Παρασκευή 6 Οκτωβρίου 2017
Escaping BRAF inhibition: a “linc” with non-coding RNAs?
One of the major challenges in the field remains the defeat of resistance towards BRAF inhibition, mainly caused by the high heterogeneity and plasticity of melanoma cells. Understanding mechanisms of drug resistance and finding new strategies to block the relapse are therefore major concerns in the melanoma field. So far however, most of the focus remained on the identification of genetic events affecting proteins-coding genes.
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Poor early response to methotrexate portends inadequate long-term outcomes in patients with moderate-to-severe psoriasis: Evidence from 2 phase 3 clinical trials
Most methotrexate-treated psoriasis patients do not achieve a long-term PASI75 (75% reduction from baseline Psoriasis Area and Severity Index score) response. Indications of nonresponse can be apparent after only 4 weeks of treatment.
Promoting sunscreen use and sun-protective practices in NCAA athletes: Impact of SUNSPORT educational intervention for student-athletes, athletic trainers, and coaches
Student-athletes (SAs) have an increased skin cancer risk on account of significant ultraviolet exposure; however, their sun-protective practices are suboptimal. A novel program, Stanford University Network for Sun Protection, Outreach, Research, and Teamwork (SUNSPORT), was designed to target SAs, coaches, and athletic trainers (ATs).
Epidemiology of Hyperhidrosis in Two Population-Based Healthcare Databases
Hyperhidrosis has a range of reported prevalence estimates with the most often cited equal to 2.8%.We describe methods using a combination of diagnosis, symptom, and prescription codes from healthcare databases to ascertain hyperhidrosis cases.This study estimates population prevalences of 1% - 1.6% for patients seeking healthcare for hyperhidrosis.
Adalimumab for nail psoriasis: Efficacy and safety from the first 26 weeks of a phase 3, randomized, placebo-controlled trial
Previous clinical trials have not evaluated improvement in nail psoriasis as a primary end point.
Refractory or relapsed aggressive B-cell lymphoma failing (R)-CHOP: An analysis of patients treated on the RICOVER-60 trial
Abstract
Background
The prognosis of elderly patients with aggressive B-NHL after first lymphoma-related treatment failure (TF-L) is not well described. Methods
We analysed patient characteristics including presence of MYC rearrangements and MYC-expression (IHC) at diagnosis and modalities of salvage therapy and their impact on the prognosis of patients between 61 to 80 years who had been treated on the RICOVER-60 trial. Results
TF-L occurred in 301 of 1222 (24.6%) patients; 297 patients could be analyzed. Prognosis was extremely poor in patients with primary progressive disease or early relapse (≤12 months) with median survivals of 3.3 and 6.4 months. Survival after TF-L was significantly lower in patients pretreated with R-CHOP compared to CHOP (23.0% vs. 36.4% at 2 years, p = 0.016). In patients with MYC translocation at diagnosis Rituximab reduced the risk of TF-L from 58.8% to 26.3%. Survival after TF-L was significant longer for patients after CHOP without MYC translocations (31.8% vs. 0% at 2 years, p < 0.001) or negative MYC-IHC (41.0% vs. 16.8% at 2 years, p = 0.017) but not after R-CHOP. 224 patients (75.4%) received salvage therapy. Rituximab was part of salvage therapy in 57.4% and improved 2-year survival rate from 20.7% to 46.8% (p < 0.001). The benefit of R was significant after first-line CHOP (2-year-OS 49.6% vs. 19.1%, p < 0.001) as well as after R-CHOP (2-year-OS 33.1% and 22.5%, p = 0.034). For patients pretreated with R-CHOP long-term survival was below 15% regardless of the treatment chosen. Conclusion
MYC rearrangement and IHC are adverse prognostic factors after TF-L for CHOP treated patients, rituximab as part of first line therapy reduced the effects of MYC-break. Rituximab improves results of any type of salvage therapy, however survival after progression/relapse of aggressive B-cell lymphoma in elderly patients pretreated with (R)-CHOP is poor regardless of treatment chosen.Micro-autologous fat transplantation for rejuvenation of the dorsal surface of the ageing hand
Rejuvenation of the dorsal surface of the hand for various conditions, such as cutaneous dyschromia, fine wrinkling, skin laxity, visible extensor tendons, and varicosities appear vital to prevent wrist and digit flexion resulting from hiding of the aged appearance of the hand. Numerous fillers have been applied to re-contour the ageing dorsal surface of the hand; the results were variable. The micro-autologous fat transplantation (MAFT) technique, proposed by Lin et al. in 2006, has demonstrated its feasibility in facial rejuvenation.
Diagnosis and management of diaper dermatitis in infants with emphasis on skin microbiota in the diaper area
Abstract
Diaper dermatitis is the most common inflammatory skin eruption within the diaper area in infants and toddlers. Although it rarely causes problems for prolonged periods of time, it causes considerable distress for both infants and parents. Diapered skin is exposed to friction, excessive hydration, varying pH, and is in constant contact with urine and feces, both of which are highly irritant to the skin. The three most common types of diaper dermatitis include chaffing dermatitis, irritant contact dermatitis, and diaper candidiasis. However, a variety of other skin conditions may manifest in the diaper area. Candida albicans and Staphylococcus aureus are most frequently isolated from the affected area and are thought to have a predominant role in diaper dermatitis. The review includes an overview of the epidemiology, etiology, and common skin microbiota in the diaper area. State-of-the-art strategies for diagnosis, management, and prevention of diaper dermatitis are also included. Appropriate skin care can help in the prevention of diaper dermatitis and can aid the reparation of the skin. This review discusses common causes, skin microbiota within the diapered area, differential diagnosis, and finally possible prevention and treatment recommendations. Recent findings have proven that the key to efficient eradication of irritant diaper dermatitis lies in its prevention.
Comparative Study of Head and Neck Mucosal Melanoma in 66 patients vs. 226 patients with Cutaneous Melanoma: A survival analysis
Abstract
Sixty-six patients (22%) had HNMM and 226 (78%) HNCM and the higher prevalence was seen in females with a similar distribution amongst the two diagnoses (p=0.8).
Symptoms were present in all patients with HNCM and in only 15% of patients with HNMM (p=0.000).
Lymph node involvement at diagnosis was present in 51% of HNMM vs. 33% of HNCM (p=0.007) and were bilateral in 44% of HNMM while in HNCM they were only ipsilateral (p=0.000).
Metastatic disease at diagnosis was similar in both groups (p=0.9).
Relapses were more frequent in the HNMM group in ~70% of the cases compared with 23% in HNCM group (p=0.000).
When comparing HNCM vs. HNMM, Overall Survival is similar, without statistical difference.
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Stop making sense of Bell’s theorem and nonlocality?
Abstract
In a recent paper on Foundations of Physics, Stephen Boughn reinforces a view that is more shared in the area of the foundations of quantum mechanics than it would deserve, a view according to which quantum mechanics does not require nonlocality of any kind and the common interpretation of Bell theorem as a nonlocality result is based on a misunderstanding. In the present paper I argue that this view is based on an incorrect reading of the presuppositions of the EPR argument and the Bell theorem and, as a consequence, is unfounded.
Comparison of the trapping effect and antioxidant enzymatic activities using three different light sources in cockchafers
Abstract
Light traps have been widely used for controlling underground pests. However, very little is known regarding the relationship between trapping effect and antioxidant enzymatic activities using light irradiation in underground pests. Thus, we determined the trapping effect of three light sources of the frequoscillation pest-killing lamp on two species of cockchafers, Serica orientalis Motschulsky (Coleoptera: Melolonthidae) and Anomala corpulenta Motschulsky (Coleoptera: Rutelidae), and evaluated the effect of the same three light sources on the activities of their antioxidant enzymes. The catches of S. orientalis were significantly higher compared to A. corpulenta using light source A in peanut fields in China. After irradiation by light source A, the malondialdehyde (MDA) contents and activities of superoxide dismutase (SOD) and glutathione S-transferases (GST) in S. orientalis were significantly and marginally significantly lower compared to A. corpulenta. Taken together, these results indicated a weaker antioxidant enzyme activity response to light stress and a larger quantity of trapping catches using light irradiation in cockchafers. Thus, we proposed a potential negative relationship between trapping effect and antioxidant enzymatic activities in response to light irradiation in cockchafers.
NO 2 inhalation enhances asthma susceptibility in a rat model
Abstract
Nitrogen dioxide (NO2) is a major air pollutant. Epidemiologic studies have found that NO2 exposure is associated with an increased risk of asthma. Nevertheless, the potential molecular mechanisms remain unclear. In this study, we investigated the effect of NO2 inhalation on the occurrence of allergic airway inflammation and its underlying mechanisms. Firstly, male Wistar rats were exposed to 2 and 5 mg/m3 NO2 (28 days, 5 h/day). The results showed that NO2 exposure could induce pulmonary inflammatory response, mucus formation, and Th1/Th2 imbalance in the lung of normal rats, resulting in allergic asthma-like features. Secondly, male Wistar rats were exposed to 5 mg/m3 NO2 (42 days, 5 h/day), sensitized with ovalbumin (OVA), challenged with aerosolized OVA, and characterized in asthma models. Results showed that NO2 exposure aggravated lung inflammation in the OVA-sensitized rats, accompanied by the increase in inflammatory cell infiltration, mucus hypersecretion, and collagen deposition. Furthermore, NO2 exposure promoted the increase in the expression of mucin gene (MUC5AC) and pro-inflammatory factors [interleukin (IL)-1β, intercellular adhesion molecule-1 (ICAM-1), and IL-6] as well as serum OVA-specific immunoglobulin E (IgE) production. Taken together, we established that NO2 exposure promotes allergic airway inflammation and increases the asthma susceptibility. The underlying mechanisms involve the promotion of activation of interleukin-4/signal transducer and activator of transcription-6 (IL-4/STAT6) pathway [IL-4 receptor (IL-4R) α, janus kinase (JAK) 1, JAK 3, and STAT6] and related transcription factor [T cell-specific protein-tyrosine kinase (Lck), extracellular-regulated kinase (ERK)1/2, and nuclear factor-κB (NF-κB)]. In particular, the imbalance of Th1/Th2 cell differentiation [IL-4, interferon (IFN)-γ, GATA-binding protein-3 (GATA-3), and T-box expressed in T cells (T-bet)] plays a pivotal role in NO2-induced inflammatory responses. These findings may provide a better understanding of mechanism of NO2-associated respiratory diseases.
Patients’ preferences for headache acute and preventive treatment
We aimed to explore patients' preferences for headache treatments with a self-administered questionnaire including the Q-No questionnaire for nocebo.
Nutritional and metabolic stressors on ovine oocyte development and granulosa cell functions in vitro
Abstract
The present study was undertaken to study the effect of ammonia, urea, non-esterified fatty acid (NEFA), and β-hydroxybutyric acid (β-OHB) on oocyte development and granulosa cell (GC) growth parameter of ovine (Ovis aries). Ovine oocytes were matured in vitro in the presence of different concentration of ammonia, urea, NEFA, and β-OHB for 24 h, in vitro inseminated and evaluated for cleavage and blastocyst yield. Same concentrations of ammonia, urea, NEFA, and β-OHB were examined on growth parameters and hormone secretion activity of granulosa cells in vitro. Real-time reverse transcription polymerase chain reaction was used to evaluate the expression of steroidogenic genes (steroidogenic cytochrome P-450 (CYP11A1, CYP19A1)), cell proliferation-related genes (GDF9, FSHr), and apoptosis-related genes (BCL-2 and BAX). The maturation, cleavage, and blastocyst production rates were significantly lowered in media containing either 200 μM ammonia or 5 mM urea or high combo NEFA or 1 μM β-OHB. Exposure of granulosa cell to 400 μM ammonia or 1 μM β-OHB or very high combo or 6 mM urea significantly decreased all the parameters examined compared to lower levels of all nutritional and metabolic stressors. Elevated concentration of metabolic stressors induced GC apoptosis through the BAX/BCL-2 pathway and reduced the steroidogenic gene messenger RNA (mRNA) expression and cell proliferation gene mRNA expression. These results suggested that the decreased function of GCs may cause ovarian dysfunction and offered an improved understanding of the molecular mechanism responsible for the low fertility in metabolic stressed condition.
