Radiation induces age-dependent deficits in cortical synaptic plasticity

Abstract

Background

Radiation-induced cognitive dysfunction is a significant side effect of cranial irradiation for brain tumors. Clinically, pediatric patients are more vulnerable than adults. However, the underlying mechanisms of dysfunction, including reasons for age dependence, are still largely unknown. Previous studies have focused on the loss of hippocampal neuronal precursor cells and deficits in memory. However, survivors may also experience deficits in attention, executive function, or other non-hippocampal–dependent cognitive domains. We hypothesized that brain irradiation induces age-dependent deficits in cortical synaptic plasticity.

Methods

In vivo recordings were used to test neuronal plasticity along the direct pathway from the CA1/subicular region to the prefrontal cortex (PFC). Specifically, long-term potentiation (LTP) in the CA1/subicular-PFC pathway was assessed after cranial irradiation of juvenile and adult Sprague Dawley rats. We further assessed a potential role for glutamate toxicity by evaluating the potential neuroprotective effects of memantine.

Results

LTP was greatly inhibited in both adult and juvenile animals at 3 days after radiation but returned to near-normal levels by 8 weeks—only in adult rats. Memantine given before, but not after, irradiation partially prevented LTP inhibition in juvenile and adult rats.

Conclusion

Cranial radiation impairs neuroplasticity along the hippocampal-PFC pathway; however, its effects vary by age. Pretreatment with memantine offered protection to both juvenile and adult animals. Deficits in cortical plasticity may contribute to radiation-induced cognitive dysfunction, including deficits in attention and age-dependent sensitivity of such pathways, which may underlie differences in clinical outcomes between juveniles and adults after cranial irradiation.

Validation of post-operative residual contrast enhancing tumor volume as an independent prognostic factor for overall survival in newly diagnosed glioblastoma

Abstract

Background

In the current study, we pooled imaging data in newly diagnosed GBM patients from international multicenter clinical trials, single institution databases, and multicenter clinical trial consortiums to identify the relationship between post-operative residual enhancing tumor volume and overall survival (OS).

Methods

Data from 1,511 newly diagnosed GBM patients from 5 data sources were included in the current study: 1) a single institution database from UCLA (N=398; Discovery); 2) patients from the Ben and Cathy Ivy Foundation for Early Phase Clinical Trials Network Radiogenomics Database (N=262 from 8 centers; Confirmation); 3) the chemoradiation placebo arm from an international phase III trial (AVAglio; N=394 from 120 locations in 23 countries; Validation); 4) the experimental arm from AVAglio examining chemoradiation plus bevacizumab (N=404 from 120 locations in 23 countries; Exploratory Set 1); and 5) an Alliance (N0874) Phase I/II trial of vorinostat plus chemoradiation (N=53; Exploratory Set 2). Post-surgical, residual enhancing disease was quantified using T1 subtraction maps. Multivariate Cox regression models were used to determine influence of clinical variables, MGMT status, and residual tumor volume on OS.

Results

A log-linear relationship was observed between post-operative, residual enhancing tumor volume and OS in newly diagnosed GBM treated with standard chemoradiation. Post-operative tumor volume is a prognostic factor for OS (P<0.01), regardless of therapy, age, and MGMT promoter methylation status.

Conclusion

Post-surgical, residual contrast-enhancing disease significantly negatively influences survival in patients with newly diagnosed glioblastoma treated with chemoradiation with or without concomitant experimental therapy.

Modeling the diffusion of D-2-hydroxyglutarate from IDH1 mutant gliomas in the central nervous system

Abstract

Background

20-30% of diffusely infiltrative gliomas in adults contain a point mutation in isocitrate dehydrogenase 1 (IDH1^mut), which increases production of D-2-hydroxyglutarate (D2HG). This is so efficient that D2HG often reaches 30 mM within IDH1^mut gliomas. Yet, while up to 100 µM D2HG can be detected in the circulating cerebrospinal fluid of IDH1^mut glioma patients, the exposure of nonneoplastic cells within and surrounding an IDH1^mut glioma to D2HG is unknown and difficult to measure directly.

Methods

Conditioned medium from patient-derived IDH1^wt and IDH1^mut glioma cells was analyzed for D2HG by liquid chromatography-mass spectrometry (LC-MS). Mathematical models of D2HG release and diffusion around an IDH1^mut glioma were independently generated based on fluid dynamics within the brain, and on previously reported intratumoral and cerebrospinal D2HG concentrations.

Results

LC-MS analysis indicates that patient-derived IDH1^mut glioma cells release 3.7-97.0 pg D2HG per cell per week. Extrapolating this to an average-sized tumor (30 mL glioma volume and 1x10⁸cells/mL tumor), the rate of D2HG release by an IDH1^mut glioma (S_A) is estimated at 3.2-83.0x10^-12 moles/ml/sec. Mathematical models estimate an S_A of 2.9-12.9x10^-12 moles/ml/sec, within the range of the in vitro LC-MS data. In even the most conservative of these models, the extracellular concentration of D2HG exceeds 3 mM within a 2 cm radius from the center of an IDH1^mut glioma.

