No abstract available
http://ift.tt/2vFAwPu
Τετάρτη 16 Αυγούστου 2017
Ocular Motor Manifestations of Multiple Sclerosis
Background: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system leading to disability, especially in young patients. Acute or chronic lesions of MS within the brainstem and the cerebellum frequently result in ocular motor disorders. Evidence Acquisition: This review encompasses the spectrum of ocular motor disorders in patients with MS emphasizing prevalence, examination findings, diagnostic features, functional consequences, classification of MS course, and management of these disturbances of ocular motility. Results: Ocular motor manifestations of MS can occur acutely in relapse or chronically, the latter as a consequence of previous relapses or as a chronic course of the disease. The most frequent and specific acute ocular motor manifestation is uni- or bilateral internuclear ophthalmoplegia (INO). The most frequent chronic manifestations include INO and cerebellar ocular motor disorders such as gaze-evoked nystagmus, saccadic hypermetria, and lack of vestibulo-ocular reflex inhibition. The most disabling syndrome is pendular nystagmus. Conclusions: The high prevalence of ocular motor manifestations emphasizes the importance of neuro-ophthalmological examination among patients with MS. Because chronic manifestations may cause minimal or no symptoms, a systematic investigation of the most common manifestations should be performed in daily practice. Appropriate treatment may improve visual outcome in some of these ocular motor disorders.http://ift.tt/2vFvUsw
Ocular and Cerebral Emboli From an Atrial Myxoma
Abstract: Emboli from an atrial myxoma resulted in asymptomatic segmental retinal and choroidal arterial hyperfluorescent lesions on retinal angiography, mimicking an arteritis. The retinal lesions disappeared after removal of the atrial myxoma. Endothelial trauma by embolic material appears to be the mechanism of the angiographic findings.http://ift.tt/2wRW3mR
The Utility of Magnetic Resonance Imaging in Assessing Patients With Pituitary Tumors Compressing the Anterior Visual Pathway
Background: Pituitary tumors are one of the most common types of intracranial neoplasms, and can cause progressive visual loss. An ongoing challenge in the management of patients with pituitary tumors is the cost, availability, and reliability of current magnetic resonance imaging (MRI) techniques to capture clinically significant incremental tumor growth. The purpose of this study was to evaluate the various MRI-based structural analyses and to explore the relationship between measures of structure and function in the afferent visual pathway of patients with pituitary tumors. Methods: We performed a critical review of literature on MRI-based structural analyses of pituitary adenomas using PubMed, Embase, Cochrane Library, and Google Scholar. In addition, preoperative structural characteristics of the optic apparatus, optic nerve compression, and optic chiasm elevation identified as important in the literature review, were examined in 18 of our patients from October 2010 to January 2014. Results: In our review of literature, a total of 443 citations were obtained from our search strategy and review of bibliographies. Eight of these studies met inclusion/exclusion criteria and were retrieved for critical review. Of the 8 included studies, only 2 studies examined the relationship between MRI-based structural measurements and postoperative visual recovery. In our small case-series, MRI analysis of chiasm elevation, severity of optic nerve compression, chiasm position, height of chiasm, tumor height, and tumor volume failed to differentiate patients with postoperative visual dysfunction vs those with visual recovery (P > 0.05). Conclusions: Although MRI-based structural analysis is an important and useful tool for managing patients with pituitary tumors, there are limited objective measures shown to be predictive of postoperative visual recovery.http://ift.tt/2wSzzlI
Limitations of Current Methodology for Assessment of Compression of the Optic Chiasm by Macroadenoma: The Neuroradiologic Perspective
No abstract availablehttp://ift.tt/2vFpqtZ
The QuantiFERON-TB Gold In-Tube Assay in Neuro-Ophthalmology
Background: Although QuantiFERON-TB Gold In-Tube (QFT-GIT) testing is regularly used to detect infection with Mycobacterium tuberculosis, its utility in a patient population with a low risk for tuberculosis (TB) has been questioned. The following is a cohort study analyzing the efficacy of QFT-GIT testing as a method for detection of active TB disease in low-risk individuals in a neuro-ophthalmologic setting. Methods: Ninety-nine patients from 2 neuro-ophthalmology centers were identified as having undergone QFT-GIT testing between January 2012 and February 2016. Patients were divided into groups of negative, indeterminate, and positive QFT-GIT results. Records of patients with positive QFT-GIT results were reviewed for development of latent or active TB, as determined by clinical, bacteriologic, and/or radiographic evidence. Results: Of the 99 cases reviewed, 18 patients had positive QFT-GIT tests. Of these 18 cases, 12 had documentation of chest radiographs or computed tomography which showed no evidence for either active TB or pulmonary latent TB infection (LTBI). Four had chest imaging which was indicative of possible LTBI. None of these 18 patients had symptoms of active TB and none developed active TB within the follow-up period. Conclusions: Based on our results, we conclude that routine testing with QFT-GIT in a low-risk cohort did not diagnose active TB infection. We do not recommend routine QFT-GIT testing for TB low-risk individuals, as discerned through patient and exposure history, ocular examination, and clinical judgment, in neuro-ophthalmology practice.http://ift.tt/2wSufi4
Color Pupillography in Dorsal Midbrain Syndrome
Objective: The purpose of this study was to evaluate the pupil response to chromatic stimuli in patients with lesions in the dorsal midbrain and possibly gain new insights into the afferent pupillary pathways. Methods: Color pupillography was performed in 5 patients with dorsal midbrain syndrome (DMS), and their results were compared with those of 20 healthy control subjects. We used full-field red stimuli (605 nm) that primarily address the rod/cone system and blue stimuli (420 nm) that preferentially activate intrinsically photosensitive retinal ganglion cells (ipRGCs) directly, with a duration of 4 seconds and a stimulus intensity of 28 lx corneal illumination under mesopic conditions. One eye was stimulated, and the consensual pupil response was recorded and analyzed. Results: The pupillary light reflex in patients with DMS was reduced, differed in shape, and showed a prolonged latency time compared to normal subjects. The blue response was less affected than the red response: the mean maximal relative amplitude (M) was 15.8% (SD = 7.8) in patients with DMS compared with 43.0% (SD = 5.5) in normal subjects for red stimulation, and M = 40.8%, SD = 8.4 (DMS) with M = 58.3%, SD = 4.8 (normals) for blue stimulation. The reduction was 63% for red stimulation but only 30% for blue stimulation in patients with DMS. Moreover, there was a preserved postillumination pupil response to blue stimulation in DMS patients. Conclusions: In DMS, the melanopsin-mediated ipRGC pathway appeared relatively preserved.http://ift.tt/2vFuNct
Selective Unidirectional Horizontal Saccadic Paralysis From Acute Ipsilateral Pontine Stroke: Response
No abstract availablehttp://ift.tt/2vFDSlI
Validity of Forced Eyelid Closure Test: A Novel Clinical Screening Test for Ocular Myasthenia Gravis
Background: Forced eyelid closure test (FECT) is a clinical screening test developed from the original Cogan lid twitch (CLT) sign to assist in the diagnosis of ocular myasthenia gravis (OMG), We evaluated the sensitivity and specificity of FECT compared with CLT and benchmarked to standard diagnostic tests. Methods: This study was a retrospective chart review of 48 patients using electronic medical records of those that presented with ptosis and/or diplopia at Doheny Eye Institute, University of California, Los Angeles between February 2015 and April 2016. Patients without FECT testing were excluded. FECT and CLT results, and final diagnosis were recorded. To perform FECT, the patient was asked to squeeze his or her eyelids shut for 5–10 seconds then open quickly and fixate in primary position. The excessive upward overshoot of eyelids movement indicated a positive FECT. The test was performed by a neuro-ophthalmologist before establishing the diagnosis. Patients who had equivocal test results and/or inconclusive final diagnosis were excluded. Results: Of the 48 patients studied, 18 patients (37.5%) had positive FECT; 15 of whom had a final diagnosis of OMG (83.3%). Of the 30 patients with negative FECT, 1 had OMG (3.3%). Of the 48 patients, 35 patients also had a documented CLT result (72.9%). CLT was positive in 11 of these 35 patients (31.4%), and 9 of these 11 had OMG (81.8%). Of the 24 patients with negative CLT, 2 of them had OMG (8.3%). Sensitivity and specificity of FECT were 94% and 91% (joint 95% confidence region: sensitivity × specificity = [0.70, 1] × [0.75, 1]). The relative true-positive fraction (rTPF) between FECT and CLT was 1.15; the relative false-positive fraction was 1.31. Conclusions: FECT is a simple clinical screening test with good sensitivity and specificity for OMG.http://ift.tt/2vFuMVX
Structure-Function Analysis of Nonarteritic Anterior Ischemic Optic Neuropathy and Age-Related Differences in Outcome
Background: The optic nerve head is vulnerable to ischemia leading to anterior ischemic optic neuropathy (AION), the most common acute optic neuropathy in those older than 50 years of age. Methods: We performed a cross-sectional study of 55 nonarteritic anterior ischemic optic neuropathy (NAION) eyes in 34 patients to assess clinical outcome and perform structure-function correlations. Results: The peak age of NAION onset was between 50 and 55 years. Sixty-seven percent of patients presented with their first event between the ages of 40 and 60 years, and 32% presented at ≤50 years. Those with NAION onset at age ≤50 years did not have significantly better visual outcome per logMAR visual acuity, automated perimetric mean deviation (PMD) or optical coherence tomography (OCT) measurements. Kaplan–Meier survival curve and multivariate Cox proportional regression analysis showed that age >50 years at NAION onset was associated with greater risk of second eye involvement, with hazard ratio of 20. Older age at onset was significantly correlated with greater thinning of the ganglion cell complex (GCC) (P = 0.022) but not with logMAR visual acuity, PMD, or thinning of retinal nerve fiber layer (RNFL). Using area under receiver operating characteristic curve analyses, we found that thinning of RNFL and GCC was best able to predict visual outcome, and that mean RNFL thickness >65 μm or macular GCC thickness >55 μm significantly correlated with good visual field outcome. Conclusions: We showed that NAION onset at age >50 years had a greater risk of second eye involvement. Patients with OCT mean RNFL thickness >65 μm and mean macular ganglion cell complex thickness >55 μm had better visual outcomes.http://ift.tt/2wRMtA5
The 43rd Annual Meeting of the North American Neuro-Ophthalmology Society in Washington, DC
No abstract availablehttp://ift.tt/2wSdy6e
Is Multiple Sclerosis Associated With a Lower Intraocular Pressure?
