Dynamic electrical synapses rewire brain networks for persistent oscillations and epileptogenesis.

One of the very fundamental attributes for telencephalic neural computation in mammals involves network activities oscillating beyond the initial trigger. The continuing and automated processing of transient inputs shall constitute the basis of cognition and intelligence but may lead to neuropsychiatric disorders such as epileptic seizures if carried so far as to engross part of or the whole telencephalic system. From a conventional view of the basic design of the telencephalic local circuitry, the GABAergic interneurons (INs) and glutamatergic pyramidal neurons (PNs) make negative feedback loops which would regulate the neural activities back to the original state. The drive for the most intriguing self-perpetuating telencephalic activities, then, has not been posed and characterized. We found activity-dependent deployment and delineated functional consequences of the electrical synapses directly linking INs and PNs in the amygdala, a prototypical telencephalic circuitry. These electrical synapses endow INs dual (a faster excitatory and a slower inhibitory) actions on PNs, providing a network-intrinsic excitatory drive that fuels the IN-PN interconnected circuitries and enables persistent oscillations with preservation of GABAergic negative feedback. Moreover, the entities of electrical synapses between INs and PNs are engaged in and disengaged from functioning in a highly dynamic way according to neural activities, which then determine the spatiotemporal scale of recruited oscillating networks. This study uncovers a special wide-range and context-dependent plasticity for wiring/rewiring of brain networks. Epileptogenesis or a wide spectrum of clinical disorders may ensue, however, from different scales of pathological extension of this unique form of telencephalic plasticity.

Surface plasmon coupling effects on the photon color conversion behaviors of colloidal quantum dots in a GaN nanoscale hole with a nearby quantum-well structure.

To improve color conversion performance for color display application, we study the near-field-induced nanoscale-cavity effects on the emission efficiency and Förster resonance energy transfer (FRET) under the condition of surface plasmon (SP) coupling by inserting colloidal quantum dots (QDs) and synthesized Ag nanoparticles (NPs) into surface nano-holes fabricated on a GaN template and an InGaN/GaN quantum-well (QW) template. In the QW template, the inserted Ag NPs are close to either QWs or QDs for producing three-body SP coupling to enhance color conversion. Time-resolved and continuous-wave photoluminescence (PL) behaviors of the QW- and QD-emitting lights are investigated. The comparison between the nano-hole samples and the reference samples of surface QD/Ag NP shows that the nanoscale-cavity effect of the nano-hole leads to the enhancements of QD emission, FRET between QDs, and FRET from QW into QD. The SP coupling induced by the inserted Ag NPs can enhance the QD emission and FRET from QW into QD. Its result is further enhanced through the nanoscale-cavity effect. The relative continuous-wave PL intensities among different color components also show the similar behaviors. By introducing SP coupling to a color conversion device with the FRET process in a nanoscale cavity structure, we can significantly improve the color conversion efficiency. Simulation results confirm the basic observations in experiment.

Characteristics of breast cancers detected by screening mammography in Taiwan: a single institute's experience.

