incidence and severity of gas-induced artefacts, compared to examinations performed without bowel preparation.



from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2CiODye

Surgical anatomy of neurovascular structures related to ventral C1-2 complex: an anatomical study.

Related Articles

Surgical anatomy of neurovascular structures related to ventral C1-2 complex: an anatomical study.

Surg Radiol Anat. 2017 Dec 26;:

Authors: Cirpan S, Sayhan S, Yonguc GN, Eyuboglu C, Güvençer M, Naderi S

Abstract
OBJECTIVE: Transoral odontoidectomy and ventral C1-2 stabilization are important surgical procedures, performed to decompress ventral spinal cord, and to stabilize craniovertebral junction. These procedures require knowledge regarding surgical anatomy of neurovascular structures ventral to the C1-2 complex. The aim of this study is to evaluate the relationships between neurovascular structures and bony landmarks in ventral atlantoaxial complex.
MATERIALS AND METHODS: This study was performed on six formaldehyde fixed cadaveric head and neck specimens. Relevant anatomical parameters, including distances from the midsagittal line to internal carotid arteries (ICA), vertebral arteries (VA), and hypoglossal nerves (HN), were measured using electronic calipers.
RESULTS: The mean distance between ICA and midsagittal line was observed as 26.13 mm at the level of axis and 24.67 mm at the level of the atlas. The mean distance between VA and midsagittal line was observed as 15.38 mm at the level of axis and 26.54 mm at the level of the atlas. The mean distance between HN and midsagittal line was observed as 33.27 and 33.58 mm at the level of the atlas and axis, respectively.
CONCLUSION: This study confirmed that ICA and HN proceeded ventrally or laterally along the lateral aspect of the C1 lateral mass; therefore, the area located ventrally along the medial components of the C1 lateral mass was the safe zone for anterior surgical approach.

PMID: 29279983 [PubMed - as supplied by publisher]

from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2E5NrMY

A 3-variable prognostic score (3-PS) for overall survival prediction in metastatic castration-resistant prostate cancer treated with 223 Radium-dichloride

Abstract

Objective

In mCRPC patients treated with ²²³Ra, a major issue is the validation of reliable prognostic and predictive biomarkers to maximize clinical benefit and minimize toxicities and costs. Bearing in mind how changes in tALP did not meet statistical requirements as surrogate marker for survival, aim of this single-center retrospective study was to characterize the prognostic and predictive role of baseline clinical variables associated with overall survival in patients receiving ²²³Ra treatment.

Methods

92 consecutive CRPC patients with symptomatic bone metastases receiving ²²³Ra treatment were included. Available baseline clinical data relevant to the survival analysis were retrospectively collected. The primary end-point of the study was overall survival, which was established from the first ²²³Ra administration until date of death from any cause.

Results

Median follow-up time from the first ²²³Ra administration was 6 months (range 1–31 months). The univariate analysis evaluating the prognostic value of all baseline clinical variables showed that patients' weight, BMI, ECOG PS, Hb and tALP values were independently associated with OS. On multivariable analysis only baseline Hb value and ECOG PS remained significantly correlated with OS. To determine reliable baseline predictive factors for survival in patients receiving ²²³Ra treatment, we produced a predictive score. We tried all possible variable combinations, and found that the best score was obtained by combining baseline ECOG PS with Hb < 12 g/dl and PSA ≥ 20 ng/ml. This resulted in a score ranging from 0 to 4, with AUC 78.4% (p < 0.001).

Conclusions

We propose a multidimensional clinical evaluation to select those mCRPC subjects suitable to receive the maximum benefit from ²²³Ra treatment.

from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2E4YpST

Restoring the Electrical Properties of CVD Graphene via Physisorption of Molecular Adsorbates

Chemical vapor deposition (CVD) is a powerful technique to produce graphene for large-scale applications. Polymer-assisted wet transfer is commonly used to move the graphene onto silicon substrates, but the resulting devices tend to exhibit p-doping, which decreases the device quality and reproducibility. In an effort to better understand the origin of this effect, we coated graphene with n-methyl-2-pyrrolidone (NMP) and hexamethyldisilazane (HMDS) molecules that exhibit negligible charge transfer to graphene but bind more strongly to graphene than ambient adsorbents. Using Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), electrical transport measurements, and quantum mechanical computer simulations, we show that the molecules help in the removal of p-doping, and our data indicate that the molecules do this by replacing ambient adsorbents (typically O2 and water) on the graphene surface. This very simple method of improving the electronic properties of CVD graphene by passivating its surface with common solvent molecules will accelerate the development of CVD graphene-based devices.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2BM8ZN8
via IFTTT

Jeffrey Lima Hayes O’Riordan

bmj;359/dec28_1/j5872/FAF1faPhysician scientist Jeffrey O’Riordan was a pioneer of the study of hormonal control of calcium and bone biology. He became influential as an investigator, doctor, and...