Objective: To determine if multiple sclerosis (MS) is associated with lower intraocular pressure (IOP) compared with individuals without MS. Methods: Thirty patients with clinically definite MS were identified and a retrospective chart review was conducted. Each patient with MS underwent IOP recording by a single investigator using kinetic applanation tonometry. Measurement of central corneal thickness (CCT) also was obtained. Similarly, 30 study controls were identified and kinetic applanation tonometry and CCT were recorded. Univariate analysis of covariance was conducted to determine a statistically significant difference between IOP between MS and control groups, controlling for age. Results: Analyses were adjusted for age and 2 subjects were excluded because of steroid use. The average IOP in MS group was 12.3 mm Hg (right eye = 12.3 mm Hg, left eye = 12.2 mm Hg) and in the control group was 17 mm Hg (right eye = 16.9 mm Hg, left eye = 17 mm Hg). There was a significant effect of presence of MS on IOP accounting for 53% variability in mean IOP (F(1,55) = 60.7; Phttp://ift.tt/2wS2t5h
Vision Loss, Rash, and Abnormal Brain Magnetic Resonance Imaging in a 17 Year Old
No abstract availablehttp://ift.tt/2wS0uhp
Evaluation of Horner Syndrome in the MRI Era
Background: To identify the etiologies of adult Horner syndrome (HS) in the MRI era using a targeted evaluation approach and to assess the value and yield of targeted imaging. Methods: A retrospective chart review was performed of 200 adult outpatients with HS, confirmed with cocaine eyedrop testing. Patients were divided into subgroups based on the presence or absence of symptoms and those who did or did not receive additional testing with hydroxyamphetamine drops. Imaging was obtained based on pharmacologic localization and/or clinical evaluation. The etiology of HS and the yield of imaging were determined in all subgroups. Results: Imaging showed causative lesions in 24 of 179 (12.84%) imaged patients with HS, and 13 (69.0%) were determined "idiopathic." Of the patients who underwent testing with hydroxyamphetamine drops (132 patients), 86 had a postganglionic localization with an imaging yield of 8.1%, and 46 had preganglionic cause with an imaging yield of 21.7%. Fifty-three patients (26.5%) never noticed ptosis/anisocoria before examination, and the imaging yield in this subgroup was 2.8%. Eighteen of the 200 patients (9.0%) had serious pathology, including carotid artery dissection, brain, or neck mass, and 6 of these (31.6%) had acute symptoms and/or pain. Conclusions: HS is most often idiopathic with serious pathology being relatively infrequent. When determining etiology, the absence of symptoms is not predictive of the pathology. However, acute onset of symptoms and/or pain are possible indicators for serious pathology. Localizing the lesion using hydroxyamphetamine drops whenever obtainable and available is still an efficient way to target imaging evaluation.http://ift.tt/2wS84IU
Endodermal Cyst of the Third Nerve in a Child
Abstract: Endodermal cysts, also known as neurogenic, neuroenteric, foregut, bronchogenic, respiratory, epithelial, teratomatous, or gastrocytoma cysts, can be found in the central nervous system, predominantly in the subarachnoid space of the cervical and thoracic spinal cord. We describe a child with an endodermal cyst of the third nerve and highlight neuroimaging findings, pathological correlation, clinical course, and patient management.http://ift.tt/2wSudqs
Morbidity and mortality in children undergoing bronchoscopy for foreign body removal
Objectives/Hypothesis
Analyze morbidity and mortality among children undergoing bronchoscopy for foreign body removal.
Study Design
Multicenter retrospective review using the American College of Surgeons Pediatric National Surgical Quality Improvement Program from 2014 and 2015.
Methods
Patients were identified using Current Procedural Terminology code 31635. Demographics, time to surgery, operative times, hospitalization time, and complications were collected. Multivariate logistic regression was used to identify predictive factors for major adverse events.
Results
Three hundred thirty-four patients were included (mean age 3.7 years, 59.0% male). Preoperative sepsis syndrome was present in 5.7% of patients and 8.1% had asthma. Of the patients, 5.1% percent of patients had a tracheostomy. Bronchoscopy was performed by an otolaryngologist (65.4%) or a pediatric surgeon (33.1%). Mean operative time was 27.4 minutes, whereas mean total operating room time was 54.6 minutes. Airway foreign bodies were located in 269 patients (80.5%), with 62.5% being located in the mainstem bronchus. Operative time was longer when foreign bodies were in the mainstem bronchus or distal to it. Mean time to surgery from admission was 0 days, and mean duration of hospitalization was 1 day. One patient (0.3%) required reoperation for respiratory reasons, and three (0.9%) required readmission for related reasons. No patients remained hospitalized at 30 days. Two (0.6%) had a postoperative pneumonia, and two (0.6%) required reintubation. One patient death (0.3%) occurred within 2 weeks of bronchoscopy. No significant differences were identified in operative time, time to surgery, or hospitalization time based on age, gender, presence of a tracheostomy, or surgical specialty.
Conclusions
Bronchoscopy for identification and removal of airway foreign bodies had minimal morbidity in this group.
Level of Evidence
2b Laryngoscope, 2017
http://ift.tt/2vL3E6c
Morbidity and mortality in children undergoing bronchoscopy for foreign body removal
Objectives/Hypothesis
Analyze morbidity and mortality among children undergoing bronchoscopy for foreign body removal.
Study Design
Multicenter retrospective review using the American College of Surgeons Pediatric National Surgical Quality Improvement Program from 2014 and 2015.
Methods
Patients were identified using Current Procedural Terminology code 31635. Demographics, time to surgery, operative times, hospitalization time, and complications were collected. Multivariate logistic regression was used to identify predictive factors for major adverse events.
Results
Three hundred thirty-four patients were included (mean age 3.7 years, 59.0% male). Preoperative sepsis syndrome was present in 5.7% of patients and 8.1% had asthma. Of the patients, 5.1% percent of patients had a tracheostomy. Bronchoscopy was performed by an otolaryngologist (65.4%) or a pediatric surgeon (33.1%). Mean operative time was 27.4 minutes, whereas mean total operating room time was 54.6 minutes. Airway foreign bodies were located in 269 patients (80.5%), with 62.5% being located in the mainstem bronchus. Operative time was longer when foreign bodies were in the mainstem bronchus or distal to it. Mean time to surgery from admission was 0 days, and mean duration of hospitalization was 1 day. One patient (0.3%) required reoperation for respiratory reasons, and three (0.9%) required readmission for related reasons. No patients remained hospitalized at 30 days. Two (0.6%) had a postoperative pneumonia, and two (0.6%) required reintubation. One patient death (0.3%) occurred within 2 weeks of bronchoscopy. No significant differences were identified in operative time, time to surgery, or hospitalization time based on age, gender, presence of a tracheostomy, or surgical specialty.
Conclusions
Bronchoscopy for identification and removal of airway foreign bodies had minimal morbidity in this group.
Level of Evidence
2b Laryngoscope, 2017
http://ift.tt/2vL3E6c
Antibiofilm properties of model composites containing quaternary ammonium methacrylates after surface texture modification
Source:Dental Materials
Author(s): Guilherme Ferreira Rego, Marina Lermen Vidal, Gil Mendes Viana, Lucio Mendes Cabral, Luis Felipe Jochims Schneider, Maristela Barbosa Portela, Larissa Maria Cavalcante
ObjectiveInvestigate antimicrobial properties and surface texture of model composites with different concentration and alkyl chain length of quaternary ammonium monomers (QAS).MethodsMonomers derived from QAS salts with alkyl chain lengths of 12 carbons ((dimethylaminododecyl methacrylate) DMADDM) and 16 carbons (dimethylaminohexadecyl methacrylate—DMAHDM) were obtained from the reactions of their respective organo-halides with the tertiary amine 2-(dimethylamino)ethyl methacrylate (DMAEMA). DMADDM and DMAHDM were incorporated into model composite in concentrations of 5 or 10%, resulting the following groups: G12.5 (DMADDM 5%), G12.10 (DMADDM 10%), G16.5 (DMAHDM 5%), G16.10 (DMAHDM 10%) and GC (control). Biofilm viability, lactic acid production and surface roughness were analysed 24h after samples preparation (initial), repeated after toothbrush abrasion and after polishing simulation. Data were submitted to ANOVA and Tukey's test (p≤0.05).ResultsThe longer the molecular chain size of QAS and the higher its concentration (G16.10), the lower was the viability and the production of lactic acid by the biofilm. No differences were detected in initial roughness' measurements among groups. However, after abrasion, there was an increase of biofilm viability and lactic acid production. Composites containing QAS presented rougher surfaces compared to the CG. After polishing, biofilm viability and surface roughness were statistically similar for all groups. Nevertheless, DMAHDM at 10% showed reduction in lactic acid production.SignificanceChain length and concentration of QAS influenced biofilm development and production of lactic acid. Longer chains and higher concentrations of QAS promoted better antimicrobial properties. Changes in surface texture caused by abrasion, decreased antibiofilm properties.
http://ift.tt/2v3Ssjv
Impact of machining on the flexural fatigue strength of glass and polycrystalline CAD/CAM ceramics
Source:Dental Materials
Author(s): Sara Fraga, Marina Amaral, Marco Antônio Bottino, Luiz Felipe Valandro, Cornelis Johannes Kleverlaan, Liliana Gressler May
ObjectivesTo assess the effect of machining on the flexural fatigue strength and on the surface roughness of different computer-aided design, computer-aided manufacturing (CAD/CAM) ceramics by comparing machined and polished after machining specimens.MethodsDisc-shaped specimens of yttria-stabilized polycrystalline tetragonal zirconia (Y-TZP), leucite-, and lithium disilicate-based glass ceramics were prepared by CAD/CAM machining, and divided into two groups: machining (M) and machining followed by polishing (MP). The surface roughness was measured and the flexural fatigue strength was evaluated by the step-test method (n=20). The initial load and the load increment for each ceramic material were based on a monotonic test (n=5). A maximum of 10,000 cycles was applied in each load step, at 1.4Hz. Weibull probability statistics was used for the analysis of the flexural fatigue strength, and Mann-Whitney test (α=5%) to compare roughness between the M and MP conditions.ResultsMachining resulted in lower values of characteristic flexural fatigue strength than machining followed by polishing. The greatest reduction in flexural fatigue strength from MP to M was observed for Y-TZP (40%; M=536.48MPa; MP=894.50MPa), followed by lithium disilicate (33%; M=187.71MPa; MP=278.93MPa) and leucite (29%; M=72.61MPa; MP=102.55MPa). Significantly higher values of roughness (Ra) were observed for M compared to MP (leucite: M=1.59μm and MP=0.08μm; lithium disilicate: M=1.84μm and MP=0.13μm; Y-TZP: M=1.79μm and MP=0.18μm).SignificanceMachining negatively affected the flexural fatigue strength of CAD/CAM ceramics, indicating that machining of partially or fully sintered ceramics is deleterious to fatigue strength.
http://ift.tt/2uL3MFF
Impact of thio-urethane additive and filler type on light-transmission and depth of polymerization of dental composites
Publication date: Available online 12 August 2017
Source:Dental Materials
Author(s): André Luis Faria-e-Silva, Carmem Silvia Pfeifer
ObjectiveThis study evaluated the effects of filler type and the addition of thio-urethane oligomers on light-transmission, polymerization kinetics and depth of cure of resin composites.MethodsBisGMA:UDMA:TEGMA (5:3:2wt%) were mixed with 0 (control) or 20wt% thio-urethane. Fillers with various sizes and refractive indices were included and refractive index (RI) measured. Unfilled resins were used as controls. The RIs of materials were measured before and after polymerization. The irradiance reaching the bottom of 3-mm thick specimens was measured during the polymerization. Degree of conversion to a depth of 5mm was mapped. An optical bench was used to simultaneously follow conversion and light transmission.ResultsThe addition of thio-urethane increased the RI for all composites. As expected, RI also increased with conversion for all materials. The one exception was for the material filled with OX-50, in which the RI of the composite decreased with conversion. In this case, the irradiance at the bottom of the 3mm specimen was also the lowest among all groups. The addition of thio-urethanes had only minimal effect on light transmission within a filler type, but led to increased conversion in depth for all groups. The filler type itself had a greater effect on light transmission, and that correlated well with the degree of conversion.SignificanceThe effect of the thio-urethane addition on degree of conversion in depth was dependent on filler type. The additive can be tailored to improve the RI match with the filler to optimize light transmission in dental composites.