BACKGROUND/AIM: Breast cancer is the most common female malignancy in the world. Nearly ninety percent of screening-detected breast cancers were diagnosed with earlier stages of 0 to II in Taiwan. It's widely acknowledged that mammography screening of breast cancer can achieve the goal of early diagnosis and treatment in terms of preventive task while neglected interval cancers are associated with unfavorable tumor characteristics and worse outcomes. The purpose of this study was to explore the characteristics of screening-detected breast cancers in Taiwan. MATERIALS AND METHODS: Both screening and diagnostic mammography examinations with accompanied BI-RADS (breast imaging-reporting and data system) classification were extracted from the health information system and linked to cancer registry in Taiwan. Enrolled population included those attending their first mammography between 2012 and 2016, excluding subjects with previous breast cancer, or with missing or incomplete data. We compared treatment outcomes between breast cancers with either initial screening or diagnostic mammography (control group), and investigated the compositions of breast cancers detected by screening mammography through direct chart reviews. RESULTS: A total of 84,246 screening and 61,230 diagnostic mammography sessions were performed from 2010 to 2020. More positive results (BI-RADS 0, 3, 4 and 5) were observed for those attending the first diagnostic than the first screening mammography (43.58% versus 16.12%, p < 0.001). Earlier stages (0 and I) distribution (92% versus 81%, p < 0.0001), better survivorship (overall survival: 96.91% versus 92.17%, p = 0.007) and a lower HER2 (human epidermal growth factor receptor II) positive status and lower tumor grade were noted in breast cancers with initial screening rather than diagnostic mammography. Among 26,103 mammography screening invitees between 2012 and 2016, 325 breast cancers were ascertained from cancer registry. Of these, 234 had one, 72 had two and 19 had three episodes of mammography before cancer diagnosis. Extensive chart reviews revealed that women with and without breast symptoms constituted 29.9 and 70.1% of the 325 screening-detected breast cancers, with the latter further divided into false negative results (interval cancer), diagnosed at the first mammography, diagnostic at the secondary or subsequent mammography and those with a delayed biopsy or confirmatory imaging constituted (5.2, 47, 10.5 and 7.4%). CONCLUSION: Screening-detected breast cancers were a mixture of women with and without symptoms, those with a false negative result, true negative results with cancer detected at subsequent mammography and non-adherers. Despite this, efficacy of mammography screening was ascertained in Taiwan from this study. To further enhance earlier detection and decrease false negativity, the impact of repeated mammography, and additional sonography for symptomatic women, compliance following a positive screening mammography should not be overemphasized.

The State of the Field of Pediatric Multimodality Neuromonitoring.

BACKGROUND: The use of multimodal neuromonitoring in pediatrics is in its infancy relative to adult neurocritical care. Multimodal neuromonitoring encompasses the amalgamation of information from multiple individual neuromonitoring devices to gain a more comprehensive understanding of the condition of the brain. It allows for adaptation to the changing state of the brain throughout various stages of injury with potential to individualize and optimize therapies. METHODS: Here we provide an overview of multimodal neuromonitoring in pediatric neurocritical care and its potential application in the future. RESULTS: Multimodal neuromonitoring devices are key to the process of multimodal neuromonitoring, allowing for visualization of data trends over time and ideally improving the ability of clinicians to identify patterns and find meaning in the immense volume of data now encountered in the care of critically ill patients at the bedside. Clinical use in pediatrics requires more study to determine best practices and impact on patient outcomes. Potential uses include guidance for targets of physiological parameters in the setting of acute brain injury, neuroprotection for patients at high risk for brain injury, and neuroprognostication. Implementing multimodal neuromonitoring in pediatric patients involves interprofessional collaboration with the development of a simultaneous comprehensive program to support the use of multimodal neuromonitoring while maintaining the fundamental principles of the delivery of neurocritical care at the bedside. CONCLUSIONS: The possible benefits of multimodal neuromonitoring are immense and have great potential to advance the field of pediatric neurocritical care and the health of critically ill children.

How Can an Na+ Channel Inhibitor Ameliorate Seizures in Lennox-Gastaut Syndrome?

