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1.
J Neural Eng ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38981500

RESUMO

OBJECTIVES: To evaluate the inter- and intra-rater reliability for the identification of bad channels among neurologists, EEG Technologists, and naïve research personnel, and to compare their performance with the automated bad channel detection (ABCD) algorithm for detecting bad channels. Methods: Six Neurologists, ten EEG Technologists, and six naïve research personnel (22 raters in total) were asked to rate 1440 real intracranial EEG channels as good or bad. Intra- and interrater kappa statistics were calculated for each group. We then compared each group to the ABCD algorithm which uses spectral and temporal domain features to classify channels as good or bad. Results: Analysis of channel ratings from our participants revealed variable intra-rater reliability within each group, with no significant differences across groups. Inter-rater reliability was moderate among neurologists and EEG Technologists but minimal among naïve participants. Neurologists demonstrated a slightly higher consistency in ratings than EEG Technologists. Both groups occasionally misclassified flat channels, and participants generally focused on low-frequency content for their assessments. The ABCD algorithm, in contrast, relied more on high-frequency content. A logistic regression model showed a linear relationship between the algorithm's ratings and user responses for predominantly good channels, but less so for channels rated as bad. Sensitivity and specificity analyses further highlighted differences in rating patterns among the groups, with neurologists showing higher sensitivity and naïve personnel higher specificity. Significance: Our study reveals the bias in human assessments of iEEG data quality and the tendency of even experienced professionals to overlook certain bad channels, highlighting the need for standardized, unbiased methods. The ABCD algorithm, outperforming human raters, suggests the potential of automated solutions for more reliable iEEG interpretation and seizure characterization, offering a reliable approach free from human biases. .

2.
PhytoKeys ; 244: 127-150, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39027483

RESUMO

Estimates of the number of vascular plant species currently under threat of extinction are shockingly high, with the highest extinction rates reported for narrow-range, woody plants, especially in biodiversity hotspots with Mediterranean and tropical climates. The large genus Erica is a prime example, as a large proportion of its 851 species, all shrubs or small trees, are endemic to the Cape Floristic Region (CFR) of South Africa. Almost two hundred are known to be threatened and a further hundred are 'Data Deficient'. We need to target conservation efforts and research to fill the most problematic knowledge gaps. This can be especially challenging in large genera, such as Erica, with numerous threatened species that are closely related. One approach involves combining knowledge of phylogenetic diversity with that of IUCN threat status to identify the most Evolutionarily Distinct and Globally Endangered (EDGE) species. We present an expanded and improved phylogenetic hypothesis for Erica (representing 65% of described species diversity) and combine this with available threat and distribution data to identify species and geographic areas that could be targeted for conservation effort to maximise preservation of phylogenetic diversity (PD). The resulting 39 EDGE taxa include 35 from the CFR. A further 32 high PD, data deficient taxa are mostly from outside the CFR, reflecting the low proportion of assessed taxa outside South Africa. The most taxon-rich areas are found in the south-western CFR. They are not the most phylogenetically diverse, but do include the most threatened PD. These results can be cross-referenced to existing living and seed-banked ex situ collections and used to target new and updated threat assessments and conservation action.

3.
Sci Rep ; 14(1): 15462, 2024 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-38965267

RESUMO

Facioscapulohumeral muscular dystrophy (FSHD) affects roughly 1 in 7500 individuals. While at the population level there is a general pattern of affected muscles, there is substantial heterogeneity in muscle expression across- and within-patients. There can also be substantial variation in the pattern of fat and water signal intensity within a single muscle. While quantifying individual muscles across their full length using magnetic resonance imaging (MRI) represents the optimal approach to follow disease progression and evaluate therapeutic response, the ability to automate this process has been limited. The goal of this work was to develop and optimize an artificial intelligence-based image segmentation approach to comprehensively measure muscle volume, fat fraction, fat fraction distribution, and elevated short-tau inversion recovery signal in the musculature of patients with FSHD. Intra-rater, inter-rater, and scan-rescan analyses demonstrated that the developed methods are robust and precise. Representative cases and derived metrics of volume, cross-sectional area, and 3D pixel-maps demonstrate unique intramuscular patterns of disease. Future work focuses on leveraging these AI methods to include upper body output and aggregating individual muscle data across studies to determine best-fit models for characterizing progression and monitoring therapeutic modulation of MRI biomarkers.


