Clinical characteristics and surgical outcomes of epilepsy associated with temporal encephalocele: A systematic review.

Temporal encephaloceles (TE) are an under-identified, potentially intervenable cause of epilepsy. This systematic review consolidates the current data to identify the major clinical, neuroimaging, and EEG features and surgical outcomes of epilepsy associated with TE. Literature searches were carried out using MEDLINE, Embase, PsycINFO, Scopus, and Cochrane Library databases from inception to December 7, 2023. Studies were included if they described clinical, neuroimaging, EEG, or surgical data in ≥5 patients with TE and epilepsy. Of 562 studies identified in the search, 24 met the eligibility criteria, reporting 423 unique patients with both epilepsy and TE. Compared to epilepsy patients without TE, those with TE had a higher mean age of seizure onset and were less likely to have a history of febrile seizures. Seizure semiologies were variable, but primarily mirrored temporal lobe onset patterns. Epilepsy patients with TE had a higher likelihood of having clinical or radiographic features of idiopathic intracranial hypertension (IIH) than those without. Brain MRI may show ipsilateral mesial temporal sclerosis (16 %). CT scans of the skull base usually revealed bony defects near the TE (90 %). Brain PET scans primarily showed ipsilateral temporal lobe hypometabolism (80 %), mostly in the anterior temporal lobe (67 %). Scalp EEG mostly lateralized ipsilateral to the implicated TE (92 % seizure onset) and localized to the temporal lobe (96 %). Intracranial EEG revealed seizure onset near the TE (11 of 12 cases including TE-adjacent electrodes) with variable timing of spread to the ipsilateral hippocampus. After surgical treatment of the TE, the rate of Engel I or ILAE 1 outcomes at one year was 75 % for lesionectomy, 85 % for anterior temporal lobectomy (ATL), and 80 % for ATL with amygdalohippocampectomy. Further studies are needed to better elucidate the relationship between IIH, TE, and epilepsy, improve the identification of TE, and optimize surgical interventions.

Perceptions of undertaking a higher degree alongside dental specialty training: A cross-sectional survey of UK dental specialty trainees.

INTRODUCTION: The curricula for UK dental specialty training have recently been under review and until 2024, completion of a research component during training in Dental Public Health, Oral Microbiology and Orthodontics has been mandatory (with an alternative route for Orthodontics involving the submission of two scientific papers for those trainees not wishing to undertake a higher degree). Anecdotally, some trainees in other dental specialties choose to undertake higher degrees alongside specialty training. AIMS: The aims were to investigate how many dental specialty registrars study for higher degrees alongside specialty training, and whether undertaking a higher degree alongside specialty training has an impact on completion of training, research skills, research experience, patient care and career opportunities. MATERIALS AND METHODS: This was a cross-sectional study design, involving the distribution of an online, anonymous questionnaire-based survey to UK dental specialty registrars in November and December 2022. RESULTS: In total, 38 questionnaires were completed, representing a 7.7% response rate of the entire dental specialty registrar cohort in the UK and 42% of those who received it. Most respondents (76.3%) were either studying or had completed a clinically relevant higher degree prior to specialty training. Most respondents (76.3%) reported that the higher degree increased career opportunities and gave them additional skills. CONCLUSIONS: Dental specialty trainees who responded to this survey perceived the higher degree to be beneficial in terms of preparing for exams, gaining skills in critical appraisal and for increasing future career opportunities.

Trends and Disparities in the Utilization of Thymectomy for Myasthenia Gravis in the United States.