Conclusions

The microenvironment of an IDH1^mut glioma is likely being exposed to high concentrations of D2HG, in the low millimolar range. This has implications for understanding how D2HG affects nonneoplastic cells in an IDH1^mut glioma.

Volumetric response quantified using T1 subtraction predicts long-term survival benefit from cabozantinib monotherapy in recurrent glioblastoma

Abstract

Background

To overcome challenges with traditional response assessment in anti-angiogenc agents, the current study uses T1 subtraction maps to quantify volumetric radiographic response in cabozantinib monotherapy, an orally bioavailable tyrosine kinase inhibitor with activity against VEGFR2, MET, and AXL, in an open-label, phase II trial in patients with recurrent glioblastoma (NCT00704288).

Methods

A total of 108 patients with adequate imaging data and confirmed recurrent GBM were included in this retrospective study from a phase II multicenter trial of cabozantinib monotherapy (XL184-201) at either 100mg (N=87) or 140mg (N=21) per day. Contrast enhanced T1-weighted digital subtraction maps were used to define volume of contrast enhancing tumor at baseline and subsequent follow-up time points. Volumetric radiographic response (>65% reduction in contrast enhancing tumor volume from pre-treatment baseline tumor volume sustained for more than 4 weeks) was tested as an independent predictor of overall survival (OS).

Results

Volumetric response rate (VRR) for all therapeutic doses was 38.9% (41.4% and 28.6% for 100mg and 140mg doses, respectively). A log-linear association between baseline tumor volume and OS (P=0.0006) and a linear correlation between initial change in tumor volume and OS (P=0.0256) were observed. A significant difference in OS was observed between responders (median OS=20.6 months) and non-responders (median OS=8.0 months) (HR=0.3050, P<0.0001). Multivariable analyses showed continuous measures of baseline tumor volume (HR=1.0233, P<0.0001) and volumetric response (HR=0.2240, P<0.0001) were independent predictors of OS.

Conclusions

T1 subtraction maps provide value in determining response in recurrent GBM treated with cabozantinib and correlated with survival benefit.

Targeting the human epidermal growth factor receptor 2 (HER2) oncogene in colorectal cancer

Abstract

BACKGROUND

Human epidermal growth factor receptor 2 (HER2) is an oncogenic driver, and a well-established therapeutic target in breast and gastric cancers. Using functional and genomic analyses of patient-derived xenografts, we previously showed that a subset (approximately 5%) of metastatic colorectal cancer (CRC) tumors are driven by amplification or mutation of HER2.

MATERIALS AND METHODS

This paper reviews the role of HER2 as an oncogenic driver, a prognostic and predictive biomarker, and a clinically actionable target in CRC, considering the specifics of HER2 testing in this tumor type.

RESULTS

While the role of HER2 as a biomarker for prognosis in CRC remains uncertain, its relevance as a therapeutic target has been established. Indeed, independent studies documented substantial clinical benefit in patients treated with biomarker-driven HER2-targeted therapies, with an impact on response rates and duration of response that compared favorably with immunotherapy and other examples of precision oncology.

CONCLUSION

HER2-targeted therapeutic strategies have the potential to change the treatment paradigm for a clinically relevant subgroup of metastatic CRC patients.

Wu Song’s Killing of His Sister-in-law: An Ethical Analysis

Abstract

The Water Margin is a great Chinese classical novel; Wu Song's 武松 killing of his sister-in-law, Pan Jinlian 潘金蓮, is one of the most popular episodes of the novel. It depicts Wu as the hero and defender of traditional values, and Pan as the adulterous woman. In contemporary discussion, there has been a dearth of ethical analyses regarding Wu's killing of Pan. How should we judge the moral status of his action? Does the killing signify Wu Song's ethical achievement or his ethical failure? What does the killing tell us about Wu's character or his virtues? Does our appraisal of Wu's action square with our modern belief regarding the treatment of women? I will examine these questions in the article.

Characteristic MR Imaging Findings of the Neonatal Brain in RASopathies [PEDIATRICS]

BACKGROUND AND PURPOSE:

Neuroimaging features in neonates with RASopathies are rarely reported, and to date, there are no neuroimaging studies conducted in this population. Our aim was to investigate the occurrence of supratentorial and posterior fossa abnormalities on brain MRIs of neonates with a RASopathy.

MATERIALS AND METHODS:

An observational case-control study of neonates with a confirmed RASopathy was conducted. The presence of an intraventricular and/or parenchymal hemorrhage and punctate white matter lesions and assessments of the splenium of the corpus callosum, gyrification of the cortical gray matter, and enlargement of the extracerebral space were noted. The vermis height, transverse cerebellar diameter, cranial base angle, tentorial angle, and infratentorial angle were measured.

