Synthesis, Optical Performance Characterization, and Durability of Electrospun PTFE-PEO Materials for Space Applications.

Passive heat management is crucial in space, especially for extended missions involving protection from sunlight. Thermal coatings with desirable optical properties can drastically reduce the power consumed by active cooling systems, thereby reserving more resources for other critical systems onboard. Specifically, materials with wavelength-dependent reflectance and emittance are desirable for managing incident sunlight and self-cooling by thermal emission. This study demonstrates the use of polymer nanofibers, specifically poly(tetrafluoroethylene) (PTFE), for passive temperature control in space applications. This study describes the electrospinning fabrication process to create nanofibers and how process parameters can be varied to control the fiber geometry. We combine poly(tetrafluoroethylene) (PTFE) and poly(ethylene oxide) (PEO) polymers to fabricate highly reflective thermal control materials by electrospinning. To understand the role of material and fiber geometry, we measure spectral reflectance, absorptance, and transmittance using spectrophotometers interfaced with integrating spheres. We control the materials' fiber geometry and solar reflectance by modifying the solution properties, flow rate, rotating collector speed, and fabrication time. With 220-1560 µm thick electrospun nanofiber materials, we demonstrate an average solar reflectance of 94.73-99.75%, with values approaching 99.9% for thicker samples, which is among the highest for space applications. Meanwhile, a thermal emittance of 81.4% was observed at 300 K for a 3360 µm thick sample. The durability of these samples was also tested under ultraviolet light and atomic oxygen. Compared to the state-of-the-art materials, the electrospun PTFE-PEO fibers present a new paradigm for passive thermal management in space applications.

Hepatomegaly and Splenomegaly: An Approach to the Diagnosis of Lysosomal Storage Diseases.

Clinical findings of hepatomegaly and splenomegaly, the abnormal enlargement of the liver and spleen, respectively, should prompt a broad differential diagnosis that includes metabolic, congestive, neoplastic, infectious, toxic, and inflammatory conditions. Among the metabolic diseases, lysosomal storage diseases (LSDs) are a group of rare and ultrarare conditions with a collective incidence of 1 in 5000 live births. LSDs are caused by genetic variants affecting the lysosomal enzymes, transporters, or integral membrane proteins. As a result, abnormal metabolites accumulate in the organelle, leading to dysfunction. Therapeutic advances, including early diagnosis and disease-targeted management, have improved the life expectancy and quality of life of people affected by certain LSDs. To access these new interventions, LSDs must be considered in patients presenting with hepatomegaly and splenomegaly throughout the lifespan. This review article navigates the diagnostic approach for individuals with hepatosplenomegaly particularly focusing on LSDs. We provide hints in the history, physical exam, laboratories, and imaging that may identify LSDs. Additionally, we discuss molecular testing, arguably the preferred confirmatory test (over biopsy), accompanied by enzymatic testing when feasible.

A novel GK Ala469Val variant resulting in glycerol kinase deficiency with concurrent hepatoblastoma: A case report.

Glycerol kinase deficiency (GKD) is a rare X-linked condition where glycerol cannot be phosphorylated to glycerol-3-phosphate, a key component of gluconeogenesis. Clinical presentation varies widely. We present a novel variant of the responsible GK in a patient with concurrent hepatoblastoma, whose course was complicated by hypoglycemia. Hepatoblastoma has not previously been described with GKD, highlighting the need for further research into GKD and its potential role in the pathogenesis of some forms of hepatoblastoma.

Improving newborn screening test performance for metachromatic leukodystrophy: Recommendation from a pre-pilot study that identified a late-infantile case for treatment.