Assuntos
Inteligência Artificial , Progressão da Doença , Imageamento por Ressonância Magnética , Distrofia Muscular Facioescapuloumeral , Humanos , Distrofia Muscular Facioescapuloumeral/diagnóstico por imagem , Distrofia Muscular Facioescapuloumeral/patologia , Imageamento por Ressonância Magnética/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Processamento de Imagem Assistida por Computador/métodos
4.
Hum Brain Mapp ; 45(10): e26775, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38970249

RESUMO

Visual entrainment is a powerful and widely used research tool to study visual information processing in the brain. While many entrainment studies have focused on frequencies around 14-16 Hz, there is renewed interest in understanding visual entrainment at higher frequencies (e.g., gamma-band entrainment). Notably, recent groundbreaking studies have demonstrated that gamma-band visual entrainment at 40 Hz may have therapeutic effects in the context of Alzheimer's disease (AD) by stimulating specific neural ensembles, which utilize GABAergic signaling. Despite such promising findings, few studies have investigated the optimal parameters for gamma-band visual entrainment. Herein, we examined whether visual stimulation at 32, 40, or 48 Hz produces optimal visual entrainment responses using high-density magnetoencephalography (MEG). Our results indicated strong entrainment responses localizing to the primary visual cortex in each condition. Entrainment responses were stronger for 32 and 40 Hz relative to 48 Hz, indicating more robust synchronization of neural ensembles at these lower gamma-band frequencies. In addition, 32 and 40 Hz entrainment responses showed typical patterns of habituation across trials, but this effect was absent for 48 Hz. Finally, connectivity between visual cortex and parietal and prefrontal cortices tended to be strongest for 40 relative to 32 and 48 Hz entrainment. These results suggest that neural ensembles in the visual cortex may resonate at around 32 and 40 Hz and thus entrain more readily to photic stimulation at these frequencies. Emerging AD therapies, which have focused on 40 Hz entrainment to date, may be more effective at lower relative to higher gamma frequencies, although additional work in clinical populations is needed to confirm these findings. PRACTITIONER POINTS: Gamma-band visual entrainment has emerged as a therapeutic approach for eliminating amyloid in Alzheimer's disease, but its optimal parameters are unknown. We found stronger entrainment at 32 and 40 Hz compared to 48 Hz, suggesting neural ensembles prefer to resonate around these relatively lower gamma-band frequencies. These findings may inform the development and refinement of innovative AD therapies and the study of GABAergic visual cortical functions.


Assuntos
Ritmo Gama , Magnetoencefalografia , Estimulação Luminosa , Córtex Visual , Humanos , Ritmo Gama/fisiologia , Masculino , Feminino , Estimulação Luminosa/métodos , Adulto , Córtex Visual/fisiologia , Adulto Jovem , Percepção Visual/fisiologia
5.
Hum Brain Mapp ; 45(11): e26787, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39023178

RESUMO

Regular cannabis use is associated with cortex-wide changes in spontaneous and oscillatory activity, although the functional significance of such changes remains unclear. We hypothesized that regular cannabis use would suppress spontaneous gamma activity in regions serving cognitive control and scale with task performance. Participants (34 cannabis users, 33 nonusers) underwent an interview regarding their substance use history and completed the Eriksen flanker task during magnetoencephalography (MEG). MEG data were imaged in the time-frequency domain and virtual sensors were extracted from the peak voxels of the grand-averaged oscillatory interference maps to quantify spontaneous gamma activity during the pre-stimulus baseline period. We then assessed group-level differences in spontaneous and oscillatory gamma activity, and their relationship with task performance and cannabis use metrics. Both groups exhibited a significant behavioral flanker interference effect, with slower responses during incongruent relative to congruent trials. Mixed-model ANOVAs indicated significant gamma-frequency neural interference effects in the left frontal eye fields (FEF) and left temporoparietal junction (TPJ). Further, a group-by-condition interaction was detected in the left FEF, with nonusers exhibiting stronger gamma oscillations during incongruent relative to congruent trials and cannabis users showing no difference. In addition, spontaneous gamma activity was sharply suppressed in cannabis users relative to nonusers in the left FEF and TPJ. Finally, spontaneous gamma activity in the left FEF and TPJ was associated with task performance across all participants, and greater cannabis use was associated with weaker spontaneous gamma activity in the left TPJ of the cannabis users. Regular cannabis use was associated with weaker spontaneous gamma in the TPJ and FEF. Further, the degree of use may be proportionally related to the degree of suppression in spontaneous activity in the left TPJ.


