Quantitative Analysis of Conebeam CT for Delineating Stents in Stent-Assisted Coil Embolization [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Innovative techniques and device-related advances have improved the outcomes of neuroendovascular treatment. 3D imaging has previously used 2 x 2 binning, but 1 x 1 binning has recently been made available. The aim of this study was to evaluate the quantitative ability of conebeam CT for stent delineation and to investigate its effectiveness in the clinical environment.

MATERIALS AND METHODS:

Four acquisition groups of 3D MIP images acquired using conebeam CT with varying conditions (acquisition time, 10 or 20 seconds and binning, 1 x 1 or 2 x 2) were compared. Two methods of analysis were performed, a phantom study and an analysis of 28 randomly selected patients. The phantom study assessed the contrast-to-noise ratio and full width at half maximum values in conebeam CT images of intracranial stent struts. In the clinical subjects, we assessed contrast-to-noise ratio, full width at half maximum, and dose-area product.

RESULTS:

In the phantom study, the contrast-to-noise ratio was not considerably different between 10- and 20-second acquisition times at equivalent binning settings. Additionally, the contrast-to-noise ratio at equivalent acquisition times did not differ considerably by binning setting. For the full width at half maximum results, equivalent acquisition times differed significantly by binning setting. In the clinical analyses, the 10-second/1 x 1 group (versus 20 second/2 x 2) showed a higher contrast-to-noise ratio (P < .05) and a dose-area product reduced by approximately 70% (P < .05), but the difference in full width at half maximum was not significant (P = .20).

CONCLUSIONS:

For stent-assisted coil embolization, quantitative assessment of conebeam CT showed that 10 second/1 x 1 was equivalent to 20 second/2 x 2 for imaging deployed intracranial stents. Furthermore, the 10-second/1 x 1 settings resulted in a much smaller DAP.

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Neuroradiology Fellowship Case Requirements Need Reform [LETTERS]

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Substantia Nigra Free Water Increases Longitudinally in Parkinson Disease [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Free water in the posterior substantia nigra obtained from a bi-tensor diffusion MR imaging model has been shown to significantly increase over 1- and 4-year periods in patients with early-stage idiopathic Parkinson disease compared with healthy controls, which suggests that posterior substantia nigra free water may be an idiopathic Parkinson disease progression biomarker. Due to the known temporal posterior-to-anterior substantia nigra degeneration in idiopathic Parkinson disease, we assessed longitudinal changes in free water in both the posterior and anterior substantia nigra in patients with later-stage idiopathic Parkinson disease and age-matched healthy controls for comparison.

MATERIALS AND METHODS:

Nineteen subjects with idiopathic Parkinson disease and 19 age-matched healthy control subjects were assessed on the same 3T MR imaging scanner at baseline and after approximately 3 years.

RESULTS:

Baseline mean idiopathic Parkinson disease duration was 7.1 years. Both anterior and posterior substantia nigra free water showed significant intergroup differences at baseline (P < .001 and P = .014, respectively, idiopathic Parkinson disease versus healthy controls); however, only anterior substantia nigra free water showed significant longitudinal group x time interaction increases (P = .021, idiopathic Parkinson disease versus healthy controls). There were no significant longitudinal group x time interaction differences found for conventional diffusion tensor imaging or free water–corrected DTI assessments in either the anterior or posterior substantia nigra.

CONCLUSIONS:

Results from this study provide further evidence supporting substantia nigra free water as a promising disease-progression biomarker in idiopathic Parkinson disease that may help to identify disease-modifying therapies if used in future clinical trials. Our novel finding of longitudinal increases in anterior but not posterior substantia nigra free water is potentially a result of the much longer disease duration of our cohort compared with previously studied cohorts and the known posterior-to-anterior substantia nigra degeneration that occurs over time in idiopathic Parkinson disease.

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Spinal Angiogram: A Treacherous Criterion Standard... [LETTERS]

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High Signal Intensity in the Dentate Nucleus and Globus Pallidus on Unenhanced T1-Weighted MR Images: Comparison between Gadobutrol and Linear Gadolinium-Based Contrast Agents [PATIENT SAFETY]

BACKGROUND AND PURPOSE:

In view of the recent observations that gadolinium deposits in brain tissue after intravenous injection, our aim of this study was to compare signal changes in the globus pallidus and dentate nucleus on unenhanced T1-weighted MR images in patients receiving serial doses of gadobutrol, a macrocyclic gadolinium-based contrast agent, with those seen in patients receiving linear gadolinium-based contrast agents.

MATERIALS AND METHODS:

This was a retrospective analysis of on-site patients with brain tumors. Fifty-nine patients received only gadobutrol, and 60 patients received only linear gadolinium-based contrast agents. Linear gadolinium-based contrast agents included gadoversetamide, gadobenate dimeglumine, and gadodiamide. T1 signal intensity in the globus pallidus, dentate nucleus, and pons was measured on the precontrast portions of patients' first and seventh brain MRIs. Ratios of signal intensity comparing the globus pallidus with the pons (globus pallidus/pons) and dentate nucleus with the pons (dentate nucleus/pons) were calculated. Changes in the above signal intensity ratios were compared within the gadobutrol and linear agent groups, as well as between groups.

RESULTS:

The dentate nucleus/pons signal ratio increased in the linear gadolinium-based contrast agent group (t = 4.215, P < .001), while no significant increase was seen in the gadobutrol group (t = –1.422, P = .08). The globus pallidus/pons ratios followed similarly, with an increase in the linear gadolinium-based contrast agent group (t = 2.931, P < .0001) and no significant change in those receiving gadobutrol (t = 0.684, P = .25).

CONCLUSIONS:

Successive doses of gadobutrol do not result in T1 shortening compared with changes seen in linear gadolinium-based contrast agents.

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Deep Learning in Neuroradiology [REVIEW ARTICLE]

SUMMARY:

Deep learning is a form of machine learning using a convolutional neural network architecture that shows tremendous promise for imaging applications. It is increasingly being adapted from its original demonstration in computer vision applications to medical imaging. Because of the high volume and wealth of multimodal imaging information acquired in typical studies, neuroradiology is poised to be an early adopter of deep learning. Compelling deep learning research applications have been demonstrated, and their use is likely to grow rapidly. This review article describes the reasons, outlines the basic methods used to train and test deep learning models, and presents a brief overview of current and potential clinical applications with an emphasis on how they are likely to change future neuroradiology practice. Facility with these methods among neuroimaging researchers and clinicians will be important to channel and harness the vast potential of this new method.

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Optimization of DARTEL Settings for the Detection of Alzheimer Disease [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Although Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra (DARTEL) has been introduced as an alternative to conventional voxel-based morphometry, there are scant data available regarding the optimal image-processing settings. The aim of this study was to optimize image-processing and ROI settings for the diagnosis of Alzheimer disease using DARTEL.

MATERIALS AND METHODS:

Between May 2002 and August 2014, we selected 158 patients with Alzheimer disease and 198 age-matched healthy subjects; 158 healthy subjects served as the control group against the patients with Alzheimer disease, and the remaining 40 served as the healthy data base. Structural MR images were obtained in all the participants and were processed using DARTEL-based voxel-based morphometry with a variety of settings. These included modulated or nonmodulated, nonsmoothed or smoothed settings with a 4-, 8-, 12-, 16-, or 20-mm kernel size. A z score was calculated for each ROI, and univariate and multivariate logistic regression analyses were performed to determine the optimal ROI settings for each dataset. The optimal settings were defined as those demonstrating the highest ² test statistics in the multivariate logistic regression analyses. Finally, using the optimal settings, we obtained receiver operating characteristic curves. The models were verified using 10-fold cross-validation.

RESULTS:

The optimal settings were obtained using the hippocampus and precuneus as ROIs without modulation and smoothing. The average area under the curve was 0.845 (95% confidence interval, 0.788–0.902).

CONCLUSIONS:

We recommend using the precuneus and hippocampus as ROIs without modulation and smoothing for DARTEL-based voxel-based morphometry as a tool for diagnosing Alzheimer disease.

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Contents

Publication date: January 2018
Source:Radiotherapy and Oncology, Volume 126, Issue 1





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Update of the systematic review of palliative radiation therapy fractionation for bone metastases

Publication date: Available online 1 February 2018
Source:Radiotherapy and Oncology
Author(s): Shayna E. Rich, Ronald Chow, Srinivas Raman, K. Liang Zeng, Stephen Lutz, Henry Lam, Maurício F. Silva, Edward Chow
PurposeRadiation therapy is an effective modality for pain management of symptomatic bone metastases. We update the previous meta-analyses of randomized trials comparing single fraction to multiple fractions of radiation therapy in patients with uncomplicated bone metastases.MethodsA literature search was conducted in Ovid Medline, Embase, and Cochrane Central Register. Ten new randomized trials were identified since 2010, five with adequate and appropriate data for inclusion, resulting in a total of 29 trials that were analyzed. Forest plots based on each study's odds ratios were computed using a random effects model and the Mantel–Haenszel statistic.ResultsIn intention-to-treat analysis, the overall response rate was similar in patients for single fraction treatments (61%; 1867/3059) and those for multiple fraction treatments (62%; 1890/3040). Similarly, complete response rates were nearly identical in both groups (23% vs 24%, respectively). Re-treatment was significantly more frequent in the single fraction treatment arm, with 20% receiving additional treatment to the same site versus 8% in the multiple fraction treatment arm (p < 0.01). No significant difference was seen in the risk of pathological fracture at the treatment site, rate of spinal cord compression at the index site, or in the rate of acute toxicity.ConclusionSingle fraction and multiple fraction radiation treatment regimens continue to demonstrate similar outcomes in pain control and toxicities, but re-treatment is more common for single fraction treatment patients.



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Editorial Board

Publication date: January 2018
Source:Radiotherapy and Oncology, Volume 126, Issue 1





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The world needs new knowledge

Publication date: January 2018
Source:Radiotherapy and Oncology, Volume 126, Issue 1
Author(s): Michael Baumann




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Differentiation between radiation-induced brain injury and glioma recurrence using 3D pCASL and dynamic susceptibility contrast-enhanced perfusion-weighted imaging

This study was performed to validate the efficacy of three-dimensional pseudocontinuous arterial spin labeling (pCASL) compared with dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI) in distinguishing radiation-induced brain injury from glioma recurrence in patients with glioma.