Background and Objectives: In 2016, a randomized controlled trial demonstrated the clinical efficacy of trans-sternal thymectomy for patients with non-thymomatous myasthenia gravis (MG). Whether large-scale changes occurred in clinical practice after this trial is unknown. Methods: We performed a retrospective longitudinal cross-sectional analysis using National Inpatient Sample (NIS) data from 2012 to 2019. Our study included hospitalized adults at least 18 years of age diagnosed with MG without an associated thymoma. We used joinpoint regression to analyze annual trends in thymectomy volume and surgical approach (minimally invasive vs trans-sternal) from 2012 to 2019. Using logistic regression models, we examined patient and hospital-level factors that may have influenced whether thymectomy was performed, such as age, sex, race, insurance payor, hospital size and teaching status, and Elixhauser Comorbidity Index. Sampling weights were applied to account for the complex survey design of NIS. Results: The total number of thymectomy procedures increased by 69.8% per year (95% CI 40.1-105.8) between 2012 and 2019. Trans-sternal thymectomies increased by 62.8% per year (95% CI 35.8-95.2) and minimally invasive thymectomies by 83.7% per year (95% CI 38.1-144.3). Thymectomies were significantly more likely to occur in 2017-2019 compared with 2012-2016 (OR 1.93, 95% CI 1.62-2.31). In a multivariable regression model, several factors decreased the odds of patients with MG having a thymectomy: older age, Black race (OR 0.62, 95% CI 0.49-0.77), female (OR 0.73, 95% CI 0.63-0.86), and higher Elixhauser Comorbidity Index. Patients in medium (OR 1.82, 95% CI 1.30-2.55) or large (OR 2.81, 95% CI 2.07-3.82) size and urban teaching hospitals (OR 6.09, 95% CI 2.65-13.97) were more likely to undergo thymectomy. Discussion: Thymectomy is being performed more frequently for non-thymomatous MG, especially after 2016 after publication of a positive phase III clinical trial. There are several disparities in thymectomy utilization that warrant further attention.

Levofloxacin prophylaxis for pediatric leukemia patients: monitoring of outcomes for sustained benefit and consequences.

Levofloxacin prophylaxis reduces bloodstream infections in neutropenic patients with acute myeloid leukemia or relapsed acute lymphoblastic leukemia. A retrospective, longitudinal cohort study compares incidence of bacteremia, multidrug-resistant organisms (MDRO), and Clostridioides difficile (CDI) between time periods of levofloxacin prophylaxis implementation. Benefits were sustained without increasing MDRO or CDI.

Uncovering the predictive pathways of lithium and sodium interchange in layered oxides.

Ion exchange is a powerful method to access metastable materials with advanced functionalities for energy storage applications. However, high concentrations and unfavourably large excesses of lithium are always used for synthesizing lithium cathodes from parent sodium material, and the reaction pathways remain elusive. Here, using layered oxides as model materials, we demonstrate that vacancy level and its corresponding lithium preference are critical in determining the accessible and inaccessible ion exchange pathways. Taking advantage of the strong lithium preference at the right vacancy level, we establish predictive compositional and structural evolution at extremely dilute and low excess lithium based on the phase equilibrium between Li0.94CoO2 and Na0.48CoO2. Such phase separation behaviour is general in both surface reaction-limited and diffusion-limited exchange conditions and is accomplished with the charge redistribution on transition metals. Guided by this understanding, we demonstrate the synthesis of NayCoO2 from the parent LixCoO2 and the synthesis of Li0.94CoO2 from NayCoO2 at 1-1,000 Li/Na (molar ratio) with an electrochemical assisted ion exchange method by mitigating the kinetic barriers. Our study opens new opportunities for ion exchange in predictive synthesis and separation applications.

Prospective Comparison of VisuALL Virtual Reality Perimetry and Humphrey Automated Perimetry in Glaucoma.

Aim and background: Automated perimetry plays an important role in the diagnosis and monitoring of glaucoma patients. The purpose of this study is to prospectively determine parity between Humphrey visual field analyzer (HVFA) perimetry (the current gold standard) and the VisuALL virtual reality perimeter (VRP). Materials and methods: In this prospective fully paired diagnostic accuracy study, patients with stable, long-term HVFA visual fields (horizontal dots for ≥4 consecutive visits on progression analysis) with preperimetric, mild, moderate, or severe visual field loss were familiarized with the VRP and then tested using its proprietary software. These results were used for point-by-point comparison with a contemporaneous HVFA test. This study was approved by the Institutional Review Board (IRB) of the University of the Incarnate Word, San Antonio, Texas, United States of America (IRB approval #20-06-002). Results: The prospective study analyzed 43 eyes of 24 glaucoma patients. Spearman's correlation of mean deviation (MD) revealed a strong correlation between HVFA and VRP with rs(41) = 0.871, p < 0.001. The overall mean difference in locus-locus sensitivity between the devices was -0.4 ± 1.5 dB but varied for different visual field locations and glaucoma severity. Conclusion: The parity between the VRP and HVFA was remarkably strong for mild and moderate glaucoma. Given its portability, ease of use, space efficiency, and low cost, the VRP presents a viable alternative. Clinical significance: Automated perimetry, specifically the HVFA, has been the gold standard for visual field assessment since its introduction. The recent COVID-19 pandemic has illuminated the advantages of the VRP, allowing for safer visual assessment for both patient and clinician alike. Our study hopes to establish parity between these systems, allowing for the efficient integration of a novel head-mounted perimetry system that can safely diagnose and monitor glaucomatous progression in clinical practice. Precis: Investigation of parity between Olleyes VisuALL virtual reality perimetry (VRP) and existing standard HVFA perimetry is essential to the diagnosis and management of glaucoma. Linear correlations between the two were established from 43 glaucomatous eyes. Parity was strong for mild and moderate glaucoma, presenting VRP as a viable alternative. How to cite this article: Griffin JM, Slagle GT, Vu TA, et al. Prospective Comparison of VisuALL Virtual Reality Perimetry and Humphrey Automated Perimetry in Glaucoma. J Curr Glaucoma Pract 2024;18(1):4-9.

