Return to play after head injury in adolescent sports: evaluating football versus other sports.

OBJECTIVE: Increased adolescent sports participation has raised concerns about higher rates of concussions, a prevalent injury among young athletes with potential long-term effects. Discrepancies in concussion recovery and management protocols across various sports underscore a critical issue in youth athletics. This study aimed to examine the relationship between sport type and the number of games missed following a concussion to inform targeted management strategies. METHODS: Data from 7445 postinjury ImPACT tests for athletes aged 12-22 years, collected from 2009 to 2019, were analyzed across different sports: baseball, basketball, cheerleading, football, ice hockey, lacrosse, soccer, softball, swimming, track and field, volleyball, and wrestling. The number of days and normalized missed games (NMG), a metric accounting for the different number of games in a season for different sports, were used to evaluate the effect of concussions across different sports. ANOVA, t-tests, and linear regression analyses were performed to model the effect of sport type on games missed in a season while controlling for sex, age, concussion history, diagnosed learning disability (DLD), and attention-deficit/hyperactivity disorder (ADHD). RESULTS: Multivariable linear regression analysis demonstrated that football participation significantly increased NMG (ß 1.681, 95% CI 0.807-2.554; p < 0.001) and days missed (ß 1.637, 95% CI 1.044-2.231; p < 0.001) after head injury. Concussion diagnoses were also found to significantly increase NMG (ß 2.344, 95% CI 1.629-3.059; p < 0.001) and days missed (ß 1.560, 95% CI 1.074-2.045; p < 0.001), as well as history of prior concussion (NMG: ß 7.791, 95% CI 7.368-8.215; p < 0.001; days missed: ß 5.232, 95% CI 4.945-5.520; p < 0.001). In contrast, factors such as age, sex, DLD, ADHD, and concussions causing loss of consciousness did not significantly affect NMG or days missed. ANOVA with Tukey Honest Significant Difference indicated that compared with football, ice hockey (mean difference [MD] 5.4 days, p = 0.011) and track and field (MD 4.1 days, p = 0.006) were associated with significantly more days being missed after head injury. Conversely, basketball (MD -3.0, p < 0.001) and volleyball (MD -2.6, p = 0.005) were associated with fewer missed games. CONCLUSIONS: Adolescents playing football missed fewer days and games after concussion than other contact and noncontact sports, including ice hockey and track and field, raising questions about variations in return-to-play protocols and cultural attitudes within sports. Further research is needed to determine the factors affecting games missed across sport types in adolescent athletics and return-to-play protocols.

Effects of hours of sleep on ImPACT concussion testing: comparing baseline with postinjury scores.

OBJECTIVE: The influence of sleep on baseline and postconcussion neurocognitive performance prior to Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) is poorly understood. Since ImPACT is widely used in youth sport to assess neurocognitive performance before and after head injury, it is important to delineate factors that affect testing performance. While some have reported correlations between fewer hours of sleep and lower scores on baseline tests, others have not observed any such associations. Therefore, the authors sought to compare the relationship between sleep and neurocognitive performance on ImPACT at both baseline and postinjury. METHODS: The authors queried a database of 25,815 ImPACT tests taken from 2009 to 2019 by athletes aged 12-22 years. There were 11,564 baseline concussion tests and 7446 postinjury concussion ImPACT tests used in the analysis. Linear regression was used to model the effect of sleep on baseline and postconcussion ImPACT scores adjusting for sex, age, learning disability, attention-deficit/hyperactivity disorder, number of prior concussions, number of games missed, and strenuous exercise before testing. RESULTS: Mean composite scores expectedly were all significantly lower in the post-head injury group compared with the baseline group. In the multivariable analysis, at baseline, hours of sleep significantly affected symptom scores (ß = -1.050, 95% CI -1.187 to -0.9138; p < 0.0001). In the postinjury multivariable analysis, verbal memory (ß = 0.4595, 95% CI 0.2080-0.7110; p = 0.0003), visual memory (ß = 0.3111, 95% CI 0.04463-0.5777; p = 0.0221), impulse control (ß = -0.2321, 95% CI -0.3581 to -0.1062; p = 0.0003), and symptom scores (ß = -0.9168, 95% CI -1.259 to -0.5750; p < 0.0001) were all affected by hours of sleep. CONCLUSIONS: Hours of sleep did not alter neurocognitive metrics at baseline but did have an impact on post-head injury metrics. These findings suggest that individuals may be able to compensate for lack of sleep at baseline but not immediately after concussion. Concussions may reduce cognitive reserve or detract from the brain's resources, making sleep even more important for proper neurocognitive functioning postconcussion. Future work will analyze the effects of sleep on postconcussion test performance.