OBJECTIVE: Lennox-Gastaut syndrome (LGS) is an epileptic encephalopathy frequently associated with multiple types of seizures. The classical Na+ channel inhibitors are in general ineffective against the seizures in LGS. Rufinamide is a new Na+ channel inhibitor, but approved for the treatment of LGS. This is not consistent with a choice of antiseizure drugs (ASDs) according to simplistic categorical grouping. METHODS: The effect of rufinamide on the Na+ channel, cellular discharges, and seizure behaviors was quantitatively characterized in native neurons and mammalian models of epilepsy, and compared with the other Na+ channel inhibitors. RESULTS: With a much faster binding rate to the inactivated Na+ channel than phenytoin, rufinamide is distinctively effective if the seizure discharges chiefly involve short bursts interspersed with hyperpolarized interburst intervals, exemplified by spike and wave discharges (SWDs) on electroencephalograms. Consistently, rufinamide, but not phenytoin, suppresses SWD-associated seizures in pentylenetetrazol or AY-9944 models, which recapitulate the major electrophysiological and behavioral manifestations in typical and atypical absence seizures, including LGS. INTERPRETATION: Na+ channel inhibitors shall have sufficiently fast binding to exert an action during the short bursts and then suppress SWDs, in which cases rufinamide is superior. For the epileptiform discharges where the interburst intervals are not so hyperpolarized, phenytoin could be better because of the higher affinity. Na+ channel inhibitors with different binding kinetics and affinity to the inactivated channels may have different antiseizure scope. A rational choice of ASDs according to in-depth molecular pharmacology and the attributes of ictal discharges is advisable. ANN NEUROL 2021;89:1099-1113.

Implementation of a Pediatric Neurocritical Care Program for Children With Status Epilepticus: Adherence to Continuous Electroencephalogram Monitoring.

OBJECTIVES: To describe adherence to continuous electroencephalogram (cEEG) monitoring as part of a pediatric neurocritical care (PNCC) program for status epilepticus (SE). DESIGN: Retrospective review of pre- and postintervention cohorts. SETTING: A pediatric referral hospital. PATIENTS: Children admitted to the PICU for SE. INTERVENTIONS: We restructured the care delivery model to include a pediatric neurointensive care unit (neuro-ICU) and expanded the cEEG capacity. We created a criteria-based cEEG pathway. We provided education to all providers including the nursing staff. MEASUREMENTS AND MAIN RESULTS: The main outcomes were: 1) the percentages of children meeting American Clinical Neurophysiology Society (ACNS) criteria who underwent cEEG monitoring and 2) the time interval between PICU arrival and cEEG initiation. PICU admissions with the diagnosis of SE from May 2017 to December 2017 served as the baseline, which was compared with the same periods in 2018 to 2020 (PNCC era).There were 60 admissions in the pre-PNCC period (2017), 111 in 2018, 118 in 2019, and 108 in 2020. The percentages of admissions from each period that met ACNS criteria for cEEG monitoring were between 84% and 97%. In the pre-PNCC era, 22 of 52 (42%) admissions meeting ACNS criteria underwent cEEG monitoring. In the PNCC era, greater than or equal to 80% of the qualified admissions underwent cEEG monitoring (74/93 [80%] in 2018, 94/115 [82%] in 2019, and 87/101 [86%] in 2020). Compared with the pre-PNCC era, the neuro-ICU had a shorter interval between PICU arrival and cEEG initiation (216 min [141-1,444 min] vs 138 min [103-211 min]). CONCLUSIONS: The implementation of a PNCC program with initiatives in care delivery, allocation of resources, and education was associated with increased adherence to best care practices for the management of SE.

Unexpected systolic anterior motion of the mitral valve-related hypoxemia during transurethral resection of the prostate under spinal anesthesia: a case report.