Feasibility of combined risk stratification with coronary CT angiography and stress myocardial SPECT in patients with chronic coronary artery disease
Abstract
Objective
To examine the additional prognostic value of coronary CT angiography (CTA) over myocardial perfusion imaging (MPI) in patients with suspected or known coronary artery disease.
Methods
A series of 157 patients (mean age 69 ± 9 years; 76% male; median follow-up 49 months; range 12–82 months) underwent stress MPI with SPECT and coronary CTA within a 6-month interval. Summed stress score (SSS) and summed difference score (SDS) of stress MPI, number of vessels with stenosis, and presence of left main trunk stenosis and high-risk plaques on coronary CTA were examined. Primary endpoints were cardiac death, acute myocardial infarction, or unstable angina requiring revascularization. Secondary endpoints were revascularization > 60 days after the latter imaging test. All patients were followed up for at least 1 year (mean 45 ± 19 months; range 12–82 months).
Results
Nine (6%) patients reached primary endpoints. Cardiac death occurred in 1 (0.6%) patient, myocardial infarction in 5 (3%), and unstable angina requiring hospitalization in 3 (2%). Elective revascularization within 60 days was performed in 31 (20%) patients. Sixteen (10%) patients required revascularization after > 60 days. Primary endpoint event-free survival rates were significantly lower in patients with myocardial ischemia (SDS ≥ 2) and high-risk plaques (HRP), and secondary endpoint event-free survival rates in patients with SSS ≥ 4 and 3VD. In multivariate analysis, Cox proportional hazards regression analysis revealed HRP (HR = 8.02; P = 0.006) and myocardial ischemia (HR = 11.487; P = 0.025) were significant predictors of primary endpoints, and 3VD of secondary endpoints (HR = 4.981; P = 0.008). Combined ischemia and HRP resulted in the significant increase of the model Chi square in prediction of primary end points from ischemia or HRP alone (17.4 vs. 9.41; P = 0.005, 17.4 vs. 9.39; P = 0.005, respectively).
Conclusion
Coronary CT angiography may provide additional prognostic information over MPI.
Packing Density Necessary to Reach a High Complete Occlusion Rate in Circumferential Unruptured Intracranial Aneurysms Treated with Stent-Assisted Coil Embolization [INTERVENTIONAL]
BACKGROUND AND PURPOSE:
This study is a homogeneous series of circumferential unruptured intracranial aneurysms with large necks treated with stent-assisted coil embolization. Our purpose was to demonstrate which value of packing density is required to produce a durable occlusion.
MATERIALS AND METHODS:We retrospectively evaluated all patients with unruptured intracranial aneurysms who were treated with stent-assisted coil embolization having late angiographic control between 2004 and 2014, in a single large cerebrovascular referral center. To calculate the packing density, aneurysm volume, and coil volume, we used an on-line system.
RESULTS:In 49 circumferential unruptured intracranial aneurysms treated with stent-assisted coil embolization, 38.7% (n = 19) had complete occlusion in the immediate control. Of those with incomplete occlusion, 80% (n = 24) progressed to complete occlusion in the late angiographic follow-up. At late angiographic control, 87.7% (n = 43) of aneurysms were completely occluded. All aneurysms with a packing density of ≥19% were completely occluded. Packing density was the only statistically significant predictor of complete occlusion. None of the aneurysms with complete occlusion at immediate control or at late angiographic control had recurrence.
CONCLUSIONS:In circumferential aneurysms treated with stent-assisted coil embolization, packing density is the main predictor of complete occlusion. In this type of aneurysm, a packing density of ≥19% was enough to reach complete occlusion; knowing this is important to avoid higher packing densities that have more risk.
In Vivo Imaging of Venous Side Cerebral Small-Vessel Disease in Older Adults: An MRI Method at 7T [ADULT BRAIN]
BACKGROUND AND PURPOSE:
Traditional neuroimaging markers of small-vessel disease focus on late-stage changes. We aimed to adapt a method of venular assessment at 7T for use in older adults. We hypothesized that poorer venular morphologic characteristics would be related to other small-vessel disease neuroimaging markers and a higher prevalence of small-vessel disease–Alzheimer disease risk factors.
MATERIALS AND METHODS:Venules were identified in periventricular ROIs on SWI and defined as tortuous or straight. The tortuosity ratio was defined as total tortuous venular length divided by total straight venular length. White matter hyperintensity burden (visually rated from 0 to 3) and the number of microbleeds (0, 1, >1) were determined. Differences in tortuous and straight venular lengths were evaluated. Relationships with demographic variables, allele producing the e4 type of apolipoprotein E (APOE4), growth factors, pulse pressure, physical activity, and Modified Mini-Mental State Examination were assessed via Spearman correlations.
RESULTS:Participants had 42% more tortuous venular tissue than straight (median, 1.42; 95% CI, 1.13–1.62). APOE4 presence was associated with a greater tortuosity ratio ( = 0.454, P = .001), and these results were robust to adjustment for confounders and multiple comparisons. Associations of the tortuosity ratio with sex and vascular endothelial growth factor did not survive adjustment. Associations of the tortuosity ratio with other variables of interest were not significant.
CONCLUSIONS:Morphologic measures of venules at 7T could be useful biomarkers of the early stages of small-vessel disease and Alzheimer disease. Longitudinal studies should examine the impact of apolipoprotein E and vascular endothelial growth factor on the risk of venular damage.
Yield of Image-Guided Needle Biopsy for Infectious Discitis: A Systematic Review and Meta-Analysis [SPINE]
BACKGROUND:
Image-guided biopsy is routinely conducted in patients with suspected discitis, though the sensitivity reported in the literature ranges widely.
PURPOSE:We applied a systematic review and meta-analysis to estimate the yield of image-guided biopsy for infectious discitis.
DATA SOURCES:We performed a literature search of 4 data bases: PubMed, Cochrane CENTRAL Register of Controlled Trials, Embase.com, and Scopus from data base inception to March 2016.
STUDY SELECTION:A screen of 1814 articles identified 88 potentially relevant articles. Data were extracted for 33 articles, which were eligible if they were peer-reviewed publications of patients with clinical suspicion of discitis who underwent image-guided biopsy.
DATA ANALYSIS:Patients with positive cultures out of total image-guided biopsy procedures were pooled to estimate yield with 95% confidence intervals. Hypothesis testing was performed with an inverse variance method after logit transformation.
DATA SYNTHESIS:Image-guided biopsy has a yield of approximately 48% (793/1763), which is significantly lower than the open surgical biopsy yield of 76% (152/201; P < .01). Biopsy in patients with prior antibiotic exposure had a yield of 32% (106/346), which was not significantly different from the yield of 43% (336/813; P = .08) in patients without prior antibiotic exposure.
LIMITATIONS:The conclusions of this meta-analysis are primarily limited by the heterogeneity of the included studies.
CONCLUSIONS:Image-guided biopsy has a moderate yield for the diagnosis of infectious discitis, which is significantly lower than the yield of open surgical biopsy. This yield is not significantly affected by prior antibiotic use.
Dual-Energy CT in Enhancing Subdural Effusions that Masquerade as Subdural Hematomas: Diagnosis with Virtual High-Monochromatic (190-keV) Images [ADULT BRAIN]
BACKGROUND AND PURPOSE:
Extravasation of iodinated contrast into subdural space following contrast-enhanced radiographic studies results in hyperdense subdural effusions, which can be mistaken as acute subdural hematomas on follow-up noncontrast head CTs. Our aim was to identify the factors associated with contrast-enhancing subdural effusion, characterize diffusion and washout kinetics of iodine in enhancing subdural effusion, and assess the utility of dual-energy CT in differentiating enhancing subdural effusion from subdural hematoma.
MATERIALS AND METHODS:We retrospectively analyzed follow-up head dual-energy CT studies in 423 patients with polytrauma who had undergone contrast-enhanced whole-body CT. Twenty-four patients with enhancing subdural effusion composed the study group, and 24 randomly selected patients with subdural hematoma were enrolled in the comparison group. Postprocessing with syngo.via was performed to determine the diffusion and washout kinetics of iodine. The sensitivity and specificity of dual-energy CT for the diagnosis of enhancing subdural effusion were determined with 120-kV, virtual monochromatic energy (190-keV) and virtual noncontrast images.
RESULTS:Patients with enhancing subdural effusion were significantly older (mean, 69 years; 95% CI, 60–78 years; P < .001) and had a higher incidence of intracranial hemorrhage (P = .001). Peak iodine concentration in enhancing subdural effusions was reached within the first 8 hours of contrast administration with a mean of 0.98 mg/mL (95% CI, 0.81–1.13 mg/mL), and complete washout was achieved at 38 hours. For the presence of a hyperdense subdural collection on 120-kV images with a loss of hyperattenuation on 190-keV and virtual noncontrast images, when considered as a true-positive for enhancing subdural effusion, the sensitivity was 100% (95% CI, 85.75%–100%) and the specificity was 91.67% (95% CI, 73%–99%).
CONCLUSIONS:Dual-energy CT has a high sensitivity and specificity in differentiating enhancing subdural effusion from subdural hematoma. Hence, dual-energy CT has a potential to obviate follow-up studies.
Flat Panel Angiography in the Cross-Sectional Imaging of the Temporal Bone: Assessment of Image Quality and Radiation Dose Compared with a 64-Section Multisection CT Scanner [HEAD & NECK]
BACKGROUND AND PURPOSE:
Cross-sectional imaging of the temporal bone is challenging because of the complexity and small dimensions of the anatomic structures. We evaluated the role of flat panel angiography in the cross-sectional imaging of the temporal bone by comparing its image quality and radiation dose with a 64-section multisection CT scanner.
MATERIALS AND METHODS:We retrospectively collected 29 multisection CT and 29 flat panel angiography images of normal whole-head temporal bones. Image quality was assessed by 2 neuroradiologists, who rated the visualization of 30 anatomic structures with a 3-point ordinal scale. The radiation dose was assessed with an anthropomorphic phantom.
RESULTS:Flat panel angiography showed better image quality than multisection CT in depicting the anterior and posterior crura of the stapes, the footplate of the stapes, the stapedius muscle, and the anterior ligament of the malleus (P < .05). In contrast, multisection CT showed better image quality than flat panel angiography in assessing the tympanic membrane, the bone marrow of the malleus and incus, the tendon of the tensor tympani, the interscalar septum, and the modiolus of the cochlea (P < .05). Flat panel angiography had a significantly higher overall image quality rating than multisection CT (P = .035). A reduction of the effective dose of approximately 40% was demonstrated for flat panel angiography compared with multisection CT.
