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Radiologists very frequently encounter incidental findings related to the thyroid gland. Given increases in imaging use over the past several decades, thyroid incidentalomas are increasingly encountered in clinical practice, and it is important for radiologists to be aware of recent developments with respect to workup and diagnosis of incidental thyroid abnormalities. Recent reporting and management guidelines, such as those from the American College of Radiology and American Thyroid Association, are reviewed along with applicable evidence in the literature. Trending topics, such as artificial intelligence approaches to guide thyroid incidentaloma workup, are also discussed.

In mild cognitive impairment (MCI), identifying individuals at high risk for progressive cognitive deterioration can be useful for prognostication and intervention. This study quantitatively characterizes cognitive decline rates in MCI and tests whether volumetric data from baseline magnetic resonance imaging (MRI) can predict accelerated cognitive decline.The authors retrospectively examined Alzheimer Disease Neuroimaging Initiative data to obtain serial Mini-Mental Status Exam (MMSE) scores, diagnoses, and the following baseline MRI volumes: total intracranial volume, whole-brain and ventricular volumes, and volumes of the hippocampus, entorhinal cortex, fusiform gyrus, and medial temporal lobe. Subjects with24 months or4 measurements of MMSE data were excluded. Predictive modeling of fast cognitive decline (defined as0.6/year) from baseline volumetric data was performed on subjects with MCI using a single hidden layer neural network.Among 698 baseline MCI subjects, the median annual decline in the MMSE score was 1.3 for converters to dementia versus 0.11 for stable MCI (P0.001). A 0.6/year threshold captured dementia conversion with 82% accuracy (sensitivity 79%, specificity 85%, area under the receiver operating characteristic curve 0.88). Regional volumes on baseline MRI predicted fast cognitive decline with a test accuracy of 71%.An MMSE score decrease of0.6/year is associated with MCI-to-dementia conversion and can be predicted from baseline MRI.

Patients undergoing MRI may experience fear, claustrophobia, or other anxiety manifestations due to the typically lengthy, spatially constrictive, and noisy MRI acquisition process and in some cases are not able to tolerate completion of the study. This article discusses several patient-centered aspects of radiology practice that emphasize interpersonal interactions. Patient education and prescan communication represent 1 way to increase patients' awareness of what to expect during MRI and therefore mitigate anticipatory anxiety. Some patient interaction strategies to promote relaxation or calming effects are also discussed. Staff teamwork and staff training in communication and interpersonal skills are also described, along with literature evidence of effectiveness with respect to patient satisfaction and productivity endpoints. Attention to how radiologists, nurses, technologists, and other members of the radiology team interact with patients before or during the MRI scan could improve patients' motivation and ability to cooperate with the MRI scanning process as well as their subjective perceptions of the quality of their care. The topics discussed in this article are relevant not only to MRI operations but also to other clinical settings in which patient anxiety or motion represent impediments to optimal workflow.

Objective: To characterize predictors of patient satisfaction in outpatient radiology, we examined whether patient satisfaction differs across radiology modalities and demographic groups. Methods: A random sampling of Press-Ganey outpatient services surveys for radiology and non-radiology visits from September 2008 to September 2017 were retrospectively analyzed. Composite scores averaged across all Likert items were analyzed as both a continuous variable and a dichotomous variable of dissatisfaction (defined as ≤3 on the 5-point scale). Results: Among 9983 radiology surveys, mammography had higher composite scores than MRI, CT, radiography, US, and NM/PET (p

Claustrophobia, other anxiety reactions, excessive motion, and other unanticipated patient events in magnetic resonance imaging (MRI) not only delay or preclude diagnostic-quality imaging but can also negatively affect the patient experience. In addition, by impeding MRI workflow, they may affect the finances of an imaging practice. This review article offers an overview of the various types of patient-related unanticipated events that occur in MRI, along with estimates of their frequency of occurrence as documented in the available literature. In addition, the financial implications of these events are discussed from a microeconomic perspective, primarily from the point of view of a radiology practice or hospital, although associated limitations and other economic viewpoints are also included. Efforts to minimize these unanticipated patient events can potentially improve not only patient satisfaction and comfort but also an imaging practice's operational efficiency and diagnostic capabilities.

Patient comfort is an important factor of a successful magnetic resonance (MR) examination, and improvements in the patient's MR scanning experience can contribute to improved image quality, diagnostic accuracy, and efficiency in the radiology department, and therefore reduced cost. Magnet designs that are more open and accessible, reduced auditory noise of MR examinations, light and flexible radiofrequency (RF) coils, and faster motion-insensitive imaging techniques can all significantly improve the patient experience in MR imaging. In this work, we review the design, development, and implementation of these physics and engineering approaches to improve patient comfort.