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Diffusion Tensor Imaging of Dystrophic Skeletal Muscle

Abstract

Purpose

To compare the influence of two different regions of interest (ROIs) on diffusion tensor metrics in dystrophic thigh muscles using a custom-made (whole muscle) ROI including and a selective ROI excluding areas of fatty replacement.

Methods

Diffusion tensor imaging (DTI) and chemical-shift-encoded water-fat magnetic resonance imaging (MRI) of the thigh was conducted on a 3-Tesla system in 15 cases with muscular dystrophy and controls. The ROIs were chosen according to patterns of fatty replacement on co-registered axial DTI and gradient echo sequence (GRE) images. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), fiber track length (FTL), and muscle fat fractions (MFF) were compared between both ROI segmentations. These comparisons, muscle-specific correlation coefficients, and the influence of ROI localization on tensor metrics were derived based on linear mixed effects regression models.

Results

In the cases a high correlation was observed for ADC and FA with MFF using a custom ROI. The correlation was weaker but still significant with a selective ROI method. Using the custom ROI, FTL correlated significantly with MFF in 3 out of 4 muscles (r ≤ −0.51). A correlation was not found for the selective ROI method. Interaction analysis revealed that the association of ADC and FA with MFF was not significantly influenced by the ROI localization. For FTL the ROI localization significantly reduced the negative association with MFF.

Conclusion

The DTI metrics and FTL of custom ROI segmentation are significantly influenced by MFF. Contrary to ADC and FA, the effect of MFF on FTL is significantly reduced when applying selective ROI segmentation, which could therefore be a better option for MR tractography.

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Freiburg Neuropathology Case Conference

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Acute lymphoblastic leukemia/lymphoma of the oral and maxillofacial region

Publication date: Available online 31 January 2018
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Celeste Sánchez Romero, Hélder Antônio Rebelo Pontes, Flávia Sirotheau Corrêa Pontes, André Caroli Rocha, Román Carlos, Javier C. Rendón, Oslei Paes de Almeida, Felipe Paiva Fonseca
ObjectiveTo describe the clinicopathological and immunohistochemical features of acute lymphoblastic leukemia/lymphoma (ALL/LBL) of the oral and maxillofacial region (OMF).Study designCases diagnosed as ALL/LBL of the OMF region were retrieved from the files of two Brazilian and one Guatemalan oral pathology services from 2005 to 2017. Microscopic and immunohistochemical features of each case were reviewed and fully described, whereas clinical data were retrieved from the pathology reports.ResultsDuring the period considered, six cases were identified. Males were the most affected (4:2), with a mean age of 19 years old. The mandible was involved in two cases, the maxilla in two, the cheek mucosa in one and the parotid gland in one case. A painful swelling was the most common presentation, and three patients also had systemic complaints. Microscopically, tumors revealed solid infiltrations of small to medium sized immature cells. The "puzzle-like" and "starry-sky" patterns were observed, and "single lane" growth was also identified. Immunohistochemically, two cases were diagnosed as T-cell ALL/LBL with the LCA+/cCD3+/CD79a+focal/CD20-/PAX5-/CD99+/CD34-/CD10+/TdT+ phenotype and four as B-cell ALL/LBL with the LCA+/CD3-/CD20-/CD79a+/CD10+/CD34variable/TdT+ predominant phenotype. The Ki67 index ranged from 80 to 99%.ConclusionOMF ALL/LBL is rare, but its microscopic features and immunohistochemical profile CD3+orCD79a+/CD10+/CD34+variable/CD99+/TdT+ contribute to the correct diagnosis.



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Rethinking isolated cleft lip and palate as a syndrome

Publication date: Available online 31 January 2018
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Mine Koruyucu, Yelda Kasimoğlu, Figen Seymen, Merve Bayram, Asli Patir, Nihan Ergöz, Elif B. Tuna, Koray Gencay, Kathleen Deeley, Diego Bussaneli, Adriana Modesto, Alexandre R. Vieira
ObjectiveThe goal of the present work was to use dental conditions that have been independently associated with cleft lip and palate (CL/P) as a tool to identify a broader collection of individuals to be used for gene identification that lead to clefts.Study designWe studied 1,573 DNA samples combining individuals that were born with CL/P, or had tooth agenesis, or supernumerary teeth, or molar incisor hypomineralization (MIH), or dental caries with the goal to identify genetic associations. We tested two single nucleotide polymorphisms that were located in the vicinity of regions suggested to contribute to supernumerary teeth. Over-representation of alleles were determined for combinations of individuals as well as for each individual phenotypic group with an alpha of 0.05.ResultsWe determined that the allele C of rs622260 was over-represented in all individuals studied when compared with a group of unrelated individuals that did not present any of the conditions described above. When subgroups were tested, associations were seen for individuals with MIH.ConclusionsAlthough we did not test this hypothesis directly here, based on associations reported previously, we believe that CL/P is actually a syndrome of alterations of the dentition and considering it that way may allow for the identification of genotype-phenotype correlations that may be useful for clinical care.



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Magnetic resonance imaging (MRI) – a diagnostic tool for postoperative evaluation of dental implants. a case report.

Publication date: Available online 31 January 2018
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Laura Wanner, Ute Ludwig, Jan-Bernd Hövener, Katja Nelson, Tabea Flügge
Objective.Compared to cone beam computed tomography (CBCT), magnetic resonance imaging (MRI) might be superior for the diagnosis of nerve lesions associated with implant placement.Study Design.A patient presented with unilateral pain associated with dysesthesia in the region of the right lower lip and chin after implant placement. Conventional orthopantomography couldn't show an association between the position of the inferior alveolar nerve and the implant. For three-dimensional display of the implant in relation to the surrounding anatomy, CBCT was compared to MRI.Results.MRI enabled the precise depiction of the implant position and its spatial relation to the inferior alveolar nerve, whereas the nerve position and its exact course within the mandible couldn't be directly displayed in CBCT.Conclusion.MRI may be a valuable, radiation-free diagnostic tool for the visualization of intraoral hard and soft tissues, offering an objective assessment of nerve injuries by a direct visualization of the inferior alveolar neurovascular bundle.



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Loss of heterozygosity (LOH) of MIR15A/MIR16-1, negative regulators of the anti-apoptotic gene BCL2, is not frequent in odontogenic keratocysts

Publication date: Available online 31 January 2018
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Taynara Asevedo Campos de Resende, Vanessa de Fátima Bernardes, Jéssica Carolina da Silva, Luiz Armando De Marco, Ricardo Santiago Gomez, Carolina Cavalieri Gomes, Marina Gonçalves Diniz
Objectives The odontogenic keratocyst (OKC) is an aggressive odontogenic cyst that shows high recurrence rate. Apart from PTCH1 mutations, few molecular alterations are described in OKCs. Low expression of microRNAs (miRNAs) miR-15a and/or miR-16-1 in association with increased expression of their target, Bcl-2, have been previously shown in OKC. In humans, MIR15A and MIR16-1 are clustered at chromosome position 13q14, and loss of heterozygosity (LOH) at this locus occurs in different tumors. We aimed to determine whether deletion at 13q14 is the potential mechanism leading to miR-15a/16-1 aberrant expression in OKC. Methods Genomic DNA was extracted from 15 formalin fixed paraffin embedded microdissected OKC cases. The polymorphic DNA markers D13S272 and D13S273 on chromosome 13q14.3, around MIR15A/MIR16-1, were amplified by PCR. LOH was examined by capillary electrophoresis DNA-fragment analysis. Results D13S272 marker showed no LOH in 12 informative cases, while 2/9 (22%) informative cases showed LOH at D13S273 marker. Conclusions LOH event at MIR15A/MIR16-1 locus is not frequent in OKC. The mechanism underlining the regulation of miR-15a and miR-16-1 expression in OKC remains to be determined.



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Prognostic indicators of improved survival and quality of life in surgically treated oral cancer.

Publication date: Available online 31 January 2018
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): G. Tirelli, A. Gatto, P. Bonini, M. Tofanelli, A. Piccinato, Z.M. Arnež
OBJECTIVENo published study has analysed the prognostic factors of surgically treated oral squamous cell carcinoma (OSCC) in relation to both survival and quality of life (QoL). The aim of this study was to analyse postoperative QoL in relation to survival in order to identify which parameters can predict the long-term outcome allowing the best QoL.STUDY DESIGNThis retrospective cohort study considered 167 patients affected by OSCC treated surgically at the Otolaryngology Department of Cattinara Hospital (Trieste, Italy) by a single surgeon. We collected data about the main prognostic factors and the postoperative QoL 12 month after surgery.RESULTSThe 5-year overall survival rate was equal to 68.1% while the 5-year disease-specific-survival (DSS) was 77.8%. In this sample, 32% of patients also underwent adjuvant radio-chemotherapy. On stepwise Cox regression, the best predictors of DSS were the N stage (p<0.001) and tumor depth of invasion (DOI)(p<0.001). QoL was affected by N stage, DOI, invasive surgical approach, radiotherapy and neck dissection (p<0.05).CONCLUSIONThe prognostic factors that affect both survival rates and residual QoL are the surgical approach, the neck stage and the DOI, all of which can be minimized by early diagnosis.



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Physiological distribution of PSMA-ligand in salivary glands and seromucous glands of the head and neck on PET/CT

Publication date: Available online 31 January 2018
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Thomas J.W. Klein Nulent, Matthijs H. Valstar, Bart de Keizer, Stefan M. Willems, Laura A. Smit, Abrahim Al-Mamgani, Ludwig E. Smeele, Robert J.J. van Es, Remco de Bree, Wouter V. Vogel
ObjectivesProstate-specific membrane antigen (PSMA) PET/CT is used for detection and (re)staging of prostate cancer. However, healthy salivary, seromucous, and lacrimal glands also show high PSMA-ligand uptake. This study aimed to describe physiological PSMA-ligand uptake distribution characteristics in the head and neck, to aid in PSMA PET/CT interpretation and to identify possible new clinical applications for PSMA-ligand imaging.Study designThirty consecutive patients who underwent PSMA PET/CT for prostate cancer were evaluated. Tracer maximum standardized uptake values (SUVmax) in the salivary, seromucous, and lacrimal glands were determined visually and quantitatively. Overall and intra-individual variations were reported.ResultsAll gland locations showed increased tracer uptake. The mean SUVmax (±SD) varied: parotid 12.3±3.9; submandibular 11.7±3.5; sublingual 4.5±1.9; soft palate 2.4±0.5; pharyngeal wall 4.3±1.3; nasal mucosa 3.4±0.9; supraglottic larynx 2.7±0.7; and lacrimal 6.2±2.2. The parotid showed the largest overall variation in SUVmax (5.2-22.9), the sublingual glands the largest mean intra-individual difference (18.1%).ConclusionsMajor and minor salivary and seromucous glands consistently show high PSMA-ligand uptake. Minor gland locations can be selectively visualized by this technique for the first time. This provides potential new applications such as quantification of present salivary gland tissues and individualization of radiotherapy for head and neck cancer or ¹⁷⁷Lu-PSMA radionuclide treatment.



