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Clinical Features, Neuropathology, and Surgical Outcome in Patients With Refractory Epilepsy and Brain Somatic Variants in the <i>SLC35A2</i> Gene.
No full textBackground and objectivesThe SLC35A2 gene, located at chromosome Xp11.23, encodes for a uridine diphosphate-galactose transporter. We describe clinical, genetic, neuroimaging, EEG, and histopathologic findings and assess possible predictors of postoperative seizure and cognitive outcome in 47 patients with refractory epilepsy and brain somatic SLC35A2 gene variants.MethodsThis is a retrospective multicenter study where we performed a descriptive analysis and classical hypothesis testing. We included the variables of interest significantly associated with the outcomes in the generalized linear models.ResultsTwo main phenotypes were associated with brain somatic SLC35A2 variants: (1) early epileptic encephalopathy (EE, 39 patients) with epileptic spasms as the predominant seizure type and moderate to severe intellectual disability and (2) drug-resistant focal epilepsy (DR-FE, 8 patients) associated with normal/borderline cognitive function and specific neuropsychological deficits. Brain MRI was abnormal in all patients with EE and in 50% of those with DR-FE. Histopathology review identified mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy in 44/47 patients and was inconclusive in 3. The 47 patients harbored 42 distinct mosaic SLC35A2 variants, including 14 (33.3%) missense, 13 (30.9%) frameshift, 10 (23.8%) nonsense, 4 (9.5%) in-frame deletions/duplications, and 1 (2.4%) splicing variant. Variant allele frequencies (VAFs) ranged from 1.4% to 52.6% (mean VAF: 17.3 ± 13.5). At last follow-up (35.5 ± 21.5 months), 30 patients (63.8%) were in Engel Class I, of which 26 (55.3%) were in Class IA. Cognitive performances remained unchanged in most patients after surgery. Regression analyses showed that the probability of achieving both Engel Class IA and Class I outcomes, adjusted by age at seizure onset, was lower when the duration of epilepsy increased and higher when postoperative EEG was normal or improved. Lower brain VAF was associated with improved postoperative cognitive outcome in the analysis of associations, but this finding was not confirmed in regression analyses.DiscussionBrain somatic SLC35A2 gene variants are associated with 2 main clinical phenotypes, EE and DR-FE, and a histopathologic diagnosis of MOGHE. Additional studies will be needed to delineate any possible correlation between specific genetic variants, mutational load in the epileptogenic tissue, and surgical outcomes
Elusive consensus: Polarization in elite communication on the COVID-19 pandemic.
No full textCues sent by political elites are known to influence public attitudes and behavior. Polarization in elite rhetoric may hinder effective responses to public health crises, when accurate information and rapid behavioral change can save lives. We examine polarization in cues sent to the public by current members of the U.S. House and Senate during the onset of the COVID-19 pandemic, measuring polarization as the ability to correctly classify the partisanship of tweets' authors based solely on the text and the dates they were sent. We find that Democrats discussed the crisis more frequently-emphasizing threats to public health and American workers-while Republicans placed greater emphasis on China and businesses. Polarization in elite discussion of the COVID-19 pandemic peaked in mid-February-weeks after the first confirmed case in the United States-and continued into March. These divergent cues correspond with a partisan divide in the public's early reaction to the crisis
Compensation from mild and severe cases of early proximal junctional kyphosis may manifest as progressive cervical deformity at two year follow-up.