For many patients, numerous unpleasant features of the magnetic resonance imaging (MRI) experience such as scan duration, auditory noise, spatial confinement, and motion restrictions can lead to premature termination or low diagnostic quality of imaging studies. This article discusses practical, patient-oriented considerations that are helpful for radiologists contemplating ways to improve the MRI experience for patients. Patient friendly scanner properties are discussed, with an emphasis on literature findings of effectiveness in mitigating patient claustrophobia, other anxiety, or motion and on reducing scan incompletion rates or need for sedation. As shorter scanning protocols designed to answer specific diagnostic questions may be more practical and tolerable to the patient than a full-length standard-of-care examination, a few select protocol adjustments potentially useful for specific clinical settings are discussed. In addition, adjunctive devices such as audiovisual or other sensory aides that can be useful distractive approaches to reduce patient discomfort are considered. These modifications to the MRI scanning process not only allow for a more pleasant experience for patients, but they may also increase patient compliance and decrease patient movement to allow more efficient acquisition of diagnostic-quality images.

Periprocedural anxiety is a major cause of morbidity, particularly for interventional radiology procedures that often depend on conscious sedation. Management of anxiety and pain during image-guided procedures has traditionally relied on pharmacologic agents such as benzodiazepines and opioids. Although generally safe, use of these medications risks adverse events, and newer noninvasive, nonpharmacologic techniques have evolved to address patient needs. In this review, we explore the roles of hypnosis, structured empathic attention, anodyne imagery, music, video glasses, and mobile applications in reducing procedural anxiety and pain with the goal of improving patient satisfaction, operational efficiency, and clinical outcomes.

Purpose: Our study investigates whether a machine-learning-based system can predict the rate of cognitive decline in mildly cognitively impaired patients by processing only the clinical and imaging data collected at the initial visit. Approach: We built a predictive model based on a supervised hybrid neural network utilizing a three-dimensional convolutional neural network to perform volume analysis of magnetic resonance imaging (MRI) and integration of nonimaging clinical data at the fully connected layer of the architecture. The experiments are conducted on the Alzheimer's Disease Neuroimaging Initiative dataset. Results: Experimental results confirm that there is a correlation between cognitive decline and the data obtained at the first visit. The system achieved an area under the receiver operator curve of 0.70 for cognitive decline class prediction. Conclusion: To our knowledge, this is the first study that predicts "slowly deteriorating/stable" or "rapidly deteriorating" classes by processing routinely collected baseline clinical and demographic data [baseline MRI, baseline mini-mental state examination (MMSE), scalar volumetric data, age, gender, education, ethnicity, and race]. The training data are built based on MMSE-rate values. Unlike the studies in the literature that focus on predicting mild cognitive impairment (MCI)-to-Alzheimer's disease conversion and disease classification, we approach the problem as an early prediction of cognitive decline rate in MCI patients.

We deem a computer to exhibit artificial intelligence (AI) when it performs a task that would normally require intelligent action by a human. Much of the recent excitement about AI in the medical literature has revolved around the ability of AI models to recognize anatomy and detect pathology on medical images, sometimes at the level of expert physicians. However, AI can also be used to solve a wide range of noninterpretive problems that are relevant to radiologists and their patients. This review summarizes some of the newer noninterpretive uses of AI in radiology.

Cerebrospinal fluid leaks pose a serious threat to patients as they represent an unchecked communication between the subarachnoid space and the extracranial environment. Accurate localization of the leakage site is essential for treatment planning. We describe the novel utilization of dual-energy computed tomography technology in cisternography in the evaluation of a patient with a cerebrospinal fluid leak.

Purpose To determine the repeatability of magnetic resonance (MR) elastography-derived shear stiffness measurements of the intervertebral disc (IVD) taken throughout the day and their relationship with IVD degeneration and subject age. Materials and Methods In a cross-sectional study, in vivo lumbar MR elastography was performed once in the morning and once in the afternoon in 47 subjects without current low back pain (IVDs = 230; age range, 20-71 years) after obtaining written consent under approval of the institutional review board. The Pfirrmann degeneration grade and MR elastography-derived shear stiffness of the nucleus pulposus and annulus fibrosus regions of all lumbar IVDs were assessed by means of principal frequency analysis. One-way analysis of variance, paired t tests, concordance and Bland-Altman tests, and Pearson correlations were used to evaluate degeneration, diurnal changes, repeatability, and age effects, respectively. Results There were no significant differences between morning and afternoon shear stiffness across all levels and there was very good technical repeatability between the morning and afternoon imaging results for both nucleus pulposus (R = 0.92) and annulus fibrosus (R = 0.83) regions. There was a significant increase in both nucleus pulposus and annulus fibrosus MR elastography-derived shear stiffness with increasing Pfirrmann degeneration grade (nucleus pulposus grade 1, 12.5 kPa ± 1.3; grade 5, 16.5 kPa ± 2.1; annulus fibrosus grade 1, 90.4 kPa ± 9.3; grade 5, 120.1 kPa ± 15.4), and there were weak correlations between shear stiffness and age across all levels (R ≤ 0.32). Conclusion Our results demonstrate that MR elastography-derived shear stiffness measurements are highly repeatable, weakly correlate with age, and increase with advancing IVD degeneration. These results suggest that MR elastography-derived shear stiffness may provide an objective biomarker of the IVD degeneration process.