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Prevalence of primary open-angle glaucoma among patients with obstructive sleep apnea

Publication date: Available online 31 January 2018
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Arthur H. Friedlander, Lindsay L. Graves, Tina I. Chang, K. Karl Kawakami, Urie K. Lee, Shannon C. Grabich, Zhuang T. Fang, Michelle R. Zeidler, JoAnn A. Giaconi
ObjectiveDetermine primary open angle glaucoma (POAG) prevalence among obstructive sleep apnea (OSA) patients because perioperative environment risks further damaging the optic nerve.Study designAnalyzed "convenience sample" referred by Sleep Medicine for oral appliances because of continuous positive pressure (CPAP) intolerance. Determined aggregate prevalence of the 3 POAG subtypes: ("classic" open angle glaucoma (COAG), normal tension glaucoma (NTG), open angle glaucoma suspect (OAGS); among the index population and compared it to that of same hospital's general population. Similarly determined were associations between OSA severity levels (apnea-hypopnea index; AHI) and POAG subtypes.ResultsAmong the study sample of 225 patients with OSA (96.4% male; mean age 58.5 ± 12.3 years), 47 (20.9%) had POAG; with subtype distribution: (COAG: 12(25.5%), NTG: 8 (17.0%), OAGS: 27 (57.4%)). The POAG prevalence rate among medical center's general population was 2.5% which was significantly less (P < .00001) than among those with comorbid OSA. Severity of the breathing disorder (AHI) failed to demonstrate a significant correlation to any POAG subtype (P > .05).ConclusionThe significant prevalence of POAG among OSA sufferers, suggests need for preoperative consultations from an ophthalmologist to determine eye health and possibly an anesthesiologist to avoid potential vision loss.



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Residents′ Perceptions of Utilization of the Current Alumni and Attending Network for a Formal Mentorship Program in an Academic Affiliated Community Hospital Radiology Residency

Publication date: Available online 31 January 2018
Source:Current Problems in Diagnostic Radiology
Author(s): Vivek S. Yedavalli, Parinda Shah
Mentor-mentee relationships within radiology residencies can add significant value to a resident′s overall experience. Studies demonstrate that mentorship programs can increase satisfaction for residents and faculty alike by reducing stress, easing career related decisions, increasing involvement with research, improving teaching and communication skills, and finally increasing leadership roles. In a survey of radiology program directors, 85% of PDs find such a program beneficial but only 57% have a formal program in place. 42% of PDs believe a structured mentorship program is necessary. Studies have also shown that female residents prefer female mentors. Alumni serve as an ideal group for resident mentorship as they do not face the pressures of internal faculty. No study to date in diagnostic radiology literature utilizes an alumni network in establishing a formal mentorship program. The objective of this study is to implement a formal mentorship program within an academic affiliated radiology residency by utilizing program alumni and internal attending physicians for potentially increasing faculty engagement, improving resident morale, research opportunities, and networking for fellowship and job opportunities.



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Independent predictors and lymph node metastasis characteristics of multifocal papillary thyroid cancer.

Independent predictors and lymph node metastasis characteristics of multifocal papillary thyroid cancer.

Medicine (Baltimore). 2018 Feb;97(5):e9619

Authors: Genpeng L, Jianyong L, Jiaying Y, Ke J, Zhihui L, Rixiang G, Lihan Z, Jingqiang Z

Abstract
The multifocal papillary thyroid cancer (PTC), with more aggressive and poorer prognosis, is not rare in papillary histotype. Few studies evaluated risk factors and lymph node metastasis in multifocal PTC. The aim of this present study focusing on risk factors and lymph node metastasis characteristics in multifocal PTC was excepted to assist clinical decisions regarding surgery.It was a retrospective study. The 1249 consecutive patients with PTC were reviewed. Of these, 570 patients who met the criteria were selected: 285 with solitary papillary thyroid cancer and 285 with multifocal PTC. The risk factors and lymph node metastasis in multifocal PTC were investigated by univariate and multivariate analysis.Multifocal PTC showed a higher positive rate of capsular invasion, extrathyroidal extension, tumor size >10 mm, pathological T classification, N+ stage, local recurrence, and radioactive iodine ablation (RAI). Capsular invasion (hazard ratio [HR], 1.589; 95% confidence interval [CI],1.352-1.984), advanced pathological T classification (HR, 3.582; 95% CI, 2.184-5.870), and pathological N+ stage (HR, 1.872; 95% CI, 1.278-2.742) were related to increased risk of multifocality and there was a significant increased HR for central neck compartment involvement in male sex (HR, 2.694; 95% CI, 1.740-4.169), advanced pathological T classification (HR, 2.403; 95% CI, 1.479-3.907) and multifocality (HR, 1.988; 95% CI, 1.361-2.906).There is a significant association between capsular invasion, advanced pathological T classification, N+ stage, and multifocal PTC. Total thyroidectomy plus prophylactic bilateral central lymph node dissection should be recommended during surgery due to a stronger predilection for level VI lymph node metastasis in multifocal PTC.

PMID: 29384841 [PubMed - in process]

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Extensor indicis proprius muscle and its variants together with the extensor digitorum brevis manus muscle: a common classification. Clinical significance in hand and reconstructive surgery.

Related Articles

Extensor indicis proprius muscle and its variants together with the extensor digitorum brevis manus muscle: a common classification. Clinical significance in hand and reconstructive surgery.

Surg Radiol Anat. 2018 Jan 30;:

Authors: Georgiev GP, Tubbs RS, Iliev A, Kotov G, Landzhov B

Abstract
PURPOSE: The extensor indicis proprius (EIP) is a muscle of the forearm that originates from the posterior surface of the ulna and the adjacent interosseous membrane and attaches to the index finger. Many anatomical variations of this muscle have been reported in the literature. The extensor digitorum brevis manus (EDBM) is a variant muscle found on the back of the wrist and hand. These muscle variants should be considered in the context of clinical syndromes and reconstructive hand surgery. The aim of the present study was to describe in detail the normal and variant anatomy of these muscles and propose new systematic classifications.
MATERIALS AND METHODS: Formol-carbol-fixed Europid upper limbs (n = 176) were examined in the Department of Anatomy, Histology and Embryology at the Medical University of Sofia for variations of the EIP and occurrences of the EDBM.
RESULTS: We found normal anatomy in 147 (84%) of the specimens examined and we measured the length and width of the muscle belly and tendon of the EIP. Variations of the EIP in the other 29 upper limbs (16%) included replacement of the EIP by an EIB, coexistence of the EIP and EIB, presence of accessory tendons, and additional muscles.
CONCLUSIONS: Knowledge of anatomical variations of forearm muscles is important because they can cause clinical syndromes or have implications for reconstructive surgery, most often as tendon transfers in response to functional loss of other forearm muscles.

PMID: 29383419 [PubMed - as supplied by publisher]

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Issue Information

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Antibiotics, Vol. 7, Pages 11: Survey of Nonprescription Medication and Antibiotic Use in Patients with Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, and Overlap Syndrome

Antibiotics, Vol. 7, Pages 11: Survey of Nonprescription Medication and Antibiotic Use in Patients with Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, and Overlap Syndrome

Antibiotics doi: 10.3390/antibiotics7010011

Authors: Katherine Sullivan Meghan Jeffres Robert Dellavalle Robert Valuck Heather Anderson

Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and overlap syndrome (SJS-TEN) are rare, serious skin and mucosa break-down conditions frequently associated with antibiotic use. The role of nonprescription medications alone, or in combination with antibiotics in triggering SJS/TEN, is largely unknown. This study summarized data collected from patient surveys about nonprescription and antibiotic use prior to a SJS/TEN diagnosis. The survey was administered online to members of the U.S. SJS Foundation who had been diagnosed with SJS/TEN or were the parent of a child who had been diagnosed with SJS/TEN. Respondents were asked about nonprescription medications taken within the year before diagnosis, and the approximate point in time before diagnosis that they had taken them. They were also asked about specific prescription medications, including antibiotics, that they took before diagnosis. An estimated 4500 patients received an invitation to complete the survey. 251 patients completed it, resulting in a response rate of 5.6%. The mean age of respondents was 43 years (SD (standard deviation) = 17.3) and 70% were female. 32.3% of respondents indicated that a prescription antibiotic triggered their reaction. 14.1% indicated a nonprescription medication had triggered their SJS/TEN, and 18.1% said a nonprescription medication may have triggered their SJS/TEN. 85.5% of respondents said they took a nonprescription medication within three months of their SJS/TEN diagnosis. Of those respondents who reported that an antibiotic triggered their SJS/TEN, 35.2% reported taking a nonprescription medication within the three months prior to their diagnosis. This survey captured valuable information about nonprescription and antibiotic use in SJS/TEN patients. It is important for future studies to estimate the impact of antibiotics on SJS/TEN, and account for nonprescription medication use in that relationship.

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Vital-SCOPE: Design and Evaluation of a Smart Vital Sign Monitor for Simultaneous Measurement of Pulse Rate, Respiratory Rate, and Body Temperature for Patient Monitoring

Consistent vital sign monitoring is critically important for early detection of clinical deterioration of patients in hospital settings. Mostly, nurses routinely measure and document the primary vital signs of all patients 2‐3 times daily to assess their condition. To reduce nurse workload and thereby improve quality of patient care, a smart vital sign monitor named “Vital‐SCOPE” for simultaneous measurement of vital signs was developed. Vital-SCOPE consists of multiple sensors, including a reflective photo sensor, thermopile, and medical radar, to be used in simultaneous pulse rate, respiratory rate, and body temperature monitoring within 10 s. It was tested in laboratory and hospital settings. Bland-Altman and Pearson’s correlation analyses were used to compare the Vital-SCOPE results to those of reference measurements. The mean difference of the respiratory rate between respiratory effort belt and Vital-SCOPE was 0.47 breaths per minute with the 95% limit of agreement ranging from −7.4 to 6.5 breaths per minute. The Pearson’s correlation coefficient was 0.63 (). Moreover, the mean difference of the pulse rate between electrocardiogram and Vital-SCOPE was 3.4 beats per minute with the 95% limit of agreement ranging from −13 to 5.8 beats per minute; the Pearson’s correlation coefficient was 0.91 (), indicating strong linear relationship.