Metachromatic leukodystrophy (MLD) is a devastating rare neurodegenerative disease. Typically, loss of motor and cognitive skills precedes early death. The disease is characterised by deficient lysosomal arylsulphatase A (ARSA) activity and an accumulation of undegraded sulphatide due to pathogenic variants in the ARSA gene. Atidarsagene autotemcel (arsa-cel), an ex vivo haematopoietic stem cell gene therapy was approved for use in the UK in 2021 to treat early-onset forms of pre- or early-symptomatic MLD. Optimal outcomes require early diagnosis, but in the absence of family history this is difficult to achieve without newborn screening (NBS). A pre-pilot MLD NBS study was conducted as a feasibility study in Manchester UK using a two-tiered screening test algorithm. Pre-established cutoff values (COV) for the first-tier C16:0 sulphatide (C16:0-S) and the second-tier ARSA tests were evaluated. Before the pre-pilot study, initial test validation using non­neonatal diagnostic bloodspots demonstrated ARSA pseudodeficiency status was associated with normal C16:0-S results for age (n = 43) and hence not expected to cause false positive results in this first-tier test. Instability of ARSA in bloodspot required transfer of NBS bloodspots from ambient temperature to -20°C storage within 7-8 days after heel prick, the earliest possible in this UK pre-pilot study. Eleven of 3687 de-identified NBS samples in the pre-pilot were positive for C16:0-S based on the pre-established COV of ≥170 nmol/l or ≥ 1.8 multiples of median (MoM). All 11 samples were subsequently tested negative determined by the ARSA COV of <20% mean of negative controls. However, two of 20 NBS samples from MLD patients would be missed by this C16:0-S COV. A further suspected false negative case that displayed 4% mean ARSA activity by single ARSA analysis for the initial test validation was confirmed by genotyping of this NBS bloodspot, a severe late infantile MLD phenotype was predicted. This led to urgent assessment of this child by authority approval and timely commencement of arsa-cel gene therapy at 11 months old. Secondary C16:0-S analysis of this NBS bloodspot was 150 nmol/l or 1.67 MoM. This was the lowest result reported thus far, a new COV of 1.65 MoM is recommended for future pilot studies. Furthermore, preliminary data of this study showed C16:1-OH sulphatide is more specific for MLD than C16:0-S. In conclusion, this pre-pilot study adds to the international evidence that recommends newborn screening for MLD, making it possible for patients to benefit fully from treatment through early diagnosis.

Neurosurgery at Baylor Scott & White Health: Recent History and a Decade of Neurosurgery Residency Training.

Neurosurgery at Baylor Scott & White Memorial Hospital in Temple, Texas began as a division in the Department of Surgery many decades ago. The hospital has long served as the flagship tertiary referral center for the Baylor Scott & White healthcare system, which merged in 2013 with Baylor University Medical Center, a hospital system based in Dallas. It is now the largest non-profit hospital system as well as the most awarded hospital system by the US News and World Report within the state of Texas. The Department of Neurosurgery was established at Baylor Scott & White Memorial Hospital in the 2006-2007 academic year. Between then and 2014, four neurosurgeons served as department chair or interim chair: Dr. Robert Buchanan, Dr. Gerhard Friehs, Dr. Ibrahim El Nihum, and Dr. David Garrett Jr. In 2014, Dr. Jason Huang was appointed chairman after a national search and established the neurosurgery residency program in 2015. The department has undergone tremendous growth under the leadership of Dr. Huang, and the residency program is a priority of the department. Surgical excellence is honed at primarily three campuses: Baylor Scott & White Memorial Hospital, Baylor Scott & White McLane Children's Medical Center, and Baylor Scott & White Medical Center - Hillcrest. In this editorial, we provide a brief history of the institution, a recent history of the neurosurgical presence at Baylor Scott & White Memorial Hospital in Temple, Texas, and briefly describe the program's future directions under the continued leadership of Dr. Jason Huang.

Lamotrigine efficacy, safety, and tolerability for women of childbearing age with bipolar I disorder: Meta-analysis from four randomized, placebo-controlled maintenance studies.