Given the rapid pace at which modern radiology is evolving and the associated paradigm shifts in health care delivery, it is critical that radiologists adapt and constantly update the skills and knowledge required to practice safe, patient-centered care. The Association of University Radiologists-Radiology Research Alliance Lifelong Learning Task Force convened to explore the current status and future directions of lifelong learning in radiology and summarized its finding in this article. We review the various learning platforms and resources available to radiologists in their self-motivated and self-directed pursuit of lifelong learning. We also discuss the challenges and perceived barriers to lifelong learning and strategies to mitigate those barriers and optimize learning outcomes.

The presence of a single nodal metastasis has significant prognostic and treatment implications for patients with head and neck cancer. This study aims to investigate whether dual-energy computed tomography (DECT)-derived iodine content and spectral attenuation curve analysis can improve detection of nodal metastasis in oropharyngeal carcinoma. Eight patients with newly diagnosed oropharyngeal squamous cell carcinoma and pathologically proven nodal metastatic disease (n = 13 metastatic nodes, n = 16 nonmetastatic nodes) who underwent contrast-enhanced DECT of the neck were retrospectively evaluated. DECT-derived iodine content (mg/mL) and monoenergetic attenuation values at 40 keV and 100 keV were obtained via circular regions of interest within metastatic and nonmetastatic cervical lymph nodes. Iodine content was significantly lower in metastatic nodes (0.96 ± 0.28 mg/mL) than in nonmetastatic nodes (1.65 ± 0.38 mg/mL, P = .002). Iodine spectral attenuation slope was significantly lower in metastatic nodes (1.33 ± 0.49 mg/mL) than in nonmetastatic nodes (1.91 ± 0.64 mg/mL, P = .015). A nodal iodine threshold of ≤1.3 mg/mL showed a sensitivity of 84.6% and a specificity of 75.0%, with an area under the curve of 0.839, P &lt, 0001. At a threshold value of ≤1.95 for nodal spectral attenuation slope, an optimized specificity of 92.3% and specificity of 50.0% was achieved, with an area under the curve of 0.68 (P = .049). DECT-derived quantitative iodine data and spectral attenuation curves may improve the diagnostic accuracy of computed tomography for nodal metastasis in patients with squamous cell carcinoma of the oropharynx.

Various imaging techniques used in stroke evaluation have complementary, evolving roles. This article reviews recent updates in emergent stroke neuroimaging. Multiple recent randomized trials showing benefit of endovascular therapy in strokes with confirmed large-vessel occlusion emphasize need for vessel imaging, typically CTA, in addition to unenhanced head CT. In addition, because recent trials published in 2018 showed efficacy of mechanical thrombectomy at up to 24 h from symptom onset in stroke patients with favorable ischemic core and/or penumbra assessments, imaging techniques to define viable and infarcted tissue, such as DWI or CT/MR perfusion imaging, have an increasing role in emergent stroke assessment. Other studies contributing to new AHA/ASA stroke guidelines are also discussed. Neuroimaging remains crucial to emergent stroke evaluation, with CTA, MRI, and perfusion studies playing an increasing role in identifying patients likely to benefit from treatment.

Purpose Examine the cost of MRI operations before and after implementation of interpersonal skills training to reduce unanticipated patient-related events in an academic medical center. Methods Teams at four MRI sites (two hospital-based, two freestanding) were trained in evidence-based communication skills in February to April 2015. Training was designed to enable staff members to help patients mobilize their innate coping skills in response to any distress they experienced during their MRI visit. Data were collected before training and afterward from January to June 2016. Staff reported the incidence of disruptive motion, sedation use, MRI delays, incomplete examinations, and no-shows. Cost and revenue associated with MRI operations and staff and physician costs were estimated using Medicare and private insurance rates and data from the US Bureau of Labor Statistics. Results The study included 12,930 outpatient MRI visits. From baseline to follow-up, average monthly patient volume increased from 1,105 to 1,463 at hospital MRI sites and from 245 to 313 at freestanding MRI sites. Patient factors necessitating sedation or interfering with image progression or quality decreased from 9.0% to 5.5% at hospital sites and from 3.1% to 1.2% at freestanding sites. These changes translated into a reduction in operational costs of $4,600 per 1,000 scheduled patients and an increase in profit of $8,370 per 1,000 scheduled patients in hospital MRI sites, and a corresponding increase in operational costs of $1,570 per 1,000 scheduled-patients and an increase in profit of $12,800 per 1,000 scheduled patients in freestanding MRI sites. Conclusions We found significant improvements in MRI operational efficiency after interpersonal skills team training, which were associated with reductions in costs and growth in revenue.