Naturalistic Object Representations Depend on Distance and Size Cues.

Egocentric distance and real-world size are important cues for object perception and action. Nevertheless, most studies of human vision rely on two-dimensional pictorial stimuli that convey ambiguous distance and size information. Here, we use fMRI to test whether pictures are represented differently in the human brain from real, tangible objects that convey unambiguous distance and size cues. Participants directly viewed stimuli in two display formats (real objects and matched printed pictures of those objects) presented at different egocentric distances (near and far). We measured the effects of format and distance on fMRI response amplitudes and response patterns. We found that fMRI response amplitudes in the lateral occipital and posterior parietal cortices were stronger overall for real objects than for pictures. In these areas and many others, including regions involved in action guidance, responses to real objects were stronger for near vs. far stimuli, whereas distance had little effect on responses to pictures-suggesting that distance determines relevance to action for real objects, but not for pictures. Although stimulus distance especially influenced response patterns in dorsal areas that operate in the service of visually guided action, distance also modulated representations in ventral cortex, where object responses are thought to remain invariant across contextual changes. We observed object size representations for both stimulus formats in ventral cortex but predominantly only for real objects in dorsal cortex. Together, these results demonstrate that whether brain responses reflect physical object characteristics depends on whether the experimental stimuli convey unambiguous information about those characteristics. Significance Statement: Classic frameworks of vision attribute perception of inherent object characteristics, such as size, to the ventral visual pathway, and processing of spatial characteristics relevant to action, such as distance, to the dorsal visual pathway. However, these frameworks are based on studies that used projected images of objects whose actual size and distance from the observer were ambiguous. Here, we find that when object size and distance information in the stimulus is less ambiguous, these characteristics are widely represented in both visual pathways. Our results provide valuable new insights into the brain representations of objects and their various physical attributes in the context of naturalistic vision.

A Technique to Quantify Very Low Activities in Regions of Interest With a Collimatorless Detector.

We present a new method to measure sub-microcurie activities of photon-emitting radionuclides in organs and lesions of small animals in vivo. Our technique, named the collimator-less likelihood fit, combines a very high sensitivity collimatorless detector with a Monte Carlo-based likelihood fit in order to estimate the activities in previously segmented regions of interest along with their uncertainties. This is done directly from the photon projections in our collimatorless detector and from the region of interest segmentation provided by an x-ray computed tomography scan. We have extensively validated our approach with 225Ac experimentally in spherical phantoms and mouse phantoms, and also numerically with simulations of a realistic mouse anatomy. Our method yields statistically unbiased results with uncertainties smaller than 20% for activities as low as ~111Bq (3nCi) and for exposures under 30 minutes. We demonstrate that our method yields more robust recovery coefficients when compared to SPECT imaging with a commercial pre-clinical scanner, specially at very low activities. Thus, our technique is complementary to traditional SPECT/CT imaging since it provides a more accurate and precise organ and tumor dosimetry, with a more limited spatial information. Finally, our technique is specially significant in extremely low-activity scenarios when SPECT/CT imaging is simply not viable.

Validity of Using the Load-Velocity Relationship to Estimate 1 Repetition Maximum in the Back Squat Exercise: A Systematic Review and Meta-Analysis.