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2CeOs73
via IFTTT

Plants use sand armour to break teeth of attacking caterpillars

Some plants are coated in sand, and it seems the sand grains act like medieval armour that protects these “psammophorous” plants from munching caterpillars

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2E7AphJ
via IFTTT

Application of image recognition-based automatic hyphae detection in fungal keratitis

Abstract

The purpose of this study is to evaluate the accuracy of two methods in diagnosis of fungal keratitis, whereby one method is automatic hyphae detection based on images recognition and the other method is corneal smear. We evaluate the sensitivity and specificity of the method in diagnosis of fungal keratitis, which is automatic hyphae detection based on image recognition. We analyze the consistency of clinical symptoms and the density of hyphae, and perform quantification using the method of automatic hyphae detection based on image recognition. In our study, 56 cases with fungal keratitis (just single eye) and 23 cases with bacterial keratitis were included. All cases underwent the routine inspection of slit lamp biomicroscopy, corneal smear examination, microorganism culture and the assessment of in vivo confocal microscopy images before starting medical treatment. Then, we recognize the hyphae images of in vivo confocal microscopy by using automatic hyphae detection based on image recognition to evaluate its sensitivity and specificity and compare with the method of corneal smear. The next step is to use the index of density to assess the severity of infection, and then find the correlation with the patients’ clinical symptoms and evaluate consistency between them. The accuracy of this technology was superior to corneal smear examination (p < 0.05). The sensitivity of the technology of automatic hyphae detection of image recognition was 89.29%, and the specificity was 95.65%. The area under the ROC curve was 0.946. The correlation coefficient between the grading of the severity in the fungal keratitis by the automatic hyphae detection based on image recognition and the clinical grading is 0.87. The technology of automatic hyphae detection based on image recognition was with high sensitivity and specificity, able to identify fungal keratitis, which is better than the method of corneal smear examination. This technology has the advantages when compared with the conventional artificial identification of confocal microscope corneal images, of being accurate, stable and does not rely on human expertise. It was the most useful to the medical experts who are not familiar with fungal keratitis. The technology of automatic hyphae detection based on image recognition can quantify the hyphae density and grade this property. Being noninvasive, it can provide an evaluation criterion to fungal keratitis in a timely, accurate, objective and quantitative manner.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2lmfkrh
via IFTTT

Early nucleus basalis of Meynert degeneration predicts cognitive decline in Parkinson’s disease

This scientific commentary refers to ‘In vivo cholinergic basal forebrain atrophy predicts cognitive decline in de novo Parkinson’s disease’ by Ray et al. (doi:10.1093/brain/awx310). 

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2E74yho
via IFTTT

The rise of a new associationist school for lesion-symptom mapping

This scientific commentary refers to ‘High-dimensional therapeutic inference in the focally damaged human brain’, by Xu et al. (doi:10.1093/brain/awx288). 

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ln3gGe
via IFTTT

Holding down the pain

This scientific commentary refers to ‘Mutations affecting glycinergic neurotransmission in hyperekplexia increase pain sensitivity’, by Vuilleumier et al. (doi:10.1093/brain/awx289). 

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2E4rldP
via IFTTT

Editorial

Brain enters its 141st year of continuous publication with this issue, and its 5th year under the current editorial team. It is tempting to be complacent, and use this editorial to list the metrics that testify to the journal’s continued success. There is, however, an important aspect where the journal does not appear to have moved as far from its 19th century origins as might be hoped. The current Editor is, in common with all 16 of his predecessors, male, as are 7 out of 9 Associate Editors, and 19 out of 24 members of the Editorial Advisory Board. How does this reflect the gender balance of authors publishing in the journal? Authors are not asked to self-identify as male or female upon submission or acceptance of manuscripts, and so the following estimates are predicated on numerous assumptions about how first names relate to gender, taking into account presumed nationality, and in a few cases supplemented by an online search of images. Between 2014 and 2017 (inclusive) first authors of original articles were more likely to be male than female in a 60:40 ratio. Using last authors as a surrogate for seniority, the male:female ratio was 76:24. These ratios have not shown any sign of shifting during the 4-year interval. This analysis has numerous potential flaws, and assumes a ‘gender binarism’ that belongs to a previous century. Nevertheless, the numbers are in line with abundant evidence of attrition of female scientists with increasing seniority in universities and other research environments. The male preponderance is not as marked as at Science, where only 25% of junior and 17% of senior author positions are held by women (Berg, 2017). This is perhaps not surprising, because medicine has a far more balanced intake than some of the physical sciences. There is, of course, not much that can be done by journals to address the imbalance whilst striving for a peer review process that avoids taking into consideration anything other than veracity, novelty and importance. One small area where the editorial team of Brain might be able to nudge the field is in inviting authors of commissioned scientific commentaries. Our efforts to date have however not been successful, as judging by the gender balance of this category of paper: 78% of authors in the last 4 years have been male. The only hint of a re-balancing is found in the Reviews and Updates, some of which are commissioned, and which go through a presubmission enquiry before authors are invited to submit. In this category the male:female ratio is 60:40. Overall, the report card for the last 4 years states, ‘Could try harder’.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ljPB2J
via IFTTT

Spread of tau deposits: can we trust in vivo findings?

This scientific commentary refers to ‘Widespread brain tau and its association with ageing, Braak stage and Alzheimer’s dementia’, by Lowe et al. (doi:10.1093/brain/awx320). 

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2lmyRZ1
via IFTTT

Dr Harrison Martland and the history of punch drunk syndrome

In 1928, pathologist Harrison Martland published a paper entitled ‘Punch Drunk’, in which he proposed a link between neurological symptoms in boxers and repetitive head trauma. Changa et al. examine Martland’s work and its influence on present day understanding of concussive head trauma in sport.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2lmyHRp
via IFTTT