In many risk-stratification systems, the decision to biopsy thyroid nodules is determined by their sonographic features and size. Nevertheless, even low-suspicion nodules are often biopsied at small size thresholds because it is assumed that larger malignant nodules are associated with poorer outcomes. The aim of this study was to quantify the effect of thyroid cancer tumor size on survival and risk of T4 stage, nodal disease, and distant metastases.The Surveillance, Epidemiology, and End Results 18 database was queried to obtain tumor size, staging information, and survival data for cases of differentiated thyroid cancer (DTC) and non-DTC reported between 2004 and 2014. Observed probabilities of tumor extent at diagnosis, including regional nodal disease and distant metastases, as a function of size and tumor histology were estimated for thyroid cancers measuring between 1 and 150 mm. A multivariate Cox regression model was used to describe all-cause mortality as a function of patient and tumor characteristics, and the functional dependence of mortality on size was computed.A total of 112,128 patients were analyzed, with 67% having thyroid cancers ≥1 cm, and 29% ≥ 2.5 cm. For DTC tumors4 cm, the risk of local invasion, nodal metastases, or distant metastases was low, and there was no size threshold associated with a sharp rise in adverse outcomes. For DTC tumors4 cm, the probability of distant metastases was3%. Older age, male sex, non-DTC histology, T4 stage, and regional and distant metastatic disease increased the all-cause mortality rate. Tumor size did not increase the mortality rate above baseline until tumors were2.5 cm.Increasing tumor size does not affect survival until a threshold of 2.5 cm. Since the dimension of nodules on ultrasound has been shown to be larger than their size at gross pathology, these findings suggest that recommended size thresholds to biopsy low-suspicion thyroid nodules can be increased.

Thyroid cancer fulfills the criteria for overdiagnosis by having a reservoir of indolent cancers and practice patterns leading to the diagnosis of incidental cancers from the reservoir. The occurrence of overdiagnosis is also supported by population-based data showing an alarming rise in thyroid cancer incidence without change in mortality. Because one of the activities leading to overdiagnosis is the workup of incidental thyroid nodules detected on imaging, it is critical that radiologists understand the issue of overdiagnosis and their role in the problem and solution. This article addresses 1) essential thyroid cancer facts, 2) the evidence supporting overdiagnosis, 3) the role of radiology in overdiagnosis, 4) harms of overdiagnosis, and 5) steps radiologists can take to minimize the problem.

There are many disorders that can occur in the thyroid gland, ranging from benign to malignant entities. This article focuses on 5 common problems of the thyroid that require special consideration with regard to optimizing imaging strategies in a multidisciplinary and collaborative platform. These problems are the incidental thyroid nodule, preoperative evaluation of goiter, hyperthyroidism, invasive thyroid cancer, and recurrent thyroid cancer. For each problem essential facts, interesting updates, imaging approach, and management pearls are reviewed.

Purpose To assess how a patient's affect on presentation relates to the likelihood of adverse events during their subsequent interventional image-guided procedures. Materials and Methods A secondary analysis was performed of an existing dataset from a clinical trial with 230 patients who underwent percutaneous peripheral vascular and renal interventions and who had completed the positive affect (PA) negative affect (NA) schedule (PANAS) before their procedures. Summary PANAS scores were split over the median and used to classify the participants into those with high vs low PA and high vs low NA. Associations between affect and the absence or presence of adverse medical events were examined by two-sided Fisher exact tests. Results Patients with high baseline NA were significantly more likely to have adverse events during their procedures than those with low baseline NA (18% vs 8%; P = .030). High baseline PA was not associated with a significantly higher frequency of subsequent adverse events compared with low PA (15% vs 9%; P = .23). Patients with high NA requested and received significantly more sedative and opioid agents than those with low NA (2.0 vs 1.0 units requested [ P = .0009]; 3.0 vs 1.0 units received [ P = .0004]). PA levels did not affect medication use. Conclusions High NA, but not PA, was associated with an increased likelihood of adverse events. Improving patients' NA before procedures seems a more suitable target than attempting to boost PA to improve the procedural experience.

The ACR's RADPEER program is currently the leading method for peer review in the United States. To date, more than 18,000 radiologists and more than 1,100 groups participate in the program. The ABR accepted RADPEER as a practice quality improvement in 2009, which can be applied toward maintenance of certification; there are currently over 2,200 practice quality improvement participants. There have been ongoing deliberations regarding the utility of RADPEER, its goals, and its scoring system since the preceding 2009 white paper. This white paper reviews the history and evolution of RADPEER and eRADPEER, the 2016 ACR Peer Review Committee's discussions, the updated recommended scoring system and lexicon for RADPEER, and updates to eRADPEER including the study type, age, and discrepancy classifications. The central goal of RADPEER to aid in nonpunitive peer learning is discussed.