CONCLUSIONS:Flat panel angiography shows strengths and weaknesses compared with multisection CT. It is more susceptible to artifacts, but due to the higher spatial resolution, it shows equal or higher image quality in assessing some bony structures of diagnostic interest. The lower radiation dose is an additional advantage of flat panel angiography.
Improved Detection of Anterior Circulation Occlusions: The "Delayed Vessel Sign" on Multiphase CT Angiography [ADULT BRAIN]
BACKGROUND AND PURPOSE:
Multiphase CTA, a technique to dynamically assess the vasculature in acute ischemic stroke, was primarily developed to evaluate collateral filling. We have observed that it is also useful in identifying distal anterior circulation occlusions due to delayed anterior circulation opacification on multiphase CTA, an observation we term the "delayed vessel sign." We aimed to determine the usefulness of this sign by comparing multiphase CTA with single-phase CTA.
MATERIALS AND METHODS:All 23 distal anterior circulation occlusions during a 2-year period were included. Ten M1-segment occlusions and 10 cases without a vessel occlusion were also included. All patients had follow-up imaging confirming the diagnosis. Initially, the noncontrast CT and first phase of the multiphase CTA study for each patient were blindly evaluated (2 neuroradiologists, 2 radiology trainees) for an anterior circulation occlusion. Readers' confidence, speed, and sensitivity of detection were recorded. Readers were then educated on the "delayed vessel sign," and each multiphase CTA study was re-examined for a vessel occlusion after at least 14 days.
RESULTS:There was significant improvement in the sensitivity of detection of distal anterior circulation vessel occlusions (P < .001), overall confidence (P < .001), and time taken to interpret (P < .001) with multiphase CTA compared with single-phase CTA. Readers preferred MIP images compared with source images in >90% of cases.
CONCLUSIONS:The delayed vessel sign is a reliable indicator of anterior circulation vessel occlusion, particularly in cases involving distal branches. Assessment of the later phases of multiphase CTA for the delayed vessel sign leads to a significant improvement in the speed and confidence of interpretation, compared with single-phase CTA.
Analysis of White Matter Damage in Patients with Multiple Sclerosis via a Novel In Vivo MR Method for Measuring Myelin, Axons, and G-Ratio [ADULT BRAIN]
BACKGROUND AND PURPOSE:
Myelin and axon volume fractions can now be estimated via MR imaging in vivo, as can the g-ratio, which equals the ratio of the inner to the outer diameter of a nerve fiber. The purpose of this study was to evaluate WM damage in patients with MS via this novel MR imaging technique.
MATERIALS AND METHODS:Twenty patients with relapsing-remitting MS with a combined total of 149 chronic plaques were analyzed. Myelin volume fraction was calculated based on simultaneous tissue relaxometry. Intracellular and CSF compartment volume fractions were quantified via neurite orientation dispersion and density imaging. Axon volume fraction and g-ratio were calculated by combining these measurements. Myelin and axon volume fractions and g-ratio were measured in plaques, periplaque WM, and normal-appearing WM.
RESULTS:All metrics differed significantly across the 3 groups (P < .001, except P = .027 for g-ratio between periplaque WM and normal-appearing WM). Those in plaques differed most from those in normal-appearing WM. The percentage changes in plaque and periplaque WM metrics relative to normal-appearing WM were significantly larger in absolute value for myelin volume fraction than for axon volume fraction and g-ratio (P < .001, except P = .033 in periplaque WM relative to normal-appearing WM for comparison between myelin and axon volume fraction).
CONCLUSIONS:In this in vivo MR imaging study, the myelin of WM was more damaged than axons in plaques and periplaque WM of patients with MS. Myelin and axon volume fractions and g-ratio may potentially be useful for evaluating WM damage in patients with MS.
Multicenter Experience with FRED Jr Flow Re-Direction Endoluminal Device for Intracranial Aneurysms in Small Arteries [INTERVENTIONAL]
BACKGROUND AND PURPOSE:
Flow diverters are emerging as an endovascular treatment alternative for proximally located intracranial aneurysms. However, treatment of aneurysms at and beyond the circle of Willis is not well-established. We assessed the clinical safety and efficacy of the Flow Re-Direction Endoluminal Device Jr (FRED Jr) dedicated to small-vessel diameters between 2.0 and 3.0 mm.
MATERIALS AND METHODS:This was a multicenter observational clinical study of 42 patients with 47 aneurysms treated by a flow-direction technique with the FRED Jr. The primary end point for clinical safety was the absence of death, major or minor stroke, and TIA. The primary end point for treatment efficacy was complete and near-complete occlusion according to the O'Kelly-Marotta grading scale at follow-up after 1, 6, and 12 months.
RESULTS:The FRED Jr deployment was technically successful in all cases. In 39/42 (93%) patients, the primary safety end point was reached; in the 3 remaining patients, 1 disabling ischemic stroke, 1 minor stroke with complete recovery at discharge, and 1 TIA were observed. Two asymptomatic, completely reversible side-branch occlusions occurred. Angiographic (DSA or flat panel CT) and clinical follow-up were available after 1 month in 41/47 (87%), 6 months in 27/47 (57%), and 12 months in 11/47 (23%) aneurysms. The primary efficacy end point was reached at 1 month in 27/41 (66%), at 6 months in 21/27 (78%), and at 12 months in 11/11 (100%) aneurysms.
CONCLUSIONS:Deployment of the FRED Jr is safe and effective in the treatment of intracranial aneurysms located in small vessels.
Endovascular Treatment of Dural Arteriovenous Fistulas of the Transverse and Sigmoid Sinuses Using Transarterial Balloon-Assisted Embolization Combined with Transvenous Balloon Protection of the Venous Sinus [INTERVENTIONAL]
BACKGROUND AND PURPOSE:
Combined transarterial balloon-assisted endovascular embolization with double-lumen balloon microcatheters and concomitant transvenous balloon protection was described as a promising treatment technique for dural arteriovenous fistulae of the transverse and sigmoid sinus. The purpose of this study was to evaluate the technical efficacy and safety of this combined treatment technique.
MATERIALS AND METHODS:Nine consecutive patients presenting with dural arteriovenous fistulas of the transverse and sigmoid sinuses underwent combined transarterial and transvenous balloon-assisted endovascular embolization. Prospectively collected data were reviewed to assess the technical success rate, complication rate, and clinical outcome.
RESULTS:Six patients presented with clinically symptomatic Borden type I, and 3 patients, with Borden type II dural arteriovenous fistulas of the transverse and sigmoid sinuses (3 men, 6 women; mean age, 50.4 years). Transarterial embolization was performed with a double-lumen balloon with Onyx and concomitant transvenous sinus protection with a dedicated venous remodeling balloon. Complete angiographic occlusion at the latest follow-up (mean, 4.8 months) was achieved in 6 patients, and near-complete occlusion, in 2 patients. Clinical cure or remission of symptoms was obtained in 6 and 2 patients, respectively. One patient with a residual fistula underwent further treatment in which the dural arteriovenous fistula was cured by sinus occlusion. Complete occlusion of the dural arteriovenous fistula was visible on the follow-up angiography after final treatment in 8 patients. One patient refused follow-up angiography but was free of symptoms. There were no immediate or delayed postinterventional complications.
CONCLUSIONS:Transarterial balloon-assisted embolization of dural arteriovenous fistulas of the transverse and sigmoid sinuses with combined transvenous balloon protection is safe and offers a high rate of complete dural arteriovenous fistula occlusion and remission of clinical symptoms.
Localizing the L5 Vertebra Using Nerve Morphology on MRI: An Accurate and Reliable Technique [SPINE]
BACKGROUND AND PURPOSE:
Multiple methods have been used to determine the lumbar vertebral level on MR imaging, particularly when full spine imaging is unavailable. Because postmortem studies show 95% accuracy of numbering the lumbar vertebral bodies by counting the lumbar nerve roots, attention to lumbar nerve morphology on axial MR imaging can provide numbering clues. We sought to determine whether the L5 vertebra could be accurately localized by using nerve morphology on MR imaging.
MATERIALS AND METHODS:One hundred eight cases with full spine MR imaging were numbered from the C2 vertebral body to the sacrum with note of thoracolumbar and lumbosacral transitional states. The origin level of the L5 nerve and iliolumbar ligament were documented in all cases. The reference standard of numbering by full spine imaging was compared with the nerve morphology numbering method. Five blinded raters evaluated all lumbar MRIs with nerve morphology technique twice. Prevalence and bias-adjusted were used to measure interrater and intrarater reliability.
RESULTS:The L5 nerve arose from the 24th presacral vertebra (L5) in 106/108 cases. The percentage of perfect agreement with the reference standard was 98.1% (95% CI, 93.5%–99.8%), which was preserved in transitional and numeric variation states. The iliolumbar ligament localization method showed 83.3% (95% CI, 74.9%–89.8%) perfect agreement with the reference standard. Inter- and intrarater reliability when using the nerve morphology method was strong.
CONCLUSIONS:The exiting L5 nerve can allow accurate localization of the corresponding vertebrae, which is essential for preprocedure planning in cases where full spine imaging is not available. This neuroanatomic method displays higher agreement with the reference standard compared with previously described methods, with strong inter- and intrarater reliability.
American Society of Functional Neuroradiology-Recommended fMRI Paradigm Algorithms for Presurgical Language Assessment [FUNCTIONAL]
INTRODUCTION:
Functional MR imaging is increasingly being used for presurgical language assessment in the treatment of patients with brain tumors, epilepsy, vascular malformations, and other conditions. The inherent complexity of fMRI, which includes numerous processing steps and selective analyses, is compounded by institution-unique approaches to patient training, paradigm choice, and an eclectic array of postprocessing options from various vendors. Consequently, institutions perform fMRI in such markedly different manners that data sharing, comparison, and generalization of results are difficult. The American Society of Functional Neuroradiology proposes widespread adoption of common fMRI language paradigms as the first step in countering this lost opportunity to advance our knowledge and improve patient care.
LANGUAGE PARADIGM REVIEW PROCESS:A taskforce of American Society of Functional Neuroradiology members from multiple institutions used a broad literature review, member polls, and expert opinion to converge on 2 sets of standard language paradigms that strike a balance between ease of application and clinical usefulness.
ASFNR RECOMMENDATIONS:The taskforce generated an adult language paradigm algorithm for presurgical language assessment including the following tasks: Sentence Completion, Silent Word Generation, Rhyming, Object Naming, and/or Passive Story Listening. The pediatric algorithm includes the following tasks: Sentence Completion, Rhyming, Antonym Generation, or Passive Story Listening.
DISCUSSION:Convergence of fMRI language paradigms across institutions offers the first step in providing a "Rosetta Stone" that provides a common reference point with which to compare and contrast the usefulness and reliability of fMRI data. From this common language task battery, future refinements and improvements are anticipated, particularly as objective measures of reliability become available. Some commonality of practice is a necessary first step to develop a foundation on which to improve the clinical utility of this field.
Higher-order theories of consciousness and what-it-is-like-ness
Abstract
Ambitious higher-order theories of consciousness aim to account for conscious states when these are understood in terms of what-it-is-like-ness. This paper considers two arguments concerning this aim, and concludes that ambitious theories fail. The misrepresentation argument against HO theories aims to show that the possibility of radical misrepresentation—there being a HO state about a state the subject is not in—leads to a contradiction. In contrast, the awareness argument aims to bolster HO theories by showing that subjects are aware of all their conscious states. Both arguments hinge on how we understand two related notions which are ubiquitous in discussions of consciousness: those of what-it-is-like-ness and there being something it is like for a subject to be in a mental state. This paper examines how HO theorists must understand the two crucial notions if they are to reject the misrepresentation argument but assert the awareness argument. It shows that HO theorists can and do adopt an understanding—the HO reading—which seems to give them what they want. But adopting the HO reading changes the two arguments. On this reading, the awareness argument tells us nothing about those states there is something it is like to be in, and so offers no support to ambitious HO theories. And to respond to the misrepresentation understood according to the HO reading is to simply ignore the argument presented, and so to give no response at all. As things stand, we should deny that HO theories can account for what-it-is-like-ness.