A fingerprint of the epileptogenic zone in human epilepsies

Abstract

Defining a bio-electrical marker for the brain area responsible for initiating a seizure remains an unsolved problem. Fast gamma activity has been identified as the most specific marker for seizure onset, but conflicting results have been reported. In this study, we describe an alternative marker, based on an objective description of interictal to ictal transition, with the aim of identifying a time-frequency pattern or ‘fingerprint’ that can differentiate the epileptogenic zone from areas of propagation. Seventeen patients who underwent stereoelectroencephalography were included in the study. Each had seizure onset characterized by sustained gamma activity and were seizure-free after tailored resection or laser ablation. We postulated that the epileptogenic zone was always located inside the resection region based on seizure freedom following surgery. To characterize the ictal frequency pattern, we applied the Morlet wavelet transform to data from each pair of adjacent intracerebral electrode contacts. Based on a visual assessment of the time-frequency plots, we hypothesized that a specific time-frequency pattern in the epileptogenic zone should include a combination of (i) sharp transients or spikes; preceding (ii) multiband fast activity concurrent; with (iii) suppression of lower frequencies. To test this hypothesis, we developed software that automatically extracted each of these features from the time-frequency data. We then used a support vector machine to classify each contact-pair as being within epileptogenic zone or not, based on these features. Our machine learning system identified this pattern in 15 of 17 patients. The total number of identified contacts across all patients was 64, with 58 localized inside the resected area. Subsequent quantitative analysis showed strong correlation between maximum frequency of fast activity and suppression inside the resection but not outside. We did not observe significant discrimination power using only the maximum frequency or the timing of fast activity to differentiate contacts either between resected and non-resected regions or between contacts identified as epileptogenic versus non-epileptogenic. Instead of identifying a single frequency or a single timing trait, we observed the more complex pattern described above that distinguishes the epileptogenic zone. This pattern encompasses interictal to ictal transition and may extend until seizure end. Its time-frequency characteristics can be explained in light of recent models emphasizing the role of fast inhibitory interneurons acting on pyramidal cells as a prominent mechanism in seizure triggering. The pattern clearly differentiates the epileptogenic zone from areas of propagation and, as such, represents an epileptogenic zone ‘fingerprint’.awx306media15687076823001

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2E5KuvC
via IFTTT

Clemastine rescues myelination defects and promotes functional recovery in hypoxic brain injury

Abstract

Hypoxia can injure brain white matter tracts, comprised of axons and myelinating oligodendrocytes, leading to cerebral palsy in neonates and delayed post-hypoxic leukoencephalopathy (DPHL) in adults. In these conditions, white matter injury can be followed by myelin regeneration, but myelination often fails and is a significant contributor to fixed demyelinated lesions, with ensuing permanent neurological injury. Non-myelinating oligodendrocyte precursor cells are often found in lesions in plentiful numbers, but fail to mature, suggesting oligodendrocyte precursor cell differentiation arrest as a critical contributor to failed myelination in hypoxia. We report a case of an adult patient who developed the rare condition DPHL and made a nearly complete recovery in the setting of treatment with clemastine, a widely available antihistamine that in preclinical models promotes oligodendrocyte precursor cell differentiation. This suggested possible therapeutic benefit in the more clinically prevalent hypoxic injury of newborns, and we demonstrate in murine neonatal hypoxic injury that clemastine dramatically promotes oligodendrocyte precursor cell differentiation, myelination, and improves functional recovery. We show that its effect in hypoxia is oligodendroglial specific via an effect on the M1 muscarinic receptor on oligodendrocyte precursor cells. We propose clemastine as a potential therapy for hypoxic brain injuries associated with white matter injury and oligodendrocyte precursor cell maturation arrest.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ln2itA
via IFTTT

Neuronal inhibition and synaptic plasticity of basal ganglia neurons in Parkinson's disease

Abstract

Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson’s disease symptoms. The therapeutic benefits of deep brain stimulation are frequency-dependent, but the underlying physiological mechanisms remain unclear. To advance deep brain stimulation therapy an understanding of fundamental mechanisms is critical. The objectives of this study were to (i) compare the frequency-dependent effects on cell firing in subthalamic nucleus and substantia nigra pars reticulata; (ii) quantify frequency-dependent effects on short-term plasticity in substantia nigra pars reticulata; and (iii) investigate effects of continuous long-train high frequency stimulation (comparable to conventional deep brain stimulation) on synaptic plasticity. Two closely spaced (600 µm) microelectrodes were advanced into the subthalamic nucleus (n = 27) and substantia nigra pars reticulata (n = 14) of 22 patients undergoing deep brain stimulation surgery for Parkinson’s disease. Cell firing and evoked field potentials were recorded with one microelectrode during stimulation trains from the adjacent microelectrode across a range of frequencies (1–100 Hz, 100 µA, 0.3 ms, 50–60 pulses). Subthalamic firing attenuated with ≥20 Hz (P < 0.01) stimulation (silenced at 100 Hz), while substantia nigra pars reticulata decreased with ≥3 Hz (P < 0.05) (silenced at 50 Hz). Substantia nigra pars reticulata also exhibited a more prominent increase in transient silent period following stimulation. Patients with longer silent periods after 100 Hz stimulation in the subthalamic nucleus tended to have better clinical outcome after deep brain stimulation. At ≥30 Hz the first evoked field potential of the stimulation train in substantia nigra pars reticulata was potentiated (P < 0.05); however, the average amplitude of the subsequent potentials was rapidly attenuated (P < 0.01). This is suggestive of synaptic facilitation followed by rapid depression. Paired pulse ratios calculated at the beginning of the train revealed that 20 Hz (P < 0.05) was the minimum frequency required to induce synaptic depression. Lastly, the average amplitude of evoked field potentials during 1 Hz pulses showed significant inhibitory synaptic potentiation after long-train high frequency stimulation (P < 0.001) and these increases were coupled with increased durations of neuronal inhibition (P < 0.01). The subthalamic nucleus exhibited a higher frequency threshold for stimulation-induced inhibition than the substantia nigra pars reticulata likely due to differing ratios of GABA:glutamate terminals on the soma and/or the nature of their GABAergic inputs (pallidal versus striatal). We suggest that enhancement of inhibitory synaptic plasticity, and frequency-dependent potentiation and depression are putative mechanisms of deep brain stimulation. Furthermore, we foresee that future closed-loop deep brain stimulation systems (with more frequent off stimulation periods) may benefit from inhibitory synaptic potentiation that occurs after high frequency stimulation.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2E5Kv2E
via IFTTT