The aim of this study was to assess the effects of team training on operational efficiency during outpatient MRI.In this institutional review board-approved, HIPAA-compliant study, six MRI outpatient sites of a midwestern hospital system were randomized to serve as controls or have their teams trained in advanced communication skills. The fourth quarter of fiscal year 2015 was the trial baseline. The trial ended in the third quarter (Q3) of fiscal year 2016 (FY16). Equipment utilization (completed scans/available slots), hourly scan rates (total orders completed per machine per hour of operation), and no-show rates stratified by time were analyzed using the Cochran-Mantel-Haenszel method, with individual comparisons performed with Bonferroni correction.The study encompassed 27,425 MRI examinations. Overall volume peaked at baseline and then declined over the following quarters. Compared with baseline, untrained sites experienced significant drops in equipment utilization (P.01 for the first quarter of FY16 and P.0001 for the second quarter of FY16 and Q3 FY16), decreasing from 77% to 65% over the study period, corresponding to a decrease from 1.15 to 0.97 in hourly scan rates. For trained sites, these metrics showed no significant change, with maintenance of hourly scan rates of 1.23 and 1.27 and equipment utilization rates of 83% and 85% between baseline and Q3 FY16. No-show rates remained stable at trained sites but increased at untrained sites in the last two quarters (P.05). Nationally benchmarked patient satisfaction percentile ranking gradually increased at trained sites from 56th at baseline to 70th and successively decreased at untrained sites from 66th to 44th.MRI outpatient facilities trained in advanced communication techniques may have more favorable operational efficiency than untrained sites in a saturated market.

BACKGROUND AND PURPOSE: Thyroid nodules are common incidental findings on CT, but there are no clear guidelines regarding their further diagnostic work-up. This study compares the performance of 2 risk-categorization methods of selecting CT-detected incidental thyroid nodules for work-up. MATERIALS AND METHODS: The 2 categorization methods were method A, based on nodule size ≥10 mm, and method B, a 3-tiered system based on aggressive imaging features, patient age younger than 35 years or nodule size of ≥15 mm. In part 1, the 2 categorization methods were applied to thyroid cancers in the SEER data base of the National Cancer Institute to compare the cancer capture rates and survival. In part two, 755 CT neck scans at our institution were retrospectively reviewed for the presence of ITNs of ≥5 mm, and the same 2 categorization methods were applied to the CT cases to compare the number of patients who would theoretically meet the criteria for work-up. Comparisons of proportions of subjects captured under methods A and B were made by using the McNemar test. RESULTS: For 84,720 subjects in the SEER data base, methods A and B each captured 74% (62,708/84,720 and 62,586/84,720, respectively) of malignancies. SEER subjects who would not have met the criteria for further work-up by both methods had equally excellent 10-year cause-specific and relative survival of >99%. For part 2, the prevalence of ITNs of ≥5 mm at our institution was 133/755 (18%). The number of ITNs that would be recommended for work-up by method A was 57/133 (43%) compared with 31/133 (23%) for method B (P < .0005). CONCLUSIONS: Compared with using a 10-mm cutoff, the 3-tiered risk-stratification method identified fewer ITNs for work-up but captured the same proportion of cancers in a national data base and showed no difference in missing high-mortality cancers.

Descending necrotising mediastinitis is a rare and serious infection with a high mortality rate, which complicates pharyngeal or odontogenic infection. Early recognition and treatment are essential in order to minimise morbidity. Evaluation with computed tomography is necessary to confirm the diagnosis and facilitate surgical planning. In addition to prompt empirical antiobiotic therapy, surgical intervention is necessary in nearly all cases. Surgical drainage and debridement may be performed through cervicotomy alone, or through combined cervicotomy and thoracotomy, depending upon the extent of disease. Hyperbaric oxygen therapy may play an auxiliary role. We present two recent cases with characteristic imaging findings, and review the relevant literature.

Dynorphins, endogenous neuropeptides found in striatonigral neurons, have been observed to exhibit dopamine-inhibitory actions and under some circumstances possess intrinsic neurotoxic activity. To test the hypothesis that dynorphin suppression mitigates effects of aging on the striatal dopaminergic system, HPLC quantitation of dopamine and related amines was performed on striatal homogenates of wild-type (WT) mice and mice lacking the prodynorphin (Pdyn) gene at varying ages. Pdyn knockout (KO) mice at 10 and 20 months show significant elevations in striatal dopamine compared to 3-month mice. Differences in tyrosine hydroxylase (TH) immunoreactivity could not account for these findings, but phosphorylation of TH at Ser40, but not Ser31, was enhanced in aged Pdyn KO mice. Systemic administration of MPTP produced significant dopamine depletion in an age-dependent manner, but Pdyn deletion conferred no protection against MPTP-induced dopamine loss, arguing against a mechanism by which Pdyn deletion enhances dopaminergic neuron survival. The above findings demonstrate an age-dependent inhibitory effect of dynorphins on striatal dopamine synthesis via modulation of TH activity.