Novel uses of bilateral advancement flaps for tip defects on the nose part I
Publication date: Available online 6 October 2017
Source:Journal of the American Academy of Dermatology
Author(s): Marloes S. van Kester, Roel E. Genders
A comparison of apremilast monotherapy and combination therapy for plaque psoriasis in clinical practice: a Canadian multicenter retrospective study
Publication date: Available online 6 October 2017
Source:Journal of the American Academy of Dermatology
Author(s): Arvin Ighani, Jorge R. Georgakopoulos, Scott Walsh, Neil H. Shear, Jensen Yeung
Machine Learning and Melanoma: The Future of Screening
Publication date: Available online 6 October 2017
Source:Journal of the American Academy of Dermatology
Author(s): Tyler Safran, Alex Viezel-Mathieu, Jason Corban, Ari Kanevsky, Stephanie Thibaudeau, Jonathan Kanevsky
Antimalarial drug toxicities in patients with cutaneous lupus and dermatomyositis: a retrospective cohort study
Publication date: Available online 6 October 2017
Source:Journal of the American Academy of Dermatology
Author(s): Lavanya Mittal, Lingqiao Zhang, Rui Feng, Victoria P. Werth
BackgroundAlthough existing evidence demonstrates the efficacy of antimalarials for rheumatic skin disease, the safety of these medications, and particularly quinacrine, remain debated.ObjectiveWe investigate the toxicity risk associated with antimalarials in patients with cutaneous lupus erythematosus (CLE) and dermatomyositis (DM).Methods532 patients (Mean age=52.29 years, Female=85.15%, Male=14.85%) were selected from two databases of CLE (69.92%) and DM (30.08%). Details regarding treatment and toxicities were extracted and five treatment courses were defined [i.e., hydroxychloroquine (HCQ), chloroquine (CQ), quinacrine (Q), hydroxychloroquine-quinacrine (HCQ-Q), and chloroquine-quinacrine (CQ-Q)]. The hazard ratio for each major toxicity was estimated using the Cox proportional hazard model to compare the different treatments to HCQ.ResultsThe most common toxicities included cutaneous eruption, gastrointestinal (GI) upset, mucocutaneous dyspigmentation, neurologic, and retinopathy. Compared to HCQ, the hazards of cutaneous eruption, GI upset, and neurologic toxicities were lower with HCQ-Q; however, this may represent selection bias. Although there was increased retinopathy risk with CQ and CQ-Q relative to HCQ, retinopathy was not seen with Q.LimitationsRetrospective analysisConclusionsWith the exception of retinopathy, which was not seen with quinacrine, the risks of other toxicities associated with quinacrine monotherapy or combinational treatment were not significantly different than with hydroxychloroquine.
Teaser
Antimalarials are effective for rheumatic skin diseases, but have been associated with retinopathy.We investigated the toxicity risk of antimalarials alone and in combination.Antimalarials were generally well tolerated and had similar risk profiles. Risk of retinopathy seems to be lowest for quinacrine, then hydroxychloroquine, and highest for chloroquine.Utilization patterns and survival outcomes after wide local excision or Mohs micrographic surgery for Merkel cell carcinoma in the United States, 2004-2009
Publication date: Available online 6 October 2017
Source:Journal of the American Academy of Dermatology
Author(s): Waqas R. Shaikh, Joseph F. Sobanko, Jeremy R. Etzkorn, Thuzar M. Shin, Christopher J. Miller
Demographic and Healthcare Service Utilization by 4,417 Patients with Hidradenitis Suppurativa
Publication date: Available online 6 October 2017
Source:Journal of the American Academy of Dermatology
Author(s): Guy Shalom, Meir Babaev, Tamar Freud, Shmuel Tiosano, Nadav Pam, Amir Horev, Jacob Dreiher, Daniel A. Vardy, Doron Comaneshter, Arnon D. Cohen
BackgroundData on the healthcare utilization of hidradenitis suppurativa (HS) patients in primary care settings are scarce.ObjectiveTo investigate the healthcare service utilization of patients with HS.Patients and methodsIn a cross-sectional study, HS patients were compared with two age- and gender-matched control groups—general population enrollees of Clalit Health Services and a group of patients with psoriasis. Healthcare services data included inpatient and outpatient community clinic visits and pharmacy claims for topical and systemic treatments. Multivariate analysis of the data for HS patients and controls was performed.ResultsThe study included 4,417 HS patients, 22,085 general population enrollees, and 4,417 patients with psoriasis. Based on multivariate analyses, HS patients had more annual dermatology clinic visits compared with the general population enrollees (OR 6.49, 95% CI 7.06–5.97) and psoriasis patients (OR 1.32, 95% CI 1.44–1.21); more annual surgical clinic visits (OR 3.78, 95% CI 3.28–4.36; OR 1.65, 95% CI 1.42–1.91, respectively); and more hospitalizations (OR 2.21, 95% CI 1.89–2.56; OR 1.51, 95% CI 1.28–1.78, respectively).LimitationsUnderestimation of HS frequency was possible.ConclusionsThe burden on healthcare systems of patients with HS is greater than that of psoriasis and the general population.
Teaser
What is already known on this topic?Hidradenitis suppurativa (HS) is associated with increased burden of healthcare utilization.What does this article add to our knowledge?Patients with HS impose an increased burden on the healthcare system compared to patients with psoriasis and to the general population.How does this information affect clinical practice and/or change patient care?These results should encourage policy-makers and healthcare providers to explore more cost-effective treatments for HS patients.Poor early response to methotrexate portends inadequate long-term outcomes in patients with moderate-to-severe psoriasis: Evidence from 2 phase 3 clinical trials
Publication date: Available online 6 October 2017
Source:Journal of the American Academy of Dermatology
Author(s): Kenneth B. Gordon, Keith A. Betts, Murali Sundaram, James E. Signorovitch, Junlong Li, Meng Xie, Eric Q. Wu, Martin M. Okun
BackgroundMost methotrexate-treated psoriasis patients do not achieve a long-term PASI75 (75% reduction from baseline Psoriasis Area and Severity Index score) response. Indications of nonresponse can be apparent after only 4 weeks of treatment.ObjectiveTo develop a prediction rule to identify patients unlikely to respond adequately to methotrexate.MethodsPatient-level data from CHAMPION (NCT00235820, N = 110) was used to construct a prediction model for week 16 PASI75 by using patient baseline characteristics and week 4 PASI25. A prediction rule was determined on the basis of the sensitivity and specificity and validated in terms of week 16 PASI75 response in an independent validation sample from trial M10-255 (NCT00679731, N = 163).ResultsPASI25 achievement at week 4 (odds ratio = 8.917) was highly predictive of response with methotrexate at week 16. Patients with a predicted response probability <30% were recommended to discontinue methotrexate. The rates of week 16 PASI75 response were 65.8% and 21.1% (P < .001) for patients recommended to continue and discontinue methotrexate, respectively.LimitationsThe CHAMPION trial excluded patients previously treated with biologics, and the M10-255 trial had no restrictions.ConclusionA prediction rule was developed and validated to identify patients unlikely to respond adequately to methotrexate. The rule indicates that 4 weeks of methotrexate might be sufficient to predict long-term response with limited safety risk.
Adalimumab for nail psoriasis: Efficacy and safety from the first 26 weeks of a phase 3, randomized, placebo-controlled trial
Publication date: Available online 6 October 2017
Source:Journal of the American Academy of Dermatology
Author(s): Boni E. Elewski, Martin M. Okun, Kim Papp, Christopher S. Baker, Jeffrey J. Crowley, Gérard Guillet, Murali Sundaram, Yves Poulin, Yihua Gu, Ziqian Geng, David A. Williams, Phoebe A. Rich
BackgroundPrevious clinical trials have not evaluated improvement in nail psoriasis as a primary end point.ObjectiveThis phase 3 trial evaluated the safety and efficacy of adalimumab in patients with moderate-to-severe fingernail psoriasis and moderate-to-severe plaque psoriasis.MethodsPatients were randomized 1:1 to 40 mg adalimumab every other week or placebo. The primary efficacy end point was at least 75% improvement in total-fingernail modified Nail Psoriasis Severity Index (NAPSI75) response rate at week 26. Ranked secondary end point scores evaluated at week 26 were total-fingernail NAPSI and modified NAPSI, nail pain, Nail Psoriasis Physical Functioning Severity, Brigham Scalp Nail Inverse Palmo-Plantar Psoriasis Index, and Physician's Global Assessment (fingernail psoriasis).ResultsOf the 217 randomized patients (108 received placebo and 109 received adalimumab), 188 (86.6%) completed 26 weeks of treatment (period A) or escaped early to the open-label period. The study met the primary end point (response rate of 3.4% with placebo vs 46.6% with adalimumab [P < .001]) and all ranked secondary end points. The serious adverse event rates (placebo vs adalimumab) in period A were 4.6% versus 7.3%; the serious infections rates were 1.9% versus 3.7%.LimitationsPatients with less than 5% BSA involvement were not eligible for enrollment.ConclusionsAfter 26 weeks of adalimumab treatment, significant improvements were seen in the primary and all ranked secondary end points and in signs and symptoms of moderate-to-severe nail psoriasis versus with placebo and no new safety risks were identified.
Promoting sunscreen use and sun-protective practices in NCAA athletes: Impact of SUNSPORT educational intervention for student-athletes, athletic trainers, and coaches
Publication date: Available online 6 October 2017
Source:Journal of the American Academy of Dermatology
Author(s): Mina S. Ally, Susan M. Swetter, Kelsey E. Hirotsu, Justin Gordon, David Kim, Ashley Wysong, Lindsy Donnelly, Shufeng Li, Kristin M. Nord
BackgroundStudent-athletes (SAs) have an increased skin cancer risk on account of significant ultraviolet exposure; however, their sun-protective practices are suboptimal. A novel program, Stanford University Network for Sun Protection, Outreach, Research, and Teamwork (SUNSPORT), was designed to target SAs, coaches, and athletic trainers (ATs).ObjectiveTo measure the impact of educational intervention on sun protection beliefs and practices of SAs.MethodsA survey of sun protection beliefs and practices was administered to National Collegiate Athletic Association athletes before and after intervention. SUNSPORT dermatologists educated SAs, coaches, and ATs regarding skin cancer risk and prevention methods. The main outcome was frequency of sunscreen use by SAs before versus after intervention.ResultsA total of 846 National Collegiate Athletic Association athletes were surveyed between September 23, 2012, and September 20, 2015. After intervention, significant increases were observed in sunscreen use 4 or more days per week by SAs (from 26% to 39% [P = .02]), SAs spoken to by their coach about sun safety (from 26% to 57% [P = .0001]), and SA recognition of higher skin cancer risk (from 54% to 67% [P = .04]).LimitationsIntervention in only 1 West Coast university and no paired data.ConclusionsFollowing the SUNSPORT intervention, SAs were significantly more likely to use sunscreen, especially if encouraged by their coach. This study emphasizes that education directed to SAs, ATs, and coaches can improve sun-protective practices in SAs.