Reply: POLR3A variants in hereditary spastic paraplegia and ataxia

Sir,

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2lkni4s
via IFTTT

POLR3A variants in hereditary spastic paraplegia and ataxia

Sir,

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2E3eMzn
via IFTTT

DGUOK recessive mutations in patients with CPEO, mitochondrial myopathy, parkinsonism and mtDNA deletions

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2lkWy3N
via IFTTT

Obligatory and facultative brain regions for voice-identity recognition

Abstract

Recognizing the identity of others by their voice is an important skill for social interactions. To date, it remains controversial which parts of the brain are critical structures for this skill. Based on neuroimaging findings, standard models of person-identity recognition suggest that the right temporal lobe is the hub for voice-identity recognition. Neuropsychological case studies, however, reported selective deficits of voice-identity recognition in patients predominantly with right inferior parietal lobe lesions. Here, our aim was to work towards resolving the discrepancy between neuroimaging studies and neuropsychological case studies to find out which brain structures are critical for voice-identity recognition in humans. We performed a voxel-based lesion-behaviour mapping study in a cohort of patients (n = 58) with unilateral focal brain lesions. The study included a comprehensive behavioural test battery on voice-identity recognition of newly learned (voice-name, voice-face association learning) and familiar voices (famous voice recognition) as well as visual (face-identity recognition) and acoustic control tests (vocal-pitch and vocal-timbre discrimination). The study also comprised clinically established tests (neuropsychological assessment, audiometry) and high-resolution structural brain images. The three key findings were: (i) a strong association between voice-identity recognition performance and right posterior/mid temporal and right inferior parietal lobe lesions; (ii) a selective association between right posterior/mid temporal lobe lesions and voice-identity recognition performance when face-identity recognition performance was factored out; and (iii) an association of right inferior parietal lobe lesions with tasks requiring the association between voices and faces but not voices and names. The results imply that the right posterior/mid temporal lobe is an obligatory structure for voice-identity recognition, while the inferior parietal lobe is only a facultative component of voice-identity recognition in situations where additional face-identity processing is required.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2E5KYSP
via IFTTT

Reply: DGUOK recessive mutations in patients with CPEO, mitochondrial myopathy, parkinsonism and mtDNA deletions

Sir,

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ll8O46
via IFTTT

Plasma oxysterols: biomarkers for diagnosis and treatment in spastic paraplegia type 5

Abstract

The hereditary spastic paraplegias are an expanding and heterogeneous group of disorders characterized by spasticity in the lower limbs. Plasma biomarkers are needed to guide the genetic testing of spastic paraplegia. Spastic paraplegia type 5 (SPG5) is an autosomal recessive spastic paraplegia due to mutations in CYP7B1, which encodes a cytochrome P450 7α-hydroxylase implicated in cholesterol and bile acids metabolism. We developed a method based on ultra-performance liquid chromatography electrospray tandem mass spectrometry to validate two plasma 25-hydroxycholesterol (25-OHC) and 27-hydroxycholesterol (27-OHC) as diagnostic biomarkers in a cohort of 21 patients with SPG5. For 14 patients, SPG5 was initially suspected on the basis of genetic analysis, and then confirmed by increased plasma 25-OHC, 27-OHC and their ratio to total cholesterol. For seven patients, the diagnosis was initially based on elevated plasma oxysterol levels and confirmed by the identification of two causal CYP7B1 mutations. The receiver operating characteristic curves analysis showed that 25-OHC, 27-OHC and their ratio to total cholesterol discriminated between SPG5 patients and healthy controls with 100% sensitivity and specificity. Taking advantage of the robustness of these plasma oxysterols, we then conducted a phase II therapeutic trial in 12 patients and tested whether candidate molecules (atorvastatin, chenodeoxycholic acid and resveratrol) can lower plasma oxysterols and improve bile acids profile. The trial consisted of a three-period, three-treatment crossover study and the six different sequences of three treatments were randomized. Using a linear mixed effect regression model with a random intercept, we observed that atorvastatin decreased moderately plasma 27-OHC (∼30%, P < 0.001) but did not change 27-OHC to total cholesterol ratio or 25-OHC levels. We also found an abnormal bile acids profile in SPG5 patients, with significantly decreased total serum bile acids associated with a relative decrease of ursodeoxycholic and lithocholic acids compared to deoxycholic acid. Treatment with chenodeoxycholic acid restored bile acids profile in SPG5 patients. Therefore, the combination of atorvastatin and chenodeoxycholic acid may be worth considering for the treatment of SPG5 patients but the neurological benefit of these metabolic interventions remains to be evaluated in phase III therapeutic trials using clinical, imaging and/or electrophysiological outcome measures with sufficient effect sizes. Overall, our study indicates that plasma 25-OHC and 27-OHC are robust diagnostic biomarkers of SPG5 and shall be used as first-line investigations in any patient with unexplained spastic paraplegia.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2E3mPMv
via IFTTT

Oestrogen receptor β ligand acts on CD11c+ cells to mediate protection in experimental autoimmune encephalomyelitis