No full textBackgroundPostoperative reciprocal changes (RC) in the cervical spine associated with varying factors of proximal junctional kyphosis (PJK) following fusions of the thoracopelvic spine are poorly understood.PurposeExplore reciprocal changes in the cervical spine associated with varying factors (severity, progression, patient age) of PJK in patients undergoing adult spinal deformity (ASD) correction.Patients and methodsRetrospective review of a multicenter ASD database.InclusionASD patients > 18 y/o, undergoing fusions from the thoracic spine (UIV: T6-T12) to the pelvis with two-year radiographic data. ASD was defined as: Coronal Cobb angle ≥ 20°, Sagittal Vertical Axis ≥ 5 cm, Pelvic Tilt ≥ 25°, and/or Thoracic Kyphosis ≥ 60°. PJK was defined as a ≥ 10° measure of the sagittal Cobb angle between the inferior endplate of the UIV and the superior endplate of the UIV + 2. Patients were grouped by mild (M; 10°-20°) and severe (S; > 20°) PJK at one year. Propensity Score Matching (PSM) controlled for CCI, age, PI and UIV. Unpaired and paired t test analyses determined difference between RC parameters and change between time points. Pearson bi-variate correlations analyzed associations between RC parameters (T4-T12, TS-CL, cSVA, C2-Slope, and T1-Slope) and PJK descriptors.Results284 ASD patients (UIV: T6: 1.1%; T7: 0.7%; T8: 4.6%; T9: 9.9%; T10: 58.8%; T11: 19.4%; T12: 5.6%) were studied. PJK analysis consisted of 182 patients (Mild = 91 and Severe = 91). Significant difference between M and S groups were observed in T4-T12 Δ1Y(- 16.8 v - 22.8, P = 0.001), TS-CLΔ1Y(- 0.6 v 2.8, P = 0.037), cSVAΔ1Y(- 1.8 v 1.9, P = 0.032), and C2 slopeΔ1Y(- 1.6 v 2.3, P = 0.022). By two years post-op, all changes in cervical alignment parameters were similar between mild and severe groups. Correlation between age and cSVAΔ1Y(R = 0.153, P = 0.034) was found. Incidence of severe PJK was found to correlate with TS-CLΔ1Y(R = 0.142, P = 0.049), cSVAΔ1Y(R = 0.171, P = 0.018), C2SΔ1Y(R = 0.148, P = 0.040), and T1SΔ2Y(R = 0.256, P = 0.003).ConclusionsCompensation within the cervical spine differed between individuals with mild and severe PJK at one year postoperatively. However, similar levels of pathologic change in cervical alignment parameters were seen by two years, highlighting the progression of cervical compensation due to mild PJK over time. These findings provide greater evidence for the development of cervical deformity in individuals presenting with proximal junctional kyphosis
Revealing parallel modulation on the sensory-motor decoder for smooth pursuit eye movements.
No full textPrimates use smooth pursuit eye movements to track moving objects. Pursuit is driven by visual commands to accelerate and supported by eye velocity feedback. We show that degraded motion reliability caused by reduced coherence in a pursuit target created from a moving patch of dots reduces the eye speed during the initiation of pursuit as well as during steady-state tracking. To understand the representation of image speed during pursuit and to ask why degraded motion reduces eye speeds, we recorded from isolated single neurons in the middle temporal area of extrastriate visual cortex (MT). Smooth pursuit is driven by sensory estimates of stimulus speed represented in MT. We sought to determine whether eye speed lags behind target speed for low dot coherence because (i) the speed representation in MT is compromised or (ii) the representation of image speed remains accurate in MT and eye speed is eroded in downstream circuits. We presented moving patches of dots of varying speeds and coherences while recording with microelectrodes from neurons in area MT. During pursuit initiation, the amplitude, but not the tuning, of MT responses depends on dot coherence. The population response gets noisier as coherence reduces the amplitude of neural (and eye movement) responses. To understand how MT drives the initiation and steady-state of pursuit, we asked whether we could decode appropriate motor commands from the MT population response and what were the properties of the successful decoders. During pursuit initiation, decoding eye speed required parallel pathways in a “gain-modulated vector averaging” decoder. One pathway estimated image speed by vector averaging and the other pathway computed the gain of sensory-motor transmission from the amplitude of the MT population response. To reproduce eye speed during steady-state tracking, yet another pathway was needed in the decoder. MT population activity is overall noisier during steady-state tracking but even for low dot coherence gain-modulated vector averaging predicts eye acceleration at a time when the eye is either stable at a speed well below target speed, or even decelerating. We could not account for the failure of eye speed to accelerate to target speed based on unresponsiveness of MT to image motion: pulsing the speed or coherence of the moving dots during steady-state tracking confirmed the responsiveness of area MT throughout pursuit. Instead, we propose a parallel effect of sensory-motor gain signals on the cerebellum’s eye velocity positive motor feedback that normally sustains steady-state eye speed. </p
Mitigation of SARS-CoV-2 transmission at a large public university
No full textIn Fall 2020, universities saw extensive transmission of SARS-CoV-2 among their populations, threatening health of the university and surrounding communities, and viability of in-person instruction. Here we report a case study at the University of Illinois at Urbana-Champaign, where a multimodal “SHIELD: Target, Test, and Tell” program, with other non-pharmaceutical interventions, was employed to keep classrooms and laboratories open. The program included epidemiological modeling and surveillance, fast/frequent testing using a novel low-cost and scalable saliva-based RT-qPCR assay for SARS-CoV-2 that bypasses RNA extraction, called covidSHIELD, and digital tools for communication and compliance. In Fall 2020, we performed >1,000,000 covidSHIELD tests, positivity rates remained low, we had zero COVID-19-related hospitalizations or deaths amongst our university community, and mortality in the surrounding Champaign County was reduced more than 4-fold relative to expected. This case study shows that fast/frequent testing and other interventions mitigated transmission of SARS-CoV-2 at a large public university
A Deep Learning Approach for Rapid and Generalizable Denoising of Photon-Counting Micro-CT Images.