Direct immunofluorescence testing in vasculitis - a single institution experience with Henoch Schönlein Purpura
Abstract
Background
Direct immunofluorescence (DIF) panels (IgG, IgA, IgM, C3 and fibrinogen) are ordered for clinically suspected vasculitis, with frequently negative results.
Methods
Cases submitted for DIF and histology (2010–2014) with "vasculitis" in the clinical data were examined, and the electronic medical record reviewed for clinical suspicion of HSP. Peri/intravascular IgA was considered "positive," other reactants "non-specific," and no immunoreactivity "negative."
Results
Vasculitis was the given indication for 20% (258/1318) of DIF studies. HSP was clinically suspected in 36% (95/258). In this setting, LCV was common (66%, 63/95) and DIF was positive in 43% (27/63). 100% of DIF+ had LCV+. In cases without HSP suspicion, 26% (42/163) were LCV+ and <1% DIF+. Of the 258 cases, LCV+ greatly enriched for DIF+ [105/258 LCV+ with 28/105 (27%) DIF+], captured 100% of HSP, and included cases with non-specific DIF/etiologic findings. In LCV- cases, DIF positivity was not seen, HSP was not diagnosed, and non-specific DIF findings were common.
Conclusions
LCV is an H&E-based histopathologic diagnosis that can have positive, negative, and non-specific DIF results that are rarely contributory except in the setting of HSP, where DIF is best utilized with IgA as the sole immunoreactant. H&E-based triage of DIF orders is recommended.
Manipulation of nitrogen leaching from tea field soil using a Trichoderma viride biofertilizer
Abstract
With the increasing use of chemical fertilizers, negative environmental impacts have greatly increased as a result from agricultural fields. The fungus Trichoderma viride used as a biofertilizer can efficiently reduce nitrous oxide (N2O) emissions from subtropical tea fields in southern China. In this paper, it was further found that T. viride biofertilizer could alleviate nitrogen (N) leaching in tea fields. Gross N leaching was 1.51 kg ha−1 year−1 with no external fertilizer input, but when 225 kg N ha−1 year−1was applied, it increased to 12.38 kg ha−1 year−1 using T. viride biofertilizer but 53.46 kg ha−1 year−1 using urea. Stepwise linear regression analysis identified the factors responsible for N leaching to be soil nitrate concentration and soil interflow, simulated here using the water balance simulation model (WaSiM-ETH). Finally, mass-scale production of T. viride biofertilizer from waste reutilization using sweet potato starch wastewater and rice straw was found to be cost-effective and feasible. These procedures could be considered a best management practice to reduce N leaching from tea fields in subtropical areas of central China and to reduce pollution from other agricultural waste products.
Degradation of propyl paraben by activated persulfate using iron-containing magnetic carbon xerogels: investigation of water matrix and process synergy effects
Abstract
An advanced oxidation process comprising an iron-containing magnetic carbon xerogel (CX/Fe) and persulfate was tested for the degradation of propyl paraben (PP), a contaminant of emerging concern, in various water matrices. Moreover, the effect of 20 kHz ultrasound or light irradiation on process performance was evaluated. The pseudo-first order degradation rate of PP was found to increase with increasing SPS concentration (25–500 mg/L) and decreasing PP concentration (1690–420 μg/L) and solution pH (9–3). Furthermore, the effect of water matrix on kinetics was detrimental depending on the complexity (i.e., wastewater, river water, bottled water) and the concentration of matrix constituents (i.e., humic acid, chloride, bicarbonate). The simultaneous use of CX/Fe and ultrasound as persulfate activators resulted in a synergistic effect, with the level of synergy (between 35 and 50%) depending on the water matrix. Conversely, coupling CX/Fe with simulated solar or UVA irradiation resulted in a cumulative effect in experiments performed in ultrapure water.
Novel Bi-allelic Splice Mutations in CARD9 Causing Adult-onset Candida Endophthalmitis
Abstract
Background
CARD9 deficiency (CANDF2; OMIM# 212050) is an autosomal-recessive monogenic inborn error of immunity conferring susceptibility to invasive fungal diseases, including the very distinct syndrome of spontaneous central nervous system candidiasis, in which opportunistic yeasts of the genus Candida infect the central nervous system (either brain parenchyma and/or meninges) in the absence of trauma, chemotherapy or underlying systemic disease.
Methods
We present a patient with spontaneous endophthalmitis of the right eye due to Candida albicans; further investigations revealed concomitant cerebral abscess. She had a history of left endophthalmitis due to the dematiaceous mold, Aureobasidium pullulans, fifteen years earlier.
Results
Targeted sequencing of the CARD9 gene revealed two novel variants (c.184G>A and c.288C>T). Analysis in silico predicted each variant altered splicing, which was confirmed by sequencing of cDNA from proband and carrier offsprings: c.184G>A results in a 4-base pair frameshift deletion with loss of allelic expression; c.288C>T results in an in-frame 36-bp pair deletion with detectable protein.
Conclusion
CARD9 deficiency can present with a phenotype of spontaneous candidal endophthalmitis. We report two novel mutations in CARD9, both affecting splicing, expanding the range of morbid variants causing CARD9 deficiency, emphasizing the importance of both genomic and cDNA sequencing for this condition.
This article is protected by copyright. All rights reserved.
Dynamic leaching behavior of geogenic As in soils after cement-based stabilization/solidification
Abstract
Cement-based stabilization/solidification (S/S) is a practical treatment approach for hazardous waste with anthropogenic As sources; however, its applicability for geogenic As-containing soil and the long-term leaching potential remain uncertain. In this study, semi-dynamic leaching test was performed to investigate the influence of S/S binders (cement blended with fuel ash (FA), furnace bottom ash (FBA), or ground granulated blast furnace slag (GGBS)) on the long-term leaching characteristics of geogenic As. The results showed that mineral admixtures with higher Ca content and pozzolanic activity were more effective in reducing the leached As concentrations. Thus, cement blended with FBA was inferior to other binders in suppressing the As leaching, while 20% replacement of ordinary Portland cement by GGBS was considered most feasible for the S/S treatment of As-containing soils. The leachability of geogenic As was suppressed by the encapsulation effect of solidified matrix and interlocking network of hydration products that were supported by scanning electron microscopy (SEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) results. The long-term leaching of geogenic As from the monolithic samples was diffusion-controlled. Increasing the Ca content in the samples led to a decrease in diffusion coefficient and an increase in feasibility for "controlled utilization" of the S/S-treated soils.
B cell tolerance to epidermal ribonuclear-associated neo-autoantigen in vivo
Summary
Defining how self-antigens are perceived by the immune system is pivotal to understand how tolerance is maintained under homeostatic conditions. Clinically relevant, natural autoantigens targeted by autoantibodies in e.g. systemic lupus erythematosus (SLE) commonly have an intrinsic ability to engage not only the B cell receptor (BCR), but also a costimulatory pathway in B cells, such as the TLR7 pathway. Here we developed a novel mouse model displaying inducible expression of a fluorescent epidermal neo-autoantigen carrying an OT-II T cell epitope, B cell antigen, and associated ribonucleic acids capable of stimulating TLR7. The neo-autoantigen was expressed in skin, but did not drain in intact form into draining lymph nodes, even after UVB stimulated induction of apoptosis in the basal layer. Adoptively transferred autoreactive B cells were follicularly excluded and perished at the T-B border in the spleen, preventing their recirculation and encounter with antigen peripherally. This transitional check-point was bypassed by crossing the reporter to a BCR knock-in line on a C4 deficient background. Adoptively transferred OT-II T cells rapidly homed into cutaneous lymph nodes and upregulated CD69. Yet surprisingly, tolerance was not broken, as the T cells subsequently downregulated activation markers and contracted. Our results highlight how sequestration of intracellular and peripheral antigen, the transitional B cell tolerance check-point, and T cell regulation cooperate to maintain immunological tolerance in vivo. This article is protected by copyright. All rights reserved.
Whole genome microarray expression analysis in blood leucocytes identifies pathways linked to signs and symptoms of a patient with hypercalprotectinaemia and hyperzincaemia
Summary
A child, 2 yr with the "hypercalprotectinemia with hyperzincemia" clinical syndrome presented with atypical symptoms and signs, notably persistent fever of around 38°C, thrombocythaemia of >700 x 109/L, and a predominance of persistent intestinal symptoms. In an effort to find a cure by identifying the dysregulated pathways we analyzed whole-genome mRNA expression by the Affymetrix HG U133 PLUS 2.0 array on three occasions 3 to 5 months apart. Major upregulation was demonstrated for the JAK/STAT pathway including in particular CD177, S100A8, S100A9, and S100A12, accounting for the thrombocytosis; a large number of interleukins, their receptors, and activators, accounting for the febrile apathic state; and the HMBG1 gene, possibly accounting for part of the intestinal symptoms. These results show that gene expression array technology may assist the clinician in the diagnostic workup of individual patients with suspected syndromal states of unknown origin, and the expression data can guide the selection of optimal treatment directed at the identified target pathways. This article is protected by copyright. All rights reserved.
Truly selective primary IgM deficiency is probably very rare
SUMMARY
Isolated decreased serum-IgM has been associated with severe and/or recurrent infections, atopy and autoimmunity. However, the reported high prevalence of clinical problems in IgM-deficient patients may reflect the skewed tertiary center population studied so far. Also, many papers on IgM-deficiency have included patients with more abnormalities than just IgM-deficiency. We studied truly selective primary IgM deficiency according to the diagnostic criteria of the European Society for Immunodeficiencies ESID (true sIgMdef) by reviewing the literature (261 patients with primary decreased serum-IgM in 46 papers) and retrospectively analyzing all patients with decreased serum-IgM in a large teaching hospital in 's-Hertogenbosch, the Netherlands (1-July-2005 to 23-March-2016; n=8,049 IgM<0.4g/l; n=2,064 solitary [IgG+IgA normal/IgM<age-matched reference]). 359/2064 (17%) cases from our cohort had primary isolated decreased serum-IgM, proven persistent in 45/359 (13%) cases; their medical charts were reviewed. Our main finding is that true sIgMdef is probably very rare. Only 6/261 (2%) literature cases and 3/45 (7%) cases from our cohort completely fulfilled the ESID criteria; 63/261 (24%) literature cases also had other immunological abnormalities and fulfilled the criteria for unclassified antibody deficiencies (unPAD) instead. The diagnosis was often uncertain (possible sIgMdef): data on IgG-subclasses and/or vaccination responses were lacking in 192/261 (74%) literature cases and 42/45 (93%) cases from our cohort. Our results also illustrate the clinical challenge of determining the relevance of a serum sample with decreased IgM; a larger cohort of true sIgMdef patients is needed to fully explore its clinical consequences. The ESID online Registry would be a good tool for this. This article is protected by copyright. All rights reserved.
Why Bother Teaching? Despairing the Ethical Through Teaching that Does Not Follow
Abstract
Contemporary education policy discourse in the United States views teaching as the primary instrument to effect student achievement, and teachers are responding by leaving the profession and discouraging students from becoming teachers. While teaching is more commonly associated with hope, I argue that the growing dissatisfaction of teachers with their profession can be understood through despair as an ethical act. Rather than disavow the role of despair in teaching and education more broadly, the critical and provocative roles of despair are emphasised here as an ethical response to a normative order of effective teaching. These roles are expressed through the question of why bother. Understanding why bother teaching as an ethical question that arises from despair serves to critique the present and provoke movement without yet projecting a future. Thus, this paper traces the ways the ethical negates a normative order to arrive at a teaching that does not follow from instrumental logic in service of a future goal, aim, or objective. This leads to a consideration of the risks involved in despairing the ethical, which I describe as a practice for which risk cannot be managed or minimised while remaining ethical.