The p38 mitogen-activated protein kinase is a stress-activated enzyme responsible for transducing inflammatory signals and initiating apoptosis. In the Alzheimer's disease (AD) brain, increased levels of phosphorylated (active) p38 were detected relative to age-matched normal brain. Intense phospho-p38 immunoreactivity was associated with neuritic plaques, neuropil threads, and neurofibrillary tangle-bearing neurons. The antibody against phosphorylated p38 recognized many of the same structures as an antibody against aberrantly phosphorylated, paired helical filament (PHF) tau, although PHF-positive tau did not cross-react with the phospho-p38 antibody. These findings suggest a neuroinflammatory mechanism in the AD brain, in which aberrant protein phosphorylation affects signal transduction elements, including the p38 kinase cascade, as well as cytoskeletal components.

Inflammation has been increasingly recognized to play an important role in the pathogenesis of Parkinson's disease (PD). Using immunocytochemistry and electron microscopy, we found that intranigral injection of lipopolysaccharide (LPS) caused marked microglial activation and a dose-dependent selective loss of dopaminergic neurons, which was mediated by apoptosis as evidenced by prominent TUNEL labeling. RNase protection assays revealed that mRNA for Bax, Fas and the pro-inflammatory cytokines interleukin (IL)-1α, IL-1β, IL-6 and tumor necrosis factor (TNF)-α were significant increased ipsilaterally in LPS-injected side of SN, while expression of the anti-apoptotic gene Bcl-2 was decreased. Osmotic pump infusion of IL-10, a global inhibitor of cytokine synthesis, protected against LPS-induced cell death of dopaminergic neurons, with a corresponding decrease in the number of activated microglia, suggesting that the reduction in microglia-mediated release of inflammatory mediators may contribute to the anti-inflammatory effect of IL-10. Our results provide evidence that LPS induces apoptotic cell death in SNpc, which is likely through the expression of Fas, Bax, caspase-3, and the pro-inflammatory cytokines.

Dynorphins, endogenous kappa-opioid agonists widely expressed in the central nervous system, have been reported to increase following diverse pathophysiological processes, including excitotoxicity, chronic inflammation, and traumatic injury. These peptides have been implicated in cognitive impairment, especially that associated with aging. To determine whether absence of dynorphin confers any beneficial effect on spatial learning and memory, knockout mice lacking the coding exons of the gene encoding its precursor prodynorphin (Pdyn) were tested in a water maze task. Learning and memory assessment using a 3-day water maze protocol demonstrated that aged Pdyn knockout mice (13-17 months) perform comparatively better than similarly aged wild-type (WT) mice, based on acquisition and retention probe trial indices. There was no genotype effect on performance in the cued version of the swim task nor on average swim speed, suggesting the observed genotype effects are likely attributable to differences in cognitive rather than motor function. Young (3-6 months) mice performed significantly better than aged mice, but in young mice, no genotype difference was observed. To investigate the relationship between aging and brain dynorphin expression in mice, we examined dynorphin peptide levels at varying ages in hippocampus and frontal cortex of WT 129SvEv mice. Quantitative radioimmunoassay demonstrated that dynorphin A levels in frontal cortex, but not hippocampus, of 12- and 24-month mice were significantly elevated compared to 3-month mice. Although the underlying mechanisms have yet to be elucidated, the results suggest that chronic increases in endogenous dynorphin expression with age, especially in frontal cortex, may adversely affect learning and memory.

Increasing evidence suggests that abnormal iron handling may be involved in the pathogenesis of Parkinson's disease. The present study investigates the role of iron and the iron-storage protein ferritin in inflammation-induced degeneration of dopaminergic neurons of the substantia nigra pars compacta. Injection of lipopolysaccharide into the globus pallidus of young and middle-aged rats substantially decreased tyrosine hydroxylase immunostaining in substantia nigra pars compacta four weeks after injection. Loss of tyrosine hydroxylase expression was accompanied by increased iron and ferritin levels in glial cells of the substantia nigra pars reticulata. Despite greater increases in nigral iron levels, ferritin induction was less pronounced in older rats, suggesting the regulation of ferritin was compromised with age. Automated movement tracking analyses showed that young rats recovered from LPS-induced locomotor deficits within four weeks, yet older rats failed to improve on measures of speed and total distance moved. Intrapallidal lipopolysaccharide injection also increased expression of alpha-synuclein and ubiquitin in tyrosine hydroxylase-positive neurons of the substantia nigra pars compacta. These results suggest that pallidal inflammation significantly increases stress on dopamine-containing neurons in the substantia nigra pars compacta. Alterations in nigral iron levels and protein handing may increase the vulnerability of nigral neurons to degenerative processes.