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Stowage Planning in Multiple Ports with Shifting Fee Minimization

This paper studies the problem of stowage planning within a vessel bay in a multiple port transportation route, aiming at minimizing the total container shifting fee. Since the access to containers is in the top-to-bottom order for each stack, reshuffle operations occur when a target container to be unloaded at its destination port is not stowed on the top of a stack at the time. Each container shift via a quay crane induces one unit of shifting fee that depends on the charge policy of the local container port. Previous studies assume that each container shift consumes a uniform cost in all ports and thus focus on minimizing the total number of shifts or the turnaround time of the vessel. Motivated by the observation that different ports are of nonuniform fee for each container shift, we propose a mixed integer programming (MIP) model for the problem to produce an optimal stowage planning with minimum total shifting fee in this work. Moreover, as the considered problem is NP-hard due to the NP-hardness of its counterpart with uniform unit shifting fee, we propose an improved genetic algorithm to solve the problem. The efficiency of the proposed algorithm is demonstrated via numerical experiments.

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A High-Speed Train Operation Plan Inspection Simulation Model

We developed a train operation simulation tool to inspect a train operation plan. In applying an improved Petri Net, the train was regarded as a token, and the line and station were regarded as places, respectively, in accordance with the high-speed train operation characteristics and network function. Location change and running information transfer of the high-speed train were realized by customizing a variety of transitions. The model was built based on the concept of component combination, considering the random disturbance in the process of train running. The simulation framework can be generated quickly and the system operation can be completed according to the different test requirements and the required network data. We tested the simulation tool when used for the real-world Wuhan to Guangzhou high-speed line. The results showed that the proposed model can be developed, the simulation results basically coincide with the objective reality, and it can not only test the feasibility of the high-speed train operation plan, but also be used as a support model to develop the simulation platform with more capabilities.

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A Four-Dimensional Hyperchaotic Finance System and Its Control Problems

The construction and several control problems of a new hyperchaotic finance system are investigated in this paper. Firstly, a new four-dimensional hyperchaotic finance system is introduced, based on which a new hyperchaos is then generated by setting parameters. And the qualitative analysis is numerically studied to confirm the dynamical processes, for example, the bifurcation diagram, Poincaré sections, Lyapunov exponents, and phase portraits. Interestingly, the obtained results show that this new system can display complex characteristics: chaotic, hyperchaotic, and quasiperiodic phenomena occur alternately versus parameters. Secondly, three single input adaptive controllers are designed to realize the control problems of such system: stabilization, synchronization, and coexistence of antisynchronization and complete synchronization, respectively. It is noted that the designed controllers are simpler than the existing ones. Finally, numerical simulations are provided to demonstrate the validity and the effectiveness of the proposed theoretical results.

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Application of a Cohesive Zone Model for Simulating Fatigue Crack Growth from Moderate to High Levels of Inconel 718

A cyclic cohesive zone model is applied to characterize the fatigue crack growth behavior of a IN718 superalloy which is frequently used in aerospace components. In order to improve the limitation of fracture mechanics-based models, besides the predictions of the moderate fatigue crack growth rates at the Paris’ regime and the high fatigue crack growth rates at the high stress intensity factor levels, the present work is also aimed at simulating the material damage uniformly and examining the influence of the cohesive model parameters on fatigue crack growth systematically. The gradual loss of the stress-bearing ability of the material is considered through the degradation of a novel cohesive envelope. The experimental data of cracked specimens are used to validate the simulation result. Based on the reasonable estimation for the model parameters, the fatigue crack growth from moderate to high levels can be reproduced under the small-scale yielding condition, which is in fair agreement with the experimental results.

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Genetic Association of Interleukin-31 Gene Polymorphisms with Epithelial Ovarian Cancer in Chinese Population

Roles of interleukin-31 (IL-31) in the development and progression of human epithelial ovarian cancer are largely unknown. Studies report that the polymorphisms, rs7977932 C>G and rs4758680 C>A in IL-31, affect the expression level of IL-31. In the present study, we examined 412 patients with epithelial ovarian cancer and 428 healthy individuals to explore whether these polymorphisms are associated with the epithelial ovarian cancer in Chinese women. The genotype of the polymorphisms in each individual was identified. The associations of the polymorphisms with patients’ clinical characteristics and outcomes were evaluated. For rs7977932, the frequency of the CG/GG was significantly decreased in patients with epithelial ovarian cancer. However, the frequency of the rs4758680 CA/AA was significantly increased in those patients. Moreover, the frequency of rs7977932 CG/GG genotype was significantly higher in patients with less advanced FIGO stages. Kaplan-Meier curve showed that patients with CG/GG genotypes of rs7977932 had a decreased risk for recurrence compared to those with CC genotype. Our findings suggested that rs7977932 and rs4758680 of IL-31 may be associated with the development and progression of the epithelial ovarian cancer in the Chinese population. IL-31, therefore, may be a potential therapeutic target for the development of drugs to treat the disease.

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Prevalence and Determinants of Peripheral Microvascular Endothelial Dysfunction in Rheumatoid Arthritis Patients: A Multicenter Cross-Sectional Study

Objectives. To define the prevalence and determinants of peripheral microvascular endothelial dysfunction (ED) in a large series of rheumatoid arthritis (RA) patients free of previous cardiovascular events. Materials and Methods. Data from 874 RA patients enrolled in the EDRA study (Endothelial Dysfunction Evaluation for Coronary Heart Disease Risk Estimation in Rheumatoid Arthritis—ClinicalTrials.gov: NCT02341066) were analyzed. Log-transformed reactive hyperemia index (Ln-RHI) was evaluated by peripheral arterial tonometry (PAT) using the EndoPAT2000 device: values of Ln-RHI 

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Transcatheter versus surgical aortic valve replacement in patients at low surgical risk: A meta-analysis of randomized trials and propensity score matched observational studies

Abstract

Background

Although transcatheter aortic valve replacement (TAVR) is officially indicated for high risk aortic stenosis (AS) patients, the procedure is increasingly being performed in patients who are not at high surgical risk, including a substantial number of low risk patients. However, data on the benefit of TAVR in this patient population is limited.

Methods

We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies with propensity score matching (PSM) of TAVR versus surgical aortic valve replacement (SAVR) in patients who are at low surgical risk. The primary outcome was all-cause mortality. The secondary outcomes included stroke, myocardial infarction, bleeding, and various procedural complications.

Results

Six studies (2 RCTs and 4 PSM studies) totaling 3,484 patients were included. Follow-up ranged from 3 months to 3 years (median 2 years). The short-term mortality was similar with either TAVR or SAVR (2.2% for TAVR and 2.6% for SAVR, RR 0.89, 95% CI 0.56–1.41, P = 0.62), however, TAVR was associated with increased risk for intermediate-term mortality (17.2% for TAVR and 12.7% for SAVR, RR 1.45, 95% CI 1.11–1.89, P = 0.006). In terms of periprocedural complications, TAVR was associated with reduced risk for bleeding and renal failure and an increase in vascular complications and Pacemaker implantation.

Conclusions

In patients who are at low surgical risk, TAVR seems to be associated with increased mortality risk. Until more data in this population is available, SAVR should remain the treatment of choice for these patients.

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Prospective, randomized comparison of 3-dimensional computed tomography guidance versus TEE data for left atrial appendage occlusion (PRO3DLAAO)

Abstract

Background

Preliminary data comparing 3-dimensional computed tomography (3D-CT) to transesophageal echocardiography (TEE) for left atrial appendage occlusion (LAAO) indicates that 3D-CT provides more accurate measurements and improves case planning. Therefore, we conducted a pilot study comparing 3D-CT to TEE in occluder selection accuracy and procedural efficiency.

Methods

From May 2016 to February 2017, 24 patients were prospectively randomized to undergo LAAO using either TEE or 3D-CT. The primary endpoint was device accuracy while the secondary endpoints included # devices per case, # guide catheters used per case, # fluoroscopy angles used, procedure time, fluoroscopy time, radiation dose, and major adverse events (stroke, MI, device embolization, perforation, death).

Results

Procedure success was 100% and 92% for the 3D-CT and 2D-TEE cohorts respectively. Accuracy for 1st device selection 92% and 27% (P = .01) for 3D-CT and 2D-TEE respectively but with intra-procedural upsizing in the 2D-TEE cohort, the 2D-TEE cohort accuracy increased to 64% while the 3D-CT groups 92% was accurate (P = .33). Case planning using 3D-CT was significantly more efficient with respect to device utilization (CT 1.33 ± 0.7 vs. 2D-TEE 2.5 ± 1.2 P = .01), guide catheters (CT 1 vs. 2D-TEE 1.7 ± 0.8 P = .01) and procedure time (3D-CT 55 ± 17 min vs. 2D-TEE 73 ± 24 min P < .05). One major adverse event, a stroke occurred in the 2D-TEE group.

Conclusion

In this single-center pilot study, CT guided LAAO case planning was associated with improved device selection accuracy and procedural efficiency. This study data supports the notion that comprehensive 3D assessment significantly simplifies LAAO, minimizing the time and number of steps needed.

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Safety and efficacy of ulnar artery approach for percutaneous cardiac catheterization: Systematic review and meta-analysis

Abstract

Background

Trans-radial access has rapidly become the standard for percutaneous coronary procedures in the last decade. As proceduralists overcome the learning curve and become more competent in trans-radial access, alternative safe access sites such as the ulnar artery have been increasingly used for emergent and elective procedures. The aim of this study was to synthesize the best available evidence of the impact on major adverse cardiac events (MACE) of ulnar artery compared to radial artery cardiac catheterization.

Methods

This review considered randomized controlled trials that included adult patients who had a percutaneous coronary procedure via the radial or ulnar artery. The intervention of interest was the use of ulnar compared to radial artery for cardiac catheterization. An extensive search was undertaken for published and unpublished trials up to May 2017. Methodological quality was assessed independently by two reviewers using the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) checklist. Data were analyzed using Review Manager.