Abstract

Oestrogen treatments are neuroprotective in a variety of neurodegenerative disease models. Selective oestrogen receptor modifiers are needed to optimize beneficial effects while minimizing adverse effects to achieve neuroprotection in chronic diseases. Oestrogen receptor beta (ERβ) ligands are potential candidates. In the multiple sclerosis model chronic experimental autoimmune encephalomyelitis, ERβ-ligand treatment is neuroprotective, but mechanisms underlying this neuroprotection remain unclear. Specifically, whether there are direct effects of ERβ-ligand on CD11c^&plus; microglia, myeloid dendritic cells or macrophages in vivo during disease is unknown. Here, we generated mice with ERβ deleted from CD11c^&plus; cells to show direct effects of ERβ-ligand treatment in vivo on these cells to mediate neuroprotection during experimental autoimmune encephalomyelitis. Further, we use bone marrow chimeras to show that ERβ in peripherally derived myeloid cells, not resident microglia, are the CD11c^&plus; cells mediating this protection. CD11c^&plus; dendritic cell and macrophages isolated from the central nervous system of wild-type experimental autoimmune encephalomyelitis mice treated with ERβ-ligand expressed less iNOS and T-bet, but more IL-10, and this treatment effect was lost in mice with specific deletion of ERβ in CD11c^&plus; cells. Also, we extend previous reports of ERβ-ligand’s ability to enhance remyelination through a direct effect on oligodendrocytes by showing that the immunomodulatory effect of ERβ-ligand acting on CD11c^&plus; cells is necessary to permit the maturation of oligodendrocytes. Together these results demonstrate that targeting ERβ signalling pathways in CD11c^&plus; myeloid cells is a novel strategy for regulation of the innate immune system in neurodegenerative diseases. To our knowledge, this is the first report showing how direct effects of a candidate neuroprotective treatment on two distinct cell lineages (bone marrow derived myeloid cells and oligodendrocytes) can have complementary neuroprotective effects in vivo.awx315media15688130498001

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ll8wdw
via IFTTT

Longitudinal structural and molecular neuroimaging in agrammatic primary progressive aphasia

Abstract

The agrammatic variant of primary progressive aphasia affects normal grammatical language production, often occurs with apraxia of speech, and is associated with left frontal abnormalities on cross-sectional neuroimaging studies. We aimed to perform a detailed assessment of longitudinal change on structural and molecular neuroimaging to provide a complete picture of neurodegeneration in these patients, and to determine how patterns of progression compare to patients with isolated apraxia of speech (primary progressive apraxia of speech). We assessed longitudinal structural MRI, diffusion tensor imaging and ¹⁸F-fluorodeoxyglucose PET in 11 agrammatic aphasia subjects, 20 primary progressive apraxia of speech subjects, and 62 age and gender-matched controls with two serial assessments. Rates of change in grey matter volume and hypometabolism, and white matter fractional anisotropy, mean diffusivity, radial diffusivity and axial diffusivity were assessed at the voxel-level and for numerous regions of interest. The greatest rates of grey matter atrophy in agrammatic aphasia were observed in inferior, middle, and superior frontal gyri, premotor and motor cortices, as well as medial temporal lobe, insula, basal ganglia, and brainstem compared to controls. Longitudinal decline in metabolism was observed in the same regions, with additional findings in medial and lateral parietal lobe. Diffusion tensor imaging changes were prominent bilaterally in inferior and middle frontal white matter and superior longitudinal fasciculus, as well as right inferior fronto-occipital fasciculus, superior frontal and precentral white matter. More focal patterns of degeneration of motor and premotor cortex were observed in primary progressive apraxia of speech. Agrammatic aphasia showed greater rates of grey matter atrophy, decline in metabolism, and white matter degeneration compared to primary progressive apraxia of speech in the left frontal lobe, predominantly inferior and middle frontal grey and white matter. Correlations were also assessed between rates of change on neuroimaging and rates of clinical decline. Progression of aphasia correlated with rates of degeneration in frontal and temporal regions within the language network, while progression of parkinsonism and limb apraxia correlated with degeneration of motor cortex and brainstem. These findings demonstrate that disease progression in agrammatic aphasia is associated with widespread neurodegeneration throughout regions of the language network, as well as connecting white matter tracts, but also with progression to regions outside of the language network that are responsible for the development of motor symptoms. The fact that patterns of progression differed from primary progressive apraxia of speech supports the clinical distinction of these syndromes.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2E52CWI
via IFTTT

Structural connectivity of right frontal hyperactive areas scales with stuttering severity

Abstract

A neuronal sign of persistent developmental stuttering is the magnified coactivation of right frontal brain regions during speech production. Whether and how stuttering severity relates to the connection strength of these hyperactive right frontal areas to other brain areas is an open question. Scrutinizing such brain–behaviour and structure–function relationships aims at disentangling suspected underlying neuronal mechanisms of stuttering. Here, we acquired diffusion-weighted and functional images from 31 adults who stutter and 34 matched control participants. Using a newly developed structural connectivity measure, we calculated voxel-wise correlations between connection strength and stuttering severity within tract volumes that originated from functionally hyperactive right frontal regions. Correlation analyses revealed that with increasing speech motor deficits the connection strength increased in the right frontal aslant tract, the right anterior thalamic radiation, and in U-shaped projections underneath the right precentral sulcus. In contrast, with decreasing speech motor deficits connection strength increased in the right uncinate fasciculus. Additional group comparisons of whole-brain white matter skeletons replicated the previously reported reduction of fractional anisotropy in the left and right superior longitudinal fasciculus as well as at the junction of right frontal aslant tract and right superior longitudinal fasciculus in adults who stutter compared to control participants. Overall, our investigation suggests that right fronto-temporal networks play a compensatory role as a fluency enhancing mechanism. In contrast, the increased connection strength within subcortical-cortical pathways may be implied in an overly active global response suppression mechanism in stuttering. Altogether, this combined functional MRI–diffusion tensor imaging study disentangles different networks involved in the neuronal underpinnings of the speech motor deficit in persistent developmental stuttering.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2liSsJx
via IFTTT