RESULTS:

We reviewed 48 brain MR studies performed at 3 academic centers in 3 countries between 2009 and 2017. Sixteen of these infants had a genetically confirmed RASopathy (group 1), and 32 healthy infants were enrolled as the control group (group 2). An increased rate of white matter lesions, extracerebral space enlargement, simplification of the cortical gyrification, and white matter abnormalities were seen in group 1 (P < .001, for each). The vermis height of patients was significantly lower, and tentorial and infratentorial angles were significantly higher in group 1 (P = .01, P < .001, and P = .001, respectively).

CONCLUSIONS:

Neonates with a RASopathy had characteristic structural and acquired abnormalities in the cortical gray matter, white matter, corpus callosum, cerebellum, and posterior fossa. This study provides novel neuroimaging findings on supratentorial and posterior fossa abnormalities in neonates with a RASopathy.

Cavitary Plaques in Otospongiosis: CT Findings and Clinical Implications [HEAD & NECK]

BACKGROUND AND PURPOSE:

Cavitary plaques have been reported as a manifestation of otospongiosis. They have been related to third window manifestations, complications during cochlear implantation, and sensorineural hearing loss. However, their etiology and clinical implications are not entirely understood. Our purpose was to determine the prevalence, imaging findings, and clinical implications of cavitary plaques in otospongiosis.

MATERIALS AND METHODS:

We identified patients with otospongiosis at a tertiary care academic medical center from January 2012 to April 2017. Cross-sectional CT images and clinical records of 47 patients (89 temporal bones) were evaluated for the presence, location, and imaging features of cavitary and noncavitary otospongiotic plaques, as well as clinical symptoms and complications in those who underwent cochlear implantation.

RESULTS:

Noncavitary otospongiotic plaques were present in 86 (97%) temporal bones and cavitary plaques in 30 (35%). Cavitary plaques predominated with increasing age (mean age, 59 years; P = .058), mostly involving the anteroinferior wall of the internal auditory canal (P = .003), and their presence was not associated with a higher grade of otospongiosis by imaging (P = .664) or with a specific type of hearing loss (P = .365). No patients with cavitary plaques had third window manifestations, and those with a history of cochlear implantation (n = 6) did not have complications during the procedure.

CONCLUSIONS:

Cavitary plaques occurred in one-third of patients with otospongiosis. Typically, they occurred in the anteroinferior wall of the internal auditory canal. There was no correlation with the degree of otospongiosis, type of hearing loss, or surgical complications. Cavitary plaques tended to present in older patients.

Who's Contributing Most to American Neuroscience Journals: American or Foreign Authors? [RESEARCH PERSPECTIVES]

BACKGROUND AND PURPOSE:

With globalization, the contributions of authors from abroad to the American published literature has increased. We sought to determine the changes with time in the proportional contributions of American and non-American authors in the American neurosciences literature. We hypothesized the following: 1) During the past 21 years, manuscript contributions of American institutions have proportionally decreased in neuroradiology, more than in neurosurgery or neurology; 2) contributions of Asian institutions have affected neuroradiology more than neurosurgery and neurology; and 3) American articles garner more citations.

MATERIALS AND METHODS:

We reviewed the May issues of 2 of the highest impact American-based neurology, neurosurgery, and neuroradiology journals published from 1997 to 2017. We counted the number of articles published by nation based on the institution of origin. We looked at trends across time and compared neurology, neurosurgery, and neuroradiology journals. We also gathered data on the number of citations of each article by nationality.

RESULTS:

We reviewed 3025 articles. There was a significantly lower ratio of American to non-American authorship in neuroradiology versus neurology/neurosurgery journals (odds ratio = 0.70; 95% confidence interval, 0.60–0.82). There was a significantly decreasing trend in American authorship across the 21 years in neuroradiology. Of the countries outside the United States, Japan contributed most for neuroradiology and neurosurgery journals, and the UK, for neurology. American-authored articles were cited, on average, 1.25 times more frequently than non-American-authored articles.

CONCLUSIONS:

Non-American contributions have impacted neuroradiology more than other clinical neuroscience fields with Asian authorship showing the greatest impact. That impact is growing, and the causes are manifold. Nonetheless American-authored articles are cited more.

Accuracy of CT Angiography for Differentiating Pseudo-Occlusion from True Occlusion or High-Grade Stenosis of the Extracranial ICA in Acute Ischemic Stroke: A Retrospective MR CLEAN Substudy [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

The absence of opacification on CTA in the extracranial ICA in acute ischemic stroke may be caused by atherosclerotic occlusion, dissection, or pseudo-occlusion. The latter is explained by sluggish or stagnant flow in a patent artery caused by a distal intracranial occlusion. This study aimed to explore the accuracy of CTA for differentiating pseudo-occlusion from true occlusion of the extracranial ICA.

MATERIALS AND METHODS:

All patients from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) with an apparent ICA occlusion on CTA and available DSA images were included. Two independent observers classified CTA images as atherosclerotic cause (occlusion/high-grade stenosis), dissection, or suspected pseudo-occlusion. Pseudo-occlusion was suspected if CTA showed a gradual contrast decline located above the level of the carotid bulb, especially in the presence of an occluded intracranial ICA bifurcation (T-occlusion). DSA images, classified into the same 3 categories, were used as the criterion standard.