Results

A total of six trials were included in the review. There was no statistically significant difference in the incidence of MACE between patients who underwent trans-ulnar or trans-radial artery catheterization (RR 0.90; 95% CI 0.66–1.23). Complications associated with access including hematoma formation, pseudo-aneurysm, and arterio-venous fistulae formation, were investigated in five trials in a total of 2,744 patients, with significantly more complications noted in the trans-ulnar group (RR 3.58; CI 2.67–4.79, P < 0.00001). There were no differences in arterial access time, fluoroscopy time, and contrast load between the two groups.

Conclusions

There is evidence to support safe use of the ulnar artery as an alternative to the radial artery for access for cardiac catheterization.

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Long-term survival after transcatheter versus surgical aortic valve replacement for aortic stenosis: A meta-analysis of observational comparative studies with a propensity-score analysis

Abstract

Objectives

To synthesize evidence regarding long-term survival after transcatheter aortic valve implantation (TAVI) versus surgical aortic valve replacement (SAVR) for severe aortic stenosis (AS) from real-world clinical practice, we performed a meta-analysis of observational studies with a propensity-score analysis and ≥3-year follow-up.

Methods

Databases including MEDLINE and EMBASE were searched through April 2017 using PubMed and OVID. Eligible studies were observational comparative studies with a propensity-score analysis of TAVI versus SAVR enrolling patients with severe AS and reporting ≥3-year all-cause mortality as an outcome. A hazard ratio (HR) with its 95% confidence interval (CI) of follow-up (including early) mortality for TAVI versus SAVR was extracted from each individual study.

Results

Our search identified 14 eligible studies enrolling a total of 4,197 patients. A pooled analysis of all the 14 studies demonstrated a statistically significant 54% increase in mortality with TAVI relative to SAVR (HR, 1.54; 95% CI, 1.31–1.81; P for effect < 0.00001; P for heterogeneity = 0.14; I² = 30%). Several sensitivity analyses did not substantially change the statistically significant benefit for SAVR. There was no evidence of significant publication bias.

Conclusions

On the basis of a meta-analysis of 14 observational comparative studies with a propensity-score analysis including a total of ≥4,000 patients, TAVI is associated with worse ≥3-year overall survival than SAVR.

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IJMS, Vol. 19, Pages 434: Photodynamic Inactivation Potentiates the Susceptibility of Antifungal Agents against the Planktonic and Biofilm Cells of Candida albicans

IJMS, Vol. 19, Pages 434: Photodynamic Inactivation Potentiates the Susceptibility of Antifungal Agents against the Planktonic and Biofilm Cells of Candida albicans

International Journal of Molecular Sciences doi: 10.3390/ijms19020434

Authors: Mu-Ching Huang Mandy Shen Yi-Jhen Huang Hsiao-Chi Lin Chin-Tin Chen

Photodynamic inactivation (PDI) has been shown to be a potential treatment modality against Candida infection. However, limited light penetration might leave some cells alive and undergoing regrowth. In this study, we explored the possibility of combining PDI and antifungal agents to enhance the therapeutic efficacy of Candida albicans and drug-resistant clinical isolates. We found that planktonic cells that had survived toluidine blue O (TBO)-mediated PDI were significantly susceptible to fluconazole within the first 2 h post PDI. Following PDI, the killing efficacy of antifungal agents relates to the PDI dose in wild-type and drug-resistant clinical isolates. However, only a 3-log reduction was found in the biofilm cells, suggesting limited therapeutic efficacy under the combined treatment of PDI and azole antifungal drugs. Using confocal microscopic analysis, we showed that TBO-mediated PDI could partially remove the extracellular polymeric substance (EPS) of biofilm. Finally, we showed that a combination of PDI with caspofungin could result in the complete killing of biofilms compared to those treated with caspofungin or PDI alone. These results clearly indicate that the combination of PDI and antifungal agents could be a promising treatment against C. albicans infections.

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Oral condyloma acuminatum in a 75-year-old geriatric patient

Condyloma acuminatum (CA) is a human papillomavirus-induced sexually transmitted disease which is characterised by epithelial proliferation in the genital region, perianal region, oral cavity and larynx. It was first reported by Knapp and Uohara in 1967. The disease is more common in children and teenagers and appears as solitary or multiple, pinkish, sessile papules or plaques with pebbled surface or as pedunculated papillary lesions. Oral lesions commonly affect the lips, floor of the mouth, lateral and ventral surfaces of tongue, buccal mucosa, soft palate and rarely gingiva. The present report deals with a case of CA affecting a 75-year-old male patient with emphasis on clinical presentation, histological features and importance of PCR for establishment of definitive diagnosis. This case is unique because CA is extremely rare in geriatric age group.

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Wave of renal impairment

We present a case of a 51-year-old man who went to the emergency department after an almost-drowning episode, presenting with muscular weakness, myalgia and dark urine. Laboratory data showed a severe rhabdomyolysis (creatine kinase 497 510 U/L). Despite aggressive fluid therapy, an oliguric acute kidney injury was established with temporary need of haemodialysis. The patient had a longtime history of exercise intolerance and family history of a metabolic myopathy, namely a sister with McArdle’s disease. The genetic test was positive. McArdle’s disease is an autosomal recessive disorder caused by mutations in the muscle glycogen phosphorylase gene that encodes the myophosphorylase. The main symptom consists in exercise intolerance and the most severe complication is rhabdomyolysis with acute renal failure. Metabolic myopathies, such as McArdle’s disease, should be considered in patients with acute renal failure due to unexplained severe rhabdomyolysis, especially if there are chronic complaints of exercise intolerance and positive family history.

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Simultaneous endoscopic full-thickness resection of two synchronous colonic granular cell tumours

Granular cell tumours (GCTs) are rare soft tissue tumours originating from Schwann cells. Due to potential malignant transformation, complete endoscopic resection should be aimed for. We report on a 49-year-old patient with two synchronous GCTs found in the caecum and the ascending colon, respectively. Synchronous endoscopic full-thickness resection (EFTR) using an all-in-one full-thickness resection device (FTRD) was performed under propofol sedation. Completeness of resection was proven histologically. No adverse events occurred. We report safe and complete simultaneous EFTR of two synchronous colonic GCTs.

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Prostatic abscess: a rare complication of staghorn calculi

A staghorn calculus is a calculus accommodating the majority of a renal calyx extending into the renal pelvis. A conservative approach to its treatment may lead to high morbidity and mortality rates. Such morbidity usually manifests with renal failure, obstructed upper urinary tractand/or life-threatening sepsis. Prostatic abscesses have never been associated with staghorn calculi in the literature. We report a case of a 70-year-old man who presented with sepsis, which was found to originate from a complex prostatic abscess. The patient had no history of urinary tract infections or risk factors. The authors believe that the incidentally identified staghorn calculi promoted the growth of Proteus mirabilis which led to the development of the prostatic abscess. The patient underwent a transurethral resection and drainage of the abscess following a failed course of antibiotic therapy. This case also highlights the paucity of guidelines available in treating prostatic abscesses.

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Treating chronic hepatitis E: when is enough enough?

We present a 38-year-old white British man who was taking long-term immunosuppressive medication following kidney transplantation. On routine review, he was noted to have an isolated and asymptomatic rise in alanine aminotransferase. After thorough investigation, he was found to have positive IgM and IgG serology to hepatitis E virus—and given the duration of his transaminitis, he was determined to have chronic hepatitis E infection. Treatment options were complicated by the presence of his kidney transplant, by chronic anaemia and by his wish for concomitant fertility treatment. Ribavirin therapy was instituted with a dramatic and immediate drop in serum viral load, although stool viraemia persisted. No clear protocols guide duration of treatment in chronic hepatitis E infection, but protracted faecal virus shedding predicts viral recrudescence, and treatment should continue at least until the stool is clear of virus.

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Metformin-associated lactic acidosis mimicking ischaemic bowel

Metformin-associated lactic acidosis (MALA) is a rare complication among patients who are diabetic, commonly presenting with non-specific findings, and developing mostly among those with other risk factors for lactic acidosis. We report the development of MALA in a 67-year-old man with diabetes who presented with progressive abdominal pain and bloody diarrhoea. On presentation the patient was in shock, with signs suggestive of peritonitis, and with severe lactic acidosis, renal failure and non-specific findings on abdominal CT. Neither the patient nor family could provide details of his home pharmaceuticals. Circulatory resuscitation with intravenous crystalloids and vasopressors was commenced, along with empiric broad-spectrum antibiotics. Emergent laparotomy did not show pathological findings. Emergent haemodialysis, initiated postoperatively, resulted in rapid resolution of shock and lactic acidosis. A list of patient’s medications, provided afterwards by the family, included metformin. Microbiological studies remained negative and renal function normalised by the time of patient’s hospital discharge after 9 days.

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Synthesis of a Cationic Polyacrylamide under UV Initiation and Its Flocculation in Estrone Removal

A ternary cationic polyacrylamide (CPAM) with the hydrophobic characteristic was prepared through ultraviolet- (UV-) initiated polymerization technique for the estrone (E1) environmental estrogen separation and removal. The monomers of acrylamide (AM), acryloyloxyethyl-trimethyl ammonium chloride (DAC), and acryloyloxyethyl dimethylbenzyl ammonium chloride (AODBAC) were used to synthesize the ternary copolymer (PADA). Fourier transform infrared spectroscopy (FT-IR), 1H nuclear magnetic resonance spectroscopy (1H NMR), thermogravimetry/differential scanning calorimetry (TG/DSC), and scanning electron microscopy (SEM) were employed to characterize the structure, thermal decomposition property, and morphology of the polymers, respectively. FT-IR and 1H NMR results indicated the successful formation of the polymers. Besides, with the introduction of hydrophobic groups (phenyl group), an irregular and porous surface morphology and a favorable thermal stability of the PADA were observed by SEM and TG/DSC analyses, respectively. At the optimal condition (pH = 7, flocculant dosage = 4.0 mg/L and E1 concentration = 0.75 mg/L), an excellent E1 flocculation performance (E1 removal rate: 90.1%, floc size: 18.3 μm, and flocculation kinetics:  s−1) was acquired by using the efficient flocculant PADA-3 (cationic degree = 40%, and intrinsic viscosity = 6.30 dL·g−1). The zeta potential and floc size analyses were used to analyze the possible flocculation mechanism for the E1 removal. Results indicated that the charge neutralization, adsorption, and birding effects were dominant in the E1 removal progress.