Graphical abstract
http://ift.tt/2uKTuFE
Lymphocyte Fate and Metabolism: A Clonal Balancing Act
Publication date: Available online 14 August 2017
Source:Trends in Cell Biology
Author(s): Simone A. Nish, Wen-Hsuan W. Lin, Steven L. Reiner
Activated lymphocytes perform a clonal balancing act, yielding a daughter cell that differentiates owing to intense PI3K signaling, alongside a self-renewing sibling cell with blunted anabolic signaling. Divergent cellular anabolism versus catabolism is emerging as a feature of several developmental and regenerative paradigms. Metabolism can dictate cell fate, in part, because lineage-specific regulators are embedded in the circuitry of conserved metabolic switches. Unequal transmission of PI3K signaling during regenerative divisions is reminiscent of compartmentalized PI3K activity during directed motility or polarized information flow in non-dividing cells. The diverse roles of PI3K pathways in membrane traffic, cell polarity, metabolism, and gene expression may have converged to instruct sibling cell feast and famine, thereby enabling clonal differentiation alongside self-renewal.
http://ift.tt/2uKZxtE
Diagnostic performance of unenhanced Computed Tomography and 18F-fluorodeoxyglucose positron emission tomography in indeterminate adrenal tumors
Summary
Objective
Evidence on the diagnostic performance of adrenal imaging is limited. We aimed to assess the diagnostic performance of unenhanced computed tomography (CT) and18F-fluorodeoxyglucose(18FDG) positron emission tomography(PET)/CT imaging in a high risk population for adrenal malignancy using an optimal reference standard.
Design
Retrospective cohort study.
Methods
Imaging studies of patients with adrenal nodules who underwent adrenal biopsy and/or adrenalectomy between 1994 and 2014 were reviewed and compared to the reference standard of histology. Eighty % of patients presented with known or suspected extra-adrenal malignancy.
Results
Unenhanced abdominal CT was performed in 353 patients with adrenal lesions; median size was 3 (0.7-15) cm and median radiodensity was 33 (-21to78) Hounsfield units (HU). Radiodensity of >10 HU diagnosed malignancy with a sensitivity of 100%, specificity of 33%, positive predictive value (PPV) of 72%, and negative predictive value (NPV) of 100%.18FDG-PET/CT was performed in 89 patients; median tumor size was 2.1 (0.7-9.2) cm. Maximum standardized uptake (SUV max) was higher in malignant lesions when compared to benign lesions (median = 10 [2.3-29.4] vs 3.7 [1.4-24.5], respectively, P<.0001). Similarly, median SUV max lesion to SUV max liver ratio (ALR) in malignant lesions was higher than in benign lesions (median = 3 [0.74-13.4] vs. 1.2 [0.5-6.6], respectively, P<.0001).18FDG-PET/CT ALR > 1.8 diagnosed malignancy with a sensitivity of 87%, specificity of 84%, PPV of 85%, and NPV of 86%.
Conclusion
Noncontract CT radiodensity of ≤10 HU excludes malignancy even in a high risk population. For indeterminate adrenal lesions, given a superior specificity, 18FDG PET/CT could be considered as a second stage imaging.
This article is protected by copyright. All rights reserved.
http://ift.tt/2fNfwky
Absorption and tolerability of taste-masked hydrocortisone granules in neonates, infants and children under 6 years of age with adrenal insufficiency
Abstract
Objectives
There is no licensed, dose-appropriate formulation of hydrocortisone for children with adrenal insufficiency (AI) and patients rely on compounded adult medication. The aim of this study was to evaluate the absorption, palatability and safety of Infacort®, an immediate-release, granule formulation of hydrocortisone with taste masking.
Study design
Single site with satellites attended by a "flying" doctor from investigator site.
Open-label, single-dose study in three consecutive child cohorts (n=24) with AI; Cohort 1, children aged 2 to <6 years (n=12); Cohort 2, infants aged 28 days to <2 years (n=6); Cohort 3, neonates aged 1 to <28 days (n=6). <comment> Au: the age ranges quoted are slightly different in each of the abstract, main text, Table 1 and Supplemental table. These have now been unified as shown here.</comment>.
Methods
Fasted children were given a single dose of Infacort® as dry granules administered directly from a capsule or spoon followed by a drink. The primary endpoint was the maximum serum cortisol concentration up to 240 minutes after Infacort® administration. Secondary endpoints were palatability and adverse events (AEs).
Results
All children showed an increase in cortisol above baseline after Infacort® (p<0.0001), with geometric mean ± SD cortisol concentration at 60 min of 575.8 ± 299.5 nmol/L. There was no failure in administration of Infacort®, and 95.5% of parents/carers preferred Infacort® to their child's current medication. In 6 children who completed the palatability questionnaire, 80% of responses were very good or neutral and 20% were adverse. No serious or severe treatment-emergent AEs were reported.
Conclusions
Infacort® is well tolerated, easy to administer to neonates, infants and children and shows good absorption, with cortisol levels at 60 minutes after administration similar to physiological cortisol levels in healthy children.
This article is protected by copyright. All rights reserved.
http://ift.tt/2i8gpVC
Editorial Board
Source:Artificial Intelligence in Medicine, Volume 79
http://ift.tt/2vKJJo0
The inter-rater reliability of observing aggression: A systematic literature review
Source:Aggression and Violent Behavior
Author(s): Kore G. Lampe, Eva A. Mulder, Olivier F. Colins, Robert R.J.M. Vermeiren
IntroductionBoth clinicians and researchers value observation as an important source of diagnostic information, especially in forensic, mental health and school settings. However, it is not well-known how reliable information collected by means of observation is.MethodsThe present study aimed to systematically review the literature on the inter-rater reliability (IRR) of observation of aggression and impulsivity.ResultsA total of 37 papers on the observation of aggression that provided information about the IRR was selected and reviewed. Forms of observation ranged from videotaped observation in a lab to participant observation in a naturalistic setting (e.g. with an observer taking part in the situation). Relatively few studies focused on observation of aggression in naturalistic settings. For various reasons, no papers on the observation of impulsivity could be included. Regardless of differences in forms and settings, the IRR of observing aggression was fair to excellent.ConclusionDifferent forms of observation (e.g. non-participant, direct) taking place in different settings (e.g. naturalistic or lab) can be executed reliably. This finding is encouraging for clinicians who want to make use of systematic observations in naturalistic settings. However, the relatively sparse research on these naturalistic observations underscores the need for research on the topic.
http://ift.tt/2v3zxF6
Swallowing Mechanics Associated With Artificial Airways, Bolus Properties, and Penetration–Aspiration Status in Trauma Patients
Purpose
Artificial airway procedures such as intubation and tracheotomy are common in the treatment of traumatic injuries, and bolus modifications may be implemented to help manage swallowing disorders. This study assessed artificial airway status, bolus properties (volume and viscosity), and the occurrence of laryngeal penetration and/or aspiration in relation to mechanical features of swallowing. Method
Coordinates of anatomical landmarks were extracted at minimum and maximum hyolaryngeal excursion from 228 videofluoroscopic swallowing studies representing 69 traumatically injured U.S. military service members with dysphagia. Morphometric canonical variate and regression analyses examined associations between swallowing mechanics and bolus properties based on artificial airway and penetration–aspiration status. Results
Significant differences in swallowing mechanics were detected between extubated versus tracheotomized (D = 1.32, p < .0001), extubated versus decannulated (D = 1.74, p < .0001), and decannulated versus tracheotomized (D = 1.24, p < .0001) groups per post hoc discriminant function analysis. Tracheotomy-in-situ and decannulated subgroups exhibited increased head/neck extension and posterior relocation of the larynx. Swallowing mechanics associated with (a) penetration–aspiration status and (b) bolus properties were moderately related for extubated and decannulated subgroups, but not the tracheotomized subgroup, per morphometric regression analysis. Conclusion
Specific differences in swallowing mechanics associated with artificial airway status and certain bolus properties may guide therapeutic intervention in trauma-based dysphagia.http://article/doi/10.1044/2017_JSLHR-S-16-0431/2649304/Swallowing-Mechanics-Associated-With-Artificial
Author Impact Metrics in Communication Sciences and Disorder Research
Purpose
The purpose was to examine author-level impact metrics for faculty in the communication sciences and disorder research field across a variety of databases. Method
Author-level impact metrics were collected for faculty from 257 accredited universities in the United States and Canada. Three databases (i.e., Google Scholar, ResearchGate, and Scopus) were utilized. Results
Faculty expertise was in audiology (24.4%; n = 490) and speech-language pathology (75.6%; n = 1,520). Women comprised 68.1% of faculty, and men comprised 31.9% of faculty. The percentage of faculty in the field of communication sciences and disorders identified in each database was 10.5% (n = 212), 44.0% (n = 885), and 84.4% (n = 1,696) for Google Scholar, ResearchGate, and Scopus, respectively. In general, author-level impact metrics were positively skewed. Metric values increased significantly with increasing academic rank (p < .05), were greater for men versus women (p < .05), and were greater for those in audiology versus speech-language pathology (p < .05). There were statistically significant positive correlations between all author-level metrics (p < .01). Conclusions
These author-level metrics may serve as a benchmark for scholarly production of those in the field of communication sciences and disorders and may assist with professional identity management, tenure and promotion review, grant applications, and employment.http://article/doi/10.1044/2017_JSLHR-H-16-0458/2650586/Author-Impact-Metrics-in-Communication-Sciences
Semantic and Phonological Encoding in Adults Who Stutter: Silent Responses to Pictorial Stimuli
Purpose
Research on language planning in adult stuttering is relatively sparse and offers diverging arguments about a potential causative relationship between semantic and phonological encoding and fluency breakdowns. This study further investigated semantic and phonological encoding efficiency in adults who stutter (AWS) by means of silent category and phoneme identification, respectively. Method
Fifteen AWS and 15 age- and sex-matched adults who do not stutter (ANS) participated. The groups were compared on the basis of the accuracy and speed of superordinate category (animal vs. object) and initial phoneme (vowel vs. consonant) decisions, which were indicated manually during silent viewing of pictorial stimuli. Movement execution latency was accounted for, and no other cognitive, linguistic, or motor demands were posed on participants' responses. Therefore, category identification accuracy and speed were considered indirect measures of semantic encoding efficiency and phoneme identification accuracy and speed of phonological encoding efficiency. Results