This meta-analysis investigated the efficacy, safety, and tolerability of lamotrigine versus placebo in preventing relapse and recurrence of mood episodes in women of childbearing age with bipolar I disorder. Following up to 16 weeks' open-label lamotrigine treatment, responders were randomized to double-blind treatment, including lamotrigine 100-400 mg/day or placebo, in four trials of up to 76 weeks. Women aged 18-45 years who received ≥ 1 dose of study treatment and had ≥ 1 efficacy assessment in the double-blind phase were pooled for efficacy analysis. The primary outcome was median time to intervention for any mood episode (TIME). Of 717 eligible women in the open-label phase, 287 responded and were randomized to lamotrigine (n = 153) or placebo (n = 134). The randomized group had a mean (SD) of 2.0(2.02) manic and 2.5(2.02) depressive episodes in the 3 years before screening. Median TIME was 323 days with lamotrigine and 127 days with placebo (HR 0.69; 95% CI 0.49, 0.96; p = 0.030). Lamotrigine delayed time to intervention for any depressive episode (HR 0.59; 95% CI 0.39, 0.90; p = 0.014) with no treatment difference for manic episodes (HR 0.91; 95% CI 0.52, 1.58; p = 0.732). 2/717 (< 1%) participants experienced serious rash-related adverse events (AEs) during the open-label phase, and 52/717 (7%) had non-serious rash-related events leading to study withdrawal. Incidence of AEs and AEs leading to withdrawal were similar between lamotrigine and placebo groups. Lamotrigine delayed relapse and recurrence of mood episodes, largely by preventing depressive episodes, and was well tolerated in women of childbearing age.

Cell-autonomous immune dysfunction driven by disrupted autophagy in C9orf72-ALS iPSC-derived microglia contributes to neurodegeneration.

Although microglial activation is widely found in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), the underlying mechanism(s) are poorly understood. Here, using human-induced pluripotent stem cell-derived microglia-like cells (hiPSC-MG) harboring the most common ALS/FTD mutation (C9orf72, mC9-MG), gene-corrected isogenic controls (isoC9-MG), and C9orf72 knockout hiPSC-MG (C9KO-MG), we show that reduced C9ORF72 protein is associated with impaired phagocytosis and an exaggerated immune response upon stimulation with lipopolysaccharide. Analysis of the C9ORF72 interactome revealed that C9ORF72 interacts with regulators of autophagy and functional studies showed impaired initiation of autophagy in mC9-MG and C9KO-MG. Coculture studies with motor neurons (MNs) demonstrated that the autophagy deficit in mC9-MG drives increased vulnerability of mC9-MNs to excitotoxic stimulus. Pharmacological activation of autophagy ameliorated both cell-autonomous functional deficits in hiPSC-MG and MN death in MG-MN coculture. Together, these findings reveal an important role for C9ORF72 in regulating immune homeostasis and identify dysregulation in myeloid cells as a contributor to neurodegeneration in ALS/FTD.

Return emergency department visits for recurrent pulmonary embolism symptoms in children and adolescents.

Rates of pulmonary embolism (PE) in children have steadily increased over the past 2 decades. Patient outcomes after hospital discharge are poorly understood, and many patients experience recurrent or persistent chest pain or dyspnea, prompting a return to care. This retrospective cohort study of patients diagnosed with PE at a large children's hospital over a 9.5-year period was performed to evaluate rates of return to the emergency department (ED) for PE-related symptoms, and to determine the utility of repeat computed tomography angiography (CTA) in this population. Ninety-six patients were diagnosed with PE during the study period. Forty-two percent of patients (n = 40) returned to the ED for PE-related symptoms and a total of 74 repeat CTAs were performed. Among those who had return visits, the mean number of return visits was 3 and the mean number of repeat CTAs was 1.8. The median time to return to the ED was 34 days. Logistic regression analysis identified increased age and female sex as risk factors for return ED visits. Eight percent of the cohort experienced PE recurrence. Recurrent PE was observed only in those with persistent or new thrombotic risk factors and was uncommon in those who remained on appropriate anticoagulation. Future work should focus on the development of a risk stratification system to identify patients at low risk of recurrence in order to minimize repeat CTA imaging.

Evaluation of venous thromboembolism risk factors reveals subtype heterogenicity in children with central venous catheters: a multicenter study from the Children's Hospital Acquired Thrombosis consortium.