An improved thioflavin-S stain, Gallyas silver stain, and two immunostainings were quantitatively compared for demonstration of neurofibrillary tangles (NFTs) on the same sections. Sections of hippocampal formation from seven cases of Alzheimer's disease (AD) were immunofluorescently stained with a commercially available polyclonal NFT antibody or a PHF-1 monoclonal antibody, followed by an improved thioflavin-S stain, and finally by Gallyas silver staining. The thioflavin-S method was improved by using a combination quenching method that removes background autofluorescence without remarkable tissue damage and by post-treatment with concentrated phosphate buffer, which minimizes photobleaching. PHF-1 or NFT immunostaining is much less sensitive than the improved thioflavin-S staining and Gallyas silver staining, particularly in the transentorhinal region. Moreover PHF-1 immunoreactivity varied greatly among AD individuals. Thioflavin-S staining and Gallyas silver staining show almost the same sensitivity in NFT demonstration, but only the former depends on the secondary protein structure of NFTs. This study suggests that the improved thioflavin-S staining is a simple, sensitive, and consistent method for demonstration of neurofibrillary pathology.

Importance Incidental thyroid nodules are defined as nodules originally detected in a patient with no thyroid-related clinical symptoms, examination findings, or suspected thyroid disease. Medical imaging for diseases in the neck, chest, and spine is a common source of incidental thyroid nodules. They are easily detected but poorly characterized. The next step is to decide whether the incidental thyroid nodule should be further evaluated with ultrasonography. Observations Indiscriminate workup of incidental thyroid nodules with ultrasonography is not cost-effective and is potentially harmful. Although the concern for malignant neoplasms drives workup, the risk for poor outcomes without evaluation is minimal. The rate of malignant tumors in patients with 1 or more thyroid nodules larger than 5 mm is only 1.6%, and most small thyroid cancers are indolent. Substantial evidence suggests that a reservoir of thyroid cancers does not progress, and workup after detection with imaging leads to epidemiologic overdiagnosis. Finally, a significant proportion of patients with benign nodules have cytologic results that are not definitive and require lobectomy. Evidence-based recommendations for incidental thyroid nodules detected at computed tomography, magnetic resonance imaging, nuclear medicine studies, and extrathyroidal ultrasonography include selection criteria for nodule workup based on suspicious imaging findings, patient age, and nodule size. In the absence of clinical risk factors or suspicious imaging findings, workup with dedicated thyroid ultrasonography is only recommended for nodules at least 1.5 cm in patients 35 years or older and for nodules at least 1.0 cm in patients younger than 35 years. Conclusions and Relevance Only a few select incidental thyroid nodules require further evaluation with ultrasonography based on recommendations that aim to diagnose clinically significant thyroid cancers while reducing unnecessary workup and provide guidance for clinical practice.

Purpose of review To discuss the problem of incidental thyroid nodules (ITN) detected on imaging; summarize the literature for workup methods; and provide recommendations based on current evidence. Recent findings ITN are a common problem, seen in 40-50% of ultrasound and 16% of computed tomography (CT) and MRI studies that include the thyroid. The personal and financial costs of workup frequently outweigh the benefits when considering that the majority of ITN are benign; 25-41% of patients undergo surgery after biopsy, of which more than half ultimately result in a benign diagnosis, and small thyroid cancers have an indolent course. Workup should consider reduction in unnecessary workup in addition to cancer diagnosis. The Society of Radiologists in Ultrasound recommendations have been proposed for ITN detected on ultrasound and found to reduce workup by 30%. For ITN detected on CT, MRI, or PET/CT, a three-tiered system categorization method reduces workup of ITN by 35-46%. Summary The ideal approach to selecting ITN detected on imaging for workup would not be to diagnose all cancers, but to diagnose cancers that have reached clinical significance, while avoiding unnecessary tests and surgery in patients with benign nodules, especially those who have limited life expectancy. The three-tiered system and the Society of Radiologists in Ultrasound recommendations are supported by existing studies and focus on reducing unnecessary biopsy.

Parkinson's disease (PD) is the most prevalent neurodegenerative movement disorder. Epidemiological studies have suggested most cases of PD are linked to environmental risk factors. Microsomal epoxide hydrolase (mEH) is a conserved enzyme that catalyzes hydrolysis of a large number of epoxide intermediates such as drugs and epoxides of environmental toxins. We hypothesize that changes in mEH are involved in the pathogenesis of PD by modulating the vulnerability of dopaminergic neurons to environmental stress. Herein we reported that acute treatment with the neurotoxin MPTP (1-methyl-4-phemyl-1,2,3,6-tetrahydropyridine) markedly increased the mEH immunoreactivity in the nigrostriatal system of C57BL/6 mice. Next, mEH knockout (KO) mice were used, and we found that tyrosine hydroxylase (TH)-positive cell loss was significantly lower in the substantia nigra of mEH KO mice compared with wild-type (WT) mice after MPTP treatment. The mean dopamine turnover ratios were significantly increased in MPTP-treated mEH KO mice compared with WT. In addition, TH is the rate-limiting enzyme for dopamine biosynthesis, and its activity is mainly regulated by TH phosphorylation at Ser-31 (pSer31) and Ser-40 (pSer40). Double immunofluorescence showed that both pSer31 and pSer40 are completely colocalized in total TH-positive cells. However, immunoblotting confirmed that there was a significantly higher level of pSer31 in mEH-KO mice when compared with WT mice after MPTP, and no marked differences among TH and its phosphorylation levels occurred after saline injection. These data suggested that mEH deficiency facilitates TH phosphorylation in the nigrostriatal dopamine system, which may be associated with an increased resistance of dopaminergic neurons to environmental toxins.