For category decisions, AWS were slower but not less accurate than ANS, with objects eliciting more errors and slower responses than animals in both groups. For phoneme decisions, the groups did not differ in accuracy, with consonant errors outnumbering vowel errors in both groups, and AWS were slower than ANS in consonant but not vowel identification, with consonant response time lagging behind vowel response time in AWS only. Conclusions
AWS were less efficient than ANS in semantic encoding, and they might harbor a consonant-specific phonological encoding weakness. Future independent studies are warranted to discover if these positive findings are replicable and a marker for persistent stuttering.http://article/doi/10.1044/2017_JSLHR-S-16-0323/2650587/Semantic-and-Phonological-Encoding-in-Adults-Who
Analysis of Item-Level Bias in the Bayley-III Language Subscales: The Validity and Utility of Standardized Language Assessment in a Multilingual Setting
Purpose
The purpose of this study was to improve standardized language assessments among bilingual toddlers by investigating and removing the effects of bias due to unfamiliarity with cultural norms or a distributed language system. Method
The Expressive and Receptive Bayley-III language scales were adapted for use in a multilingual country (Singapore). Differential item functioning (DIF) was applied to data from 459 two-year-olds without atypical language development. This involved investigating if the probability of success on each item varied according to language exposure while holding latent language ability, gender, and socioeconomic status constant. Associations with language, behavioral, and emotional problems were also examined. Results
Five of 16 items showed DIF, 1 of which may be attributed to cultural bias and another to a distributed language system. The remaining 3 items favored toddlers with higher bilingual exposure. Removal of DIF items reduced associations between language scales and emotional and language problems, but improved the validity of the expressive scale from poor to good. Conclusions
Our findings indicate the importance of considering cultural and distributed language bias in standardized language assessments. We discuss possible mechanisms influencing performance on items favoring bilingual exposure, including the potential role of inhibitory processing.http://article/doi/10.1044/2017_JSLHR-L-16-0196/2649302/Analysis-of-ItemLevel-Bias-in-the-BayleyIII
Histochemical and immunohistochemical examination of odontoblasts (petroblasts) in petrodentine formation of lungfish
Publication date: November 2017
Source:Archives of Oral Biology, Volume 83
Author(s): Shunya Oka, Ichiro Sasagawa, Mikio Ishiyama
ObjectivePetrodentine, the core of the lungfish tooth plate, is a well-mineralized tissue similar to mammalian enamel and analogous to enameloid in fish teeth. Petrodentine is formed solely by petroblasts, which are specialized odontoblasts, whereas enameloid is a composite tissue produced by both odontoblasts and dental epithelial cells. To clarify the details of petrodentine formation, petroblasts were investigated using histochemical and immunohistochemical techniques.MethodsExtant lungfish (Lepidosiren paradoxa) were used in this study. Tooth plates during the stage of petrodentine formation were observed by means of histochemistry and immunohistochemistry. Commercial kits were used to detect enzyme activity. Correlative sections were immunostained using antibodies against selected peptides. Routine staining such as periodic acid-Schiff (PAS) reaction to identify glycogen and Elastica van Gieson staining for the detection of elastic fibers in histological sections were performed. In addition, conventional transmission electron microscopy was used for observing the fine structure.ResultsPetroblasts showed marked acid and alkaline phosphatase activities, and positive immunoreactivities against anti-nestin, anti-V-ATPase, and anti-Ca2+-ATPase, during the maturation stage, but in the matrix formation stage, reactions were much weaker than that of the maturation stage. During the maturation stage, petroblasts showed intense PAS reactivity, and glycogen particles were observed in petroblasts by transmission electron microscopy. Glucose transporter 1-immunoreactivity was observed in petroblasts in the matrix formation stage and the initial to mid part of the maturation stage.ConclusionsThe results in this study suggested that petroblasts have two functional stages, matrix formation and maturation, and glycogen plays an important role in the modulation of petroblasts.
http://ift.tt/2fNBP9u
Diabetes increases interleukin-17 levels in periapical, hepatic, and renal tissues in rats
Publication date: November 2017
Source:Archives of Oral Biology, Volume 83
Author(s): Mariane Maffei Azuma, João Eduardo Gomes-Filho, Annelise Katrine Carrara Prieto, Renata Oliveira Samuel, Valéria Marçal Felix de Lima, Dóris Hissako Sumida, Edilson Ervolino, Luciano Tavares Angelo Cintra
ObjectivesThis study aimed to evaluate the association between endodontic infection and diabetes on interleukin-17 levels in periapical, hepatic, and renal tissues of rats.DesignForty male rats were divided into groups: normoglycemic rats (N), normoglycemic rats with apical periodontitis (N-AP), rats with experimental diabetes (ED), and rats with experimental diabetes and apical periodontitis (ED-AP). Diabetes was induced by intravenous streptozotocin injection, and blood sugar levels were monitored to confirm disease development. Apical periodontitis (AP) was induced by pulp exposure to the oral environment during 30days. After 30days, hepatic and renal tissues were obtained, and IL-17 levels were quantified by ELISA. The right hemi-jaw was used to quantify IL-17 levels by immunohistochemistry. The values obtained in parametric tests were tabulated and analyzed statistically by analysis of variance (ANOVA) and Tukey tests, and the values obtained for scores were statistically analyzed by using the Kruskal-Wallis and Dun tests. The level of significance was set at 5%.ResultsED and ED-AP groups expressed significantly higher IL-17 levels in both hepatic and renal tissues (p<0.05), compared to N and N-AP groups. Apical periodontitis (AP) in ED-AP group was significantly more severe than that in N-AP group (p<0.05). Furthermore, there was a significantly larger increase in the IL-17 levels in ED-AP group compared to N group (p<0.05).ConclusionOur results indicate that diabetes increases IL-17 levels in hepatic and renal tissues and also enhances IL-17 production in apical periodontitis area of rats.
http://ift.tt/2fM65S4
Diamond nanoparticles for image-guided drug delivery application
Publication date: 30 August 2017
Source:Journal of Biotechnology, Volume 256, Supplement
Author(s): Yu Chung Lin, Zhe Rui Lin, Chia Chi Chang, Elena Perevedentseva, Chia Liang Cheng
http://ift.tt/2uRkgby
Lineage-Restricted Mammary Stem Cells Sustain the Development, Homeostasis, and Regeneration of the Estrogen Receptor Positive Lineage
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Alexandra Van Keymeulen, Marco Fioramonti, Alessia Centonze, Gaëlle Bouvencourt, Younes Achouri, Cédric Blanpain
The mammary gland (MG) is composed of different cell lineages, including the basal and the luminal cells (LCs) that are maintained by distinct stem cell (SC) populations. LCs can be subdivided into estrogen receptor (ER)+ and ER− cells. LCs act as the cancer cell of origin in different types of mammary tumors. It remains unclear whether the heterogeneity found in luminal-derived mammary tumors arises from a pre-existing heterogeneity within LCs. To investigate LC heterogeneity, we used lineage tracing to assess whether the ER+ lineage is maintained by multipotent SCs or by lineage-restricted SCs. To this end, we generated doxycycline-inducible ER-rtTA mice that allowed us to perform genetic lineage tracing of ER+ LCs and study their fate and long-term maintenance. Our results show that ER+ cells are maintained by lineage-restricted SCs that exclusively contribute to the expansion of the ER+ lineage during puberty and their maintenance during adult life.
Graphical abstract
Teaser
Van Keymeulen et al. performed lineage tracing of estrogen receptor (ER)-expressing cells in the mammary gland. They show that the ER+ cells are maintained by lineage-restricted stem cells that exclusively contribute to the expansion of the ER+ lineage during puberty and to their maintenance during adult life.http://ift.tt/2vKJEB0
MicroRNA-9 Couples Brain Neurogenesis and Angiogenesis
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Romain Madelaine, Steven A. Sloan, Nina Huber, James H. Notwell, Louis C. Leung, Gemini Skariah, Caroline Halluin, Sergiu P. Paşca, Gill Bejerano, Mark A. Krasnow, Ben A. Barres, Philippe Mourrain
In the developing brain, neurons expressing VEGF-A and blood vessels grow in close apposition, but many of the molecular pathways regulating neuronal VEGF-A and neurovascular system development remain to be deciphered. Here, we show that miR-9 links neurogenesis and angiogenesis through the formation of neurons expressing VEGF-A. We found that miR-9 directly targets the transcription factors TLX and ONECUTs to regulate VEGF-A expression. miR-9 inhibition leads to increased TLX and ONECUT expression, resulting in VEGF-A overexpression. This untimely increase of neuronal VEGF-A signal leads to the thickening of blood vessels at the expense of the normal formation of the neurovascular network in the brain and retina. Thus, this conserved transcriptional cascade is critical for proper brain development in vertebrates. Because of this dual role on neural stem cell proliferation and angiogenesis, miR-9 and its downstream targets are promising factors for cellular regenerative therapy following stroke and for brain tumor treatment.
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Teaser
The coordination of neuronal and vascular cell development is critical to ensure the proper formation of the vertebrate brain. Madelaine et al. show that the microRNA-9 couples neurogenesis and brain angiogenesis through the inhibition of Tlx and Onecut transcription factors regulating neuronal VEGF-A expression.http://ift.tt/2w3uDNh
Human GW182 Paralogs Are the Central Organizers for RNA-Mediated Control of Transcription
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Jessica A. Hicks, Liande Li, Masayuki Matsui, Yongjun Chu, Oleg Volkov, Krystal C. Johnson, David R. Corey
In the cytoplasm, small RNAs can control mammalian translation by regulating the stability of mRNA. In the nucleus, small RNAs can also control transcription and splicing. The mechanisms for RNA-mediated nuclear regulation are not understood and remain controversial, hindering the effective application of nuclear RNAi and investigation of its natural regulatory roles. Here, we reveal that the human GW182 paralogs TNRC6A/B/C are central organizing factors critical to RNA-mediated transcriptional activation. Mass spectrometry of purified nuclear lysates followed by experimental validation demonstrates that TNRC6A interacts with proteins involved in protein degradation, RNAi, the CCR4-NOT complex, the mediator complex, and histone-modifying complexes. Functional analysis implicates TNRC6A, NAT10, MED14, and WDR5 in RNA-mediated transcriptional activation. These findings describe protein complexes capable of bridging RNA-mediated sequence-specific recognition of noncoding RNA transcripts with the regulation of gene transcription.