Democracy and Education: A Theoretical Proposal for the Analysis of Democratic Practices in Schools
Abstract
In the educational sphere, the concept of democracy is used in many and varied ways, though the hegemonic school culture often starts from a concept of democracy that is taken for granted, and it is understood that the entire educational community shares a similar concept. As a result of the research project "Democracy, participation and inclusive education in schools" (EDU2012-39556-C02-01/02) we realized that the above-mentioned concept is used without being accurately defined in the school setting. This observation is what has prompted us to write this article, basically structured in two parts. In the first part, based on the theoretical debate occurring in the field of social sciences, we delimit the concept of democracy and structure it in four basic dimensions: governance, inhabitance, otherness and ethos. In the second part, we specify and examine in depth these four dimensions in the school setting in order to construct a broad and transversal, yet specific, definition, with which to be able to develop ambitious democratic projects and, in turn, contribute to scientific debate.
An Approach to Simone Weil’s Philosophy of Education Through the Notion of Reading
Abstract
This paper introduces Simone Weil's notion of reading and some of its implications to education. Weil's philosophy, in particular her notion of attention has caught interest of some education scholars; however, the existing studies are still underdeveloped. Introducing Weil's notion of reading, which has not been studied almost at all by educationists but its significance is well-recognized by Weil scholars, I intend to set forth a more nuanced understanding of Weil's attention that is necessary to further discuss Weil's potential contribution to education research. Attention to other people, hence love of others, is reframed as "reading better." We read better not simply by purifying our reading through detachment and self-negation, which is how the notion of attention is often understood and thus found problematic, but by incorporating multiple perspectives (readings) and finding balance among them. Learning to read better, then, is not merely inward effort of detachment done through introspection, but it also necessarily involves outward effort of working with other people and the world. It is through interacting with others, we may learn our own readings, recognize others' readings, and seeking for just balance among them. This latter element which has been greatly dismissed is indispensable for any serious discussions of Weil's philosophy in education.
Nietzsche on Aesthetics, Educators and Education
Abstract
This essay argues that much can be gained from a close examination of Nietzsche's work with respect to education. In order to contextualise my argument, I provide a brief critique of Nietzsche's thinking on aesthetics, educators and education. I then turn my attention to the work of Thus Spoke Zarathustra, the figures Zarathustra and the Übermensch, and other Nietzschean works with a view to outline what I mean by a Nietzschean education. My central thesis being that a Nietzschean education is primarily concerned with the cultivation of the self. This is certainly not an easy undertaking as it requires both an educator and education that can reveal to students "what one is" now (being), and who they could become (becoming). In order to bring this about, Nietzsche employs the use of an aesthetic model (ideal type) in the form of an exemplar for students to aspire to become. Here, the exemplar plays an important educative function in Nietzsche's thinking because the role of the ideal type is to unsettle the student so that they are inspired to attain their unattained self that they recognise in the other. Consequently, what makes my account of a Nietzschean education significant is due to its concern with fostering timeless educational aims, such as learning to see, think, speak, write, and feel, by unsettling students with an ideal educator and true education so that students can get a sense of who they are now and who they could become.
Democratic Education in the Mode of Populism
Abstract
This paper seeks to bring John Dewey's pragmatist philosophy of democratic education and the public into dialogue with Ernesto Laclau's theory of populism. Recognizing populism as an integral aspect of democracy, rather than as its antithesis, the purpose of this paper is to provide a theoretical account of populism as being of educational relevance in two respects. First, it argues that the populist logic specifies a set of formal elements by which democratic education could operate as a collective enterprise. Second, it asserts that the notion of populism supplements any congenial understanding of democratic education by bringing political demands, conflicts and affects to the fore. Finally, the paper discusses the risks and possibilities inherent in visualizing populism as an educational modus.
Monstrous Generosity: Pedagogical Affirmations of the “Improper”
Abstract
This article focuses upon monstrously generous teaching styles, enacted in neocolonial educational contexts, where the interactions between students and teachers are sometimes tense and mistrustful. The tensions between students and teachers are explained by discussing the ways in which schools—in the theoretical perspective of Roberto Esposito—operate to immunize the society against youth deemed improper. Utilizing the theories of Antonio Negri, James Baldwin, and W.E.B. Du Bois, the characterization of students as monstrous is discussed and an inversion is suggested, whereby students deemed to be monstrous are considered the source of reinvigorating visions of society. The pedagogical approaches of teachers who seek to welcome and nurture monstrous students are described, relying upon the accounts of great teachers offered by educators and sociologists. In practice, monstrously generous teachers make supererogatory gestures in their interactions with students, as a way of signaling to heavily-armored youth that they are willing to enter reciprocal relationships with them. Once youth drop their armor and begin to share their perspectives, monstrously generous teachers develop multiple means of helping youth develop their worldviews, without surveillance or censor.
Biofilm formation, antibiotic susceptibility and RAPD genotypes in Pseudomonas aeruginosa clinical strains isolated from single centre intensive care unit patients
Abstract
The aim of this study was to analyse genotypes, antimicrobial susceptibility patterns and serotypes in Pseudomonas aeruginosa clinical strains, including the clonal dissemination of particular strains throughout various intensive care units in one medical centre. Using random amplified polymorphic DNA (RAPD–PCR) and P. aeruginosa antisera, 22 different genotypes and 8 serotypes were defined among 103 isolates from 48 patients. No direct association between P. aeruginosa strain genotypes and serotypes was observed. RAPD typing in strains with the same serotype revealed different genotypes and, on the contrary, most strains with a different serotype displayed the same amplification pattern. The resulting banding patterns showed a high degree of genetic heterogeneity among all isolates from the patients examined, suggesting a non-clonal relationship between isolates from these patients. A higher degree of antibiotic resistance and stronger biofilm production in common genotypes compared to rare ones and genetic homogeneity of the most resistant strains indicated the role of antibiotic pressure in acquiring resistant and more virulent strains in our hospital. In conclusion, genetic characterisation of P. aeruginosa strains using RAPD method was shown to be more accurate in epidemiological analyses than phenotyping.
Analysis of antimicrobial and immunomodulatory substances produced by heterofermentative Lactobacillus reuteri
Abstract
Antimicrobial and immunomodulatory potential of various Lactobacillus reuteri strains is closely connected to their metabolite production profile under given cultivation conditions. We determined the in vitro production of antimicrobial substances such as organic acids, ethanol, and reuterin by four strains of L. reuteri (L. reuteri E, L. reuteri KO5, L. reuteri CCM 3625, and L. reuteri ATCC 55730). All studied L. reuteri strains showed the ability to produce lactic acid, acetic acid, and ethanol with concominant consumption of glucose and together with phenyllactic acid—a potent antifungal compound—with concominant consumption of phenylalanine. The reuterin production from glycerol was confirmed for all analyzed lactobacilli strains except L. reuteri CCM 3625. Production of organic acids, ethanol, and reuterin is significantly involved in antimicrobial activity of lactobacilli which was determined using the dual-culture overlay diffusion method against six indicator bacteria and five indicator moulds. In comparison to the referential L. reuteri ATCC 55730, the highest inhibition potential was observed against Escherichia coli CCM 3988 and Pseudomonas aeruginosa CCM 3955. Among analyzed indicators of moulds, the growth of Alternaria alternata CCM F-128 was the most inhibited by all four analyzed L. reuteri strains. Finally, the immunomodulatory potential of analyzed lactobacilli were proven by the determination of the in vitro production of biogenic amines histamine and tyramine. L. reuteri CCM 3625 was able to produce tyramine, and L. reuteri E and L. reuteri KO5 were able to produce histamine under given cultivation conditions.
Serological, culture and molecular survey of Mycobacterium avium paratuberculosis in a goat flock in Tuscany
Abstract
Mycobacterium avium paratuberculosis (Map) is a pathogen which causes a chronic progressive granulomatous enteritis known as paratuberculosis or Johne's disease and it primarily affects wild and domestic ruminants. The aim of this research was to examine a flock which consisted of 294 goats and was located in Garfagnana district (Tuscany, Italy) performing ELISA tests, culture and IS900 PCR assay; direct diagnostic methods were carried out not only on bulk tank milk and cheese samples but also on individual milk and tissue specimens collected from nine subjects positive to ELISA tests. Out of 294 animals, 20 goats (6.8%) were positive to ELISA surveys. Bulk tank milk samples were negative to culture and to PCR assay carried out on the DNA extracted directly from them, while, with respect to cheese, Map was detected by culture in 2/12 (16.66%) cheeses ripened for 3–7 days, and by PCR in 2/12 (16.66%) cheeses ripened for 3–7 days and in 3/12 (25%) cheeses ripened for 45 days. Regarding individual milk samples, Map was detected by culture in 2/9 (22.22%) specimens and by PCR in 5/9 (55.55%) samples. Furthermore, Map was isolated from the intestine in 9/9 (100%) animals, from the mesenteric lymph nodes in 8/9 (88.88%) subjects, from the liver in 4/9 (44.44%) goats, from the spleen in 5/9 (55.55%) animals, while Map DNA was found in all the tissue samples analyzed.
The results demonstrated the presence of paratuberculosis in a goat flock located in Garfagnana district (Tuscany, Italy).
Burkholderia cepacia complex in cystic fibrosis in the post-epidemic period: multilocus sequence typing-based approach
Abstract
Cystic fibrosis (CF) patients in the Czech Republic suffered in the late 1990s from an epidemic with ST32 strain of Burkholderia cepacia complex (Bcc). Cohort segregation of Bcc and of ST32 positive patients was introduced in 1999 and 2002, respectively. We performed a study to evaluate the molecular epidemiology of Bcc infection after implementation of these infection control measures. Patients attending the Prague CF adult Centre from 2000 to 2015 were included in the present study. Demographic data and microbial statuses were collected from patient records. All Bcc isolates were analyzed using multilocus sequence typing (MLST). The prevalences of epidemic strain ST32 and of other Bcc strains were calculated. Ninety out of 227 CF patients were infected with Bcc during the study period. The prevalence of ST32 cases significantly decreased from 46.5% in 2000–2001 to 10.4% in 2014–2015 (P < 0.001) due to occurrence of only one new case in 2003, as well as to the death of 72% of ST32-infected patients. Conversely, there was a significant increase in prevalence of other Bcc strains, which rose from 0 to 14.9% (P = 0.015) and of transient infections. A micro-epidemic of infection with ST630 strain was observed in 2014 in lung transplant patients hospitalized in intensive care unit. The prevalence of epidemic strain ST32 decreased, whereas that of non-clonal strains of Bcc increased. Routine use of MLST allowed early detection of new and potentially epidemic strains.
Distribution and antifungal susceptibility of yeasts isolates from intensive care unit patients
Abstract
Yeasts frequently colonize non-sterile sites in the body. The aim of the study was to determine distribution in clinical samples and antifungal susceptibility to five antifungals. From January 2013 through June 2015, 800 isolates were obtained from intensive care unit patients. Candida albicans (58.9%), Candida glabrata (20.4%), Candida krusei (8.6%), and Candida parapsilosis (3.6%) were the leading species. Majority of the C. albicans isolates were susceptible to the fluconazole. Elevated voriconazole minimal inhibitory concentrations (MICs) were observed in isolates exhibiting high fluconazole MICs, most frequently in C. glabrata. Isolates with echinocandins MICs suggesting reduced susceptibility were only sporadic cases with the exception of Trichosporon spp. The amphotericin B MICs were slightly higher for some C. krusei.