BACKGROUND: Acutely ill and medically complex children frequently rely on central venous catheters (CVCs) to provide life-sustaining treatment. Unfortunately, catheter-related thrombosis (CRT) is a serious and common complication. Little is known why some with a CVC develop CRT and others develop venous thromboembolism unrelated to the CVC (non-CRT). OBJECTIVES: The aim of this study was to identify factors associated with CRT in children with hospital-acquired venous thromboembolism (HA-VTE). METHODS: This case-case study included participants in the Children's Hospital Acquired Thrombosis Registry with HA-VTE and CVC aged 0 to 21 years from 8 US children's hospitals. Participants were excluded if they developed HA-VTE prior to CVC insertion or if the CVC insertion date was unknown. Logistic regression models were used to assess associations between clinical factors and CRT status. RESULTS: There were 1144 participants with HA-VTE who had a CVC. CRT developed in 833 participants, and 311 developed non-CRT. Multivariable analysis showed increased odds of CRT (compared with non-CRT) in participants with peripherally inserted central catheters (odds ratio [OR], 3.80; 95% CI, 2.04-7.10; p < .001), CVCs inserted in the femoral vein (OR, 4.45; 95% CI, 1.70-11.65; p = .002), multiple CVCs (OR, 1.42; 95% CI, 1.18-1.71; p < .001), and CVC malfunction (OR, 3.30; 95% CI, 1.80-6.03; p < .001). CONCLUSION: The findings of this study provide new insights on risk factor differences between CRT and non-CRT. Prevention efforts should be directed at modifying the type of CVC, insertion location, and/or number of CVCs placed, if possible, to decrease the incidence of CRT.

Astrocytes mediate cell non-autonomous correction of aberrant firing in human FXS neurons.

Pre-clinical studies of fragile X syndrome (FXS) have focused on neurons, with the role of glia remaining largely underexplored. We examined the astrocytic regulation of aberrant firing of FXS neurons derived from human pluripotent stem cells. Human FXS cortical neurons, co-cultured with human FXS astrocytes, fired frequent short-duration spontaneous bursts of action potentials compared with less frequent, longer-duration bursts of control neurons co-cultured with control astrocytes. Intriguingly, bursts fired by FXS neurons co-cultured with control astrocytes are indistinguishable from control neurons. Conversely, control neurons exhibit aberrant firing in the presence of FXS astrocytes. Thus, the astrocyte genotype determines the neuronal firing phenotype. Strikingly, astrocytic-conditioned medium, and not the physical presence of astrocytes, is capable of determining the firing phenotype. The mechanistic basis of this effect indicates that the astroglial-derived protein, S100ß, restores normal firing by reversing the suppression of a persistent sodium current in FXS neurons.

The hemostatic profile of cold-stored whole blood from non-greyhound and greyhound dogs over 42 days.

Objectives: To compare the hemostatic characteristics of cold-stored whole blood (CSWB) from non-greyhound dogs (NGD) and greyhound dogs (GD) over 42 days of storage, notably, platelet closure time (PCT) (NGD only), manual platelet count (PLT) (GD only), ellagic acid (INTEM) and tissue factor activated (EXTEM) rotational thromboelastometry, prothrombin (PT) and activated partial thromboplastin time (aPTT), fibrinogen concentration (FIB), and the activities of factors (F) FII, FV, FVII, FVIII, FIX, FX, FXIII antigen (FXIII:Ag), and von Willebrand factor antigen (vWF:Ag). Design: Whole blood from 10 NGD and 10 GD, was refrigerated in CPD blood bags at 4°C for 42 days. Blood was analyzed before refrigeration (day 0) and at day 1 (d1), 3, 5, 7, 10, 14, 17, 21, 24, 28, 31, 35, 38, and 42. Multivariate linear mixed effects models were created to evaluate coagulation parameters over time and compare NGD and GD. Data are summarized as estimated marginal means with 95% confidence intervals. Significance was set at P < 0.05. Results: The PCT for all NGD CSWB was above the device limit by d7. The PLT for GD CSWB did not change during storage. The mean alpha-angle for INTEM and EXTEM decreased to <50% of baseline at d38 and d31 for NGD, and d31 and d17 for GD CSWB. The mean maximum clot firmness (MCF) for INTEM and EXTEM reduced to <50% of baseline at d42 and d28 for both GD and NGD. PT and aPTT for NGD and GD increased over time. For NGD CSWB, the mean FVIII and vWF:Ag activities decreased to <50% of baseline at d7 and d28, respectively, and FIB reached 0.982 g/dL by d24. For GD CSWB, FVIII, FXIII:Ag and FV activities decreased to <50% of baseline by d3, d38, and d38, respectively, and FIB was 0.982 g/dL at baseline. Alpha-angle and MCF for both INTEM and EXTEM, and activities for FII, FV, FIX, FXIII:Ag were significantly lower, and vWF:Ag was significantly higher overall in GD CSWB compared with NGD. A significant difference in the pattern of change over time was detected between NGD and GD in EXTEM alpha-angle, INTEM and EXTEM MCF, FII, and FVIII activities. Conclusions: The in vitro viscoelastic parameters of GD and NGD CSWB declines over 42 days, but numerous hemostatic parameters (INTEM and EXTEM alpha-angle and MCF, activity of FII, FV, FV, FVII, FIX, FX, FXIII:Ag, vWF:Ag, and FIB) remain within 50% of baseline for more than 14 days. CSWB from GD compared to NGD has reduced hemostatic activity overall, but a similar pattern of decline for most parameters over time.