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Teaser
Nuclear RNAi has the potential to add a previously unrecognized layer of control over mammalian gene expression. Hicks et al. use mass spectrometry to expand identification of protein partners that may play roles in RNA-mediated regulation of transcription and splicing.http://ift.tt/2w3pSTN
Subnuclear Relocalization of Structure-Specific Endonucleases in Response to DNA Damage
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Irene Saugar, Alberto Jiménez-Martín, José Antonio Tercero
Structure-specific endonucleases contribute to the maintenance of genome integrity by cleaving DNA intermediates that need to be resolved for faithful DNA repair, replication, or recombination. Despite advances in the understanding of their function and regulation, it is less clear how these proteins respond to genotoxic stress. Here, we show that the structure-specific endonuclease Mus81-Mms4/EME1 relocalizes to subnuclear foci following DNA damage and colocalizes with the endonucleases Rad1-Rad10 (XPF-ERCC1) and Slx1-Slx4. Recruitment takes place into a class of stress foci defined by Cmr1/WDR76, a protein involved in preserving genome stability, and depends on the E2-ubiquitin-conjugating enzyme Rad6 and the E3-ubiquitin ligase Bre1. Foci dynamics show that, in the presence of DNA intermediates that need resolution by Mus81-Mms4, Mus81 foci persist until this endonuclease is activated by Mms4 phosphorylation. Our data suggest that subnuclear relocalization is relevant for the function of Mus81-Mms4 and, probably, of the endonucleases that colocalize with it.
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Teaser
Saugar et al. find that, under conditions of DNA damage, the structure-specific endonuclease Mus81-Mms4/EME1 relocalizes to subnuclear foci, where it colocalizes with the endonucleases Rad1-Rad10 and Slx1-Slx4. Relocalization takes place to a class of stress-induced foci defined by the Cmr1 protein and correlates with the function of the endonuclease.http://ift.tt/2w3AXV3
The Phage Nucleus and Tubulin Spindle Are Conserved among Large Pseudomonas Phages
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Vorrapon Chaikeeratisak, Katrina Nguyen, MacKennon E. Egan, Marcella L. Erb, Anastasia Vavilina, Joe Pogliano
We recently demonstrated that the large Pseudomonas chlororaphis bacteriophage 201φ2-1 assembles a nucleus-like structure that encloses phage DNA and segregates proteins according to function, with DNA processing proteins inside and metabolic enzymes and ribosomes outside the nucleus. Here, we investigate the replication pathway of the Pseudomonas aeruginosa bacteriophages φKZ and φPA3. Bacteriophages φKZ and φPA3 encode a proteinaceous shell that assembles a nucleus-like structure that compartmentalizes proteins and DNA during viral infection. We show that the tubulin-like protein PhuZ encoded by each phage assembles a bipolar spindle that displays dynamic instability and positions the nucleus at midcell. Our results suggest that the phage spindle and nucleus play the same functional role in all three phages, 201φ2-1, φKZ, and φPA3, demonstrating that these key structures are conserved among large Pseudomonas phages.
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Teaser
The nucleus and spindle are defining features of eukaryotic cells that separate them from bacteria and archaea. Chaikeeratisak et al. show that a tubulin-based spindle and a nucleus-like structure are conserved among large Pseudomonas phages, providing insight into the evolution of these key cell biological structures.http://ift.tt/2w3svVu
NKX2-1 Is Required in the Embryonic Septum for Cholinergic System Development, Learning, and Memory
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Lorenza Magno, Caswell Barry, Christoph Schmidt-Hieber, Polyvios Theodotou, Michael Häusser, Nicoletta Kessaris
The transcription factor NKX2-1 is best known for its role in the specification of subsets of cortical, striatal, and pallidal neurons. We demonstrate through genetic fate mapping and intersectional focal septal deletion that NKX2-1 is selectively required in the embryonic septal neuroepithelium for the development of cholinergic septohippocampal projection neurons and large subsets of basal forebrain cholinergic neurons. In the absence of NKX2-1, these neurons fail to develop, causing alterations in hippocampal theta rhythms and severe deficiencies in learning and memory. Our results demonstrate that learning and memory are dependent on NKX2-1 function in the embryonic septum and suggest that cognitive deficiencies that are sometimes associated with pathogenic mutations in NKX2-1 in humans may be a direct consequence of loss of NKX2-1 function.
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Teaser
NKX2-1 is a highly conserved patterning gene in the developing forebrain, mutations in which can lead to a spectrum of disorders including cognitive deficiencies. Using genetic fate mapping and intersectional deletion, Magno et al. demonstrate a requirement for embryonic septal NKX2-1 in forebrain cholinergic system development and learning and memory.http://ift.tt/2w3Yvc6
OCT4 and SOX2 Work as Transcriptional Activators in Reprogramming Human Fibroblasts
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Santosh Narayan, Gene Bryant, Shivangi Shah, Georgina Berrozpe, Mark Ptashne
SOX2 and OCT4, in conjunction with KLF4 and cMYC, are sufficient to reprogram human fibroblasts to induced pluripotent stem cells (iPSCs), but it is unclear if they function as transcriptional activators or as repressors. We now show that, like OCT4, SOX2 functions as a transcriptional activator. We substituted SOX2-VP16 (a strong activator) for wild-type (WT) SOX2, and we saw an increase in the efficiency and rate of reprogramming, whereas the SOX2-HP1 fusion (a strong repressor) eliminated reprogramming. We report that, at an early stage of reprogramming, virtually all DNA-bound OCT4, SOX2, and SOX2-VP16 were embedded in putative enhancers, about half of which were created de novo. Those associated with SOX2-VP16 were, on average, stronger than those bearing WT SOX2. Many newly created putative enhancers were transient, and many transcription factor locations on DNA changed as reprogramming progressed. These results are consistent with the idea that, during reprogramming, there is an intermediate state that is distinct from both parental cells and iPSCs.
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Teaser
Narayan et al. show that substituting SOX2 with the strong activator SOX2-VP16 increases reprogramming efficiency of human fibroblasts, especially those cultured from older donors. Thousands of enhancers are created and destroyed in the course of reprogramming, including many enhancers created at binding sites of OCT4 or SOX2.http://ift.tt/2w3Brds
Chromatin and Transcriptional Analysis of Mesoderm Progenitor Cells Identifies HOPX as a Regulator of Primitive Hematopoiesis
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Nathan J. Palpant, Yuliang Wang, Brandon Hadland, Rebecca J. Zaunbrecher, Meredith Redd, Daniel Jones, Lil Pabon, Rajan Jain, Jonathan Epstein, Walter L. Ruzzo, Ying Zheng, Irwin Bernstein, Adam Margolin, Charles E. Murry
We analyzed chromatin dynamics and transcriptional activity of human embryonic stem cell (hESC)-derived cardiac progenitor cells (CPCs) and KDR+/CD34+ endothelial cells generated from different mesodermal origins. Using an unbiased algorithm to hierarchically rank genes modulated at the level of chromatin and transcription, we identified candidate regulators of mesodermal lineage determination. HOPX, a non-DNA-binding homeodomain protein, was identified as a candidate regulator of blood-forming endothelial cells. Using HOPX reporter and knockout hESCs, we show that HOPX regulates blood formation. Loss of HOPX does not impact endothelial fate specification but markedly reduces primitive hematopoiesis, acting at least in part through failure to suppress Wnt/β-catenin signaling. Thus, chromatin state analysis permits identification of regulators of mesodermal specification, including a conserved role for HOPX in governing primitive hematopoiesis.
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Teaser
Palpant et al. analyze gene expression and chromatin dynamics in cardiovascular progenitor cells derived from hPSCs to elucidate genes governing cell fate. HOPX is identified as a regulator of primitive hematopoiesis, providing insight into controlling cell lineages from pluripotency for disease modeling or therapeutic applications.http://ift.tt/2w2SJrk
Multipotent Basal Stem Cells, Maintained in Localized Proximal Niches, Support Directed Long-Ranging Epithelial Flows in Human Prostates
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Mohammad Moad, Edouard Hannezo, Simon J. Buczacki, Laura Wilson, Amira El-Sherif, David Sims, Robert Pickard, Nicholas A. Wright, Stuart C. Williamson, Doug M. Turnbull, Robert W. Taylor, Laura Greaves, Craig N. Robson, Benjamin D. Simons, Rakesh Heer
Sporadic mitochondrial DNA mutations serve as clonal marks providing access to the identity and lineage potential of stem cells within human tissues. By combining quantitative clonal mapping with 3D reconstruction of adult human prostates, we show that multipotent basal stem cells, confined to discrete niches in juxta-urethral ducts, generate bipotent basal progenitors in directed epithelial migration streams. Basal progenitors are then dispersed throughout the entire glandular network, dividing and differentiating to replenish the loss of apoptotic luminal cells. Rare lineage-restricted luminal stem cells, and their progeny, are confined to proximal ducts and provide only minor contribution to epithelial homeostasis. In situ cell capture from clonal maps identified delta homolog 1 (DLK1) enrichment of basal stem cells, which was validated in functional spheroid assays. This study establishes significant insights into niche organization and function of prostate stem and progenitor cells, with implications for disease.
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Teaser
Moad et al. find that multipotent prostate basal stem cells, marked by delta homolog 1 (DLK1), reside in proximal ducts and generate directed large-scale epithelial flows traversing the entire length of the branching gland network. This work describes mechanisms underlying 3D epithelial homeostasis in a complex branching tissue.http://ift.tt/2w3vrBD
An Integrated Systems Biology Approach Identifies TRIM25 as a Key Determinant of Breast Cancer Metastasis
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Logan A. Walsh, Mariano J. Alvarez, Erich Y. Sabio, Marsha Reyngold, Vladimir Makarov, Suranjit Mukherjee, Ken-Wing Lee, Alexis Desrichard, Şevin Turcan, Martin G. Dalin, Vinagolu K. Rajasekhar, Shuibing Chen, Linda T. Vahdat, Andrea Califano, Timothy A. Chan
At the root of most fatal malignancies are aberrantly activated transcriptional networks that drive metastatic dissemination. Although individual metastasis-associated genes have been described, the complex regulatory networks presiding over the initiation and maintenance of metastatic tumors are still poorly understood. There is untapped value in identifying therapeutic targets that broadly govern coordinated transcriptional modules dictating metastatic progression. Here, we reverse engineered and interrogated a breast cancer-specific transcriptional interaction network (interactome) to define transcriptional control structures causally responsible for regulating genetic programs underlying breast cancer metastasis in individual patients. Our analyses confirmed established pro-metastatic transcription factors, and they uncovered TRIM25 as a key regulator of metastasis-related transcriptional programs. Further, in vivo analyses established TRIM25 as a potent regulator of metastatic disease and poor survival outcome. Our findings suggest that identifying and targeting keystone proteins, like TRIM25, can effectively collapse transcriptional hierarchies necessary for metastasis formation, thus representing an innovative cancer intervention strategy.