Further characterization and independent validation of a DNA aptamer-quantum dot-based magnetic sandwich assay for Campylobacter
Abstract
Previously reported DNA aptamers developed against surface proteins extracted from Campylobacter jejuni were further characterized by aptamer-based Western blotting and shown to bind epitopes on proteins weighing ~16 and 60 kD from reduced C. jejuni and Campylobacter coli lysates. Proteins of these approximate weights have also been identified in traditional antibody-based Western blots of Campylobacter spp. Specificity of the capture and reporter aptamers from the previous report was further validated by aptamer-based ELISA-like (ELASA) colorimetric microplate assay. Finally, the limit of detection of the previously reported plastic-adherent aptamer-magnetic bead and aptamer-quantum dot sandwich assay (PASA) was validated by an independent food safety testing laboratory to lie between 5 and 10 C. jejuni cells per milliliter in phosphate buffered saline and repeatedly frozen and thawed chicken rinsate. Such ultrasensitive and rapid (30 min) aptamer-based assays could provide alternative or additional screening tools to enhance food safety testing for Campylobacter and other foodborne pathogens.
Using phenotype microarrays in the assessment of the antibiotic susceptibility profile of bacteria isolated from wastewater in on-site treatment facilities
Abstract
The scope of the study was to apply Phenotype Biolog MicroArray (PM) technology to test the antibiotic sensitivity of the bacterial strains isolated from on-site wastewater treatment facilities. In the first step of the study, the percentage values of resistant bacteria from total heterotrophic bacteria growing on solid media supplemented with various antibiotics were determined. In the untreated wastewater, the average shares of kanamycin-, streptomycin-, and tetracycline-resistant bacteria were 53, 56, and 42%, respectively. Meanwhile, the shares of kanamycin-, streptomycin-, and tetracycline-resistant bacteria in the treated wastewater were 39, 33, and 29%, respectively. To evaluate the antibiotic susceptibility of the bacteria present in the wastewater, using the phenotype microarrays (PMs), the most common isolates from the treated wastewater were chosen: Serratia marcescens ss marcescens, Pseudomonas fluorescens, Stenotrophomonas maltophilia, Stenotrophomonas rhizophila, Microbacterium flavescens, Alcaligenes faecalis ss faecalis, Flavobacterium hydatis, Variovorax paradoxus, Acinetobacter johnsonii, and Aeromonas bestiarum. The strains were classified as multi-antibiotic-resistant bacteria. Most of them were resistant to more than 30 antibiotics from various chemical classes. Phenotype microarrays could be successfully used as an additional tool for evaluation of the multi-antibiotic resistance of environmental bacteria and in preliminary determination of the range of inhibition concentration.
Colonization by non-pathogenic bacteria alters mRNA expression of cytochromes P450 in originally germ-free mice
Abstract
Gut microbiota provides a wide range of beneficial function for the host and has an immense effect on the host's health state. It has also been shown that gut microbiome is often involved in the biotransformation of xenobiotics; however, the molecular mechanisms of the interaction between the gut bacteria and the metabolism of drugs by the host are still unclear. To investigate the effect of microbial colonization on messenger RNA (mRNA) expression of liver cytochromes P450 (CYPs), the main drug-metabolizing enzymes, we used germ-free (GF) mice, lacking the intestinal flora and mice monocolonized by non-pathogenic bacteria Lactobacillus plantarum NIZO2877 or probiotic bacteria Escherichia coli Nissle 1917 compared to specific pathogen-free (SPF) mice. Our results show that the mRNA expression of Cyp1a2 and Cyp2e1 was significantly increased, while the expression of Cyp3a11 mRNA was decreased under GF conditions compared to the SPF mice. The both bacteria L. plantarum NIZO2877 and E. coli Nissle 1917 given to the GF mice decreased the level of Cyp1a2 mRNA and normalized it to the control level. On the other hand, the colonization by these bacteria had no effect on the expression of Cyp3a11 mRNA in the liver of the GF mice (which remained decreased). Surprisingly, monocolonization with chosen bacterial strains has shown a different effect on the expression of Cyp2e1 mRNA in GF mice. Increased level of Cyp2e1 expression observed in the GF mice was found also in mice colonized by L. plantarum NIZO2877; however, the colonization with probiotic E. coli Nissle 1917 caused a decrease in Cyp2e1 expression and partially restored the SPF mice conditions.
The effect of the colostral cells on gene expression of cytokines in cord blood cells
Abstract
Beneficial effect of maternal milk is acknowledged, but there is still question whether maternal milk from allergic mother is as good as from healthy one. In our study, we have assayed the effect of cells from colostrum of healthy and allergic mothers on gene expression of cytokines in cord blood cells of newborns of healthy and allergic mothers. Cytokines typical for Th1 (IL-2, IFN-gamma), Th2 (IL-4, IL-13), Tregs (IL-10, TGF-beta), and IL-8 were followed. We were not able to detect significant influence of colostral cells on gene expression of cytokines in cord blood after 2-day coculture using Transwell system. There was no difference in gene expression of cytokines in nonstimulated cord blood cells of newborns of healthy and allergic mothers, but generally increased gene expression of cytokines except IL-10 and TGF-beta after polyclonal stimulation was detected in cord blood cells of children of allergic mothers. There was no difference in IL-10 expression in stimulated cord blood cells of children of healthy and allergic mothers. Gene expression of TGF-beta was even decreased in stimulated cord blood cells of children of allergic mothers in comparison to healthy ones. We have not observed difference in the capacity of colostral cells of healthy and allergic mothers to influence gene expression of cytokines in cord blood cells, but we have described difference in the reactivity of cord blood cells between children of allergic and healthy mothers.
Safety assessment of commensal enterococci from dogs
Abstract
Enterococci form a complex, diverse, and very important group of bacteria from the technological and food safety aspect, or from the health-improving aspect as probiotics. Generally, enterococci are considered to be of low pathogenic potential, which is associated mostly with clinical strains. In these strains, production of virulence factors as well as resistance to many antimicrobial drugs could complicate treatment of nosocomial infections. Because there is a lack of information on incidence of these attributes in animal commensal enterococci, we screened 160 strains originating from feces of clinically healthy dogs in Eastern Slovakia (n = 105). The predominant species were Enterococcus faecium (57.5%) followed by Enterococcus faecalis (21.9%), and Enterococcus hirae (17.5%), while Enterococcus casseliflavus (1.9%) and Enterococcus mundtii (1.2%) rarely occurred. Among the tested antibiotics, gentamicin (high level) was the most effective drug against canine enterococci (95% of isolates were sensitive). In contrast, the highest resistance recorded (71.9%) was to teicoplanin. PCR screening showed the highest incidence of virulence genes in E. faecalis species. The most frequently detected were genes encoding adhesins efa Afm and efa Afs and sex pheromone cpd. IS16 gene, a marker specific for hospital strains, appeared in nine E. faecium strains. No strain was positive for DNase activity, 8.8% of the isolated strains showed gelatinase activity, and almost 100% strains produced tyramine. It seems commensal-derived enterococci from dogs could also to some extent be potential reservoir of risk factors for other microbiota or organisms.
Characterization of a metagenome-derived protease from contaminated agricultural soil microorganisms and its random mutagenesis
Abstract
Proteases are typical key enzymes that hydrolyze proteins into amino acids and peptides. Numerous proteases have been studied, but the discovery of metagenome-derived proteases is still significant for both commercial applications and basic research. An unexplored protease gene sep1A was identified by function-based screening from a plasmid metagenomic library derived from uncultured contaminated agricultural soil microorganisms. The putative protease gene was subcloned into pET-32a (+) vector and overexpressed in E. coli BL21(DE3) pLysS, then the recombinant protein was purified to homogeneity. The detailed biochemical characterization of the Sep1A protein was performed, including its molecular characterization, specific activity, pH-activity profile, metal ion-activity profile, and enzyme kinetic assays. Furthermore, the protein engineering approach of random mutagenesis via error-prone PCR was applied on the original Sep1A protein. Biochemical characterization demonstrated that the purified recombinant Ep48 protein could hydrolyze casein. Compared with the original Sep1A protein, the best variant of Ep48 in the random mutagenesis library, with the Gln307Leu and Asp391Gly changes, exhibited 2.62-fold activity at the optimal reaction conditions of 50 °C and pH 9.0. These results are the first step toward a better understanding of the properties of Sep1A protein. Protein engineering with error-prone PCR paves the way toward the metagenome-derived genes for biotechnological applications.
Novel phytoceramides containing fatty acids of diverse chain lengths are better than a single C18-ceramide N-stearoyl phytosphingosine to improve the physiological properties of human stratum corneum.
Novel phytoceramides containing fatty acids of diverse chain lengths are better than a single C18-ceramide N-stearoyl phytosphingosine to improve the physiological properties of human stratum corneum.
Clin Cosmet Investig Dermatol. 2017;10:363-371
Authors: Oh MJ, Cho YH, Cha SY, Lee EO, Kim JW, Kim SK, Park CS
Abstract
Ceramides in the human stratum corneum (SC) are a mixture of diverse N-acylated fatty acids (FAs) with different chain lengths. C24 is the major class of FAs of ceramides. However, there are also other classes of ceramides with diverse chain lengths of FAs, and these lengths generally range from C16 to C26. This study aimed to prepare several types of phytoceramide containing diverse chain lengths of N-acylated FAs and compare them with C18-ceramide N-stearoyl phytosphingosine (NP) in terms of their effects on the physiological properties of the SC. We chose natural oils, such as horse fat oil, shea butter, sunflower oil, and a mixture of macadamia nut, shea butter, moringa, and meadowfoam seed oil, as sources of FAs and phytosphingosine as a sphingoid backbone to synthesize diverse phytoceramides. Each phytoceramide exhibited a distinctive formation of the lamellar structure, and their FA profiles were similar to those of their respective natural oil. The skin barrier properties, as analyzed in human skin, clearly demonstrated that all the phytoceramides improved the recovery rate of the damaged SC and enhanced hydration better than C18-ceramide NP did. In conclusion, natural oil-derived phytoceramides could represent a novel class of ceramides for cosmetic applications in the development of an ideal skin barrier moisturizer.
PMID: 28979153 [PubMed]
Psychische Begleiterkrankungen beim Knochen- und Weichteilsarkom
Abstract
Hintergrund
Sarkome umfassen eine seltene und histologisch heterogene Gruppe solider maligner Tumoren. Patienten mit Sarkom sind eine bisher vergleichsweise wenig untersuchte Patientengruppe.
Ziel der Arbeit
Die Arbeit gibt einen Überblick über psychische Komorbiditäten von Patienten mit Knochen- und Weichteilsarkom.
Material und Methoden
Im Rahmen des Artikels wurde eine umfassende Literaturrecherche zum Thema psychische Komorbiditäten und emotionale Belastungen beim Sarkom durchgeführt und narrativ zusammengefasst. Dabei wurden auch entsprechende Determinanten sowie mögliche Ursachen berücksichtigt. Darüber hinaus werden Möglichkeiten zur Nutzung von „patient-reported outcomes" (PRO, Therapiebeurteilungen aus Patientensicht) zur Identifizierung psychischer Komorbiditäten diskutiert.