BACKGROUND: Dynamic obstruction of the left ventricular outflow tract resulting from systolic anterior motion of the mitral valve can be an unexpected cause of acute and severe perioperative hypotension in noncardiac surgery. We report a patient undergoing spinal anesthesia for transurethral resection of the prostate who experienced sudden hypoxemia caused by systolic anterior motion-induced mitral regurgitation but with a clinically picture simulating fluid overload. CASE PRESENTATION: An 83-year-old man with a history of hypertension was scheduled for transurethral resection of the prostate. One hour after spinal anesthesia, he developed acute restlessness and dyspnea, with pink frothy sputum and progressive hypoxemia. Slight hypertension was noted, and an electrocardiogram showed atrial fibrillation with a rapid ventricular response. Furosemide and nitroglycerin were thus administered for suspected fluid overload or transurethral resection of the prostate syndrome; however, he then became severely hypotensive. After tracheal intubation, intraoperative transesophageal echocardiography was promptly performed, which revealed an empty hypercontractile left ventricle, significant mitral regurgitation and mosaic flow signal in the left ventricular outflow tract. Following aggressive fluid therapy, his hemodynamic changes stabilized. Repeat echocardiography in intensive care unit confirmed the presence of systolic anterior motion of the anterior mitral leaflet obstructing the left ventricular outflow tract. We speculate that pulmonary edema was induced by systolic anterior motion-associated mitral regurgitation and rapid atrial fibrillation, and the initial management had worsened his hypovolemia and provoked left ventricular outflow tract obstruction and hemodynamic instability. CONCLUSIONS: Pulmonary edema caused by systolic anterior motion of the mitral valve can be difficult to clinically differentiate from that induced by fluid overload. Therefore, bedside echocardiography is paramount for timely diagnosis and prompt initiation of appropriate therapy in the perioperative care setting.

Clinical presentation of new onset refractory status epilepticus in children (the pSERG cohort).

OBJECTIVE: We aimed to characterize the clinical profile and outcomes of new onset refractory status epilepticus (NORSE) in children, and investigated the relationship between fever onset and status epilepticus (SE). METHODS: Patients with refractory SE (RSE) between June 1, 2011 and October 1, 2016 were prospectively enrolled in the pSERG (Pediatric Status Epilepticus Research Group) cohort. Cases meeting the definition of NORSE were classified as "NORSE of known etiology" or "NORSE of unknown etiology." Subgroup analysis of NORSE of unknown etiology was completed based on the presence and time of fever occurrence relative to RSE onset: fever at onset (≤24 h), previous fever (2 weeks-24 h), and without fever. RESULTS: Of 279 patients with RSE, 46 patients met the criteria for NORSE. The median age was 2.4 years, and 25 (54%) were female. Forty (87%) patients had NORSE of unknown etiology. Nineteen (48%) presented with fever at SE onset, 16 (40%) had a previous fever, and five (12%) had no fever. The patients with preceding fever had more prolonged SE and worse outcomes, and 25% recovered baseline neurological function. The patients with fever at onset were younger and had shorter SE episodes, and 89% recovered baseline function. SIGNIFICANCE: Among pediatric patients with RSE, 16% met diagnostic criteria for NORSE, including the subcategory of febrile infection-related epilepsy syndrome (FIRES). Pediatric NORSE cases may also overlap with refractory febrile SE (FSE). FIRES occurs more frequently in older children, the course is usually prolonged, and outcomes are worse, as compared to refractory FSE. Fever occurring more than 24 h before the onset of seizures differentiates a subgroup of NORSE patients with distinctive clinical characteristics and worse outcomes.

Factors associated with long-term outcomes in pediatric refractory status epilepticus.

OBJECTIVE: This study was undertaken to describe long-term clinical and developmental outcomes in pediatric refractory status epilepticus (RSE) and identify factors associated with new neurological deficits after RSE. METHODS: We performed retrospective analyses of prospectively collected observational data from June 2011 to March 2020 on pediatric patients with RSE. We analyzed clinical outcomes from at least 30 days after RSE and, in a subanalysis, we assessed developmental outcomes and evaluated risk factors in previously normally developed patients. RESULTS: Follow-up data on outcomes were available in 276 patients (56.5% males). The median (interquartile range [IQR]) follow-up duration was 1.6 (.9-2.7) years. The in-hospital mortality rate was 4% (16/403 patients), and 15 (5.4%) patients had died after hospital discharge. One hundred sixty-six (62.9%) patients had subsequent unprovoked seizures, and 44 (16.9%) patients had a repeated RSE episode. Among 116 patients with normal development before RSE, 42 of 107 (39.3%) patients with available data had new neurological deficits (cognitive, behavioral, or motor). Patients with new deficits had longer median (IQR) electroclinical RSE duration than patients without new deficits (10.3 [2.1-134.5] h vs. 4 [1.6-16] h, p = .011, adjusted odds ratio = 1.003, 95% confidence interval = 1.0008-1.0069, p = .027). The proportion of patients with an unfavorable functional outcome (Glasgow Outcome Scale-Extended score ≥ 4) was 22 of 90 (24.4%), and they were more likely to have received a continuous infusion. SIGNIFICANCE: About one third of patients without prior epilepsy developed recurrent unprovoked seizures after the RSE episode. In previously normally developing patients, 39% presented with new deficits during follow-up, with longer electroclinical RSE duration as a predictor.