Identifying Predictors of Initial Surgical Failure during Minimally Invasive Endoscopic Intracerebral Hemorrhage Evacuation.

Background and Purpose: Intracerebral hemorrhage (ICH) is a common and severe disease with high rates of morbidity and mortality; however, minimally invasive surgical (MIS) hematoma evacuation represents a promising avenue for treatment. In February of 2019, the MISTIE III study found that stereotactic thrombolysis with catheter drainage did not benefit patients with supratentorial spontaneous ICH but that a clinical benefit may be present when no more than 15 mL of hematoma remains at the end of treatment. Intraoperative CT (iCT) imaging has the ability to assess whether or not this surgical goal has been met in real time, allowing for operations to add additional CT-informed 'evacuation periods' (EPs) to achieve the surgical goal. Here, we report on the frequency and predictors of initial surgical failure on at least one iCT requiring additional EPs in a large cohort of patients undergoing endoscopic minimally invasive ICH evacuation with the SCUBA technique. Methods: All patients who underwent minimally invasive endoscopic evacuation of supratentorial spontaneous ICH in a major health system between December 2015 and October 2018 were included in this study. Patient demographics, clinical and radiographic features, procedural details, and outcomes were analyzed retrospectively from a prospectively collected database. Procedures were characterized as initially successful when the first iCT demonstrated that surgical success had been achieved and initially unsuccessful when the surgical goal was not achieved, and additional EPs were performed. The surgical goal was prospectively identified in December of 2015 as leaving no more than 20% of the preoperative hematoma volume at the end of the procedure. Descriptive statistics and regression analyses were performed to identify predictors of initial failure and secondary rescue. Results: Patients (100) underwent minimally invasive endoscopic ICH evacuation in the angiography suite during the study time period. In 14 cases, the surgical goal was not met on the first iCT and multiple Eps were performed; in 10 cases the surgical goal was not met, and no additional EPs were performed. In 14 cases, the surgical goal was never achieved. When additional EPs were performed, a rescue rate of 71.4% (10/14) was seen, bringing the total percentage of cases meeting the surgical goal to 86% across the entire cohort. Cases in which the surgical goal was not achieved were significantly associated with older patients (68 years vs. 60 years; p = 0.0197) and higher rates of intraventricular hemorrhage (34.2% vs. 70.8%; p = 0.0021). Cases in which the surgical goal was rescued from initial failure had similar levels of IVH, suggesting that these additional complexities can be overcome with the use of additional iCT-informed EPs. Conclusions: Initial and ultimate surgical failure occurs in a small percentage of patients undergoing minimally invasive endoscopic ICH evacuation. The use of intraoperative imaging provides an opportunity to evaluate whether or not the surgical goal has been achieved, and to continue the procedure if the surgeon feels that more evacuation is achievable. Now that level-one evidence exists to target a surgical evacuation goal during minimally invasive ICH evacuation, intraoperative imaging, such as iCT, plays an important role in aiding the surgical team to achieve the surgical goal.

Bone Cements Used in Vertebral Augmentation: A State-of-the-art Narrative Review.

Vertebral compression fractures (VCFs) are common in osteoporotic patients, with a frequency projected to increase alongside a growing geriatric population. VCFs often result in debilitating back pain and decreased mobility. Cement augmentation, a minimally invasive surgical technique, is widely used to stabilize fractures and restore vertebral height. Acrylic-based cements and calcium phosphate cements are currently the two primary fill materials utilized for these procedures. Despite their effectiveness, acrylic bone cements and calcium phosphate cements have been associated with various intraoperative and postoperative incidents impacting VCF treatment. Over the past decade, discoveries in the field of biomedical engineering and material science have shown advancements toward addressing these limitations. This narrative review aims to assess the potential pitfalls and barriers of the various types of bone cements.

Magnetic Hyperthermia Therapy for High-Grade Glioma: A State-of-the-Art Review.