RESULTS:

In 108 of 476 patients (23%), CTA showed an apparent extracranial carotid occlusion. DSA was available in 46 of these, showing an atherosclerotic cause in 13 (28%), dissection in 16 (35%), and pseudo-occlusion in 17 (37%). The sensitivity for detecting pseudo-occlusion on CTA was 82% (95% CI, 57–96) for both observers; specificity was 76% (95% CI, 56–90) and 86% (95% CI, 68–96) for observers 1 and 2, respectively. The value for interobserver agreement was .77, indicating substantial agreement. T-occlusions were more frequent in pseudo- than true occlusions (82% versus 21%, P < .001).

CONCLUSIONS:

On CTA, extracranial ICA pseudo-occlusions can be differentiated from true carotid occlusions.

MRI Planimetry and Magnetic Resonance Parkinsonism Index in the Differential Diagnosis of Patients with Parkinsonism [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Differential diagnosis of multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration from Parkinson disease on clinical grounds is often difficult. MR imaging biomarkers could assist in a more accurate diagnosis. We examined the utility of MR imaging surface measurements (MR imaging planimetry) in the differential diagnosis of patients with parkinsonism.

MATERIALS AND METHODS:

Fifty-two patients with Parkinson-plus (progressive supranuclear palsy, n = 24; corticobasal degeneration, n = 9; multiple system atrophy, n = 19), 18 patients with Parkinson disease, and 15 healthy controls were included. Corpus callosum, midbrain, and pons surfaces; relevant indices; and the Magnetic Resonance Parkinsonism Index were calculated. Corpus callosum subsection analysis was performed, and the corpus callosum posteroanterior gradient was introduced.

RESULTS:

A Magnetic Resonance Parkinsonism Index value of >12.6 discriminated progressive supranuclear palsy from other causes of parkinsonism with a 91% sensitivity and 95% specificity. No planimetry measurement could accurately discriminate those with multiple system atrophy with parkinsonism from patients with Parkinson disease. A corpus callosum posteroanterior gradient value of ≤191 was highly specific (97%) and moderately sensitive (75%) for the diagnosis of corticobasal degeneration versus all other groups. A midbrain-to-corpus callosum posteroanterior gradient ratio of ≤0.45 was highly indicative of progressive supranuclear palsy over corticobasal degeneration (sensitivity 86%, specificity 88%).

CONCLUSIONS:

MR imaging planimetry measurements are potent imaging markers of progressive supranuclear palsy and promising markers of corticobasal degeneration but do not seem to assist in the diagnosis of multiple system atrophy with parkinsonism.

Slow Collateral Flow Is Associated with Thrombus Extension in Patients with Acute Large-Artery Occlusion [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

It is still poorly understood about the dynamic changes of the thrombus after intravenous thrombolysis and how the remaining thrombus affects clinical outcome in human stroke. Collateral flow was assumed to help to deliver endo/exogenous tissue-type plasminogen activator to the clot. We aimed to analyze the impact of collateral flow on the dynamic changes of the thrombus in patients with acute large-artery occlusion who received intravenous thrombolysis.

MATERIALS AND METHODS:

We reviewed consecutive patients with acute ischemic stroke with M1 segment or distal internal carotid artery occlusion who underwent multimodal MR imaging or CT perfusion before and 24 hours after intravenous thrombolysis without recanalization. Patients were divided into 3 groups (thrombus extension, shortening, and no change) according to thrombus-length change between baseline and 24 hours. Collateral flow was measured with arrival time delay and the collateral scoring system. Poor outcome was defined as a 3-month modified Rankin Scale score of ≥3.

RESULTS:

Among 51 patients, 18 (35.3%) had thrombus extension, 14 (27%) had thrombus shortening, and 19 (37.3%) had thrombus without change. Arrival time delay was independently associated with thrombus extension (OR = 1.499; 95% CI, 1.053–2.135; P = .025). Similarly, the collateral score on the peak artery phase was independently associated with thrombus extension (OR = 0.456; 95% CI, 0.211–0.984; P = .045), whereas baseline National Institutes of Health Stroke Scale score (OR = 0.768; 95% CI, 0.614–0.961; P = .021) and baseline thrombus length (OR = 1.193; 95% CI, 1.021–1.394; P = .026) were associated with thrombus shortening. All patients with thrombus extension had poor outcomes.

CONCLUSIONS:

Slow collateral flow was related to thrombus extension in patients with large-artery occlusion without recanalization after intravenous thrombolysis.

Edge Contrast of the FLAIR Hyperintense Region Predicts Survival in Patients with High-Grade Gliomas following Treatment with Bevacizumab [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Treatment with bevacizumab is standard of care for recurrent high-grade gliomas; however, monitoring response to treatment following bevacizumab remains a challenge. The purpose of this study was to determine whether quantifying the sharpness of the fluid-attenuated inversion recovery hyperintense border using a measure derived from texture analysis—edge contrast—improves the evaluation of response to bevacizumab in patients with high-grade gliomas.