An Emerging Treatment Alternative for Anemia in Chronic Kidney Disease Patients: A Review of Daprodustat

Abstract

This article reviews an emerging therapeutic agent, which is currently in phase III development for the treatment of anemia secondary to chronic kidney disease, covering promising phase II results, drug characteristics, and the current phase III trials, which, if approved, may significantly impact the management of anemia in this patient population.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2E3Oj4H
via IFTTT

Intragastric Balloon Treatment for Obesity: FDA Safety Updates

Abstract

Over the past year, the FDA has issued two letters to healthcare providers alerting them to adverse events associated with ORBERA and ReShape intragastric balloons (IGBs), including several deaths. Both IGB devices were FDA-approved for use in the US in the summer of 2015. Although the adverse events cited in the two letters occurred following FDA approval, there was already evidence prior to FDA approval that the safety and efficacy of ReShape and ORBERA were highly questionable. Since January 1, 2006, ORBERA and Reshape IGB have been implicated in 33 deaths. Given the cited evidence, we recommend FDA withdrawal of these two devices.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2pMVqvg
via IFTTT

Giant Valley-Isospin Conductance Oscillations in Ballistic Graphene

At high magnetic fields the conductance of graphene is governed by the half-integer quantum Hall effect. By local electrostatic gating a p–n junction perpendicular to the graphene edges can be formed, along which quantum Hall channels copropagate. It has been predicted by Tworzidło and co-workers that if only the lowest Landau level is filled on both sides of the junction, the conductance is determined by the valley (isospin) polarization at the edges and by the width of the flake. This effect remained hidden so far due to scattering between the channels copropagating along the p–n interface (equilibration). Here we investigate p–n junctions in encapsulated graphene with a movable p–n interface with which we are able to probe the edge-configuration of graphene flakes. We observe large quantum conductance oscillations on the order of e2/h which solely depend on the p–n junction position providing the first signature of isospin-defined conductance. Our experiments are underlined by quantum transport calculations.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2C40iSw
via IFTTT

Focal cortical thinning in patients with stable relapsing-remitting multiple sclerosis: cross-sectional-based novel estimation of gray matter kinetics

Abstract

Purpose

The aim of our study is to identify radiological patterns of cortical gray matter atrophy (CGMA) that correlate with disease duration in patients with relapsing-remitting multiple sclerosis (RRMS).

Methods

RRMS patients were randomly selected from the Sheba Multiple Sclerosis (MS) center computerized data registry based on stratification of disease duration up to 10 years. Patients were scanned by 3.0 T (Signa, GE) MRI, using a T1 weighted 3D high resolution, FSPGR, MS protocol. Neurological disability was assessed by the Expanded Disability Status Scale (EDSS). FreeSurfer was used to obtain brain volumetric segmentation and to perform cortical thickness surface-based analysis. Clusters of change in cortical thickness with correlation to disease duration were produced.

Results

Two hundred seventy-one RRMS patients, mean ± SD age 33.0 ± 7.0 years, EDSS 1.6 ± 1.2, disease duration 5.0 ± 3.4 years. Cortical thickness analysis demonstrated focal areas of cerebral thinning that correlated with disease duration. Seven clusters accounting for 11.7% of the left hemisphere surface and eight clusters accounting for 10.6% of the right hemisphere surface were identified, with cluster-wise probability of p < 0.002 and p < 0.02, respectively.The clusters included bilateral involvement of areas within the cingulate, precentral, postcentral, paracentral, superior-parietal, superior-frontal gyri and insular cortex. Mean and cluster-wise cortical thickness negatively correlated with EDSS score, p < 0.001, with stronger Spearman rho for cluster-wise measurements.

Conclusions

We identified CGMA patterns in sensitive brain regions which give insight and better understanding of the progression of cortical gray matter loss in relation to dissemination in space and time. These patterns may serve as markers to modulate therapeutic interventions to improve the management of MS patients.

from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2C498j6

The gene product of a Trypanosoma equiperdum ortholog of the cAMP-dependent protein kinase regulatory subunit is a monomeric protein that is not capable of binding cyclic nucleotides

Publication date: Available online 27 December 2017
Source:Biochimie
Author(s): José Bubis, Juan Carlos Martínez, Maritza Calabokis, Joilyneth Ferreira, Carlos E. Sanz-Rodríguez, Victoria Navas, José Leonardo Escalona, Yurong Guo, Susan S. Taylor
The full gene sequence encoding for the Trypanosoma equiperdum ortholog of the cAMP-dependent protein kinase (PKA) regulatory (R) subunits was cloned. A poly-His tagged construct was generated [TeqR-like(His)8], and the protein was expressed in bacteria and purified to homogeneity. The size of the purified TeqR-like(His)8 was determined to be ∼ 57,000 Da by molecular exclusion chromatography indicating that the parasite protein is a monomer. Limited proteolysis with various proteases showed that the T. equiperdum R-like protein possesses a hinge region very susceptible to proteolysis. The recombinant TeqR-like(His)8 did not bind either [³H] cAMP or [³H] cGMP up to concentrations of 0.40 and 0.65 μM, respectively, and neither the parasite protein nor its proteolytically generated carboxy-terminal large fragments were capable of binding to a cAMP-Sepharose affinity column. Bioinformatics analyses predicted that the carboxy-terminal region of the trypanosomal R-like protein appears to fold similarly to the analogous region of all known PKA R subunits. However, the protein amino-terminal portion seems to be unrelated and shows homology with proteins that contained Leu-rich repeats, a folding motif that is particularly appropriate for protein-protein interactions. In addition, the three-dimensional structure of the T. equiperdum protein was modeled using the crystal structure of the bovine PKA R^Iα subunit as template. Molecular docking experiments predicted critical changes in the environment of the two putative nucleotide binding clefts of the parasite protein, and the resulting binding energy differences support the lack of cyclic nucleotide binding in the trypanosomal R-like protein.