Assuntos
Cognição , Ritmo Gama , Magnetoencefalografia , Humanos , Masculino , Feminino , Adulto , Adulto Jovem , Ritmo Gama/fisiologia , Cognição/fisiologia , Mapeamento Encefálico , Testes Neuropsicológicos , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Uso da Maconha
6.
Med Mycol ; 62(7)2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38982313

RESUMO

The yeasts Cryptococcus neoformans and Cryptococcus gattii are fungal pathogens that can be isolated from the environment, including the surfaces of many plants. Cryptococcus gattii caused an outbreak on Vancouver Island, British Columbia beginning in 1999 that has since spread to the Pacific Northwest of the United States. Coastal Douglas fir (Pseudotsuga menziesii) is an important lumber species and a major component of the ecosystems in this area. Previous research has explored Cryptococcus survival and mating on Douglas fir plants and plant-derived material, but no studies have been done on the production of cryptococcal virulence factors by cells grown on those media. Here, we investigated the effects of growth on Douglas fir-derived media on the production of the polysaccharide capsule and melanin, two of the most important cryptococcal virulence factors. We found that while the capsule was mostly unchanged by growth in Douglas fir media compared to cells grown in defined minimal media, Cryptococcus spp. can use substrates present in Douglas fir to synthesize functional and protective melanin. These results suggest mechanisms by which Cryptococcus species may survive in the environment and emphasize the need to explore how association with Douglas fir trees could affect its epidemiology for human cryptococcosis.


Cryptococcus gattii is a fungal pathogen that can be found in the environment. It is responsible for causing an outbreak in British Columbia, Canada, in the late 90s. In our study, we created media from Douglas fir, a tree commonly found in the affected areas. We examined the production of virulence factors by Cryptococcus cells grown in this media.


Assuntos
Cryptococcus neoformans , Meios de Cultura , Melaninas , Fatores de Virulência , Melaninas/biossíntese , Melaninas/metabolismo , Cryptococcus neoformans/patogenicidade , Cryptococcus neoformans/crescimento & desenvolvimento , Cryptococcus neoformans/efeitos dos fármacos , Cryptococcus neoformans/metabolismo , Meios de Cultura/química , Cryptococcus gattii/patogenicidade , Cryptococcus gattii/crescimento & desenvolvimento , Cryptococcus gattii/efeitos dos fármacos , Cápsulas Fúngicas/metabolismo , Viabilidade Microbiana , Criptococose/microbiologia , Humanos
7.
J Pediatr Surg ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38834410

RESUMO

INTRODUCTION: Pulmonary abscess is a complication of lung infection with localized necrosis and purulent cavity formation. Pulmonary abscesses are typically managed using antibiotic therapy with anatomic surgical resection reserved as a rescue. Percutaneous drainage is considered relatively contraindicated in some centers due to perceived risk of bronchopleural fistula. However, drain placement has been frequently employed at our institution. The purpose of this study was to review and describe our longitudinal experience. METHODS: Medical records of children diagnosed with lung abscess and treated with percutaneous drainage from 2005 through 2023 were reviewed. Patient clinical parameters, follow-up imaging, and clinical outcomes were evaluated. RESULTS: Percutaneous drainage (n = 24) or aspiration alone (n = 4) under imaging guidance was performed by interventional radiologists for 28 children with lung abscesses. A single catheter (8-12 Fr) was deployed in the pulmonary abscess cavity and remained for a median of 6 days (IQR: 6-8 days). The median hospital stay was 10 days (IQR: 8.8-14.8 days). The technical success rate for percutaneous drainage or aspiration of primary pulmonary abscesses was 100% (26/26). Two children were later diagnosed with secondarily infected congenital pulmonary airway malformations that were both successfully drained and ultimately surgically resected. The abscess cavities resolved in all patients and catheters were removed upon clinical, radiographic, and laboratory improvement. Complications included the presence of two bronchopleural fistula, both of which were treated with immediate pleural drain placement. CONCLUSION: Percutaneous drainage of pulmonary abscesses is an effective therapeutic option in children and can be considered alongside antibiotics as part of the initial treatment for pulmonary abscesses. Bronchopleural fistula can occur, but at a lower frequency than previously reported. LEVEL OF EVIDENCE: Level V.