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Modified Descemet’s Stripping Automated Endothelial Keratoplasty: The Use of Ophthalmic Viscoelastic Devices in Hypotonic Eyes That Had Undergone Glaucoma Filtering Surgeries

Purpose. Descemet’s stripping automated endothelial keratoplasty (DSAEK) is more difficult in hypotonic eyes with filtering bleb, due to the difficulties in elevating the intraocular pressure (IOP). We report a new method that uses ophthalmic viscoelastic devices (OVDs) to achieve good graft adhesion. Case Presentation. We performed modified DSAEK surgery on 2 eyes of 2 patients, who had previously undergone a trabeculectomy. Both eyes had functioning filtering blebs; the IOP was lower than 10 mmHg without medication. After the graft was inserted into the anterior chamber, the conjunctiva was penetrated, apart from the bleb, using a 30 G needle, and Healon V® was injected into the bleb until the encapsulated space was filled completely. Air was subsequently injected into the anterior chamber to promote the graft attachment to the back surface of the cornea. The IOP was elevated above 40 mmHg in both eyes 1 h after surgery and then decreased to less than 30 mmHg over the subsequent 3 h period. The implanted graft showed good adhesion and no dislocation. Conclusions. Our novel DSAEK procedure that adds one step of OVD injection into the filtering bleb may be useful for hypotonic eyes that had undergone filtering surgeries.

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Deep Learning for Computer Vision: A Brief Review

Over the last years deep learning methods have been shown to outperform previous state-of-the-art machine learning techniques in several fields, with computer vision being one of the most prominent cases. This review paper provides a brief overview of some of the most significant deep learning schemes used in computer vision problems, that is, Convolutional Neural Networks, Deep Boltzmann Machines and Deep Belief Networks, and Stacked Denoising Autoencoders. A brief account of their history, structure, advantages, and limitations is given, followed by a description of their applications in various computer vision tasks, such as object detection, face recognition, action and activity recognition, and human pose estimation. Finally, a brief overview is given of future directions in designing deep learning schemes for computer vision problems and the challenges involved therein.

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Stimuli-Responsive Hydrogels Based on Polyglycerol Crosslinked with Citric and Fatty Acids

Polyglycerol-based hydrogels from biodegradable raw materials were synthesized by crosslinking reactions of polyglycerol with citric and fatty acids. Three hydrogels were studied varying molar ratios of crosslinking agent. It was found that crosslink amount, type, and size play a crucial role in swelling, thermal, mechanical, and stimuli-responsive properties. The hydrogels absorption capacity changed in response to temperature and pH external stimuli. The hydrogel with the highest swelling capacity absorbed more than 7 times its own weight at room temperature and pH 5. This material increased 14 times its own weight at pH 10. Creep-recovery tests were performed to study the effect of crosslinking agent on mechanical properties. Deformation and percentage of recovery of synthesized hydrogels were obtained. Formation of hydrogels was confirmed using FTIR, and physicochemical properties were analyzed by Scanning Electron Microscopy (SEM), Differential Scanning Calorimetric (DSC), and Dynamic Mechanical Analysis (DMA). This paper aims to give a contribution to biobased hydrogel knowledge from chemical, physicochemical, and mechanical point of view.

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Estimation of Crop Evapotranspiration Using Satellite Remote Sensing-Based Vegetation Index

Irrigation water is limited and scarce in many areas of the world, including Comarca Lagunera, Mexico. Thus better estimations of irrigation water requirements are essential to conserve water. The general objective was to estimate crop water demands or crop evapotranspiration () at different scales using satellite remote sensing-based vegetation index. The study was carried out in northern Mexico (Comarca Lagunera) during four growing seasons. Six, eleven, three, and seven clear Landsat images were acquired for 2013, 2014, 2015, and 2016, respectively, for the analysis. The results showed that was low at initial and early development stages, while was high during mid-season and harvest stages. These results are not new but give us confidence in the rest of our results. Daily maps helped to explain the variability of crop water use during the growing season. Based on the results we can conclude that maps developed from remotely sensed multispectral vegetation indices are a useful tool for quantifying crop water consumption at regional and field scales. Using maps at the field scale, farmers can supply appropriate amounts of irrigation water corresponding to each growth stage, leading to water conservation.

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Effect of Resveratrol Dry Suspension on Immune Function of Piglets

Resveratrol, a polyphenolic plant antitoxin, has a wide range of pharmacological activities. In this study, we systematically evaluated the effects of resveratrol dry suspension (RDS) on immune function in piglets that were treated with different doses of RDS for 2 weeks. The results showed that the RDS has significant effects on the development, maturation, proliferation, and transformation of T lymphocytes. RDS could regulate humoral immune responses by upregulating the release of IFN-γ and downregulating the release of TNF-α. After piglets were vaccinated against classical swine fever virus and foot-and-mouth disease virus, the antibody titers were significantly increased. RDS treatment showed an excellent resistance to enhance T-SOD activity. Values of blood routine and blood biochemistry showed no toxicity. These results suggested that RDS could be considered as an adjuvant to enhance immune responses to vaccines, as well as dietary additives for animals to enhance humoral and cellular immunity.

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Effect of Coronary Slow Flow on Intrinsicoid Deflection of QRS Complex

Coronary slow flow is a rare, clinically important entity observed in acute coronary syndrome. The pathophysiological mechanism is not fully elucidated. We investigated patients with chest pain who had angiographic features consistent with the coronary slow flow. One hundred ten patients were included. Electrocardiography, echocardiography, and angiography results were retrospectively noted. The mean age was 56.4. Fifty-eight were male, and fifty-two were female. The control group consisted of patients with normal angiography. Patients had higher diastolic blood pressure, lower mean ejection fraction, higher average left ventricular end-diastolic diameter, and higher mean left atrial size than the control group (, resp.). Patients had higher average V1 ID, V6 ID, P wave dispersion, TFC LAD, TFC Cx, TFC RCA, and TFC levels than the control group. A significant linear positive relationship was found between the V1 ID and the TFC LAD, TFC Cx, TFC RCA, and TFC; also between the V6 ID and the TFC LAD, TFC Cx, TFC RCA, and TFC. Angiographic and electrocardiographic features are suggestive and diagnostic for the coronary slow flow syndrome. Although when regarded as a benign condition, coronary slow flow should be diagnosed, followed up, and treated as many of laboratory features suggest ischemic events.

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Microfluidic Biosensor Based on Microwave Substrate-Integrated Waveguide Cavity Resonator

A microfluidic biosensor is proposed using a microwave substrate-integrated waveguide (SIW) cavity resonator. The main objectives of this noninvasive biosensor are to detect and analyze biomaterial using tiny liquid volumes (3 μL). The sensing mechanism of our proposed biosensor relies on the dielectric perturbation phenomenon of biomaterial under test, which causes a change in resonance frequency and return loss (amplitude). First, an SIW cavity is realized on a Rogers RT/Duroid 5870 substrate. Then, a microwell made from polydimethylsiloxane (PDMS) material is loaded on the SIW cavity to observe the perturbation phenomenon. The microwell is filled with phosphate-buffered saline (PBS) solution (reference biological medium). To demonstrate the sensing behavior, the fibroblast (FB) cells from the lungs of a human male subject are analyzed and one-port S-parameters are measured. The resonance frequency of the structure with FB cells is observed to be 13.48 GHz. The reproducibility and repeatability of our proposed biosensor are successfully demonstrated through full-wave simulations and measurements. The resonance frequency of the FB-loaded microwell showed a shift of 170 MHz and 20 MHz, when compared to those of empty and PBS-loaded microwells. Its analytical limit of detection is 213 cells/μL. Our proposed biosensor is noncontact and reliable. Furthermore, it is miniaturized, inexpensive, and fabricated using simple- and easy-design processes.

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ENO1 Overexpression in Pancreatic Cancer Patients and Its Clinical and Diagnostic Significance

We investigated in this study the expression of ENO1 in tissues and plasma of PDAC patients to evaluate its clinicopathological and diagnostic significance. ENO1 protein expression was detected in tissue microarray of human PDAC and adjacent noncancer tissues. Electrochemiluminescence immunoassay and amplified luminescent proximity homogeneous assay (AlphaLISA) were performed to measure CA19-9 and ENO1 concentration in plasma from PDAC patients and healthy controls. We demonstrated that ENO1 overexpression is positively correlated with clinical stage, lymph node metastasis, and poor prognosis of PDAC; ENO1 may function as a hopeful candidate diagnostic marker in combination with CA19-9 in PDAC diagnosis.

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Transcatheter Aortic Valve Implantation in a Nonagenarian with Aortic Aneurysm: Futility or Utility?

Transcatheter aortic valve implantation (TAVI) has emerged as the standard of care for older patients with symptomatic severe aortic stenosis (AS) at high or excessive operative risk. There remain patients that are of such considerable risk that even TAVI can be futile. Such patients present ethical conundrums for institutional heart teams. Herein we present a case of a 90-year-old female patient with symptomatic severe AS and significant comorbidities including diffuse peripheral vascular disease and a large ascending aortic aneurysm. Would TAVI be utile or futile in this patient?

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Alveolar Ridge Preservation Using a Novel Synthetic Grafting Material: A Case with Two-Year Follow-Up

This case report highlights the use of a novel in situ hardening synthetic (alloplastic), resorbable, bone grafting material composed of beta tricalcium phosphate and calcium sulfate, for alveolar ridge preservation. A 35-year-old female patient was referred by her general dentist for extraction of the mandibular right first molar and rehabilitation of the site with a dental implant. The nonrestorable tooth was “atraumatically” extracted without raising a flap, and the socket was immediately grafted with the synthetic biomaterial and covered with a hemostatic fleece. No membrane was used, and the site was left uncovered without obtaining primary closure, in order to heal by secondary intention. After 12 weeks, the architecture of the ridge was preserved, and clinical observation revealed excellent soft tissue healing without loss of attached gingiva. At reentry for placement of the implant, a bone core biopsy was obtained, and primary implant stability was measured by final seating torque and resonance frequency analysis. Histological analysis revealed pronounced bone regeneration while high levels of primary implant stability were recorded. The implant was successfully loaded 12 weeks after placement. Clinical and radiological follow-up examination at two years revealed stable and successful results regarding biological, functional, and esthetic parameters.