ABSTRACT: LeMense, AT, Malone, GT, Kinderman, MA, Fedewa, MV, and Winchester, LJ. Validity of using the load-velocity relationship to estimate 1 repetition maximum in the back squat exercise: a systematic review and meta-analysis. J Strength Cond Res 38(3): 612-619, 2024-The one repetition maximum (1RM) test is commonly used to assess muscular strength. However, 1RM testing can be time consuming, physically taxing, and may be difficult to perform in athletics team settings with practice and competition schedules. Alternatively, 1RM can be estimated from bar or movement velocity at submaximal loads using the minimum velocity threshold (MVT) method based on the load-velocity relationship. Despite its potential utility, this method's validity has yielded inconsistent results. The purpose of this systematic review and meta-analysis was to assess the validity of estimated 1RM from bar velocity in the back squat exercise. A systematic search of 3 electronic databases was conducted using combinations of the following keywords: "velocity-based training," "load-velocity profiling," "mean velocity," "mean propulsive velocity," "peak velocity," "maximal strength," "1RM," "estimation," "prediction," "back squat," and "regression." The search identified 372 unique articles, with 4 studies included in the final analysis. Significance was defined as a p level less than 0.05. A total of 27 effects from 71 subjects between the ages of 17-25 years were analyzed; 85.2% of effects were obtained from male subjects. Measured 1RMs ranged from 86.5 to 153.1 kg, whereas estimated 1RMs ranged from 88.6 to 171.6 kg. Using a 3-level random effects model, 1RM back squat was overestimated when derived from bar velocity using the MVT method (effect sizes [ES] = 0.5304, 95% CI: 0.1878-0.8730, p = 0.0038). The MVT method is not a viable option for estimating 1RM in the free weight back squat. Strength and conditioning professionals should exercise caution when estimating 1RM from the load-velocity relationship.

Epidemiologic investigation of pediatric distal humerus fractures: An American insurance claims database study.

BACKGROUND: Distal humerus elbow fractures are one of the most common traumatic fractures seen in pediatric patients and present as three main types: Supracondylar (SC), lateral condyle (LC), and medial epicondyle (ME) fractures. AIM: To evaluate the epidemiology of pediatric distal humerus fractures (SC, LC, and ME) from an American insurance claims database. METHODS: A retrospective review was performed on patients 17 years and younger with the ICD 9 and 10 codes for SC, LC and ME fractures based on the IBM Truven MarketScan® Commercial and IBM Truven MarketScan Medicare Supplemental databases. Patients from 2015 to 2020 were queried for treatments, patient age, sex, length of hospitalization, and comorbidities. RESULTS: A total of 1133 SC, 154 LC, and 124 ME fractures were identified. SC fractures had the highest percentage of operation at 83%, followed by LC (78%) and ME fractures (41%). Male patients were, on average, older than female patients for both SC and ME fractures. CONCLUSION: In the insurance claims databases used, SC fractures were the most reported, followed by LC fractures, and finally ME fractures. Age was identified to be a factor for how a pediatric distal humerus fractures, with patients with SC and LC fractures being younger than those with ME fractures. The peak age per injury per sex was similar to reported historic central tendencies, despite reported trends for younger physiologic development.

A multiplexed microfluidic continuous-flow electroporation system for efficient cell transfection.

Cellular therapies have the potential to advance treatment for a broad array of diseases but rely on viruses for genetic reprogramming. The time and cost required to produce viruses has created a bottleneck that constricts development of and access to cellular therapies. Electroporation is a non-viral alternative for genetic reprogramming that bypasses these bottlenecks, but current electroporation technology suffers from low throughput, tedious optimization, and difficulty scaling to large-scale cell manufacturing. Here, we present an adaptable microfluidic electroporation platform with the capability for rapid, multiplexed optimization with 96-well plates. Once parameters are optimized using small volumes of cells, transfection can be seamlessly scaled to high-volume cell manufacturing without re-optimization. We demonstrate optimizing transfection of plasmid DNA to Jurkat cells, screening hundreds of different electrical waveforms of varying shapes at a speed of ~3 s per waveform using ~20 µL of cells per waveform. We selected an optimal set of transfection parameters using a low-volume flow cell. These parameters were then used in a separate high-volume flow cell where we obtained similar transfection performance by design. This demonstrates an alternative non-viral and economical transfection method for scaling to the volume required for producing a cell therapy without sacrificing performance. Importantly, this transfection method is disease-agnostic with broad applications beyond cell therapy.