Magnetic hyperthermia therapy (MHT) is a re-emerging treatment modality for brain tumors where magnetic nanoparticles (MNPs) are locally delivered to the brain and then activated with an external alternating magnetic field (AMF) to generate localized heat at a site of interest. Due to the recent advancements in technology and theory surrounding the intervention, clinical and pre-clinical trials have demonstrated that MHT may enhance the effectiveness of chemotherapy and radiation therapy (RT) for the treatment of brain tumors. The future clinical success of MHT relies heavily on designing MNPs optimized for both heating and imaging, developing reliable methods for the local delivery of MNPs, and designing AMF systems with integrated magnetic particle imaging (MPI) for use in humans. However, despite the progression of technological development, the clinical progress of MHT has been underwhelming. This review aims to summarize the current state-of-the-art of MHT and offers insight into the current barriers and potential solutions for moving MHT forward.

Lipoprotein (a) is a predictor of non-achievement of LDL-C goals in patients with chronic heart disease. / Lipoproteína (a) es un factor predictor de no consecución de objetivos de C-LDL en pacientes con cardiopatía isquémica crónica.

INTRODUCTION AND OBJECTIVES: Lipoprotein (a) [Lp(a)] concentration influences serum low-density lipoprotein cholesterol (LDL-C) levels. How it influences the achievement of LDL-C targets established in the guidelines is not well studied. Our aim was to know the prevalence of elevated Lp(a) levels in patients with coronary artery disease, and to assess its influence on the achievement of LDL-C targets. METHOD: We conducted a cross-sectional study in a cardiology department in Spain. A total of 870 patients with stable coronary artery disease had their lipid profile determined, including Lp(a). Patients were stratified into 2 groups according to Lp(a)>50mg/dL and Lp(a)≤50mg/dL. The association of Lp(a)>50mg/dL with achievement of LDL-C targets was assessed by logistic regression analysis. RESULTS: The prevalence of Lp(a)>50mg/dL was 30.8%. Patients with Lp(a)>50mg/dL had higher baseline (142.30±47.54 vs. 130.47±40.75mg/dL; p=0.0001) and current (72.91±26.44 vs. 64.72±25.30mg/dL; p=0.0001), despite the fact that they were treated with more high-potency statins (77.2 vs. 70.9%; p=0.058) and more combination lipid-lowering therapy (37.7 vs. 25.7%; p=0.001). The proportion of patients achieving target LDL-C was lower in those with Lp(a)>50mg/dL. Independent predictors of having elevated Lp(a) levels>50mg/dL were the use of high-potency statins (OR 1.5; 95% CI 1.08-2.14), combination lipid-lowering therapy with ezetimibe (OR 2.0; 95% CI 1.45-2.73) and failure to achieve a LDL-C ≤55mg/dL (OR 2.3; 95% CI 1.63-3.23). CONCLUSIONS: Elevated Lp(a) levels influence LDL-C levels and hinder the achievement of targets in patients at very high cardiovascular risk. New drugs that act directly on Lp(a) are needed in these patients.

A genetic association study of circulating coagulation factor VIII and von Willebrand factor levels.

ABSTRACT: Coagulation factor VIII (FVIII) and its carrier protein von Willebrand factor (VWF) are critical to coagulation and platelet aggregation. We leveraged whole-genome sequence data from the Trans-Omics for Precision Medicine (TOPMed) program along with TOPMed-based imputation of genotypes in additional samples to identify genetic associations with circulating FVIII and VWF levels in a single-variant meta-analysis, including up to 45 289 participants. Gene-based aggregate tests were implemented in TOPMed. We identified 3 candidate causal genes and tested their functional effect on FVIII release from human liver endothelial cells (HLECs) and VWF release from human umbilical vein endothelial cells. Mendelian randomization was also performed to provide evidence for causal associations of FVIII and VWF with thrombotic outcomes. We identified associations (P < 5 × 10-9) at 7 new loci for FVIII (ST3GAL4, CLEC4M, B3GNT2, ASGR1, F12, KNG1, and TREM1/NCR2) and 1 for VWF (B3GNT2). VWF, ABO, and STAB2 were associated with FVIII and VWF in gene-based analyses. Multiphenotype analysis of FVIII and VWF identified another 3 new loci, including PDIA3. Silencing of B3GNT2 and the previously reported CD36 gene decreased release of FVIII by HLECs, whereas silencing of B3GNT2, CD36, and PDIA3 decreased release of VWF by HVECs. Mendelian randomization supports causal association of higher FVIII and VWF with increased risk of thrombotic outcomes. Seven new loci were identified for FVIII and 1 for VWF, with evidence supporting causal associations of FVIII and VWF with thrombotic outcomes. B3GNT2, CD36, and PDIA3 modulate the release of FVIII and/or VWF in vitro.