Benzodiazepine administration patterns before escalation to second-line medications in pediatric refractory convulsive status epilepticus.

OBJECTIVE: This study was undertaken to evaluate benzodiazepine (BZD) administration patterns before transitioning to non-BZD antiseizure medication (ASM) in pediatric patients with refractory convulsive status epilepticus (rSE). METHODS: This retrospective multicenter study in the United States and Canada used prospectively collected observational data from children admitted with rSE between 2011 and 2020. Outcome variables were the number of BZDs given before the first non-BZD ASM, and the number of BZDs administered after 30 and 45 min from seizure onset and before escalating to non-BZD ASM. RESULTS: We included 293 patients with a median (interquartile range) age of 3.8 (1.3-9.3) years. Thirty-six percent received more than two BZDs before escalating, and the later the treatment initiation was after seizure onset, the less likely patients were to receive multiple BZD doses before transitioning (incidence rate ratio [IRR] = .998, 95% confidence interval [CI] = .997-.999 per minute, p = .01). Patients received BZDs beyond 30 and 45 min in 57.3% and 44.0% of cases, respectively. Patients with out-of-hospital seizure onset were more likely to receive more doses of BZDs beyond 30 min (IRR = 2.43, 95% CI = 1.73-3.46, p < .0001) and beyond 45 min (IRR = 3.75, 95% CI = 2.40-6.03, p < .0001) compared to patients with in-hospital seizure onset. Intermittent SE was a risk factor for more BZDs administered beyond 45 min compared to continuous SE (IRR = 1.44, 95% CI = 1.01-2.06, p = .04). Forty-seven percent of patients (n = 94) with out-of-hospital onset did not receive treatment before hospital arrival. Among patients with out-of-hospital onset who received at least two BZDs before hospital arrival (n = 54), 48.1% received additional BZDs at hospital arrival. SIGNIFICANCE: Failure to escalate from BZDs to non-BZD ASMs occurs mainly in out-of-hospital rSE onset. Delays in the implementation of medical guidelines may be reduced by initiating treatment before hospital arrival and facilitating a transition to non-BZD ASMs after two BZD doses during handoffs between prehospital and in-hospital settings.

Super-Refractory Status Epilepticus in Children: A Retrospective Cohort Study.