Chronic demyelination of rabbit lesions is attributable to failed oligodendrocyte progenitor cell repopulation.

The failure of remyelination in the human CNS contributes to axonal injury and disease progression in multiple sclerosis (MS). In contrast to regions of chronic demyelination in the human brain, remyelination in murine models is preceded by abundant oligodendrocyte progenitor cell (OPC) repopulation, such that OPC density within regions of demyelination far exceeds that of normal white matter (NWM). As such, we hypothesized that efficient OPC repopulation was a prerequisite of successful remyelination, and that increased lesion volume may contribute to the failure of OPC repopulation in human brain. In this study, we characterized the pattern of OPC activation and proliferation following induction of lysolecithin-induced chronic demyelination in adult rabbits. The density of OPCs never exceeded that of NWM and oligodendrocyte density did not recover even at 6 months post-injection. Rabbit OPC recruitment in large lesions was further characterized by chronic Sox2 expression in OPCs located in the lesion core and upregulation of quiescence-associated Prrx1 mRNA at the lesion border. Surprisingly, when small rabbit lesions of equivalent size to mouse were induced, they too exhibited reduced OPC repopulation. However, small lesions were distinct from large lesions as they displayed an almost complete lack of OPC proliferation following demyelination. These differences in the response to demyelination suggest that both volume dependent and species-specific mechanisms are critical in the regulation of OPC proliferation and lesion repopulation and suggest that alternate models will be necessary to fully understand the mechanisms that contribute to failed remyelination in MS.

Is the Sport Concussion Assessment Tool 5th Edition a useful concussion assessment tool in head-injured patients presenting to the emergency department?

OBJECTIVE: Concussion is a common ED complaint, but diagnosis is challenging as there are no validated objective measures. Use of concussion tools derived from sports medicine is common, but these tools are not well validated in ED settings. The aim of this study was to assess the ability of the Sport Concussion Assessment Tool 5th Edition (SCAT5) to identify concussion in ED patients presenting following head injury. METHODS: We conducted a prospective observational study of head-injured adult patients presenting to ED between March and July 2021. ED diagnosis of concussion was used as the diagnostic standard, and we assessed the diagnostic performance of the SCAT5 test and its three subsections (Standardised Assessment of Concussion (SAC), Post-Concussion Symptom Scale (PCSS) and Modified Balance Error Scoring System (mBESS)) against this. RESULTS: Thirty-two head-injured participants were enrolled, 19 of whom had a discharge diagnosis of concussion, alongside 17 controls. Median time for SCAT5 testing was 21 (interquartile range 16-27) min. Fifteen (30.6%) participants were interrupted during testing. Area under the curve (AUC) (95% confidence interval) for the SAC, PCSS and mBESS were 0.51 (0.34-0.68), 0.92 (0.84-0.99) and 0.66 (0.47-0.85), respectively. Sensitivity and specificity of sections were as follows: entire SCAT5 (100.0%, 20.0%), SAC (48.1%, 60.0%), PCSS (89.7%, 85.0%) and mBESS (83.3%, 58.8%). Using PCSS alone would have identified 17 of 19 concussions. CONCLUSION: The SCAT5 test had a low specificity, was long and was frequently interrupted. We suggest it is not an ideal assessment to use in ED. The PCSS score performed well and was easy to complete. It may be useful as a standalone tool to simplify ED concussion identification.