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Role of MicroRNAs in Obesity-Induced Metabolic Disorder and Immune Response

In all living organisms, metabolic homeostasis and the immune system are the most fundamental requirements for survival. Recently, obesity has become a global public health issue, which is the cardinal risk factor for metabolic disorder. Many diseases emanating from obesity-induced metabolic dysfunction are responsible for the activated immune system, including innate and adaptive responses. Of note, inflammation is the manifest accountant signal. Deeply studied microRNAs (miRNAs) have participated in many pathways involved in metabolism and immune responses to protect cells from multiple harmful stimulants, and they play an important role in determining the progress through targeting different inflammatory pathways. Thus, immune response and metabolic regulation are highly integrated with miRNAs. Collectively, miRNAs are the new targets for therapy in immune dysfunction.

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Acquired Elliptocytosis as a Manifestation of Myelodysplastic Syndrome Associated with Deletion of Chromosome 20q

Elliptocytosis is commonly seen as a hereditary condition. We present a case of myelodysplastic syndrome (MDS) del(q20) variant with concomitant acquired elliptocytosis. A 73-year-old male with a history of prostate cancer presented to the hospital for evaluation of bleeding gums. Initial evaluation showed Hgb of 9.3 gm/dl, hematocrit of 28%, platelet count of 36,000 K/cmm, and WBC of 1.8 K/cmm with an ANC of 0.8 K/cmm. A slightly elevated bilirubin of 1.2 mg/dl spurred a hemolytic workup. Peripheral smear showed frequent elliptocytes, teardrop cells, schistocytes, and occasional spherocytes. Bone marrow biopsy did not show significant fibrosis to explain the elliptocytosis. Cytogenetics showed 20q deletion, and later, he was started on therapy for intermediate risk MDS. Bone marrow biopsy after completion of 6 cycles showed complete cytogenetic remission with significant improvement in elliptocytosis. Elliptocytosis in the setting of MDS has rarely been reported, and association with 20q deletion is even rarer. Animal studies have shown that haploinsufficiency of L3MBTL1 contributes to some (20q−) myeloproliferative neoplasms and myelodysplastic syndromes by affecting erythroid differentiation. Our case report raises interesting questions: Does MDS with rarely reported elliptocytosis indicate a disease process that is different from the usual 20q deletion? Is haploinsufficiency of L3MBTL1 responsible for this manifestation?

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Pharmacogenomic biomarkers do not predict response to drotrecogin alfa in patients with severe sepsis

To explore potential design for pharmacogenomics trials in sepsis, we investigate the interaction between pharmacogenomic biomarkers and response to drotrecogin alfa (activated) (DrotAA). This trial was desig...

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IJERPH, Vol. 15, Pages 245: Empowering Retailers to Refuse to Sell Tobacco Products to Minors

IJERPH, Vol. 15, Pages 245: Empowering Retailers to Refuse to Sell Tobacco Products to Minors

International Journal of Environmental Research and Public Health doi: 10.3390/ijerph15020245

Authors: Min-Li Chen Li-Na Chou Ya-Cheng Zheng

Tobacco smoking and exposure to secondhand smoke are major environmental risk factors that negatively influence health. It is recommended that tobacco product manufacturers and retailers receive empowerment counseling programs to achieve adolescent health targets. The present study conducted an empowerment counseling session to counsel tobacco product retailers in refusing to sell tobacco products to minors. The three stages of this study were conducted from March 2015 to February 2017. The results revealed that 74% of retailers were selling tobacco products to minors at baseline, 40% at stage two and 15% at stage three. These represent significant reductions in selling tobacco products to minors (all stage differences p &lt; 0.001). However, experimental design studies could be used to examine the empowerment counseling program for preventing tobacco sales to minors in the future. Moreover, health care providers should collaborate with tobacco product retailers to design unique empowerment counseling sessions for specific regions to improve retailers’ capabilities for self-management in terms of tobacco hazard prevention.

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Antitumor activity of antibody against cytotoxic T lymphocyte epitope peptide of lymphocyte-specific protein tyrosine kinase

Abstract

Although humoral responses against cytotoxic T lymphocyte epitope peptides from lymphocyte-specific protein tyrosine kinase antigen have been observed in the majority of healthy donors and cancer patients, the biological activity of the antibody has not been determined. Then we investigated the biological activity of monoclonal antibody against cytotoxic T lymphocyte epitope peptide of lymphocyte-specific protein tyrosine kinase antigen at positions 486–494 (anti-lymphocyte-specific protein tyrosine kinase-486 monoclonal antibody). This monoclonal antibody induced dendritic cell maturation from murine bone marrow cells by the immune complex form in vitro, and inhibited tumor growth in association with a suppression of tumor infiltrating T cells, including T regulatory cells in a murine model using the female BALB/cCrlCrlj mice (H-2K^d). More potent tumor inhibition was observed when this monoclonal antibody was administered prior to the peptide vaccination. These results may help to unveil the biological activity of anti-lymphocyte-specific protein tyrosine kinase peptide antibodies against cytotoxic T lymphocyte epitope peptides.

This article is protected by copyright. All rights reserved.

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Area of residual tumor is a robust prognostic marker for patients with rectal cancer undergoing preoperative therapy

Abstract

The aim of this study was to elucidate differences in the histological features of rectal cancer between patients treated with preoperative chemoradiotherapy and those treated with preoperative chemotherapy. Area of residual tumor (ART) was also evaluated for its utility as a potential prognostic marker between them.

Sixty-eight patients with rectal cancer who underwent sphincter-saving surgery were enrolled in this study. Of these, 39 patients received preoperative chemoradiotherapy (CRT group) and 29 patients received preoperative (neoadjuvant) chemotherapy (NAC group). ART was determined by using morphometric software. Tumors in the two groups were compared for differences in their histological features and clinical outcomes.

Tumors in the CRT and NAC groups varied greatly with regard to their histological features after preoperative therapy. Tumors in the CRT group showed more marked fibrosis than those in the NAC group. The total ART (T-ART) were significantly smaller in tumors in the CRT group than those in the NAC group. On the other hand, in circumferential resection margin (CRM)-negative pathologic stage (ypStage) 0-III cases, clinical outcome were not statistically different between the CRT and NAC groups. ART and ypTNM classification, but not Dworak regression grade and fibrotic change, was associated with clinical outcome both in preoperative CRT and NAC groups.

Tumors in those undergoing preoperative CRT and NAC were shown to differ significantly in their histological features. ART-based assessment may provide useful prognostic information, regardless of preoperative therapy.

This article is protected by copyright. All rights reserved.

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Antibodies, Vol. 7, Pages 9: Structural Changes in Stx1 Engineering Monoclonal Antibody Improves Its Functionality as Diagnostic Tool for a Rapid Latex Agglutination Test

Antibodies, Vol. 7, Pages 9: Structural Changes in Stx1 Engineering Monoclonal Antibody Improves Its Functionality as Diagnostic Tool for a Rapid Latex Agglutination Test

Antibodies doi: 10.3390/antib7010009

Authors: Daniela Luz Emerson Shiga Gang Chen Wagner Quintilio Fernanda Andrade Andrea Maranhão Bruna Caetano Thaís Mitsunari Míriam Silva Letícia Rocha Ana Moro Sachdev Sidhu Roxane Piazza

Stx1 toxin is one of the AB5 toxins of Shiga toxin-producing Escherichia coli (STEC) responsible for foodborne intoxication during outbreaks. The single-chain variable fragment (scFv) is the most common recombinant antibody format; it consists of both variable chains connected by a peptide linker with conserved specificity and affinity for antigen. The drawbacks of scFv production in bacteria are the heterologous expression, conformation and stability of the molecule, which could change the affinity for the antigen. In this work, we obtained a stable and functional scFv-Stx1 in bacteria, starting from IgG produced by hybridoma cells. After structural modifications, i.e., change in protein orientation, vector and linker, its solubility for expression in bacteria was increased as well as the affinity for its antigen, demonstrated by a scFv dissociation constant (KD) of 2.26 × 10−7 M. Also, it was able to recognize purified Stx1 and cross-reacted with Stx2 toxin by ELISA (Enzyme-Linked Immunosorbent Assay), and detected 88% of Stx1-producing strains using a rapid latex agglutination test. Thus, the scFv fragment obtained in the present work is a bacteria-produced tool for use in a rapid diagnosis test, providing an alternative for STEC diagnosis.

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Phytochemical investigation and antimicrobial appraisal of Parrotiopsis jacquemontiana (Decne) Rehder

Parrotiopsis jacquemontiana (Decne) Rehder. is locally used for skin infections and in wound healing. In this study we have evaluated methanol extract of its leaves and derived fractions against the clinical mult...

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Urox containing concentrated extracts of Crataeva nurvala stem bark, Equisetum arvense stem and Lindera aggregata root, in the treatment of symptoms of overactive bladder and urinary incontinence: a phase 2, randomised, double-blind placebo controlled trial

Storage lower urinary tract symptoms (LUTS) including overactive bladder (OAB) and urinary incontinence (UI) affect millions of people worldwide, significantly impacting quality of life. Plant based medicines ...

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Attitudes and knowledge about direct and indirect risks among conventional and complementary health care providers in cancer care

Many complementary therapies offer benefits for patients with cancer. Others may be risky for patients due to negative interactions with conventional treatment and adverse effects. Therefore, cancer patients n...

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Comparative efficacy of Chinese herbal injections for treating chronic heart failure: a network meta-analysis

On account of deterioration of chronic heart failure (CHF) and extensive exploration of Chinese herbal injections (CHIs), we performed a network meta-analysis to investigate the efficacy of CHIs (Huangqi injec...

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The association between cold hypersensitivity in the hands and feet and chronic disease: results of a multicentre study

Cold hypersensitivity in the hands and feet (CHHF) is a common symptom in Korea and patients with CHHF complain of coldness in the hands and feet in an environment that is not considered cold by unaffected peo...

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Nice, the NHS, and Cancer Drugs

This Viewpoint describes reforms to the ways the National Health Service (NHS) appraises cost-effectiveness and coverage of cancer drugs in England and Wales, the role of the National Institute for Health and Care Excellence (NICE) in the process, and changes in drug approval rates and access to new drugs as a result.