Effect of light stress on lutein production with associated phosphorus removal from a secondary effluent by the autoflocculating microalgae consortium BR-UANL-01.

Microalgae have become promising microorganisms for generating high-value commercial products and removing pollutants in aquatic systems. This research evaluated the impact of sunlight intensity on intracellular pigment generation and phosphorus removal from secondary effluents by autoflocculating microalgae consortium BR-UANL-01 in photobioreactor culture. Microalgae were grown in a secondary effluent from a wastewater treatment plant, using a combination of low and high light conditions (photon irradiance; 44 µmol m-2 s-1 and ≈ 1270 µmol m-2 s-1, respectively) and 16:8 h light:dark and 24:0 h light:dark (subdivided into 18:6 LED:sunlight) photoperiods. The autoflocculant rate by consortium BR-UANL-01 was not affected by light intensity and achieved 98% in both treatments. Microalgae produced significantly more lutein, (2.91 mg g-1) under low light conditions. Phosphate removal by microalgae resulted above 85% from the secondary effluent, due to the fact that phosphorus is directly associated with metabolic and replication processes and the highest antioxidant activity was obtained in ABTS•+ assay by the biomass under low light condition (51.71% µmol ET g-1). In conclusion, the results showed that the autoflocculating microalgae consortium BR-UANL-01 is capable of synthesizing intracellular lutein, which presents antioxidant activity, using secondary effluents as a growth medium, without losing its autoflocculating activity and assimilating phosphorus.

3D reconstruction of murine mitochondria reveals changes in structure during aging linked to the MICOS complex.

During aging, muscle gradually undergoes sarcopenia, the loss of function associated with loss of mass, strength, endurance, and oxidative capacity. However, the 3D structural alterations of mitochondria associated with aging in skeletal muscle and cardiac tissues are not well described. Although mitochondrial aging is associated with decreased mitochondrial capacity, the genes responsible for the morphological changes in mitochondria during aging are poorly characterized. We measured changes in mitochondrial morphology in aged murine gastrocnemius, soleus, and cardiac tissues using serial block-face scanning electron microscopy and 3D reconstructions. We also used reverse transcriptase-quantitative PCR, transmission electron microscopy quantification, Seahorse analysis, and metabolomics and lipidomics to measure changes in mitochondrial morphology and function after loss of mitochondria contact site and cristae organizing system (MICOS) complex genes, Chchd3, Chchd6, and Mitofilin. We identified significant changes in mitochondrial size in aged murine gastrocnemius, soleus, and cardiac tissues. We found that both age-related loss of the MICOS complex and knockouts of MICOS genes in mice altered mitochondrial morphology. Given the critical role of mitochondria in maintaining cellular metabolism, we characterized the metabolomes and lipidomes of young and aged mouse tissues, which showed profound alterations consistent with changes in membrane integrity, supporting our observations of age-related changes in muscle tissues. We found a relationship between changes in the MICOS complex and aging. Thus, it is important to understand the mechanisms that underlie the tissue-dependent 3D mitochondrial phenotypic changes that occur in aging and the evolutionary conservation of these mechanisms between Drosophila and mammals.

Three-dimensional mitochondria reconstructions of murine cardiac muscle changes in size across aging.

With sparse treatment options, cardiac disease remains a significant cause of death among humans. As a person ages, mitochondria breakdown and the heart becomes less efficient. Heart failure is linked to many mitochondria-associated processes, including endoplasmic reticulum stress, mitochondrial bioenergetics, insulin signaling, autophagy, and oxidative stress. The roles of key mitochondrial complexes that dictate the ultrastructure, such as the mitochondrial contact site and cristae organizing system (MICOS), in aging cardiac muscle are poorly understood. To better understand the cause of age-related alteration in mitochondrial structure in cardiac muscle, we used transmission electron microscopy (TEM) and serial block facing-scanning electron microscopy (SBF-SEM) to quantitatively analyze the three-dimensional (3-D) networks in cardiac muscle samples of male mice at aging intervals of 3 mo, 1 yr, and 2 yr. Here, we present the loss of cristae morphology, the inner folds of the mitochondria, across age. In conjunction with this, the three-dimensional (3-D) volume of mitochondria decreased. These findings mimicked observed phenotypes in murine cardiac fibroblasts with CRISPR/Cas9 knockout of Mitofilin, Chchd3, Chchd6 (some members of the MICOS complex), and Opa1, which showed poorer oxidative consumption rate and mitochondria with decreased mitochondrial length and volume. In combination, these data show the need to explore if loss of the MICOS complex in the heart may be involved in age-associated mitochondrial and cristae structural changes.NEW & NOTEWORTHY This article shows how mitochondria in murine cardiac changes, importantly elucidating age-related changes. It also is the first to show that the MICOS complex may play a role in outer membrane mitochondrial structure.