OBJECTIVES: To characterize the pediatric super-refractory status epilepticus population by describing treatment variability in super-refractory status epilepticus patients and comparing relevant clinical characteristics, including outcomes, between super-refractory status epilepticus, and nonsuper-refractory status epilepticus patients. DESIGN: Retrospective cohort study with prospectively collected data between June 2011 and January 2019. SETTING: Seventeen academic hospitals in the United States. PATIENTS: We included patients 1 month to 21 years old presenting with convulsive refractory status epilepticus. We defined super-refractory status epilepticus as continuous or intermittent seizures lasting greater than or equal to 24 hours following initiation of continuous infusion and divided the cohort into super-refractory status epilepticus and nonsuper-refractory status epilepticus groups. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 281 patients (157 males) with a median age of 4.1 years (1.3-9.5 yr), including 31 super-refractory status epilepticus patients. Compared with nonsuper-refractory status epilepticus group, super-refractory status epilepticus patients had delayed initiation of first nonbenzodiazepine-antiseizure medication (149 min [55-491.5 min] vs 62 min [33.3-120.8 min]; p = 0.030) and of continuous infusion (495 min [177.5-1,255 min] vs 150 min [90-318.5 min]; p = 0.003); prolonged seizure duration (120 hr [58-368 hr] vs 3 hr [1.4-5.9 hr]; p < 0.001) and length of ICU stay (17 d [9.5-40 d] vs [1.8-8.8 d]; p < 0.001); more medical complications (18/31 [58.1%] vs 55/250 [22.2%] patients; p < 0.001); lower return to baseline function (7/31 [22.6%] vs 182/250 [73.4%] patients; p < 0.001); and higher mortality (4/31 [12.9%] vs 5/250 [2%]; p = 0.010). Within the super-refractory status epilepticus group, status epilepticus resolution was attained with a single continuous infusion in 15 of 31 patients (48.4%), two in 10 of 31 (32.3%), and three or more in six of 31 (19.4%). Most super-refractory status epilepticus patients (30/31, 96.8%) received midazolam as first choice. About 17 of 31 patients (54.8%) received additional treatments. CONCLUSIONS: Super-refractory status epilepticus patients had delayed initiation of nonbenzodiazepine antiseizure medication treatment, higher number of medical complications and mortality, and lower return to neurologic baseline than nonsuper-refractory status epilepticus patients, although these associations were not adjusted for potential confounders. Treatment approaches following the first continuous infusion were heterogeneous, reflecting limited information to guide clinical decision-making in super-refractory status epilepticus.

Secretory Carcinoma of the Breast: A Case Report and Literature Review.

Secretory carcinoma of the breast is a rare subtype of breast cancer. It can occur at any age but is usually diagnosed in patients under 30 years. It is the most common subtype of breast malignancy in the pediatric population and has a favorable outcome. Surgical excision is the best treatment and adjuvant therapies are still under debate. We present the case report of a 26-year-old patient with secretory carcinoma of the breast, including imaging, histologic findings, and clinical outcome.

Desensitization of NMDA channels requires ligand binding to both GluN1 and GluN2 subunits to constrict the pore beside the activation gate.

N-methyl-D-aspartate (NMDA) receptor channels are activated by glutamate (or NMDA) and glycine. The channels also undergo desensitization, which denotes decreased channel availability, after prolonged exposure to the activating ligands. Glycine apparently has a paradoxical negative effect on desensitization, as the increase in ambient glycine in concentrations required for channel activation would increase sustained NMDA receptor currents. We hypothesized that this classical "glycine-dependent desensitization" could be glycine-dependent activation in essence. By performing electrophysiological recordings and biophysical analyses with rat brain NMDA receptors heterogeneously expressed in Xenopus laevis oocytes, we characterized that the channel opened by "only" NMDA (in nominally glycine-free condition probably with the inevitable nanomolar glycine) would undergo a novel form of deactivation rather than desensitization, and is thus fully available for subsequent activation. Moreover, external tetrapentylammonium ions (TPentA), tetrabutylammonium ions, and tetrapropylammonium ions (TPA, in higher concentrations) block the pore and prohibit channel desensitization with a simple "foot-in-the-door" hindrance effect. TpentA and TPA have the same voltage dependence but show different flow dependence in binding affinity, revealing a common binding site at an electrical distance of ~0.7 from the outside yet differential involvement of the flux-coupling region in the external pore mouth. The smaller tetraethylammonium ion and the larger tetrahexylammonium and tetraheptylammonium ions may block the channel but could not affect desensitization. We conclude that NMDA receptor desensitization requires concomitant binding of both glycine and glutamate, and thus movement of both GluN1 and GluN2 subunits. Desensitization gate itself embodies a highly restricted pore reduction with a physical distance of ~4 Å from the charged nitrogen atom of bound tetraalkylammonium ions, and is located very close to the activation gate in the bundle-crossing region in the external pore vestibule.

Validation of the diagnosis and triage algorithm for acute myocardial infarction in the setting of left bundle branch block.