The Relationship Between Choroidal Abnormalities and Visual Outcomes in Pediatric Patients With NF1-Associated Optic Pathway Gliomas.

BACKGROUND: Choroidal abnormalities (CAs) visualized on near-infrared reflectance (NIR) imaging are a new diagnostic criterion for neurofibromatosis type 1 (NF1), but the association between the presence of CAs and visual function remains unknown. This study evaluated the relationship between visual acuity (VA) with the presence, number, or total area of CAs visualized by NIR in children with NF1-associated optic pathway gliomas (NF1-OPGs). METHODS: Patients (<18 years) enrolled in a prospective longitudinal study of children with NF1-associated OPGs from 3 institutions were eligible if they had optical coherence tomography (OCT) of the macula (Heidelberg Spectralis) with ≥1 year of follow-up. The central 30° NIR images were reviewed by 2 neuro-ophthalmologists who manually calculated the number and total area of CAs. VA (logMAR) was measured using a standardized protocol. Cross-sectional associations of presence, number, and total area of CAs with VA, retinal nerve fiber layer thickness (RNFL), and ganglion cell-inner plexiform layer thickness were evaluated at the first and most recent visits using regression models. Intereye correlation was accounted for using generalized estimating equations. RESULTS: Eighty-two eyes of 41 children (56% female) were included. The mean ± SD age at the first OCT was 10.1 ± 3.3 years, with a mean follow-up of 20.4 ± 7.2 months. At study entry, CAs were present in 46% of eyes with a mean number of 2.1 ± 1.7 and a mean total area of 2.0 ± 1.7 mm 2 per eye. At the most recent follow-up, CAs were present in 48% of eyes with a mean number of 2.2 ± 1.8 lesions and a mean total area of 2.3 ± 2.1 mm 2 per eye. Neither VA nor OCT parameters at first and follow-up visits were associated with the presence, number, or total area of CAs (all P > 0.05). CONCLUSIONS: CAs are prevalent but not ubiquitous, in children with NF1-OPGs. Although CAs are a diagnostic criterion for NF1, their presence and size do not appear to be associated with visual function.

Critical Review on the Use of Extractives of Naturally Durable Woods as Natural Wood Protectants.

Naturally durable wood pre-dates preservative-treated wood and has been demonstrated to offer a suitable service life for certain applications where preservative-treated wood is not feasible. Heartwood extractives have been demonstrated to impart bio-deteriorative resistance to naturally durable wood species. These extractives are typically found in the heartwood of living trees and are produced either by the death of parenchyma cells or as the result of external stimuli. The mechanisms of natural durability are not well understood, as heartwood extractives can be extremely variable in their distribution, composition, and efficacy in both living and harvested trees. The underlying complexity of heartwood extractives has hindered their standardization in residential building codes for use as wood preservatives. The use of naturally durable lumber is not always feasible, as woods with exceptionally durable heartwood do not typically yield lumber with acceptable machining properties. A potential approach to overcome the inherent difficulty in establishing guidelines for the appropriate use of naturally durable wood is to focus solely on the extractives as a source of bioactive protectants based on the strategies used on living and dead wood to repel the agents of biodeterioration. This critical review summarizes the relevant literature on naturally durable woods, their extractives, and their potential use as bio-inspired wood protectants. An additional discussion will be aimed at underscoring the past difficulties in adopting this approach and how to overcome the future hurdles.

Age and Comorbidities Are Associated With Therapeutic Inertia Among Older Adults With Uncontrolled Blood Pressure.