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Teaser
Aberrantly activated transcriptional networks drive metastatic dissemination. Walsh et al. reverse engineer a breast cancer-specific regulatory network, uncovering a transcriptional hierarchy underlying breast cancer metastasis. Findings suggest that collapsing transcriptional hierarchies by targeting keystone proteins, such as TRIM25, is critical to affect the coordinated transcriptomic reprogramming required for metastasis.http://ift.tt/2vKKOMK
CD44 Interacts with HIF-2α to Modulate the Hypoxic Phenotype of Perinecrotic and Perivascular Glioma Cells
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Elinn Johansson, Elisa S. Grassi, Vasiliki Pantazopoulou, Bei Tong, David Lindgren, Tracy J. Berg, Elin J. Pietras, Håkan Axelson, Alexander Pietras
Hypoxia-inducible factors enhance glioma stemness, and glioma stem cells have an amplified hypoxic response despite residing within a perivascular niche. Still, little is known about differential HIF regulation in stem versus bulk glioma cells. We show that the intracellular domain of stem cell marker CD44 (CD44ICD) is released at hypoxia, binds HIF-2α (but not HIF-1α), enhances HIF target gene activation, and is required for hypoxia-induced stemness in glioma. In a glioma mouse model, CD44 was restricted to hypoxic and perivascular tumor regions, and in human glioma, a hypoxia signature correlated with CD44. The CD44ICD was sufficient to induce hypoxic signaling at perivascular oxygen tensions, and blocking CD44 cleavage decreased HIF-2α stabilization in CD44-expressing cells. Our data indicate that the stem cell marker CD44 modulates the hypoxic response of glioma cells and that the pseudo-hypoxic phenotype of stem-like glioma cells is achieved by stabilization of HIF-2α through interaction with CD44, independently of oxygen.
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Teaser
Hypoxia-inducible factors (HIFs) maintain glioma stemness, and stem-like glioma cells have an amplified hypoxic response compared to bulk tumor cells. Johansson et al. show that the glioma stem cell marker CD44 is activated under hypoxia and interacts with HIF-2α to enhance the hypoxic and pseudo-hypoxic phenotype of glioma stem cells.http://ift.tt/2vKaits
Pharmacologic or Genetic Targeting of Glutamine Synthetase Skews Macrophages toward an M1-like Phenotype and Inhibits Tumor Metastasis
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Erika M. Palmieri, Alessio Menga, Rosa Martín-Pérez, Annamaria Quinto, Carla Riera-Domingo, Giacoma De Tullio, Douglas C. Hooper, Wouter H. Lamers, Bart Ghesquière, Daniel W. McVicar, Attilio Guarini, Massimiliano Mazzone, Alessandra Castegna
Glutamine-synthetase (GS), the glutamine-synthesizing enzyme from glutamate, controls important events, including the release of inflammatory mediators, mammalian target of rapamycin (mTOR) activation, and autophagy. However, its role in macrophages remains elusive. We report that pharmacologic inhibition of GS skews M2-polarized macrophages toward the M1-like phenotype, characterized by reduced intracellular glutamine and increased succinate with enhanced glucose flux through glycolysis, which could be partly related to HIF1α activation. As a result of these metabolic changes and HIF1α accumulation, GS-inhibited macrophages display an increased capacity to induce T cell recruitment, reduced T cell suppressive potential, and an impaired ability to foster endothelial cell branching or cancer cell motility. Genetic deletion of macrophagic GS in tumor-bearing mice promotes tumor vessel pruning, vascular normalization, accumulation of cytotoxic T cells, and metastasis inhibition. These data identify GS activity as mediator of the proangiogenic, immunosuppressive, and pro-metastatic function of M2-like macrophages and highlight the possibility of targeting this enzyme in the treatment of cancer metastasis.
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Teaser
Palmieri et al. show that inhibiting glutamine synthetase activity in M2 macrophages skews their polarization toward an HIF1α-mediated M1 state, which impairs cytotoxic T cell recruitment and angiogenesis. As a consequence of a more pronounced immunostimulatory and antiangiogenic effect, GS ablation in macrophages translates into prevention of metastasis.http://ift.tt/2vKhmGy
Therapeutic Antibodies to Ganglioside GD2 Evolved from Highly Selective Germline Antibodies
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Eric Sterner, Megan L. Peach, Marc C. Nicklaus, Jeffrey C. Gildersleeve
Antibodies play a crucial role in host defense and are indispensable research tools, diagnostics, and therapeutics. Antibody generation involves binding of genomically encoded germline antibodies followed by somatic hypermutation and in vivo selection to obtain antibodies with high affinity and selectivity. Understanding this process is critical for developing monoclonal antibodies, designing effective vaccines, and understanding autoantibody formation. Prior studies have found that antibodies to haptens, peptides, and proteins evolve from polyspecific germline antibodies. The immunological evolution of antibodies to mammalian glycans has not been studied. Using glycan microarrays, protein microarrays, cell binding studies, and molecular modeling, we demonstrate that therapeutic antibodies to the tumor-associated ganglioside GD2 evolved from highly specific germline precursors. The results have important implications for developing vaccines and monoclonal antibodies that target carbohydrate antigens. In addition, they demonstrate an alternative pathway for antibody evolution within the immune system that is distinct from the polyspecific germline pathway.
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Sterner et al. demonstrate that germline antibodies to the mammalian glycan GD2 have unexpectedly high selectivity. No cross-reactivity was observed on a glycan microarray with 500 components or a human proteome array with 19,000 proteins. Molecular dynamics reveal pre-organized and relatively rigid binding pockets for the germline antibodies.http://ift.tt/2vKKNsa
The Tumor Suppressor p53 Limits Ferroptosis by Blocking DPP4 Activity
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Yangchun Xie, Shan Zhu, Xinxin Song, Xiaofang Sun, Yong Fan, Jinbao Liu, Meizuo Zhong, Hua Yuan, Lin Zhang, Timothy R. Billiar, Michael T. Lotze, Herbert J. Zeh, Rui Kang, Guido Kroemer, Daolin Tang
Ferroptosis is a form of regulated cell death that may facilitate the selective elimination of tumor cells. The tumor suppressor p53 (TP53) has been demonstrated to promote ferroptosis via a transcription-dependent mechanism. Here, we show that TP53 limits erastin-induced ferroptosis by blocking dipeptidyl-peptidase-4 (DPP4) activity in a transcription-independent manner. Loss of TP53 prevents nuclear accumulation of DPP4 and thus facilitates plasma-membrane-associated DPP4-dependent lipid peroxidation, which finally results in ferroptosis. These findings reveal a direct molecular link between TP53 and DPP4 in the control of lipid metabolism and may provide a precision medicine strategy for the treatment of colorectal cancer by induction of ferroptosis.
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Xie et al. find that TP53 antagonizes ferroptosis in colorectal cancer (CRC) cells by favoring the localization of DPP4 toward a nuclear, enzymatically inactive pool. This pathway is different from the previously identified function of TP53 as a positive regulator of ferroptosis in non-CRC cells.http://ift.tt/2vKn636
Antibiotics Disrupt Coordination between Transcriptional and Phenotypic Stress Responses in Pathogenic Bacteria
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Paul A. Jensen, Zeyu Zhu, Tim van Opijnen
Bacterial genes that change in expression upon environmental disturbance have commonly been seen as those that must also phenotypically matter. However, several studies suggest that differentially expressed genes are rarely phenotypically important. We demonstrate, for Gram-positive and Gram-negative bacteria, that these seemingly uncoordinated gene sets are involved in responses that can be linked through topological network analysis. However, the level of coordination is stress dependent. While a well-coordinated response is triggered in response to nutrient stress, antibiotics trigger an uncoordinated response in which transcriptionally and phenotypically important genes are neither linked spatially nor in their magnitude. Moreover, a gene expression meta-analysis reveals that genes with large fitness changes during stress have low transcriptional variation across hundreds of other conditions, and vice versa. Our work suggests that cellular responses can be understood through network models that incorporate regulatory and genetic relationships, which could aid drug target predictions and genetic network engineering.
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Jensen et al. interrogate stress responses in bacteria using genome-wide techniques and metabolic modeling. The authors find that phenotypic and transcriptional stress networks are distinct. Moreover, nutrient and antibiotic stresses respectively lead to coordinated and uncoordinated responses. Network models are thus key to understanding cellular responses, thereby aiding in predicting bacterial behavior.http://ift.tt/2vKDz7C
Uncoupling the Mitogenic and Metabolic Functions of FGF1 by Tuning FGF1-FGF Receptor Dimer Stability
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Zhifeng Huang, Yi Tan, Junlian Gu, Yang Liu, Lintao Song, Jianlou Niu, Longwei Zhao, Lakshmi Srinivasan, Qian Lin, Jingjing Deng, Yang Li, Daniel J. Conklin, Thomas A. Neubert, Lu Cai, Xiaokun Li, Moosa Mohammadi
The recent discovery of metabolic roles for fibroblast growth factor 1 (FGF1) in glucose homeostasis has expanded the functions of this classically known mitogen. To dissect the molecular basis for this functional pleiotropy, we engineered an FGF1 partial agonist carrying triple mutations (FGF1ΔHBS) that diminished its ability to induce heparan sulfate (HS)-assisted FGF receptor (FGFR) dimerization and activation. FGF1ΔHBS exhibited a severely reduced proliferative potential, while preserving the full metabolic activity of wild-type FGF1 in vitro and in vivo. Hence, suboptimal FGFR activation by a weak FGF1-FGFR dimer is sufficient to evoke a metabolic response, whereas full FGFR activation by stable and sustained dimerization is required to elicit a mitogenic response. In addition to providing a physical basis for the diverse activities of FGF1, our findings will impact ongoing drug discoveries targeting FGF1 and related FGFs for the treatment of a variety of human diseases.
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Huang et al. report that quantitative differences in FGF-FGFR dimer stability give rise to different thresholds of intracellular signals to determine mitogenic versus metabolic activities of FGFs.http://ift.tt/2vKn37q
Circadian and Feeding Rhythms Orchestrate the Diurnal Liver Acetylome
Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Daniel Mauvoisin, Florian Atger, Loïc Dayon, Antonio Núñez Galindo, Jingkui Wang, Eva Martin, Laetitia Da Silva, Ivan Montoliu, Sebastiano Collino, Francois-Pierre Martin, Joanna Ratajczak, Carles Cantó, Martin Kussmann, Felix Naef, Frédéric Gachon
Lysine acetylation is involved in various biological processes and is considered a key reversible post-translational modification in the regulation of gene expression, enzyme activity, and subcellular localization. This post-translational modification is therefore highly relevant in the context of circadian biology, but its characterization on the proteome-wide scale and its circadian clock dependence are still poorly described. Here, we provide a comprehensive and rhythmic acetylome map of the mouse liver. Rhythmic acetylated proteins showed subcellular localization-specific phases that correlated with the related metabolites in the regulated pathways. Mitochondrial proteins were over-represented among the rhythmically acetylated proteins and were highly correlated with SIRT3-dependent deacetylation. SIRT3 activity being nicotinamide adenine dinucleotide (NAD)+ level-dependent, we show that NAD+ is orchestrated by both feeding rhythms and the circadian clock through the NAD+ salvage pathway but also via the nicotinamide riboside pathway. Hence, the diurnal acetylome relies on a functional circadian clock and affects important diurnal metabolic pathways in the mouse liver.