MATERIALS AND METHODS:

MRIs were evaluated in 33 patients with high-grade gliomas before and after the initiation of bevacizumab. Volumes of interest within the FLAIR hyperintense region were segmented. Edge contrast magnitude for each VOI was extracted using gradients of the 3D FLAIR images. Cox proportional hazards models were generated to determine the relationship between edge contrast and progression-free survival/overall survival using age and the extent of surgical resection as covariates.

RESULTS:

After bevacizumab, lower edge contrast of the FLAIR hyperintense region was associated with poorer progression-free survival (P = .009) and overall survival (P = .022) among patients with high-grade gliomas. Kaplan-Meier curves revealed that edge contrast cutoff significantly stratified patients for both progression-free survival (log-rank ² = 8.3, P = .003) and overall survival (log-rank ² = 5.5, P = .019).

CONCLUSIONS:

Texture analysis using edge contrast of the FLAIR hyperintense region may be an important predictive indicator in patients with high-grade gliomas following treatment with bevacizumab. Specifically, low FLAIR edge contrast may partially reflect areas of early tumor infiltration. This study adds to a growing body of literature proposing that quantifying features may be important for determining outcomes in patients with high-grade gliomas.

Clival Malformations in CHARGE Syndrome [PEDIATRICS]

BACKGROUND AND PURPOSE:

CHARGE syndrome is a multisystemic congenital disorder, most commonly including coloboma, heart malformations, choanal atresia, developmental delay, and genital and ear anomalies. The diagnostic criteria for CHARGE syndrome have been refined with time. However, limited reports describe skull base and craniocervical junction abnormalities. Recently, a coronal clival cleft has been identified in association with CHARGE syndrome. The aim of our study was to assess the prevalence of clival pathology in CHARGE syndrome.

MATERIALS AND METHODS:

In this retrospective study, the CT/MR imaging data base at a single academic children's hospital was queried for the phrase "CHARGE syndrome" during a 17-year period (2001–2017). Electronic medical records were reviewed to confirm the diagnosis. Images were assessed for skull base anomalies, specifically clival hypoplasia and dysplasia.

RESULTS:

The search yielded 42 examinations (21 CTs and 21 MRIs) from 15 distinct patients (mean age, 4.1 ± 5.6 years; range, 2 days to 19 years). CHARGE syndrome diagnosis was confirmed either by clinical and genetic testing (n = 6) or by clinical diagnosis only (n = 9). A coronal clival cleft was identified in 87% of patients (37 examinations, n = 13 patients), either partial (53%) or complete (33%). Clival hypoplasia without clefting was present in all 5 examinations from the remaining 2 patients.

CONCLUSIONS:

Clival pathology is universal in CHARGE syndrome. Coronal clival clefts are extremely common, representing a useful additional diagnostic finding. Detection of a clival cleft should alert the radiologist to examine the palate, choana, eyes, ears, and olfactory centers for other signs of CHARGE syndrome.

Different relationships between personal exposure and ambient concentration by particle size

Abstract

Ambient particulate matter (PM) concentrations at monitoring stations were often used as an indicator of population exposure to PM in epidemiological studies. The correlation between personal exposure and ambient concentrations of PM varied because of diverse time-activity patterns. The aim of this study was to determine the relationship between personal exposure and ambient concentrations of PM₁₀ and PM_2.5 with minimal impact of time-activity pattern on personal exposure. Performance of the MicroPEM, v3.2 was evaluated by collocation with central ambient air monitors for PM₁₀ and PM_2.5. A field technician repeatedly conducted measurement of 24 h personal exposures to PM₁₀ and PM_2.5 with a fixed time-activity pattern of office worker over 26 days in Seoul, Korea. The relationship between the MicroPEM and the ambient air monitor showed good linearity. Personal exposure and ambient concentrations of PM_2.5 were highly correlated with a fixed time-activity pattern compared with PM₁₀. The finding implied a high infiltration rate of PM_2.5 and low infiltration rate of PM₁₀. The relationship between personal exposure and ambient concentrations of PM₁₀ and PM_2.5 was different for high level episodes. In the Asian dust episode, staying indoors could reduce personal exposure to PM₁₀. However, personal exposure to PM_2.5 could not be reduced by staying indoors during the fine dust advisory episode.

The association between serum copper concentrations and cardiovascular disease risk factors in children and adolescents in NHANES

Abstract

Copper is an essential element in human beings, alterations in serum copper levels could potentially have effect on human health. To date, no data are available regarding how serum copper affects cardiovascular disease (CVD) risk factors in children and adolescents. We examined the association between serum copper levels and CVD risk factors in children and adolescents. We analyzed data consisting of 1427 subjects from a nationally representative sample of the US population in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. The CVD risk factors included total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, fasting glucose, glycohemoglobin, fasting insulin, and blood pressure. Multivariate and generalized linear regressions were performed to investigate associations adjusted for age, gender, ethnicity, poverty:income ratio (PIR), BMI, energy intake, and physical activity. We found significant associations between serum copper and total cholesterol (coefficient = 0.132; 95% CI 0.081, 0.182; P for trend < 0.001), glycohemoglobin (coefficient = 0.044; 95% CI 0.020, 0.069; P < 0.001), and fasting insulin (coefficient = 0.730; 95% CI 0.410, 1.050; P < 0.001) among the included participants. Moreover, in the generalized linear models, subjects with the highest copper levels demonstrated a 0.83% (95% CI 0.44%, 1.24%) greater increase in serum total cholesterol (p for trend < 0.001) when compared to participants with the lowest copper concentrations. Our results provide the first epidemiological evidence that serum copper concentrations are associated with total cholesterol concentrations in children and adolescents. However, the underlying mechanisms still need further exploration.