BACKGROUND: Lack of initiation or escalation of blood pressure (BP) lowering medication when BP is uncontrolled, termed therapeutic inertia (TI), increases with age and may be influenced by comorbidities. METHODS: We examined the association of age and comorbidities with TI in 22,665 visits with a systolic BP ≥140 mm Hg and/or diastolic BP ≥90 mm Hg among 7,415 adults age ≥65 years receiving care in clinics that implemented a hypertension quality improvement program. Generalized linear mixed models were used to determine the association of comorbidity number with TI by age group (65-74 and ≥75 years) after covariate adjustment. RESULTS: Baseline mean age was 75.0 years (SD 7.8); 41.4% were male. TI occurred in 79.0% and 83.7% of clinic visits in age groups 65-74 and ≥75 years, respectively. In age group 65-74 years, prevalence ratio of TI with 2, 3-4, and ≥5 comorbidities compared with zero comorbidities was 1.07 (95% confidence interval [CI]: 1.04, 1.12), 1.08 (95% CI: 1.05, 1.12), and 1.15 (95% CI: 1.10, 1.20), respectively. The number of comorbidities was not associated with TI prevalence in age group ≥75 years. After implementation of the improvement program, TI declined from 80.3% to 77.2% in age group 65-74 years and from 85.0% to 82.0% in age group ≥75 years (P < 0.001 for both groups). CONCLUSIONS: TI was common among older adults but not associated with comorbidities after age ≥75 years. A hypertension improvement program had limited impact on TI in older patients.

"Over-reviewing" of research? An analysis of orthodontic reviews.

INTRODUCTION: Research overviews may be undertaken to identify gaps in the literature, evaluate existing systematic reviews (SRs), and summarize evidence. This paper aims to profile overviews that have been conducted in orthodontics and related interventions since 2012 and to evaluate the degree of overlap among these overviews. METHODS: Overviews published between January 1, 2012 and June 20, 2023 were identified using an electronic search involving Google Scholar and PubMed. A descriptive summary was produced, and citation matrices were used to evaluate the percentage of overlap between overviews using corrected covered area and covered area. This was classified as slight, moderate, high, or very high. RESULTS: A total of 35 overviews were identified across a wide range of topics. Eight overviews included <10 SRs; 21 had 10-20 SRs; and 6 included >20 SRs (median no. of SRs per overview, 15; range, 3-62). Meta-analysis was conducted in only 5 overviews. Overlap between overviews on the same topic ranged from slight (2.7%) to very high (53.8%). CONCLUSIONS: Almost all overview topics address treatments and their effects, with a wide variation in the number and quality of SRs included. There is considerable overlap in some orthodontic overviews, suggesting unnecessary duplication and research waste. Researchers should be encouraged to focus on primary data collection to add more high-quality data to SRs, which will ultimately enhance the yield from secondary and tertiary orthodontic research.

A generalization of the maximum likelihood expectation maximization (MLEM) method: Masked-MLEM.

Objective.In our previous work on image reconstruction for single-layer collimatorless scintigraphy, we developed the min-min weighted robust least squares (WRLS) optimization algorithm to address the challenge of reconstructing images when both the system matrix and the projection data are uncertain. Whereas the WRLS algorithm has been successful in two-dimensional (2D) reconstruction, expanding it to three-dimensional (3D) reconstruction is difficult since the WRLS optimization problem is neither smooth nor strongly-convex. To overcome these difficulties and achieve robust image reconstruction in the presence of system uncertainties and projection noise, we propose a generalized iterative method based on the maximum likelihood expectation maximization (MLEM) algorithm, hereinafter referred to as the Masked-MLEM algorithm.Approach.In the Masked-MLEM algorithm, only selected subsets ('masks') from the system matrix and the projection contribute to the image update to satisfy the constraints imposed by the system uncertainties. We validate the Masked-MLEM algorithm and compare it to the standard MLEM algorithm using experimental data obtained from both collimated and uncollimated imaging instruments, including parallel-hole collimated SPECT, 2D collimatorless scintigraphy, and 3D collimatorless tomography. Additionally, we conduct comprehensive Monte Carlo simulations for 3D collimatorless tomography to further validate the effectiveness of the Masked-MLEM algorithm in handling different levels of system uncertainties.Main results.The Masked-MLEM and standard MLEM reconstructions are similar in cases with negligible system uncertainties, whereas the Masked-MLEM algorithm outperforms the standard MLEM algorithm when the system matrix is an approximation. Importantly, the Masked-MLEM algorithm ensures reliable image reconstruction across varying levels of system uncertainties.Significance.With a good choice of system uncertainty and without requiring accurate knowledge of the actual system matrix, the Masked-MLEM algorithm yields more robust image reconstruction than the standard MLEM algorithm, effectively reducing the likelihood of erroneously reconstructing higher activities in regions without radioactive sources.