Graphical abstract
Teaser
Mauvoisin et al. provide a rhythmic acetylome map of the mouse liver. Rhythmic acetylated proteins showed subcellular localization-specific phases with an over-representation of SIRT3 targets. Feeding rhythms and the circadian clock regulate NAD+ synthesis through the salvage and nicotinamide riboside pathways, affecting metabolite accumulation.http://ift.tt/2vJTHWV
Are facial injuries really different? An observational cohort study comparing appearance concern and psychological distress in facial trauma and non-facial trauma patients
Facial injuries are widely assumed to lead to stigma and significant psychosocial burden. Experimental studies of face perception support this idea, but there is very little empirical evidence to guide treatment. This study sought to address the gap.Data were collected from 193 patients admitted to hospital following facial or other trauma. Ninety (90) participants were successfully followed up eight months later. Participants completed measures of appearance concern and psychological distress (post-traumatic stress symptoms, depressive symptoms, anxiety symptoms).
http://ift.tt/2w3u7P0
Patient Rated Long-Term Results after Complete Denervation of the Wrist
The aim of this study was to examine the long-term results after the denervation of the wrist. Between 1977 and 2001 we treated 375 patients in our clinic. The mean age was 43.5 years, 81% were male and 19% female. The long-term results were assessed by a questionnaire assessing pain on a visual analogue scale and patient satisfaction and by the DASH questionnaire. After a mean follow-up of 12.23 years, we found an overall pain reduction of 52.1%. In 67.7% of the patients we found a relief of pain; of these patients, 44% are free of pain until today, and 56% were temporarily asymptomatic.
http://ift.tt/2vJYtnq
Subungual Melanoma – Management in the Modern Era
Subungual melanoma is a rare subtype of cutaneous melanoma that arises from the structures of the nail apparatus. It presents most commonly in older patients and at an advanced stage.A retrospective review of all patients with subungual melanoma in a single institution over a 15-year period was performed. 54 patients were included (26 males, average age 62.9 years). 28 cases involved the upper limb. Median tumour thickness was 4.5mm. 18 patients had lymph node metastasis at diagnosis, including 11 of 36 patients with positive sentinel lymph node biopsy.
http://ift.tt/2w3BW7l
Reconstructive microsurgical approach for treatment of pyoderma gangrenosum
Pyoderma gangrenosum (PG) is a rare type of autoimmune disease that results in progressive ulcers with or without previous trauma. PG is not well understood to date, and its treatment therefore remains a challenge. Because of the disease's systemic characteristic and the unpredictability of the clinical course, no gold standard treatment is available, especially concerning surgical procedures to treat pyodermic lesions. Often, PG is not recognized during routine clinical practice, and standard ulcer treatment (conservative wound care, debridement, skin grafting, and local flap coverage) is started; this induces an autoinflammatory response, resulting in disastrous ulcers, thereby making free flap coverage necessary.
http://ift.tt/2vKxIPG
Putting the heart into microvascular training: The Micropump, a practical “heart-like” device to enhance vascular anastomosis non-living simulation
Non-living simulation models are effective training platforms in learning to achieve a structurally patent microvascular anastomosis. However, a gap still exists between non-living and living models in providing physiological feedback. We have an ethical obligation to optimise non-living resources, to minimise the use of living animals in microsurgical training.
http://ift.tt/2w3wgu9
Anatomic and high resolution computed tomographic angiography study of the lateral femoral condyle flap: implications for surgical dissection
The Lateral femoral condyle (LFC) flap is a vascularized bone flap based on the superior lateral genicular artery (SLGA). Harvest technique for this flap has not yet been demonstrated. The purpose of this study was to better delineate the blood supply to the bone and skin to allow for a safe and effective harvest.
http://ift.tt/2vKDSPQ
Does videoendoscopy provide three-dimensional vision in closed rhinoplasty?
Rhinoplasty is a common procedure in cosmetic surgery all over the world. Patients desire enhancement of their facial beauty by the correction of preexisting nasal deformities. Precisely performed operations lead to better results, and, enhancing technical accuracy accordingly results in more successful outcomes.Endoscopy helps us to visualize the closed parts of the body with the aid of an illuminated optical device. The objective behind present case series was bringing the advantages of open and closed rhinoplasty together by using endoscopic vision systems.
http://ift.tt/2w3a2bR
An implant for autologous soft tissue reconstruction based on an adipose-derived stem cell colonized alginate scaffold
Adipose-derived stem cells represent an interesting option for soft tissue replacement since they are easy to procure and can generate their own blood supply through the production of angiogenic factors. We seeded adipose-derived stem cells on a bioresorbable, biocompatible polymer alginate scaffold to generate autologous soft tissue constructs for repair.
http://ift.tt/2vK4LTJ
Analysis of the Correlation between Deformational Plagiocephaly and Neurodevelopment delay
Deformational plagiocephaly (DP) refers to cranial asymmetry resulting from uneven external forces. A strong association exists between DP and developmental delay. We investigated the effect of DP severity on developmental delay.
http://ift.tt/2w3ofp7
Does self-consciousness of appearance influence postoperative satisfaction in rhinoplasty?
Facial plastic surgeons and patients benefit from knowledge about how psychological aspects can influence the outcome of cosmetic surgery. The influence of pre-operative self-consciousness of appearance and its effect on benefit after surgery in rhinoplasty patients has not been explored before in other studies.
http://ift.tt/2vK4T5F
Starting a sentinel node service for melanoma: is there a role for predictive nomograms?
A letter to author regarding predictive nomograms for sentinel node status in melanoma.
http://ift.tt/2w2wv92
Antibiotic Prophylaxis in Breast Reduction Surgery: A Systematic Review and Meta-analysis
To determine the effectiveness and harm of using antibiotic prophylaxis versus placebo or no intervention in patients undergoing breast reduction surgery to prevent surgical site infection.
http://ift.tt/2vJDQrj
Editorial Board
Publication date: 23 August 2017
Source:Journal of Proteomics, Volume 166
http://ift.tt/2fMPcqB
Applications of Resting State Functional MR Imaging to Neuropsychiatric Diseases
Source:Neuroimaging Clinics of North America
Author(s): Godfrey David Pearlson
Teaser
Resting state studies in neuropsychiatric disorders have already provided much useful information, but the field is regarded as being at a relatively preliminary stage and subject to several design issues that set limits on the overall utility.http://ift.tt/2wgJuDs
Validation of the Choking Risk Assessment and Pneumonia Risk Assessment for adults with Intellectual and Developmental Disability (IDD)
Source:Research in Developmental Disabilities, Volume 69
Author(s): Justine Joan Sheppard, Georgia A. Malandraki, Paula Pifer, Jill Cuff, Michelle Troche, Bronwyn Hemsley, Susan Balandin, Avinash Mishra, Roberta Hochman
BackgroundRisk assessments are needed to identify adults with intellectual and developmental disability (IDD) at high risk of choking and pneumonia.AimTo describe the development and validation of the Choking Risk Assessment (CRA) and the Pneumonia Risk Assessment (PRA) for adults with IDD.MethodsTest items were identified through literature review and focus groups. Five-year retrospective chart reviews identified a positive choking group (PCG), a negative choking group (NCG), a positive pneumonia group (PPG), and a negative pneumonia group (NPG). Participants were tested with the CRA and PRA by clinicians blind to these testing conditions.ResultsThe CRA and PRA differentiated the PCG (n=93) from the NCG (n=526) and the PPG (n=63) from the NPG (n=209) with high specificity (0.91 and 0.92 respectively) and moderate to average sensitivity (0.53 and 0.62 respectively). Further analyses revealed associations between clinical diagnoses of dysphagia and choking (p=0.043), and pneumonia (p<0.001).ConclusionsThe CRA and PRA are reliable, valid risk indicators for choking and pneumonia in adults with IDD. Precautions for mitigating choking and pneumonia risks can be applied selectively thus avoiding undue impacts on quality of life and unnecessary interventions for low risk individuals.
http://ift.tt/2w371Io
Anodization of Magnesium for Biomedical Applications – Processing, Characterization, Degradation and Cytocompatibility
Publication date: Available online 14 August 2017
Source:Acta Biomaterialia
Author(s): Aaron F. Cipriano, Jiajia Lin, Christopher Miller, Alan Lin, Mayra C. Cortez Alcaraz, Pedro Soria, Huinan Liu
This article reports anodization of Mg in KOH electrolyte and the associated surface, degradation, and biological properties for bioresorbable implant applications. The preparation procedures for electrodes and anodization setup significantly enhanced reproducibility of samples. The results of anodization performed at the applied potentials of 1.8, 1.9, or 2.0 V showed that the sample anodized at 1.9 V and annealed, referred to as the 1.9 AA sample, had homogenous surface microstructure and elemental composition, and a reduction in corrosion current density in the electrochemical testing. In comparison with Mg control, the 1.9 AA sample showed a distinct mode of degradation, e.g., continuous growth of a passivation layer enriched with Ca and P instead of typical localized pitting and undermining, and a greater release rate of Mg2+ ions when immersed in physiologically relevant media. In the direct culture with bone marrow derived mesenchymal stem cells (BMSCs) in vitro, the 1.9 AA sample did not affect BMSC adhesion and morphology under indirect contact; however, the 1.9 AA sample showed a reduction in cell spreading under direct contact. The change in surface topography/composition at the dynamic interface of the anodized-annealed Mg sample might have contributed to the change in BMSC morphology. In summary, this study demonstrated the potential of anodic oxidation to modulate the degradation behaviors of Mg-based biomaterials and BMSC responses in vitro, and confirmed the value of direct culture method for studying cytocompatibility of Mg-based biomaterials for medical implant applications.Statement of SignificanceMagnesium (Mg)-based biomaterials have been specifically designed and actively explored for biodegradable implant applications since the early 2000s. To realize the benefits of Mg-based materials for medical implant applications, it is critical to control the rate of Mg degradation (i.e. corrosion) in the body. We investigated an environmentally friendly anodization process using KOH electrolytes for modifying the surface of Mg-based materials, and the resulted surface, degradation, and biological properties for biomedical applications. This study reported critical considerations that are important for repeatability of anodization process, homogeneity of surface microstructure and composition, and in vitro evaluations of the degradation and biological properties of surface treated Mg samples. The details in preparation of electrodes, anodization setup, annealing, and sample handling before and after surface treatment (e.g. re-embedding) reported in this article are valuable for studying a variety of electrochemical processes for surface treatment of Mg-based metals, with enhanced reproducibility.