Background Accumulating evidence suggests that inflammation plays an important role in the progression of Parkinson's disease (PD). Among many inflammatory factors found in the PD brain, cyclooxygenase (COX), specifically the inducible isoform, COX-2, is believed to be a critical enzyme in the inflammatory response. Induction of COX-2 is also found in an experimental model of PD produced by administration of 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Method COX-2-deficient mice or C57BL/6 mice were treated with MPTP to investigate the effects of COX-2 deficiency or by using various doses of valdecoxib, a specific COX-2 inhibitor, which induces inhibition of COX-2 on dopaminergic neuronal toxicity and locomotor activity impairment. Immunohistochemistry, stereological cell counts, immunoblotting, an automated spontaneous locomotor activity recorder and rotarod behavioral testing apparatus were used to assess microglial activation, cell loss, and behavioral impariments. Results MPTP reduced tyrosine hydroxylase (TH)-positive cell counts in the substantia nigra pars compacta (SNpc); total distance traveled, vertical activity, and coordination on a rotarod; and increased microglia activation. Valdecoxib alleviated the microglial activation, the loss of TH-positive cells and the decrease in open field and vertical activity. COX-2 deficiency attenuated MPTP-induced microglial activation, degeneration of TH-positive cells, and loss of coordination. Conclusion These results indicate that reducing COX-2 activity can mitigate the secondary and progressive loss of dopaminergic neurons as well as the motor deficits induced by MPTP, possibly by suppression of microglial activation in the SNpc.

The regional, cellular, and subcellular localization of phosphorylated p38 MAPK (pp38) was examined by immunocytochemistry, immuofluorescent multiple labeling, and immunoblotting of extracts as well as immunoprecipitates of human postmortem tissue from control and Alzheimer's disease (AD) cases at different Braak stages. "Early AD" cases (Braak stages IV-V) and a subset of Braak stage VI cases have high levels of pp38 immunoreactivity, with the most dense immunoreactivity located in CA2 and subiculum followed by CA1 in the hippocampus. On the contrary, very little pp38 was detected in age-matched controls (Braak stages 0-II). More importantly, as revealed by various multiple labeling experiments, pp38 immunoreactivity is mainly located in neurons bearing early neurofibrillary pathology, but not in typically fibrillar tangles that are densely stained by thioflavin-S. Most pp38-positive neurons only contain a small amount of phospho-tau. Additionally, pp38 immunoreactivity was not associated with senile plaques. At the subcellular level, pp38-immunoreactive granules are usually larger than the granules stained with the lysosomal marker cathepsin D. Immunoblotting with different extraction buffers and immunoprecipitation indicate that pp38 does not or only loosely binds to phospho-tau. Taken together, this study demonstrates that p38 MAPK is activated at early stages of neurofibrillary degeneration in AD hippocampus. The p38 activation may also be linked to neurodegeneration through mechanisms other than neurofibrillary tangle formation.

Methods currently available for detecting neurofibrillary pathology are indirect and depend on staining with exogenous chemicals or antibodies. In the present study, we report a novel method named intrinsic fluorescence induction (IFI), which allows direct visualization of neurofibrillary tangles (NFTs), neuropil threads (NTs), and neuritic plaques (NPs) in tissue sections of Alzheimer's disease (AD) brain. The IFI method is based on both induction of a red intrinsic fluorescence and quenching red background autofluorescence. The IFI procedure includes sustained hydrophobic treatment, protein secondary structure enhancement and incubation in high concentration of phosphate buffer. Following this procedure, a unique red fluorescence is generated from the structures of NFTs, NTs, and NPs in brain sections from AD patients. Sequential application of mild permanganate oxidation and 1% sodium borohydride selectively removes the red background autofluorescence, while the latter enhances the intrinsic fluorescence of neurofibrillary pathology. Comparative studies reveal that the IFI method is as sensitive as Gallyas silver staining, and more sensitive than Bielschowsky silver staining or PHF-1 immunostaining in detecting NFTs in the pre-alpha layer of entorhinal cortex and the pri-alpha layer of the entorhinal/transentorhinal cortex. Furthermore, the IFI method is sensitive in displaying plaque neurites and threads, but not NFTs in the hippocampus. This novel finding provides a direct method for detecting neurofibrillary pathology in particular regions of AD brain and a novel tool for AD research.