Contrasting congener profiles for persistent organic pollutants and PAH monitoring in European storm petrels ( Hydrobates pelagicus ) breeding in Ireland: a preen oil versus feathers approach

Abstract

Persistent organic pollutants (POPs) and polycyclic aromatic hydrocarbons (PAHs) are anthropogenic contaminants of environmental concern due to their persistence in the environment and capacity to accumulate in biota. Many of these contaminants have been found to have ill effects over wildlife and humans. Birds are known to be particularly affected through endocrine disruption and eggshell thinning. POPs have been banned or restricted through the Stockholm Convention (2001), making monitoring essential for tracking effects of regulation. Seabirds have been used as monitoring tools for being top predators and consuming a diverse array of prey in different trophic levels. Non-destructive sampling has become widely popular using feathers and preen oil, as opposed to carcasses and internal organs. This study aimed to set baseline levels of POP and PAH concentration in a highly pelagic and abundant seabird in Ireland and the Atlantic, the European storm petrel, Hydrobates pelagicus, and to investigate the profiles of contaminant congeners in preen oil and feathers, comparatively. Mean concentrations in preen oil followed: PCB (10.1 ng/g ww) > PAH (7.1 ng/g ww) > OCP (5.4 ng/g ww) > PBDE (3.9 ng/g ww), whilst mean concentrations in feathers followed the order: PAH (38.9 ng/g ww) > PCB (27.2 ng/g ww) > OCP (17.9 ng/g ww) > PBDE (4.5 ng/g ww). Congener profiles highly differed between preen oil and feathers, and little correlation was found between the matrices. These results demonstrate that the sampling of a single matrix alone (preen oil or feathers) might produce confounding results on contamination in seabirds and that more than one matrix is recommended to obtain a full picture of contamination by persistent organic pollutants.

Moving beyond surveys to assess patient preferences

Relationship of inhaled corticosteroid adherence to asthma exacerbations in patients with moderate to severe asthma

Publication date: Available online 5 April 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Alberto Papi, Dermot Ryan, Joan B. Soriano, Henry Chrystyn, Leif Bjermer, Roberto Rodríguez-Roisin, Myrna B. Dolovich, Mark Harris, Lucy Wood, Maria Batsiou, Susannah I. Thornhill, David B. Price
BackgroundPatients with asthma and elevated blood eosinophils are at increased risk of severe exacerbations. Management of these patients should consider non-adherence to inhaled corticosteroid (ICS) therapy as a factor for increased exacerbation risk.ObjectiveTo investigate whether poor adherence to ICS therapy explains the occurrence of asthma exacerbations in patients with elevated blood eosinophil levels.MethodsThis historical cohort study identified patients within the Optimum Patient Care Research Database, aged ≥18 years, at Global Initiative for Asthma (GINA) steps 3 or 4, with ≥2 ICS prescriptions during the year prior to clinical review. Patient characteristics and adherence (based on prescription refills and patient self-report) for ICS therapy were analysed for those with elevated (>400 cells/μL) or normal (≤400 cells/μL) blood eosinophils.ResultsWe studied 7,195 patients (66% female, mean age 60 years) with median eosinophil count of 200 cells/μL and found 81% to be non-fully adherent to ICS therapy. 1,031 patients (14%) had elevated blood eosinophil counts (58% female, mean age 60 years), 83% of whom were non-fully adherent to ICS. An increased proportion of adherent patients in the elevated blood eosinophil group had ≥2 exacerbations (14.0% vs 7.2%; p=0.003) and uncontrolled asthma (73% vs 60.8%; p=0.004) as compared to non-fully adherent patients.ConclusionsApproximately one in seven patients had elevated eosinophils. Adherence to ICS therapy was not associated with decreased exacerbations for these patients. Additional therapy should be considered for these patients, such as biologics, which have been previously shown to improve control in severe uncontrolled eosinophilic asthma.