BACKGROUND: Detecting acute ST-segment elevation myocardial infarction (STEMI) in the setting of left bundle branch block (LBBB) remains a challenge to clinicians. Several diagnostic and triage algorithms have been proposed to accurately identify LBBB patients with an acute culprit vessel. We aimed to validate the algorithm proposed by Cai et al., which uses patients' hemodynamic status and the modified Sgarbossa electrocardiography criteria to guide reperfusion therapy. METHODS: This retrospective study was performed with a chart review in emergency departments (EDs) of 2 medical centers, 2 regional hospitals, and 1 local hospital. From January 2010 to December 2014, 2432 consecutive patients were diagnosed as having STEMI in the ED, including 65 patients with LBBB (2.6%). RESULTS: The patients with LBBB were older and more frequently presented with acute pulmonary edema (58.5% vs 22.1%, p < 0.001), cardiogenic shock (16.9% vs 6.3% p = 0.006), and VT/VF episodes (7.7% vs 2.2%, p = 0.034) and had a higher 30-day mortality rate (20.0% vs 10.4% p = 0.032) than those without LBBB. We then tested the algorithm proposed by Cai et al. and noted a sensitivity of 93.8% in identifying a culprit lesion. CONCLUSIONS: The inconsistency of the guideline recommendations reflects the uncertainty of diagnostic and therapeutic strategies and the pressing need for tools to accurately identify the true acute myocardial infarction in patients presenting with chest pain and LBBB. The algorithm proposed by Cai et al. had good sensitivity and would allow emergency physicians to implement the timely treatment protocol for this high-risk population.

Changes in synaptic AMPA receptor concentration and composition in chronic temporal lobe epilepsy.

Excitotoxicity caused by excessive stimulation of glutamate receptors, resulting in pathologically increased Ca2+-concentrations, is a decisive factor in neurodegenerative diseases. We investigated long-term changes in synaptic contents of AMPA receptor subunits that play important roles in calcium regulation in chronic epilepsy. Such plastic changes may be either adaptive or detrimental. We used a kainic acid (KA)-based rat model of chronic temporal lobe epilepsy (TLE). Using hippocampal synaptosomes, we found significant reductions in the concentration of the AMPA receptor subunits GluA1 and GluA2, and the NMDA receptor subunit NR2B. The relative size of GluA1 and GluA2 reductions were almost identical, at 28% and 27%, respectively. In order to determine whether the synaptic reduction of the AMPA receptor subunits actually reflected the pool of receptors present along the postsynaptic density (PSD), as opposed to cytoplasmic or extrasynaptic pools, we performed postembedding immunogold electron microscopy (EM) of GluA1 and GluA2 in Schaffer collateral synapses in the hippocampal CA1 area. We found significant reductions, at 32% and 52% of GluA1 and GluA2 subunits, respectively, along the PSD, indicating that these synapses undergo lasting changes in glutamatergic neurotransmission during chronic TLE. When compared to the overall concentration and composition of AMPA receptors expressed in the brain, there was a relative increase in GluA2-lacking AMPA receptor subunits following chronic epilepsy. These changes in synaptic AMPA receptor subunits may possibly contribute to further aggravate the excitotoxic vulnerability of the neurons as well as have significant implications for hippocampal cognitive functions.

Ultrasound-Guided Prolotherapy for Acromial Enthesopathy and Acromioclavicular Joint Arthropathy: A Single-Arm Prospective Study.