A multiplexed microfluidic continuous-flow electroporation system for efficient cell transfection.

Cellular therapies have the potential to advance treatment for a broad array of diseases but rely on viruses for genetic reprogramming. The time and cost required to produce viruses has created a bottleneck that constricts development of and access to cellular therapies. Electroporation is a non-viral approach for genetic reprogramming that bypasses these bottlenecks, but current electroporation technology suffers from low throughput, tedious optimization, and difficulty scaling to large-scale cell manufacturing. Here, we present an adaptable microfluidic electroporation platform with the capability for rapid, multiplexed optimization with 96-well plates. Once parameters are optimized using small volumes of cells, transfection can be seamlessly scaled to high-volume cell manufacturing without re-optimization. We demonstrate optimizing transfection of plasmid DNA to Jurkat cells, screening hundreds of different electrical waveforms of varying shapes at a speed of ~3 s per waveform using ~ 20 µL of cells per waveform. We selected an optimal set of transfection parameters using a low-volume flow cell. These parameters were then used in a separate high-volume flow cell where we obtained similar transfection performance by design. This demonstrates an economical method for scaling to the volume required for producing a cell therapy without sacrificing performance.

Prenatal alcohol exposure and cognition at midlife: Evidence of fluid cognition deficits in two cohorts.

BACKGROUND: Prenatal alcohol exposure (PAE) impacts cognition in childhood and early adulthood. Here we evaluate the cognitive abilities of middle-aged adults with and without a history of PAE. METHODS: Participants (N = 200) were recruited from longitudinal cohorts in the Atlanta and Seattle metropolitan areas and completed measures comprising the National Institutes of Health Toolbox's Fluid Cognition Composite. RESULTS: We found that individuals with PAE had lower Fluid Cognition Summary scores and lower Dimensional Change Card Sort and Flanker task subtest scores than non-PAE controls, after accounting for both potentially confounding demographic variables using propensity scores and the effects of study site. When we evaluated the effects of PAE with and without dysmorphic physical features, we found that middle-aged adults in both groups had lower fluid cognition scores than non-PAE controls. However, only the presence of PAE with dysmorphic features was associated with lower performance on the Dimensional Change Card Sort Test and Flanker tasks. CONCLUSION: While all participants with PAE had lower fluid cognition, those with PAE and dysmorphic features also exhibited specific deficits in their performance on measures of inhibition, attention, and cognitive flexibility. Thus, PAE is associated with ongoing cognitive deficits in middle adulthood, which can be observed most clearly among individuals with dysmorphic features.

The impact of changes in gadolinium-enhancement on disease progression in children with neurofibromatosis type 1-associated optic pathway glioma: a retrospective analysis.

PURPOSE: There has been limited investigation of imaging features associated with visual acuity (VA) decline and initiation of treatment for patients with neurofibromatosis type 1 (NF1) and optic pathway glioma (OPG). METHODS: To evaluate the association of increased gadolinium enhancement with decline in VA, initiation of chemotherapy, and tumor growth, we performed a retrospective cohort study of children diagnosed with NF1-OPG between January 2006 to June 2016. Two cohorts were defined: a new diagnosis and a longitudinal cohort. Outcomes were examined at 1 and 2 years from initial diagnosis, and 1 and 2 years from initial increase in enhancement in the longitudinal cohort. RESULTS: Eighty patients were eligible; all 80 contributed to the new diagnosis cohort and 73 to the longitudinal cohort. Fifty-six patients (70%) demonstrated enhancing NF1-OPG at diagnosis. 39% of patients in the new diagnosis cohort and 45% of those in the longitudinal cohort developed increased enhancement during the study period. There was no significant association between increases in enhancement and VA decline in the newly diagnosed or longitudinal cohorts, as well as with initiation of treatment in the longitudinal cohort. Although there was an association of enhancement increase with treatment in the new diagnosis cohort, this association was not maintained when stratified by concurrent change in tumor size. CONCLUSION: Increased gadolinium-enhancement independent of a concurrent increase in tumor size on MRI should not be used as a marker of NF1-OPG progression and does not appear to be associated with visual decline or initiation of chemotherapy.