Graphical abstract
http://ift.tt/2uJUOsx
A pH-sensitive methenamine mandelate-loaded nanoparticle induces DNA damage and apoptosis of cancer cells
Publication date: Available online 16 August 2017
Source:Acta Biomaterialia
Author(s): Linhua Zhang, Wenbo Hao, Lv Xu, Yongfeng Gao, Xusheng Wang, Dunwan Zhu, Zhuo Chen, Xudong Zhang, Hongbo Chen, Lin Mei
Methenamine mandelate is a urinary antibacterial agent, which can be converted to formaldehyde in urine that has a relatively low pH of average 5.5-6.8. Here, we prepare a pH-sensitive PLGA-based nanoparticle containing both methenamine mandelate and NaHCO3. Methenamine mandelate/NaHCO3-coloaded nanoparticle could enter cells via endosome/lysosome pathway. The pH in lysosomes and endo-lysosomes is approximately 5.0. In the acidic environment, NaHCO3 reacts with proton and produce CO2 bubbles, which burst nanoparticles and lead to the rapidly release of methenamine mandelate. Meanwhile, methenamine mandelate was then quickly converted to a sufficient amount of formaldehyde in this acidic environment, which induced DNA damage and DNA damage response (DDR). Consequently, methenamine mandelate/NaHCO3-coloaded nanoparticles caused cell cycle arrest, cell growth inhibition and apoptosis of cancer cells. Moreover, methenamine mandelate/NaHCO3-coloaded nanoparticles also show intensive inhibitory effect on the growth of MCF-7 xenograft tumor in vivo. Therefore, methenamine mandelate/NaHCO3-coloaded nanoparticle is a promising type of formulation for the treatment of cancer, which could give the "old drug" methenamine mandelate a new anti-cancer function in clinical.Statement of SignificanceMethenamine mandelate is a urinary antibacterial agent, which can be converted to formaldehyde in urine that has a relatively low pH of average 5.5-6.8. Here, we prepare a pH-sensitive PLGA-based nanoparticle containing both methenamine mandelate and NaHCO3. Methenamine mandelate/NaHCO3-coloaded nanoparticle could enter cells via endosome/lysosome pathway. The pH in lysosomes and endo-lysosomes is approximately 5.0. In the acidic environment, NaHCO3 reacts with proton and produce CO2 bubbles, which burst nanoparticles and lead to the rapidly release of methenamine mandelate. Meanwhile, methenamine mandelate was then quickly converted to a sufficient amount of formaldehyde in this acidic environment, which induced DNA damage and DNA damage response (DDR). Methenamine mandelate/NaHCO3-coloaded nanoparticle is a promising type formulation for the treatment of cancer, which could give the "old drug" methenamine mandelate a new anti-cancer function in clinical.
Graphical abstract
http://ift.tt/2uKpfi6
Sol gel-derived hydroxyapatite films over porous calcium polyphosphate substrates for improved tissue engineering of osteochondral-like constructs
Publication date: Available online 14 August 2017
Source:Acta Biomaterialia
Author(s): Whitaik David Lee, Rahul Gawri, Robert M. Pilliar, William L. Stanford, Rita A. Kandel
Integration of in vitro-formed cartilage on a suitable substrate to form tissue-engineered implants for osteochondral defect repair is a considerable challenge. In healthy cartilage, a zone of calcified cartilage (ZCC) act as an intermediary for mechanical force transfer from soft to hard tissue, as well as an effective interlocking structure to better resist interfacial shear forces. We have developed biphasic constructs that consist of scaffold-free cartilage tissue grown in vitro on, and interdigitated with, porous calcium polyphosphate (CPP) substrates. However, as CPP degrades, it releases inorganic polyphosphates (polyP) that can inhibit local mineralization, thereby preventing the formation of a ZCC at the interface. Thus, we hypothesize that coating CPP substrate with a layer of hydroxyapatite (HA) might prevent or limit this polyP release. To investigate this we tested both inorganic or organic sol-gel processing methods, as a barrier coating on CPP substrate to inhibit polyP release. Both types of coating supported the formation of ZCC in direct contact with the substrate, however the ZCC appeared more continuous in the tissue formed on the organic HA sol gel coated CPP. Tissues formed on coated substrates accumulated comparable quantities of extracellular matrix and mineral, but tissues formed on organic sol-gel (OSG)-coated substrates accumulated less polyP than tissues formed on inorganic sol-gel (ISG)-coated substrates. Constructs formed with OSG-coated CPP substrates had greater interfacial shear strength than those formed with ISG-coated and non-coated substrates. These results suggest that the OSG coating method can modify the location and distribution of ZCC and can be used to improve the mechanical integrity of tissue-engineered constructs formed on porous CPP substrates.Statement of SignificanceArticular cartilage interfaces with bone through a zone of calcified cartilage. This study describes a method to generate an "osteochondral-like" implant that mimics this organization using isolated deep zone cartilage cells and a sol-gel hydroxyl appetite coated bone substitute material composed of calcium polyphosphate (CPP). Developing a layer of calcified cartilage at the interface should contribute to enhancing the success of this "osteochondral-like" construct following implantation to repair cartilage defects.
Graphical abstract
http://ift.tt/2i75E5R
Atypical presentation of anti-N-methyl-D-aspartate receptor encephalitis: two case reports
Anti-N-methyl-D-aspartate receptor encephalitis is a rare autoimmune disease characterized by severe neurological and psychiatric symptoms and a difficult diagnosis.
http://ift.tt/2v35Tji
Highly absorbing multispectral near-infrared polymer nanoparticles from one conjugated backbone for photoacoustic imaging and photothermal therapy
Publication date: November 2017
Source:Biomaterials, Volume 144
Author(s): Haobin Chen, Jian Zhang, Kaiwen Chang, Xiaoju Men, Xiaofeng Fang, Libo Zhou, Dongliang Li, Duyang Gao, Shengyan Yin, Xuanjun Zhang, Zhen Yuan, Changfeng Wu
Semiconducting polymers with specific absorption are useful in various applications, including organic optoelectronics, optical imaging, and nanomedicine. However, the optical absorption of a semiconducting polymer with a determined structure is hardly tunable when compared with that of inorganic semiconductors. In this work, we show that the optical absorption of polymer nanoparticles from one conjugated backbone can be effectively tuned through judicious design of the particle morphology and the persistence length of polymers. Highly absorbing near-infrared (NIR) polymers based on diketopyrrolopyrrole-dithiophene (DPP-DT) are synthesized to have different molecular weights (MWs). The DPP-DT polymer with a large molecular weight and high persistence length exhibited remarkably high optical absorption with a peak mass extinction coefficient of 81.7 L g−1 cm−1, which is one of the highest value among various photothermal agents reported to date. Particularly, the polymer nanoparticles with different sizes exhibit broadly tunable NIR absorption peaks from 630 to 811 nm. The PEGylated small polymer dots (Pdots) show good NIR light-harvesting efficiency and high non-radiative decay rates, resulting in a relatively high photothermal conversion efficiency in excess of 50%. Thus, this Pdot-based platform can serve as promising photothermal agents and photoacoustic probes for cancer theranostics.
Graphical abstract
http://ift.tt/2uR7r0O
Traceable PEO-poly(ester) micelles for breast cancer targeting: The effect of core structure and targeting peptide on micellar tumor accumulation
Publication date: November 2017
Source:Biomaterials, Volume 144
Author(s): Shyam M. Garg, Igor M. Paiva, Mohammad R. Vakili, Rania Soudy, Kate Agopsowicz, Amir H. Soleimani, Mary Hitt, Kamaljit Kaur, Afsaneh Lavasanifar
Traceable poly(ethylene oxide)-poly(ester) micelles were developed through chemical conjugation of a near-infrared (NIR) dye to the poly(ester) end by click chemistry. This strategy was tried for micelles with poly(ε-caprolactone) (PCL) or poly(α-benzyl carboxylate-ε-caprolactone) (PBCL) cores. The surface of both micelles was also modified with the breast cancer targeting peptide, P18-4. The results showed the positive contribution of PBCL over PCL core on micellar thermodynamic and kinetic stability as well as accumulation in primary orthotopic MDA-MB-231 tumors within 4–96 h following intravenous administration in mice. This was in contrast to in vitro studies where better uptake of PEO-PCL versus PEO-PBCL micelles by MDA-MB-231 cells was observed. The presence of P18-4 enhanced the in vitro cell uptake and homing of both polymeric micelles in breast tumors, but only at early time points. In conclusion, the use of developed NIR labeling technique provided means for following the fate of PEO-poly(ester) based nano-carriers in live animals. Our results showed micellar stabilization through the use of PBCL over PCL cores, to have a more significant effect in enhancing the level and duration of nano-carrier accumulation in primary breast tumors than the modification of polymeric micellar surface with breast tumor targeting peptide, P18-4.
Graphical abstract
http://ift.tt/2uQRis7
Wilms tumor screening in diffuse capillary malformation with overgrowth and macrocephaly–capillary malformation: A retrospective study
CLOVES (congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and skeletal anomalies) syndrome is associated with regional bony and/or soft tissue overgrowth, capillary malformation, and an increased risk for Wilms tumor.
http://ift.tt/2wbBZ1s
Chondrosarcoma of the Epiglottis: A Case Report and Literature Review
Laryngeal chondrosarcoma (LCS) is an exceedingly rare malignancy and least frequently reported in the epiglottis.
http://ift.tt/2vKiSbQ
Medications and Adverse Voice Effects
To identify the medications used by patients with dysphonia, describe the voice symptoms reported on initial speech-language pathology (SLP) examination, evaluate the possible direct and indirect effects of medications on voice production, and determine the association between direct and indirect adverse voice effects and self-reported voice symptoms, hydration and smoking habits, comorbidities, vocal assessment, and type and degree of dysphonia.
http://ift.tt/2w2EYIZ
Atypical presentation of anti-N-methyl-D-aspartate receptor encephalitis: two case reports
Anti-N-methyl-D-aspartate receptor encephalitis is a rare autoimmune disease characterized by severe neurological and psychiatric symptoms and a difficult diagnosis.
http://ift.tt/2v35Tji
Facilitation and Debriefing in Simulation Education
Successful simulation requires effective facilitation and debriefing to achieve educational goals. Simulation educational methods are diverse, ranging from partial task training to complicated, interdisciplinary team training. Various debriefing models have emerged based on method of instruction, learner experience, time and equipment capability, and physical facilities. The general structure of most debriefing sessions focuses on participant reactions, followed by analysis, and ending with a discussion of lessons learned. Two leading debriefing models, the Structured and Supported Debriefing Model and the Debriefing with Good Judgment Model, are described in further detail.
http://ift.tt/2fLxHqN
Otologic Skills Training
This article presents a summary of the current simulation training for otologic skills. There is a wide variety of educational approaches, assessment tools, and simulators in use, including simple low-cost task trainers to complex computer-based virtual reality systems. A systematic approach to otologic skills training using adult learning theory concepts, such as repeated and distributed practice, self-directed learning, and mastery learning, is necessary for these educational interventions to be effective. Future directions include development of measures of performance to assess efficacy of simulation training interventions and, for complex procedures, improvement in fidelity based on educational goals.
http://ift.tt/2i7BlM7
Improving Rhinology Skills with Simulation
The convergence of technology and medicine has led to many advances in surgical training. Novel surgical simulators have led to significantly improved skills of graduating surgeons, leading to decreased time to proficiency, improved efficiency, decreased errors, and improvement in patient safety. Endoscopic sinus surgery poses a steep learning curve given the complex 3-dimensional anatomy of the nasal and paranasal cavities, and the necessary visual-spatial motor skills and bimanual dexterity. This article focuses on surgical simulation in rhinological training and how innovative high-fidelity and low-fidelity simulators can maximize resident training and improve procedural skills before operating in the live environment.
http://ift.tt/2fLGrNA
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