OBJECTIVES: Prolotherapy is an injection-based complementary treatment for various musculoskeletal diseases. The aim of this study was to evaluate the therapeutic efficacy of ultrasound-guided prolotherapy in the treatment of acromial enthesopathy and acromioclavicular joint arthropathy. METHODS: Thirty-one patients with chronic moderate-to-severe shoulder pain were recruited from September 2015 to September 2017. Ultrasound-guided prolotherapy was performed by injecting 10 mL of a 15% dextrose solution into the acromial enthesis of the deltoid or acromioclavicular joint capsule aseptically. Prolotherapy was given in 2 sessions separated by a 1-month interval. The pretreatment-to-posttreatment change in the pain visual analog scale (VAS) score was recorded as the primary outcome. The mean follow-up duration was 61.8 days. A paired t test was used to assess the difference in pretreatment and posttreatment VAS scores. A univariate logistic regression analysis was conducted to identify the demographic variables associated with substantial pain reduction after the intervention. Substantial pain reduction was defined as a posttreatment VAS score of 3 or less. RESULTS: Twenty of the 31 patients reported substantial pain reduction without adverse effects after the intervention. The mean VAS score reduction ± SD was 4.3 ± 2.6 (pretreatment, 6.8 ± 1.5; posttreatment, 2.5 ± 2.1; P < .01). CONCLUSIONS: Ultrasound-guided prolotherapy with a 15% dextrose solution is an effective and safe therapeutic option for moderate-to-severe acromial enthesopathy and acromioclavicular joint arthropathy.

Percutaneous ethanol ablation of intrahepatic arterial pseudoaneurysm: A case report.

Hepatic arterial pseudoaneurysm is a rare but potentially fatal condition that requires prompt management. We report a case of hepatic arterial pseudoaneurysm developed after radiofrequency ablation of a hepatocellular carcinoma. The patient was successfully treated with percutaneous absolute ethanol injection under ultrasound guidance. Follow-up studies with ultrasound and computed tomography for 2 years after treatment revealed no evidence of local recurrence of hepatocellular carcinoma and of the pseudoaneurysm.

Microcalcifications Detected at Screening Mammography: Synthetic Mammography and Digital Breast Tomosynthesis versus Digital Mammography.

Purpose To compare the performance of two-dimensional synthetic mammography (SM) plus digital breast tomosynthesis (DBT) versus conventional full-field digital mammography (FFDM) in the detection of microcalcifications on screening mammograms. Materials and Methods In this retrospective multireader observer study, 72 consecutive screening mammograms recalled for microcalcifications from June 2015 through August 2016 were evaluated with both FFDM and DBT. The data set included 54 mammograms with benign microcalcifications and 18 mammograms with malignant microcalcifications, and 20 additional screening mammograms without microcalcifications used as controls. FFDM alone was compared to synthetic mammography plus DBT. Four readers independently reviewed each data set and microcalcification recalls were tabulated. Sensitivity and specificity for microcalcification detection were calculated for SM plus DBT and for FFDM alone. Interreader agreement was calculated with Fleiss kappa values. Results Reader agreement was kappa value of 0.66 (P < .001) for FFDM and 0.63 (P < .001) for SM plus DBT. For FFDM, the combined reader sensitivity for all microcalcifications was 80% (229 of 288; 95% confidence interval [CI]: 74%, 84%) and for malignant microcalcifications was 92% (66 of 72; 95% CI: 83%, 97%). For SM plus DBT, the combined reader sensitivity for all microcalcifications was 75% (215 of 288; 95% CI: 69%, 80%) and for malignant microcalcifications was 94% (68 of 72; 95% CI: 86%, 98%). For FFDM, the combined reader specificity for all microcalcifications was 98% (78 of 80; 95% CI: 91%, 100%) and for malignant microcalcifications was 98% (78 of 80; 95% CI: 91%, 100%). For SM plus DBT, combined reader specificity for all microcalcifications was 95% (76 of 80; 95% CI: 88%, 99%) and for malignant microcalcifications was 95% (76 of 80; 95% CI: 88%, 99%). Mixed-effects model concluded no differences between modalities (‒0.03; 95% CI: ‒0.08, 0.01; P = .13). Conclusion Relative to full-field digital mammography, synthetic mammography plus digital breast tomosynthesis had similar sensitivity and specificity for the detection of microcalcifications previously identified for recall at screening mammography. © RSNA, 2018 See also the editorial by Bae and Moon in this issue.