A comparative trial of ice application versus EMLA cream in alleviation of pain during botulinum toxin injections for palmar hyperhidrosis

BI1 is associated with microvascular protection in cardiac ischemia reperfusion injury via repressing Syk–Nox2–Drp1-mitochondrial fission pathways

Abstract

Background

Mitochondrial fission has been identified as the pathogenesis underlying the development of cardiac microvascular ischemia reperfusion (IR) injury, although the regulatory signaling upstream from fission is far from clear. Bax inhibitor is a novel anti-apoptotic factor, and, however, its role of cardiac microvascular IR injury and mitochondrial homeostasis remains unclear.

Methods

The cardiac microvascular IR injury was performed in WT mice and BI1 transgenic (BI^TG ) mice. The alterations of microvascular structure and function were detected via electron microscope, immunohistochemistry and immunofluorescence in vivo. Cardiac microvascular endothelial cells were isolated form WT and BI^TG mice and underwent hypoxia/reoxygenation injury in vitro. Cellular viability and apoptosis were analyzed via MTT assay and caspase-3 activity. Mitochondrial function, morphology and apoptosis were detected. Signaling pathways were analyzed via inhibitor, siRNA and mutant plasmid.

Results

Herein, we demonstrated that Bax inhibitor 1 (BI1) was downregulated following cardiac microvascular IR injury, and its expression correlated negatively with microvascular collapse, endothelial cell apoptosis and mitochondrial damage. However, compared to wild-type mice, BI1 transgenic mice were actually protected from the acute microvascular injury and mitochondrial dysfunction. Functional studies illustrated that reintroduced BI1 directly interacted with and inhibited the Syk pathway, leading to the inactivation of Nox2. Subsequently, less Nox2 was associated with ROS downregulation, inhibiting Drp1 phosphorylated activation. Through repression of the Syk–Nox2–Drp1 signaling axis, BI1 strongly disrupted mitochondrial fission, abolishing mitochondrial apoptosis and thus sustaining endothelial cell viability.

Conclusions

In summary, our report illustrates that BI1 functions as a novel microvascular guardian in cardiac IR injury that operates via inhibition of the Syk–Nox2–Drp1-mitochondrial fission signaling axis. Thus, novel therapeutic strategies to regulate the balance between BI1 and mitochondrial fission could provide a survival advantage to microvasculature following IR stress.

Community response to a sustainable restoration plan for a superfund site

Abstract

Large-scale copper (Cu) mining activities in Michigan's Upper Peninsula produced millions of metric tons of mining wastes also known as stamp sands. The stamp sands containing high concentrations of Cu were disposed of into several lakes connected to the Lake Superior. Eventually, as aquatic organisms in these lakes started to exhibit toxicity symptoms, the stamp sands were dredged and discarded on the lake shores. Consequently, these areas turned into degraded, marginal lands and were collectively classified as a Torch Lake Superfund site by the US EPA. Due to the lack of vegetative cover, the Cu-rich stamp sands eroded into the lakes, affecting the aquatic life. To alleviate this issue, a sustainable restoration plan (SRP) was developed and tested in a greenhouse environment prior to field implementation. Cold-tolerant oilseed crops, camelina (Camelina sativa) and field pennycress (Thlaspi arvense), were grown on compost-fertilized stamp sands, which reduced soil erosion by acting as a vegetative cap. Oilseed plants produced normal yield, demonstrating their potential utilization as biofuel feedstock. Prior to implementing the SRP in field-scale in the Torch Lake Superfund site, a public opinion survey of the local community was conducted to understand the views of residents. Door-to-door survey was performed in July–August 2015, which yielded a response rate of 68.1%. Results showed that residents were generally concerned with stamp sand erosion into the Torch Lake and were overwhelmingly supportive of the SRP, which would not only provide environmental benefits but could boost the local economy via biofuel production. To gauge the general environmental awareness of the respondents, the survey included questions on climate change. Most of the respondents acknowledged that climate change is real and anthropogenically mediated. Having college education and a relatively high annual household income showed a positive and significant correlation with climate change awareness.

Moving beyond surveys to assess patient preferences

Publication date: Available online 5 April 2018
Source:Journal of the American Academy of Dermatology
Author(s): Clifford S. Perlis

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.