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2E6uSbw
via IFTTT

Bacterial LPX motif-harboring virulence factors constitute a species-spanning family of cell-penetrating effectors

Abstract

Effector proteins are key virulence factors of pathogenic bacteria that target and subvert the functions of essential host defense mechanisms. Typically, these proteins are delivered into infected host cells via the type III secretion system (T3SS). Recently, however, several effector proteins have been found to enter host cells in a T3SS-independent manner thereby widening the potential range of these virulence factors. Prototypes of such bacteria-derived cell-penetrating effectors (CPEs) are the Yersinia enterocolitica-derived YopM as well as the Salmonella typhimurium effector SspH1. Here, we investigated specifically the group of bacterial LPX effector proteins comprising the Shigella IpaH proteins, which constitute a subtype of the leucine-rich repeat protein family and share significant homologies in sequence and structure. With particular emphasis on the Shigella-effector IpaH9.8, uptake into eukaryotic cell lines was shown. Recombinant IpaH9.8 (rIpaH9.8) is internalized via endocytic mechanisms and follows the endo-lysosomal pathway before escaping into the cytosol. The N-terminal alpha-helical domain of IpaH9.8 was identified as the protein transduction domain required for its CPE ability as well as for being able to deliver other proteinaceous cargo. rIpaH9.8 is functional as an ubiquitin E3 ligase and targets NEMO for poly-ubiquitination upon cell penetration. Strikingly, we could also detect other recombinant LPX effector proteins from Shigella and Salmonella intracellularly when applied to eukaryotic cells. In this study, we provide further evidence for the general concept of T3SS-independent translocation by identifying novel cell-penetrating features of these LPX effectors revealing an abundant species-spanning family of CPE.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2zEQmIR
via IFTTT

Viruses, Vol. 10, Pages 10: Genotypic and Phylogenetic Insights on Prevention of the Spread of HIV-1 and Drug Resistance in “Real-World” Settings

Viruses, Vol. 10, Pages 10: Genotypic and Phylogenetic Insights on Prevention of the Spread of HIV-1 and Drug Resistance in “Real-World” Settings

Viruses doi: 10.3390/v10010010

Authors: Bluma Brenner Ruxandra-Ilinca Ibanescu Isabelle Hardy Michel Roger

HIV continues to spread among vulnerable heterosexual (HET), Men-having-Sex with Men (MSM) and intravenous drug user (IDU) populations, influenced by a complex array of biological, behavioral and societal factors. Phylogenetics analyses of large sequence datasets from national drug resistance testing programs reveal the evolutionary interrelationships of viral strains implicated in the dynamic spread of HIV in different regional settings. Viral phylogenetics can be combined with demographic and behavioral information to gain insights on epidemiological processes shaping transmission networks at the population-level. Drug resistance testing programs also reveal emergent mutational pathways leading to resistance to the 23 antiretroviral drugs used in HIV-1 management in low-, middle- and high-income settings. This article describes how genotypic and phylogenetic information from Quebec and elsewhere provide critical information on HIV transmission and resistance, Cumulative findings can be used to optimize public health strategies to tackle the challenges of HIV in “real-world” settings.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2C2W6lR
via IFTTT

Viruses, Vol. 10, Pages 9: The Abrogation of Phosphorylation Plays a Relevant Role in the CCR5 Signalosome Formation with Natural Antibodies to CCR5

Viruses, Vol. 10, Pages 9: The Abrogation of Phosphorylation Plays a Relevant Role in the CCR5 Signalosome Formation with Natural Antibodies to CCR5

Viruses doi: 10.3390/v10010009

Authors: Assunta Venuti Claudia Pastori Gabriel Siracusano Rosamaria Pennisi Agostino Riva Massimo Tommasino Maria Sciortino Lucia Lopalco

The exposure to CCR5 (CC chemokine receptor 5) specific natural antibodies in vitro produces a Class B β-arrestin2-dependent CCR5 retention with the aid of ERK1, due to the formation of a CCR5 signalosome, which remains stable for at least 48 h. Considering that β-arrestins and MAPKs are receptive to environmental signals, their signal complexes could be one of the key junction for GPCRs internalization related signal transduction. Here, we demonstrate that, in T cells, the phosphorylation status of either CCR5 receptor or ERK1 protein is necessary to drive the internalized receptor into the early endosomes, forming the CCR5 signalosome. In particular, our data show that β-arrestin2/ERK1 complex is a relevant transducer in the CCR5 signaling pathway. Understanding the mechanism of CCR5 regulation is essential for many inflammatory disorders, tumorigenesis and viral infection such as HIV.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2zGR5JI
via IFTTT

A Novel Model of Cancer-Induced Peripheral Neuropathy and the Role of TRPA1 in Pain Transduction