Preliminary assessment of the subjective effects of electronic-cigarettes in young-adult low-dose electronic-cigarette users: Effects of nicotine dose and e-liquid flavor.

OBJECTIVE: The present study evaluated the effects of nicotine concentration (0-10 mg/ml) and flavor (gummy bear vs unflavored) on the subjective experiences of vaporized nicotine in young adult low-dose nicotine (3 mg/ml) ECIG users. PARTICIPANTS: Eight young adult ECIG users were recruited. METHODS: A single blinded crossover study was used. Participants were instructed to take ten 1.5 second puffs, each separated by 20 seconds. After self-administration, heart rate was recorded, and participants completed the Drug Effects, Direct Effects of Nicotine, and Direct Effects of ECIG questionnaires. RESULTS: ECIG user's standard daily nicotine dose influenced the rewarding and aversive effects of nicotine as the 10 mg/ml dose was found to be aversive in this user group. The combination of flavor and nicotine increased the subjective effects of ECIGs. CONCLUSIONS: Flavored e-liquids contribute to the reinforcing properties of nicotine by enhancing the subjective effects, which may lead to continued ECIG use.

A randomised, double-blind, placebo-controlled study to evaluate the safety and efficacy of lamotrigine in the maintenance treatment of Chinese adult patients with bipolar I disorder.

BACKGROUND: Lamotrigine is approved as a maintenance therapy for bipolar I disorder in many countries, including China in 2021. This study evaluated the efficacy and safety of lamotrigine in controlling relapse and/or recurrence of mood episodes in Chinese patients with bipolar I disorder. METHODS: Patients aged ≥ 18 years with bipolar I disorder who met response criteria (Clinical Global Impression-Severity [CGI-S] score of ≤ 3 for ≥ 4 consecutive weeks) during treatment with lamotrigine in a 6-16 week open-label (OL) phase, and who were maintained for ≥ 1 week on lamotrigine 200 mg/day monotherapy, were randomised (1:1) to continue receiving lamotrigine 200 mg/day or switch to placebo in a 36-week randomised double-blind (RD) phase. The primary efficacy outcome measure was time from entry into the RD phase to intervention for relapse and/or recurrence of a mood episode (TIME). Post hoc analyses assessed the impact of OL baseline mood severity on TIME. Safety assessments were conducted throughout the study. RESULTS: Of 420 patients treated in the OL phase, 264 were randomised to receive lamotrigine (n = 131) or placebo (n = 133). Overall, 112 patients had an intervention for relapse and/or recurrence of a mood episode (lamotrigine, n = 50/130 [38.5%]; placebo, n = 62/133 [46.6%]), with no significant difference in TIME between groups (adjusted hazard ratio [95% confidence interval (CI)] 0.93 [0.64, 1.35]; p = 0.701). Post hoc analyses indicated a significant difference in TIME, favouring lamotrigine over placebo, for patients with baseline CGI-S score ≥ 4 (hazard ratio [95% CI] 0.52 [0.30, 0.89]; p = 0.018) and with baseline Hamilton Depression Rating Scale ≥ 18 or Young Mania Rating Scale ≥ 10 (0.44 [hazard ratio [95% CI] 0.25, 0.78]; p = 0.005). Lamotrigine was well tolerated with no new safety signals. CONCLUSIONS: Lamotrigine was not significantly superior to placebo in preventing relapse and/or recurrence of mood episodes in this study of Chinese patients with bipolar I disorder but post hoc analyses suggested a therapeutic benefit in patients with moderate/severe mood symptoms at baseline. The discrepancy between these findings and the positive findings of the pivotal studies may be attributable to the symptom severity of the bipolar patients recruited, a high dropout rate, and the comparatively short duration of the RD phase rather than race/ethnicity differences. Clinical trial registration ClinicalTrial.gov Identifier NCT01602510; 21st May 2012; https://clinicaltrials.gov/ct2/show/NCT01602510 .