Whole genome analysis of plasma fibrinogen reveals population-differentiated genetic regulators with putative liver roles.

Genetic studies have identified numerous regions associated with plasma fibrinogen levels in Europeans, yet missing heritability and limited inclusion of non-Europeans necessitates further studies with improved power and sensitivity. Compared with array-based genotyping, whole genome sequencing (WGS) data provides better coverage of the genome and better representation of non-European variants. To better understand the genetic landscape regulating plasma fibrinogen levels, we meta-analyzed WGS data from the NHLBI's Trans-Omics for Precision Medicine (TOPMed) program (n=32,572), with array-based genotype data from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium (n=131,340) imputed to the TOPMed or Haplotype Reference Consortium panel. We identified 18 loci that have not been identified in prior genetic studies of fibrinogen. Of these, four are driven by common variants of small effect with reported MAF at least 10% higher in African populations. Three ( SERPINA1, ZFP36L2 , and TLR10) signals contain predicted deleterious missense variants. Two loci, SOCS3 and HPN , each harbor two conditionally distinct, non-coding variants. The gene region encoding the protein chain subunits ( FGG;FGB;FGA ), contains 7 distinct signals, including one novel signal driven by rs28577061, a variant common (MAF=0.180) in African reference panels but extremely rare (MAF=0.008) in Europeans. Through phenome-wide association studies in the VA Million Veteran Program, we found associations between fibrinogen polygenic risk scores and thrombotic and inflammatory disease phenotypes, including an association with gout. Our findings demonstrate the utility of WGS to augment genetic discovery in diverse populations and offer new insights for putative mechanisms of fibrinogen regulation. Key Points: Largest and most diverse genetic study of plasma fibrinogen identifies 54 regions (18 novel), housing 69 conditionally distinct variants (20 novel).Sufficient power achieved to identify signal driven by African population variant.Links to (1) liver enzyme, blood cell and lipid genetic signals, (2) liver regulatory elements, and (3) thrombotic and inflammatory disease.

Surgical techniques for evacuation of chronic subdural hematoma: a mini-review.

Chronic subdural hematoma is one of the most common neurosurgical pathologies with over 160,000 cases in the United States and Europe each year. The current standard of care involves surgically evacuating the hematoma through a cranial opening, however, varied patient risk profiles, a significant recurrence rate, and increasing financial burden have sparked innovation in the field. This mini-review provides a brief overview of currently used evacuation techniques, including emerging adjuncts such as endoscopic assistance and middle meningeal artery embolization. This review synthesizes the body of available evidence on efficacy and risk profiles for each critical aspect of surgical technique in cSDH evacuation and provides insight into trends in the field and promising new technologies.

Bibliometric Analysis of International Medical Graduates and Professorship Promotion in Neurosurgery.