Intranasal instillation of iron oxide nanoparticles induces inflammation and perturbation of trace elements and neurotransmitters, but not behavioral impairment in rats

Abstract

Over the last decades, engineered nanomaterials have been widely used in various applications due to their interesting properties. Among them, iron oxide nanoparticles (IONPs) are used as theranostic agents for cancer, and also as contrast agents in magnetic resonance imaging. With the increasing production and use of these IONPs, there is an evident raise of IONP exposure and subsequently a higher risk of adverse outcome for humans and the environment. In this work, we aimed to investigate the effects of sub-acute IONP exposure on Wistar rat, particularly (i) on the emotional and learning/memory behavior, (ii) on the hematological and biochemical parameters, (iii) on the neurotransmitter content, and (vi) on the trace element homeostasis. Rats were treated during seven consecutive days by intranasal instillations at a dose of 10 mg/kg body weight. The mean body weight increased significantly in IONP-exposed rats. Moreover, several hematological parameters were normal in treated rats except the platelet count which was increased. The biochemical study revealed that phosphatase alkaline level decreased in IONP-exposed rats, but no changes were observed for the other hepatic enzymes (ALT and AST) levels. The trace element homeostasis was slightly modulated by IONP exposure. Sub-acute intranasal exposure to IONPs increased dopamine and norepinephrine levels in rat brain; however, it did not affect the emotional behavior, the anxiety index, and the learning/memory capacities of rats.

Skin Barrier Restoration and Moisturization Using Horse Oil-Loaded Dissolving Microneedle Patches

Background: Horse oil (HO) has skin barrier restoration and skin-moisturizing effects. Although cream formulations have been used widely and safely, their limited penetration through the stratum corneum is a major obstacle to maximizing the cosmetic efficacy of HO. Therefore, we aimed to encapsulate HO in a cosmetic dissolving microneedle (DMN) for efficient transdermal delivery. Methods: To overcome these limitations of skin permeation, HO-loaded DMN (HO-DMN) patches were developed and evaluated for their efficacy and safety using in vitro and clinical studies. Results: Despite the lipophilic nature of HO, the HO-DMN patches had a sharp shape and uniform array, with an average length and tip diameter of 388.36 ± 16.73 and 38.54 ± 5.29 µm, respectively. The mechanical strength of the HO-DMN patches was sufficient (fracture force of 0.29 ± 0.01 N), and they could successfully penetrate pig skin. During the 4-week clinical evaluation, HO-DMN patches caused significant improvements in skin and dermal density, skin elasticity, and moisturization. Additionally, a brief safety assessment showed that the HO-DMN patches induced negligible adverse events. Conclusion: The HO-DMNs are efficient, safe, and convenient for wide use in cosmetic applications for skin barrier restoration and moisturization.
Skin Pharmacol Physiol 2018;31:163–171

Outcomes From Lateral Eyelid Coupling for Facial Paralysis Using Modified Tarsoconjunctival Flap

This cohort study assesses whether lateral eyelid coupling in patients with facial paralysis improves quality of life as measured by the Facial Clinimetric Evaluation scale and Moe Ectropion Grading Scale.

Volumizing Hyaluronic Acid Filler for Infraorbital Hollows

This observational study reports safety and patient satisfaction outcomes of Juvéderm Voluma XC hyaluronic acid filler for correction of infraorbital hollows.

Polygenic risk score: use in migraine research

The latest Genome-Wide Association Study identified 38 genetic variants associated with migraine. In this type of studies the significance level is very difficult to achieve (5 × 10− 8) due to multiple testing. T...

Registration of 3D freehand ultrasound to a bone model for orthopedic procedures of the forearm

Abstract

Purpose

For guidance of orthopedic surgery, the registration of preoperative images and corresponding surgical plans with the surgical setting can be of great value. Ultrasound (US) is an ideal modality for surgical guidance, as it is non-ionizing, real time, easy to use, and requires minimal (magnetic/radiation) safety limitations. By extracting bone surfaces from 3D freehand US and registering these to preoperative bone models, complementary information from these modalities can be fused and presented in the surgical realm.

Methods

A partial bone surface is extracted from US using phase symmetry and a factor graph-based approach. This is registered to the detailed 3D bone model, conventionally generated for preoperative planning, based on a proposed multi-initialization and surface-based scheme robust to partial surfaces.

Results

36 forearm US volumes acquired using a tracked US probe were independently registered to a 3D model of the radius, manually extracted from MRI. Given intraoperative time restrictions, a computationally efficient algorithm was determined based on a comparison of different approaches. For all 36 registrations, a mean (± SD) point-to-point surface distance of \(0.57\,(\pm \,0.08)\,\hbox {mm}\) was obtained from manual gold standard US bone annotations (not used during the registration) to the 3D bone model.

Conclusions

A registration framework based on the bone surface extraction from 3D freehand US and a subsequent fast, automatic surface alignment robust to single-sided view and large false-positive rates from US was shown to achieve registration accuracy feasible for practical orthopedic scenarios and a qualitative outcome indicating good visual image alignment.

Patient-specific catheter shaping for the minimally invasive closure of the left atrial appendage

Abstract

Purpose

The minimally invasive closure of the left atrial appendage is a promising alternative to anticoagulation for stroke prevention in patients suffering from atrial fibrillation. One of the challenges of this procedure is the correct positioning and the coaxial alignment of the tip of the catheter sheath to the implant landing zone.