Ergebnisse
Bei Patienten mit Sarkom zeigen sich deutlich erhöhte psychosoziale Belastungen und psychische Komorbiditäten bei Diagnosestellung, während der Therapie und im weiteren Lebensverlauf. Besonders häufig werden dabei Depressionen (Prävalenz: 23–30%) und Angststörungen (Prävalenz: 13–19%) beschrieben. Zudem sind Sarkompatienten bereits vor der Diagnosestellung häufiger von psychischen Erkrankungen betroffen als krebsfreie Personen. Einschränkungen der Lebensqualität sind insbesondere unmittelbar bei Diagnosestellung und während der Therapie häufig.
Schlussfolgerung
Zur frühzeitigen Identifikation und Behandlung von psychischen Begleiterkrankungen sollten Patienten mit Sarkom sorgfältig und regelmäßig bezüglich emotionaler Belastungen und psychischer Erkrankungsmuster gescreent werden. Außerdem sollte eine adäquate psychoonkologische Betreuung sichergestellt sein. Die routinemäßige Erfassung und Integration von PRO in den Versorgungsalltag kann dabei zu einer deutlichen Verbesserung der Versorgung von Patienten mit Sarkomerkrankungen führen.
Teilchenstrahltherapie in der Radioonkologie
Zusammenfassung
Die Protonentherapie ist eine Form der Teletherapie in der Radioonkologie, welche verwendet wird, um maligne Tumoren zu behandeln. Die Protonen werden im Zyklotron oder Synchrotron beschleunigt, um die Tumoren mit hochenergetischen Partikeln von bis zu 230 Megaelektronenvolt (MeV) mittels Passive-Scattering- oder aktivem Scanning-Beam-Verfahren zu bestrahlen. Durch die spezifischen physikalischen Eigenschaften der Protonen kann mit hochpräziser Planung das Zielvolumen bestrahlt und die hinter dem Zielvolumen liegenden Risikoorgane i. Allg. besser geschont werden als mit Photonen. Neben erwachsenen Patienten mit Tumoren der Schädelbasis oder Chordomen/Chondrosarkomen profitieren v. a. Kinder von dieser Therapie, da mit Protonen die integrale Körperdosis sowie die Dosis auf heranwachsende strahlensensible Organe reduziert werden kann. Die Protonentherapie umfasst ein breites Forschungsgebiet, daher sollten momentan alle Patienten in Studien behandelt werden.
Comparison of transient severe motion in gadoxetate disodium and gadopentetate dimeglumine-enhanced MRI: effect of modified breath-holding method
Abstract
Objectives
To compare the occurrence of transient severe motion (TSM) between gadoxetate disodium- and gadopentetate dimeglumine-enhanced MRI and between gadoxetate disodium-enhanced MRI scans obtained with and without the application of a modified breath-holding technique.
Methods
We reviewed 80 patients who underwent two magnetic resonance examinations (gadoxetate disodium-enhanced MRI and gadopentetate dimeglumine-enhanced MRI) with the application of a modified breath-holding technique (dual group). This group was compared with 100 patients who underwent gadoxetate disodium-enhanced MRI without the application of the modified breath-holding technique (single group). Patient risk factors and motion scores (1 [none] to 5 [non-diagnostic]) for each dynamic-phase imaging were analysed.
Results
In the dual group, mean motion scores did not differ significantly between gadoxetate disodium- and gadopentetate dimeglumine-enhanced MRI (p=0.096–0.807) in any phase. However, in all phases except the late dynamic phase, mean motion scores of the dual group were significantly lower than those in the single group. TSM incidence did not differ significantly between gadoxetate disodium- and gadopentetate dimeglumine-enhanced MRI in the dual group (3.8% vs. 1.3%, p=0.620).
Conclusion
With proper application of the modified breath-holding technique, TSM occurrence with gadoxetate disodium-enhanced MRI was comparable to that associated with gadopentetate dimeglumine-enhanced MRI.
Key Points
• The modified breath-holding method significantly reduced the incidence of TSM.
• Gadoxetate disodium and gadopentetate dimeglumine showed comparable motion scores.
• TSM incidence was comparable between gadoxetate disodium- and gadopentetate dimeglumine-enhanced MRI.
Comparative reliability and diagnostic performance of conventional 3T magnetic resonance imaging and 1.5T magnetic resonance arthrography for the evaluation of internal derangement of the hip
Abstract
Objective
To compare the diagnostic accuracy of conventional 3T MRI against 1.5T MR arthrography (MRA) in patients with clinical femoroacetabular impingement (FAI).
Methods
Sixty-eight consecutive patients with clinical FAI underwent both 1.5T MRA and 3T MRI. Imaging was prospectively analysed by two musculoskeletal radiologists, blinded to patient outcomes and scored for internal derangement including labral and cartilage abnormality. Interobserver variation was assessed by kappa analysis. Thirty-nine patients subsequently underwent hip arthroscopy and surgical results and radiology findings were analysed.
Results
Both readers had higher sensitivities for detecting labral tears with 3T MRI compared to 1.5T MRA (not statistically significant p=0.07). For acetabular cartilage defect both readers had higher statistically significant sensitivities using 3T MRI compared to 1.5T MRA (p=0.02). Both readers had a slightly higher sensitivity for detecting delamination with 1.5T MRA compared to 3T MRI, but these differences were not statistically significant (p=0.66). Interobserver agreement was substantial to perfect agreement for all parameters except the identification of delamination (3T MRI showed moderate agreement and 1.5T MRA substantial agreement).
Conclusion
Conventional 3T MRI may be at least equivalent to 1.5T MRA in detecting acetabular labrum and possibly superior to 1.5T MRA in detecting cartilage defects in patients with suspected FAI.
Key Points
• Conventional 3T MRI is equivalent to 1.5T MRA for diagnosing labral tears.
• Conventional 3T MRI is superior to 1.5T MRA for diagnosing acetabular cartilage defect.
• Conventional 3T MRI is equivalent to 1.5T MRA for diagnosing cartilage delamination.
• Symptom severity score was significantly higher (p<0.05) in group proceeding to surgery.
Does trade matter for carbon emissions in OECD countries? Evidence from a new trade openness measure
Abstract
This paper analyzes the impacts of the per capita income, the per capita energy consumption, and the trade openness on the level of per capita carbon emissions in the panel dataset of 35 Organization for Economic Cooperation and Development (OECD) countries over the period 1960–2013. Along with the nominal trade openness, the paper uses a different trade openness measure, so called as the "trade potential index" (TPI). To the best of our knowledge, this is the first paper that uses the TPI in the empirical environmental Kuznets curve (EKC) hypothesis literature. The paper finds that the EKC hypothesis is valid and there is an "inverted-U" relationship between the income and the carbon emissions. In addition, the paper observes that there is a positive effect of the energy consumption on the carbon emissions. Furthermore, the results indicate that both trade openness measures are negatively associated with the carbon emissions in the OECD countries in the long run.
How Frequent Is Itch? Facts and Thoughts of a Long Neglected Aspect of Itch
Abstract
Purpose of Review
Itch is the most frequent symptom of the skin, but its epidemiology including frequency has not been researched until a few years ago. Data is limited due to, e.g., the undulatory pattern of this symptom and the wide clinical spectrum such as itch being associated with a skin disease and itch on normal-looking skin. In addition, itch is an interdisciplinary symptom that is not paid attention to the same way in all clinical disciplines. This diversity may explain the incompleteness of epidemiological data of itch.
Recent Findings
With a recurrent symptom, it is important to consider different prevalence estimates (point-, 12-month, and lifetime prevalence) and to have a clear definition of itch. Recent population-based research demonstrates that more people suffer from chronic itch than previously assumed.
Summary
The chapter summarizes new findings concerning the epidemiology of itch in the general population and in selected patient populations.
Association of weight change with progression of meniscal intrasubstance degeneration over 48 months: Data from the Osteoarthritis Initiative
Abstract
Objectives
To investigate the association of weight change over 48 months with progression of meniscal intrasubstance degeneration (MID).
Methods
We studied 487 subjects with MID at baseline and after 48 months using 3-T MRI with the same protocol (FSE sequences with and without fat suppression). These participants lost weight (≥3%, n = 141), had moderate weight gain (3–10%, n = 77), substantial weight gain (>10%, n = 15) or maintained stable weight (n = 254). Progression of MID to a meniscal tear was assessed using the WORMS grading system and compared among weight change groups using logistic regression. ANOVA and chi-square tests were used to study the differences in subjects' characteristics.
Results
Progression of MID increased from weight loss to substantial weight gain (p < 0.001) and was significantly more likely with both moderate weight gain (odds ratio [OR], 4.9; 95% confidence interval [CI] 2.4–8.9) and substantial weight gain (OR, 9.5; 95% CI 3.2–28.5) compared to stable weight. Results were similar in both menisci for moderate weight gain (medial: OR, 6.8; 95% CI 3.5–11.3; lateral: OR, 2.6; 95% CI 1.1–6.6) and substantial weight gain (medial: OR, 21.0; 95% CI 5.1–80.7; lateral: OR, 9.7; 95% CI 0.95–100.2).
Conclusion
Weight gain is associated with an increased likelihood that meniscal intrasubstance degeneration will progress with the risk increasing with greater weight gain.
Key Points
• Subjects who gained weight were more likely to develop meniscal tears.
• Greater amount of weight gain was associated with an increasing likelihood of progression.
• Prevention of weight gain has health benefits for the meniscus.
Incidental perifissural nodules on routine chest computed tomography: lung cancer or not?
Abstract
Objectives
Perifissural nodules (PFNs) are a common finding on chest CT, and are thought to represent non-malignant lesions. However, data outside a lung cancer-screening setting are currently lacking.
Methods
In a nested case-control design, out of a total cohort of 16,850 patients ≥ 40 years of age who underwent routine chest CT (2004-2012), 186 eligible subjects with incident lung cancer and 511 controls without were investigated. All non-calcified nodules ≥ 4 mm were semi-automatically annotated. Lung cancer location and subject characteristics were recorded.
Results
Cases (56 % male) had a median age of 64 years (IQR 59–70). Controls (60 % male) were slightly younger (p<0.01), median age of 61 years (IQR 51–70). A total of 262/1,278 (21 %) unique non-calcified nodules represented a PFN. None of these were traced to a lung malignancy over a median follow-up of around 4.5 years. PFNs were most often located in the lower lung zones (72 %, p<0.001). Median diameter was 4.6 mm (range: 4.0–8.1), volume 51 mm3 (range: 32–278). Some showed growth rates < 400 days.
Conclusions
Our data show that incidental PFNs do not represent lung cancer in a routine care, heterogeneous population. This confirms prior screening-based results.
Key Points
• One-fifth of non-calcified nodules represented a perifissural nodule in our non-screening population.
• PFNs fairly often show larger size, and can show interval growth.
• When morphologically resembling a PFN, nodules are nearly certainly not a malignancy.
• The assumed benign aetiology of PFNs seems valid outside the screening setting.
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Publication date: Available online 25 July 2018 Source: Journal of Photochemistry and Photobiology B: Biology Author(s): Marco Ballestr...
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Editorial AJR Reviewers: Heartfelt Thanks From the Editors and Staff Thomas H. Berquist 1 Share + Affiliation: Citation: American Journal...
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Publication date: Available online 28 September 2017 Source: Actas Dermo-Sifiliográficas Author(s): F.J. Navarro-Triviño