BACKGROUND: International medical graduates (IMGs) comprise ∼25% of physicians in the United States. Differences in promotion rates from assistant to associate to full professorship based on medical school location have been understudied. We aim to stratify odds of professional advancement by 3 categories: IMG with U.S. residency, IMG with international residency, and U.S. medical with U.S. residency training. METHODS: We created and queried a database after exclusions of 1334 neurosurgeons including multiple demographic factors: academic productivity and promotion rates. Stratified logistic regression modeled odds of promotion including the variables: decades out of training, Scopus h-index, gender, and training location. Odds ratios (ORs) and 95% confidence intervals (CIs) for each variable were calculated. RESULTS: Significant predictors of increased associate versus assistant professorship included decades out of training (OR = 2.519 [95% CI: 2.07-3.093], P < 0.0001) and Scopus h-index (OR = 1.085 [95% CI: 1.064-1.108], P < 0.0001) while international medical school with U.S. residency (OR = 0.471 [95% CI: 0.231-0.914], P = 0.0352) was associated with decreased promotion. Significant predictors of associate versus full professorship were decades out of training (OR = 2.781 [95% CI: 2.268-3.444], P < 0.0001) and Scopus h-index (OR = 1.064 [95% CI: 1.049-1.080], P < 0.0001). Attending medical school or residency internationally was not associated with odds of full professorship. CONCLUSIONS: Time out of residency and Scopus h-index were associated with higher academic rank regardless of career level. Attending medical school internationally with U.S. residency was associated with lower odds of associate professorship promotion over 10 years. There was no relationship between IMG and full professorship promotion. IMGs who attended residency internationally did not have lower promotion rates. These findings suggest it may be harder for IMGs to earn promotion from assistant to associate professor in neurosurgery.

Isolated tricuspid valve Group B Streptococcal endocarditis with septic pulmonary embolism and multiple mycotic aneurysms of the pulmonary arteries.

A diabetic woman in her 30s was admitted to our medical centre for persistent fever associated with worsening cough, easy fatigability and pleuritic chest pain noted after childbirth. Investigations revealed an isolated tricuspid valve endocarditis from Group B Streptococcus Despite appropriate antibiotic coverage, her symptoms persisted with worsening dyspnoea; hence, a CT pulmonary angiogram was done which showed septic pulmonary embolism and multiple mycotic aneurysms of the pulmonary arteries. She was treated with antibiotics and underwent tricuspid valve replacement and was discharged well with a return to her baseline functional capacity on subsequent follow-ups.

Validation of a Temperature-Feedback Controlled Automated Magnetic Hyperthermia Therapy Device.

We present in vivo validation of an automated magnetic hyperthermia therapy (MHT) device that uses real-time temperature input measured at the target to control tissue heating. MHT is a thermal therapy that uses heat generated by magnetic materials exposed to an alternating magnetic field. For temperature monitoring, we integrated a commercial fiber optic temperature probe containing four gallium arsenide (GaAs) temperature sensors. The controller device used temperature from the sensors as input to manage power to the magnetic field applicator. We developed a robust, multi-objective, proportional-integral-derivative (PID) algorithm to control the target thermal dose by modulating power delivered to the magnetic field applicator. The magnetic field applicator was a 20 cm diameter Maxwell-type induction coil powered by a 120 kW induction heating power supply operating at 160 kHz. Finite element (FE) simulations were performed to determine values of the PID gain factors prior to verification and validation trials. Ex vivo verification and validation were conducted in gel phantoms and sectioned bovine liver, respectively. In vivo validation of the controller was achieved in a canine research subject following infusion of magnetic nanoparticles (MNPs) into the brain. In all cases, performance matched controller design criteria, while also achieving a thermal dose measured as cumulative equivalent minutes at 43 °C (CEM43) 60 ± 5 min within 30 min.

Dystrophinopathy Phenotypes and Modifying Factors in DMD Exon 45-55 Deletion.

OBJECTIVE: Duchenne muscular dystrophy (DMD) exon 45-55 deletion (del45-55) has been postulated as a model that could treat up to 60% of DMD patients, but the associated clinical variability and complications require clarification. We aimed to understand the phenotypes and potential modifying factors of this dystrophinopathy subset. METHODS: This cross-sectional, multicenter cohort study applied clinical and functional evaluation. Next generation sequencing was employed to identify intronic breakpoints and their impact on the Dp140 promotor, intronic long noncoding RNA, and regulatory splicing sequences. DMD modifiers (SPP1, LTBP4, ACTN3) and concomitant mutations were also assessed. Haplotypes were built using DMD single nucleotide polymorphisms. Dystrophin expression was evaluated via immunostaining, Western blotting, reverse transcription polymerase chain reaction (PCR), and droplet digital PCR in 9 muscle biopsies. RESULTS: The series comprised 57 subjects (23 index) expressing Becker phenotype (28%), isolated cardiopathy (19%), and asymptomatic features (53%). Cognitive impairment occurred in 90% of children. Patients were classified according to 10 distinct index-case breakpoints; 4 of them were recurrent due to founder events. A specific breakpoint (D5) was associated with severity, but no significant effect was appreciated due to the changes in intronic sequences. All biopsies showed dystrophin expression of >67% and traces of alternative del45-57 transcript that were not deemed pathogenically relevant. Only the LTBP4 haplotype appeared associated the presence of cardiopathy among the explored extragenic factors. INTERPRETATION: We confirmed that del45-55 segregates a high proportion of benign phenotypes, severe cases, and isolated cardiac and cognitive presentations. Although some influence of the intronic breakpoint position and the LTBP4 modifier may exist, the pathomechanisms responsible for the phenotypic variability remain largely unresolved. ANN NEUROL 2022;92:793-806.