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microRNA-4331 Promotes Transmissible Gastroenteritis Virus (TGEV)-induced Mitochondrial Damage Via Targeting RB1, Upregulating Interleukin-1 Receptor Accessory Protein (IL1RAP), and Activating p38 MAPK Pathway In Vitro [Research]

Transmissible gastroenteritis virus (TGEV), a member of the coronaviridae family, could cause fatal diarrhea of piglets and result in numerous economic losses. Previous studies demonstrated that TGEV infection could lead to mitochondrial damage and upregulate miR-4331 level. So miR-4331 may play an important regulatory role in the control of mitochondrial function. To explore the potential role of miR-4331 in mitochondrial damage, we adopted a strategy consisting of quantitative proteomic analysis of porcine kidney (PK-15) cells in response to miR-4331 and TGEV infection. Eventually, 69 differentially expressed proteins were gained. The target of miR-4331 was identified. The effects of miR-4331 and its target RB1 on mitochondrial Ca²⁺ level, mitochondrial membrane potential (MMP), interleukin-1 receptor accessory protein (IL1RAP), p38 MAPK signaling pathway were investigated. The results showed that miR-4331 elevated mitochondrial Ca²⁺ level, reduced MMP, targets Retinoblastoma 1 (RB1), upregulated IL1RAP, and induced activation of p38 MAPK pathway during TGEV infection. RB1 was identified as the direct targets of miR-4331 and downregulated IL1RAP, suppressed the activation of p38 MPAK, and attenuated TGEV-induced mitochondrial damage. In addition, IL1RAP played a positive role in activating p38 MAPK signaling and negative role in TGEV-induced mitochondrial damage. The data indicate that miR-4331 aggravates TGEV-induced mitochondrial damage by repressing expression of RB1, promoting IL1RAP, and activating p38 MAPK pathway.

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Multiplexed Biomarker Panels Discriminate Zika and Dengue Virus Infection in Humans [Research]

Zika virus (ZIKV) and dengue virus (DENV) are closely related flaviviruses that cause widespread, acute febrile illnesses, notably microcephaly for fetuses of infected pregnant women. Detecting the viral cause of these illnesses is paramount to determine risks to patients, counsel pregnant women, and help fight outbreaks. A combined diagnostic algorithm for ZIKV and DENV requires Reverse transcription polymerase chain reaction (RT-PCR) and IgM antibody detection. RT-PCR differentiates between DENV and ZIKV infections during the acute phases of infection, but differentiation based on IgM antibodies is currently nearly impossible in endemic areas. We have developed a ZIKV/DENV protein array and tested it with serum samples collected from ZIKV- and DENV-infected patients and healthy subjects in Puerto Rico. Our analyses reveal a biomarker panel that are capable of discriminating ZIKV and DENV infections with high accuracy, including Capsid protein from African ZIKV strain MR766, and other 5 pair of proteins (NS1, NS2A, NS3, NS4B and NS5) from ZIKV and DENV respectively. Both sensitivity and specificity of the test for ZIKV from DENV are around 90%. We propose that the ZIKV/DENV protein array will be used in future studies to discriminate patients infected with ZIKV from DENV.

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Outer Membrane Vesicles (OMV)-based and Proteomics-driven Antigen Selection Identifies Novel Factors Contributing to Bordetella pertussis Adhesion to Epithelial Cells [Research]

Despite high vaccination coverage world-wide, whooping cough, a highly contagious disease caused by Bordetella pertussis, is recently increasing in occurrence suggesting that novel vaccine formulations targeted at the prevention of colonization and transmission should be investigated. To identify new candidates for inclusion in the acellular formulation, we used spontaneously released outer membrane vesicles (OMV)¹ as a potential source of key adhesins. The enrichment of Bvg+ OMV with adhesins and the ability of anti-OMV serum to inhibit the adhesion of B. pertussis to lung epithelial cells in vitro were demonstrated. We employed a proteomic approach to identify the differentially expressed proteins in OMV purified from bacteria in the Bvg+ and Bvg– virulence phases, thus comparing the outer membrane protein pattern of this pathogen in its virulent or avirulent state. Six of the most abundant outer membrane proteins were selected as candidates to be evaluated for their adhesive properties and vaccine potential. We generated E. coli strains singularly expressing the selected proteins and assessed their ability to adhere to lung epithelial cells in vitro. Four out of the selected proteins conferred adhesive ability to E. coli. Three of the candidates were specifically detected by anti-OMV mouse serum suggesting that these proteins are immunogenic antigens able to elicit an antibody response when displayed on the OMV. Anti-OMV serum was able to inhibit only BrkA-expressing E. coli adhesion to lung epithelial cells. Finally, stand-alone immunization of mice with recombinant BrkA resulted in significant protection against infection of the lower respiratory tract after challenge with B. pertussis. Taken together, these data support the inclusion of BrkA and possibly further adhesins to the current acellular pertussis vaccines to improve the impact of vaccination on the bacterial clearance.

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Compartment-resolved Proteomic Analysis of Mouse Aorta during Atherosclerotic Plaque Formation Reveals Osteoclast-specific Protein Expression [Research]

Atherosclerosis leads to vascular lesions that involve major rearrangements of the vascular proteome, especially of the extracellular matrix (ECM). Using single aortas from ApoE knock out mice, we quantified formation of plaques by single-run, high-resolution mass spectrometry (MS)-based proteomics. To probe localization on a proteome-wide scale we employed quantitative detergent solubility profiling. This compartment- and time-resolved resource of atherogenesis comprised 5117 proteins, 182 of which changed their expression status in response to vessel maturation and atherosclerotic plaque development. In the insoluble ECM proteome, 65 proteins significantly changed, including relevant collagens, matrix metalloproteinases and macrophage derived proteins. Among novel factors in atherosclerosis, we identified matrilin-2, the collagen IV crosslinking enzyme peroxidasin as well as the poorly characterized MAM-domain containing 2 (Mamdc2) protein as being up-regulated in the ECM during atherogenesis. Intriguingly, three subunits of the osteoclast specific V-ATPase complex were strongly increased in mature plaques with an enrichment in macrophages thus implying an active de-mineralization function.

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The interactome of intact mitochondria by cross-linking mass spectrometry provides evidence for coexisting respiratory supercomplexes [Research]

Mitochondria exert an immense amount of cytophysiological functions, but the structural basis of most of these processes is still poorly understood. Here we use cross-linking mass spectrometry to probe the organization of proteins in native mouse heart mitochondria. Our approach provides the largest survey of mitochondrial protein interactions reported so far. In total, we identify 3,322 unique residue-to-residue contacts involving half of the mitochondrial proteome detected by bottom-up proteomics. The obtained mitochondrial protein interactome gives insights in the architecture and submitochondrial localization of defined protein assemblies, and reveals the mitochondrial localization of four proteins not yet included in the MitoCarta database. As one of the highlights, we show that the oxidative phosphorylation complexes I-V exist in close spatial proximity, providing direct evidence for supercomplex assembly in intact mitochondria. The specificity of these contacts is demonstrated by comparative analysis of mitochondria after high salt treatment, which disrupts the native supercomplexes and substantially changes the mitochondrial interactome.

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Extended Linkers Improve the Detection of Protein-protein Interactions (PPIs) by Dihydrofolate Reductase Protein-fragment Complementation Assay (DHFR PCA) in Living Cells [Technological Innovation and Resources]

Understanding the function of cellular systems requires describing how proteins assemble with each other into transient and stable complexes and to determine their spatial relationships. Among the tools available to perform these analyses on a large scale is Protein-fragment Complementation Assay based on the dihydrofolate reductase (DHFR PCA). Here we test how longer linkers between the fusion proteins and the reporter fragments affect the performance of this assay. We investigate the architecture of the RNA polymerases, the proteasome and the conserved oligomeric Golgi (COG) complexes in living cells and performed large-scale screens with these extended linkers. We show that longer linkers significantly improve the detection of protein-protein interactions and allow to measure interactions further in space than the standard ones. We identify new interactions, for instance between the retromer complex and proteins related to autophagy and endocytosis. Longer linkers thus contribute an enhanced additional tool to the existing toolsets for the detection and measurements of protein-protein interactions and protein proximity in living cells.

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Lipopolysaccharide Upregulates Palmitoylated Enzymes of the Phosphatidylinositol Cycle: An Insight from Proteomic Studies [Research]

Lipopolysaccharide (LPS) is a component of the outer membrane of Gram-negative bacteria that induces strong proinflammatory reactions of mammals. These processes are triggered upon sequential binding of LPS to CD14, a GPI-linked plasma membrane raft protein, and to the TLR4/MD2 receptor complex. We have found earlier that upon LPS binding, CD14 triggers generation of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P₂], a lipid controlling subsequent proinflammatory cytokine production. Here we show that stimulation of RAW264 macrophage-like cells with LPS induces global changes of the level of fatty-acylated, most likely palmitoylated, proteins. Among the acylated proteins that were up-regulated in those conditions were several enzymes of the phosphatidylinositol cycle. Global profiling of acylated proteins was performed by metabolic labeling of RAW264 cells with 17ODYA, an analogue of palmitic acid functionalized with an alkyne group, followed by detection and enrichment of labeled proteins using biotin-azide/streptavidin and their identification with mass spectrometry. This proteomic approach revealed that 154 fatty-acylated proteins were up-regulated, 186 downregulated, and 306 not affected in cells stimulated with 100 ng/ml LPS for 60 min. The acylated proteins affected by LPS were involved in diverse biological functions, as found by Ingenuity Pathway Analysis. Detailed studies of 17ODYA-labeled and immunoprecipitated proteins revealed that LPS induces S-palmitoylation, hence activation, of type II phosphatidylinositol 4-kinase (PI4KII) β, which phosphorylates phosphatidylinositol to phosphatidylinositol 4-monophosphate, a PI(4,5)P₂ precursor. Silencing of PI4KIIβ and PI4KIIα inhibited LPS-induced expression and production of proinflammatory cytokines, especially in the TRIF-dependent signaling pathway of TLR4. Reciprocally, this LPS-induced signaling pathway was significantly enhanced after overexpression of PI4KIIβ or PI4KIIα; this was dependent on palmitoylation of the kinases. However, the S-palmitoylation of PI4KIIα, hence its activity, was constitutive in RAW264 cells. Taken together the data indicate that LPS triggers S-palmitoylation and activation of PI4KIIβ, which generates PI(4)P involved in signaling pathways controlling production of proinflammatory cytokines.

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