Method

In this paper, a novel preoperative planning system is proposed that allows patient-individual shaping of catheters to facilitate the correct positioning of the catheter sheath by offering a patient-specific catheter shape. Based on preoperative three-dimensional image data, anatomical points and the planned implant position are marked interactively and a patient-specific catheter shape is calculated if the standard catheter is not considered as suitable. An approach to calculate a catheter shape with four bends by maximization of the bending radii is presented. Shaping of the catheter is supported by a bending form that is automatically generated in the planning program and can be directly manufactured by using additive manufacturing methods.

Results

The feasibility of the planning and shaping of the catheter could be successfully shown using six data sets. The patient-specific catheters were tested in comparison with standard catheters by physicians on heart models. In four of the six tested models, the participating physicians rated the patient-individual catheters better than the standard catheter.

Conclusion

The novel approach for preoperatively planned and shaped patient-specific catheters designed for the minimally invasive closure of the left atrial appendage could be successfully implemented and a feasibility test showed promising results in anatomies that are difficult to access with the standard catheter.

Trends on PM 2.5 research, 1997–2016: a bibliometric study

Reduction mechanism of hexavalent chromium by functional groups of undissolved humic acid and humin fractions of typical black soil from Northeast China

Abstract

Soil organic matters (SOM) have a great retention effect on Cr(VI) migration in subsurface environment, which act as the main electron donors for Cr(VI) reduction; however, Cr(VI) reduction mechanism by different SOM fractions is still unclear, such as undissolved humic acid (HA) and humin (HM). In this study, HA and HM fractions extracted from typical black soil from Northeast China were used to investigate the reaction mechanism between humus functional groups and Cr(VI). According to the results, phenol and hydroxyl were determined as the main electron donors for Cr(VI) reduction by HA and HM instead of carboxyl and carbonyl, which were more likely involved in Cr complexation. Furthermore, Cr(VI) reduction was more dependent on aromatic carbon, rather than aliphatic carbon, and functional groups on the particle surfaces of HA and HM were much more active for Cr(VI) reduction than their interior part. Additionally, HM was found to have a relatively low Cr(VI) reduction capability compared with HA resulting from its high content of cellulose structures that are quite resistant to Cr(VI) oxidation. These results suggest that in the soil environment, undissolved HA tends to play a much more important role than HM in Cr(VI) reduction and retention in the condition that their mass contents are comparable.

Correction to: The semantic plights of the ante-rem structuralist

Abstract

In the original publication of the article, footnote 17 was incorrectly published. The corrected footnote is given below.

Cathodic microbial community adaptation to the removal of chlorinated herbicide in soil microbial fuel cells

Abstract

The microbial fuel cell (MFC) that uses a solid electrode as the inexhaustible electron acceptor is an innovative remediation technology that simultaneously generates bioelectricity. Chlorinated pollutants are better metabolized by reductive dechlorination in proximity to the cathode. Here, the removal efficiency of the herbicide metolachlor (ML) increased by 262 and 176% in soil MFCs that were spiked with 10 (C10) and 20 mg/kg (C20) of ML, respectively, relative to the non-electrode controls. The bioelectricity output of the C10 and C20 increased by over two- and eightfold, respectively, compared to that of the non-ML control, with maximum current densities of 49.6 ± 2.5 (C10) and 78.9 ± 0.6 mA/m² (C20). Based on correlations between ML concentrations and species abundances in the MFCs, it was inferred that Azohydromonas sp., Sphingomonas sp., and Pontibacter sp. play a major role in ML removal around the cathode, with peak removal efficiencies of 56 ± 1% (C10) and 58 ± 1% (C20). Moreover, Clostridium sp., Geobacter sp., Bacillus sp., Romboutsia sp., and Terrisporobacter sp. may be electricigens or closely related microbes due to the significant positive correlation between the bioelectricity generation levels and their abundances around the anode. This study suggests that a directional adaptation of the microbial community has taken place to increase both the removal of chlorinated herbicides around the cathode and the generation of bioelectricity around the anode in bioelectrochemical remediation systems.

Mixed strategy to allocate resources with air pollution treatment in China: based on the analytic network process and large-group decision-making method

Abstract

The resource allocation of air pollution treatment in China is a complex problem, since many alternatives are available and many criteria influence mutually. A number of stakeholders participate in this issue holding different opinions because of the benefits they value. So a method is needed, based on the analytic network process (ANP) and large-group decision-making (LGDM), to rank the alternatives considering interdependent criteria and stakeholders' opinions. In this method, the criteria related to air pollution treatment are examined by experts. Then, the network structure of the problem is constructed based on the relationships between the criteria. Further, every participant in each group provide comparison matrices by judging the importance between criteria according to dominance, regarding a certain criteria (or goal), and the geometric average comparison matrix of each group is obtained. The decision weight of each group is derived by combining the subjective weight and the objective weight, in which the subjective weight is provided by organizers, while the objective weight is determined by considering the consensus levels of groups. The final comparison matrices are obtained by the geometric average of comparison matrices and the decision weights. Next, the resource allocation is made according to the priorities of the alternatives using the super decision software. Finally, an example is given to illustrate the use of the proposed method.

CORRECTION

Publication date: Available online 4 April 2018
Source:Journal of the American Academy of Dermatology