Multiomic atlas with functional stratification and developmental dynamics of zebrafish cis-regulatory elements.

Zebrafish, a popular organism for studying embryonic development and for modeling human diseases, has so far lacked a systematic functional annotation program akin to those in other animal models. To address this, we formed the international DANIO-CODE consortium and created a central repository to store and process zebrafish developmental functional genomic data. Our data coordination center ( https://danio-code.zfin.org ) combines a total of 1,802 sets of unpublished and re-analyzed published genomic data, which we used to improve existing annotations and show its utility in experimental design. We identified over 140,000 cis-regulatory elements throughout development, including classes with distinct features dependent on their activity in time and space. We delineated the distinct distance topology and chromatin features between regulatory elements active during zygotic genome activation and those active during organogenesis. Finally, we matched regulatory elements and epigenomic landscapes between zebrafish and mouse and predicted functional relationships between them beyond sequence similarity, thus extending the utility of zebrafish developmental genomics to mammals.

Microencapsulation of steroidal saponins from agave sap concentrate using different carriers in spray drying.

Concentrated agave sap is a product with in vivo proven hypocholesterolemic and hypoglycemic activities, as well as in vitro anticancer potential. In the present work, a factorial design was used to determine the suitable drying conditions of concentrated agave by studying the effect of inlet temperature (150 °C, 180 °C and 210 °C) and the type of carrier agent (maltodextrin, hydroxypropyl methylcellulose, guar gum and xanthan gum). The response variables for each treatment were the product recovery and microencapsulated saponins. Further characterization of concentrated agave powders was performed: solubility in water, hygroscopicity, moisture content, tap density, bulk density, Carr's index followability and morphology by scanning electron microscopy analysis. The hydroxypropyl methylcellulose proved to improve physicochemical properties and enhance product yield, using 210 °C inlet temperature and a mix of carrier agents of maltodextrin/hydroxypropyl methylcellulose/xanthan gum at 50/48.5/1.5 (w/w/w) proportion exhibited the highest saponin recovery of 53.81%. Moreover, different carrier agents in powders revealed two shapes, regular spherical shape with smooth surface and collapsed shapes. The use of polymers excipients helped to decrease the stickiness of the desired product and enhanced the powder stability and microencapsulation of the steroidal saponins.

Caracterización clínica e imagenológica de una serie de pacientes con disección de arterias cervicales e intracraneales / Cervicocranial arterial dissection: experience in 57 patients

Background: Cervicocranial arterial dissection (CIAD) is an important cause of stroke. Aim: To describe the clinical and imaging characteristics of patients with CIAD. Material and Methods: An anonymous registry was made including all patients admitted to a private hospital with a diagnosis of CIAD. Patients were subdivided as having an anterior or posterior circulation dissection (ACD or PCD, respectively). Results: Fifty-seven patients aged 40 ± 8 years (60% women) were included in the study, 39 with PCD and 18 with ACD. Cervical pain was the most common symptom. CIAD was diagnosed with no clinical or imaging signs of stroke in 49% of patients. Fifty one percent of patients had focal neurological deficits and 72% had a NIH stroke score below five. No significant differences between patients with ACD or PCD were found. Fifty patients received antiplatelet therapy (simple or dual), seven patients were anticoagulated and 13 were subjected to stenting due to progression of stenosis with hemodynamic involvement or bilateral dissection with scarce collaterals. The lesion was located in V3 segment in 27 patients and cervical segment of the internal carotid in 16 cases. A favorable Modified Rankin Scale (0-2) was achieved in 85.9%, with a trend towards achieving better functional prognosis in PCD. Conclusions: Due to the greater availability of non-invasive imaging methods, 50% of these patients with CIAD did not have a stroke. Thus, an earlier and more timely management is feasible.