No full textPhoton-counting CT (PCCT) is powerful for spectral imaging and material decomposition but produces noisy weighted filtered backprojection (wFBP) reconstructions. Although iterative reconstruction effectively denoises these images, it requires extensive computation time. To overcome this limitation, we propose a deep learning (DL) model, UnetU, which quickly estimates iterative reconstruction from wFBP. Utilizing a 2D U-net convolutional neural network (CNN) with a custom loss function and transformation of wFBP, UnetU promotes accurate material decomposition across various photon-counting detector (PCD) energy threshold settings. UnetU outperformed multi-energy non-local means (ME NLM) and a conventional denoising CNN called UnetwFBP in terms of root mean square error (RMSE) in test set reconstructions and their respective matrix inversion material decompositions. Qualitative results in reconstruction and material decomposition domains revealed that UnetU is the best approximation of iterative reconstruction. In reconstructions with varying undersampling factors from a high dose ex vivo scan, UnetU consistently gave higher structural similarity (SSIM) and peak signal-to-noise ratio (PSNR) to the fully sampled iterative reconstruction than ME NLM and UnetwFBP. This research demonstrates UnetU's potential as a fast (i.e., 15 times faster than iterative reconstruction) and generalizable approach for PCCT denoising, holding promise for advancing preclinical PCCT research
Republication of "Osteochondral Lesions of the Talus: Current Concepts in Diagnosis and Treatment".
No full textOsteochondral lesions of the talus (OLTs) are a difficult pathologic entity to treat. They require a strong plan. Lesion size, location, chronicity, and characteristics such as displacement and the presence of subchondral cysts help dictate the appropriate treatment required to achieve a satisfactory result. In general, operative treatment is reserved for patients with displaced OLTs or for patients who have failed nonoperative treatment for 3 to 6 months. Operative treatments can be broken down into cartilage repair, replacement, and regenerative strategies. There are many promising treatment options, and research is needed to elucidate which are superior to minimize the morbidity from OLTs
What's fishy about protamine? Clinical use, adverse reactions, and potential alternatives.
No full textProtamine, a highly basic protein isolated from salmon sperm, is the only clinically available agent to reverse the anticoagulation of unfractionated heparin. Following intravenous administration, protamine binds to heparin in a nonspecific electrostatic interaction to reverse its anticoagulant effects. In clinical use, protamine is routinely administered to reverse high-dose heparin anticoagulation in cardiovascular procedures, including cardiac surgery with cardiopulmonary bypass. Despite the lack of supportive evidence regarding protamine's effectiveness to reverse low-molecular-weight heparin, it is recommended in guidelines with low-quality evidence. Different dosing strategies have been reported for reversing heparin in cardiac surgical patients based on empiric dosing, pharmacokinetics, or point-of-care measurements of heparin levels. Protamine administration is associated with a spectrum of adverse reactions that range from vasodilation to life-threatening cardiopulmonary dysfunction and shock. The life-threatening responses appear to be hypersensitivity reactions due to immunoglobulin E and/or immunoglobulin G antibodies. However, protamine and heparin-protamine complexes can activate complement inflammatory pathways and inhibit other coagulation factors. Although alternative agents for reversing heparin are not currently available for clinical use, additional research continues evaluating novel therapeutic approaches