Background. Models of cancer-induced neuropathy are designed by injecting cancer cells near the peripheral nerves. The interference of tissue-resident immune cells does not allow a direct contact with nerve fibres which affects the tumor microenvironment and the invasion process. Methods. Anaplastic tumor-1 (AT-1) cells were inoculated within the sciatic nerves (SNs) of male Copenhagen rats. Lumbar dorsal root ganglia (DRGs) and the SNs were collected on days 3, 7, 14, and 21. SN tissues were examined for morphological changes and DRG tissues for immunofluorescence, electrophoretic tendency, and mRNA quantification. Hypersensitivities to cold, mechanical, and thermal stimuli were determined. HC-030031, a selective TRPA1 antagonist, was used to treat cold allodynia. Results. Nociception thresholds were identified on day 6. Immunofluorescent micrographs showed overexpression of TRPA1 on days 7 and 14 and of CGRP on day 14 until day 21. Both TRPA1 and CGRP were coexpressed on the same cells. Immunoblots exhibited an increase in TRPA1 expression on day 14. TRPA1 mRNA underwent an increase on day 7 (normalized to 18S). Injection of HC-030031 transiently reversed the cold allodynia. Conclusion. A novel and a promising model of cancer-induced neuropathy was established, and the role of TRPA1 and CGRP in pain transduction was examined.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2E1IAMG
via IFTTT

Benign Recurrent Sixth Nerve Palsy in a Child

Benign recurrent sixth nerve palsy in children is rare. It typically occurs following viral illness or immunization, and prognosis is usually excellent. However, it is always a diagnosis of exclusion given the more serious alternative causes. Therefore, a thorough examination with brain imaging is recommended. The authors report a child with six recurrent episodes of isolated benign sixth nerve palsy.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2pNgpy2
via IFTTT

Impact of Chestnut and Quebracho Tannins on Rumen Microbiota of Bovines

The use of phytogenic dietary additives is being evaluated as a means to improve animal productivity. The effect of tannins seems to be the influence not only directly on the digestive process through binding of dietary proteins but also indirectly over their effects on gastrointestinal microbiota. High-throughput sequencing of 16S rRNA gene was used to analyze the impact of dietary supplementation with a blend of chestnut and quebracho tannins on the rumen microbiota of Holstein steers. Bacterial richness was lower in tannins treated animals, while the overall population structure of rumen microbiota was not significantly disturbed by tannins. The ratio of the phyla Firmicutes and Bacteroidetes, a parameter associated with energy harvesting function, was increased in tannins supplemented animals, essentially due to the selective growth of Ruminococcaceae over members of genus Prevotella. Fibrolytic, amylolytic, and ureolytic bacterial communities in the rumen were altered by tannins, while methanogenic archaea were reduced. Furthermore, ruminal pH was significantly higher in animals supplemented with tannins than in the control group, while urease activity exhibited the opposite pattern. Further work is necessary to assess the relation between tannins impact on rumen microbiota and alteration of rumen fermentation parameters associated with bovine performance.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2E3T6mu
via IFTTT

The Association between Monocyte Surface CD163 and Insulin Resistance in Patients with Type 2 Diabetes

Aim. To investigate the association between monocyte CD163 and insulin resistance in patients with type 2 diabetes. Methods. One hundred sixty-six patients with type 2 diabetes without inflammatory or chronic kidney disease were recruited. The monocyte CD163 levels were measured by flow cytometry and soluble CD163 (sCD163) by ELISA. Insulin resistance was evaluated by the index of the homeostasis model assessment (HOMA-R). Results. The median sCD163 and monocyte CD163 expression levels were 582.9 (472.4–720.0) ng/ml and 6061 (4486–7876) mean fluorescent intensity (MFI), respectively. In a simple regression analysis, monocyte CD163 was inversely correlated with log [HOMA-R] (, ), and sCD163 was positively correlated with log [HOMA-R] (, ). In multiple regression analyses, monocyte CD163 was an independent contributor to log [HOMA-R] (, ) even after adjustment of various clinical factors for HOMA-R (, ), whereas sCD163 was not. Conclusions. Monocyte surface CD163 expression levels were more significantly associated with insulin resistance than sCD163 in patients with type 2 diabetes, suggesting a novel pathophysiological role of CD163.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2pNgqlA
via IFTTT

Circulating Nesfatin-1 Levels and Type 2 Diabetes: A Systematic Review and Meta-Analysis

The role of nesfatin-1 in glucose homeostasis has been investigated previously. However, although numerous studies have examined the relationships between circulating nesfatin-1 levels and type 2 diabetes, the conclusions are contradictory. We aimed to probe the relationship between circulating nesfatin-1 levels and type 2 diabetes by meta-analysis. Seven studies including 328 type 2 diabetes patients and 294 control subjects were included. Although there was no obvious difference in circulating nesfatin-1 levels between patients with type 2 diabetes and the control group (MD = −0.04; 95% CI = −0.32 to −0.23), subgroup analysis showed higher nesfatin-1 levels in newly diagnosed type 2 diabetes patients (MD = 0.59; 95% CI = 0.45 to 0.74) and significantly lower nesfatin-1 levels in type 2 diabetes patients receiving antidiabetic treatment (MD = −0.26; 95% CI = −0.33 to −0.20). In conclusion, the analysis supports a relationship between circulating nesfatin-1 levels and type 2 diabetes, where newly diagnosed type 2 diabetes was associated with an elevated Nesfatin-1 level, and type 2 diabetes patients receiving antidiabetic treatment showed lower circulating nesfatin-1 levels.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2E3fyfF
via IFTTT