8.
J Surg Res ; 300: 503-513, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38875949

RESUMO

INTRODUCTION: Typical first-line management of children with intussusception is enema reduction; however, failure necessitates surgical intervention. The number of attempts varies by clinician, and predictors of failed nonoperative management are not routinely considered in practice. The purpose of this study is to create a scoring system that predicts risk of nonoperative failure and need for surgical intervention. METHODS: Children diagnosed with intussusception upon presentation to the emergency department of a tertiary children's hospital between 2019 and 2022 were retrospectively identified. Univariable logistic regression identified predictors of nonoperative failure used as starting covariates for multivariable logistic regression with final model determined by backwards elimination. Regression coefficients for final predictors were used to create the scoring system and optimal cut-points were delineated. RESULTS: We identified 143 instances of ultrasound-documented intussusception of which 28 (19.6%) required operative intervention. Predictors of failed nonoperative management included age ≥4 y (odds ratio [OR] 32.83, 95% confidence interval [CI]: 1.91-564.23), ≥1 failed enema reduction attempts (OR 189.53, 95% CI: 19.07-1884.11), presenting heart rate ≥128 (OR 3.38, 95% CI: 0.74-15.36), presenting systolic blood pressure ≥115 mmHg (OR 6.59, 95% CI: 0.93-46.66), and trapped fluid between intussuscepted loops on ultrasound (OR 17.54, 95% CI: 0.77-397.51). Employing these factors, a novel risk scoring system was developed (area under the curve 0.96, 95% CI: 0.93-0.99). Scores range from 0 to 8; ≤2 have low (1.1%), 3-4 moderate (50.0%), and ≥5 high (100%) failure risk. CONCLUSIONS: Using known risk factors for enema failure, we produced a risk scoring system with outstanding discriminate ability for children with intussusception necessitating surgical intervention. Prospective validation is warranted prior to clinical integration.


Assuntos
Intussuscepção , Falha de Tratamento , Humanos , Intussuscepção/terapia , Intussuscepção/diagnóstico , Intussuscepção/diagnóstico por imagem , Estudos Retrospectivos , Feminino , Masculino , Lactente , Pré-Escolar , Criança , Medição de Risco/métodos , Enema , Ultrassonografia , Fatores de Risco
9.
Risk Anal ; 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38945529

RESUMO

This article presents a risk analysis of large language models (LLMs), a type of "generative" artificial intelligence (AI) system that produces text, commonly in response to textual inputs from human users. The article is specifically focused on the risk of LLMs causing an extreme catastrophe in which they do something akin to taking over the world and killing everyone. The possibility of LLM takeover catastrophe has been a major point of public discussion since the recent release of remarkably capable LLMs such as ChatGPT and GPT-4. This arguably marks the first time when actual AI systems (and not hypothetical future systems) have sparked concern about takeover catastrophe. The article's analysis compares (A) characteristics of AI systems that may be needed for takeover, as identified in prior theoretical literature on AI takeover risk, with (B) characteristics observed in current LLMs. This comparison reveals that the capabilities of current LLMs appear to fall well short of what may be needed for takeover catastrophe. Future LLMs may be similarly incapable due to fundamental limitations of deep learning algorithms. However, divided expert opinion on deep learning and surprise capabilities found in current LLMs suggests some risk of takeover catastrophe from future LLMs. LLM governance should monitor for changes in takeover characteristics and be prepared to proceed more aggressively if warning signs emerge. Unless and until such signs emerge, more aggressive governance measures may be unwarranted.

10.
Mediastinum ; 8: 35, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38881806

RESUMO

Background and Objective: Thymectomy as a management strategy for juvenile myasthenia gravis (JMG) has been increasingly adopted with the advent of minimally invasive surgical techniques. This review evaluates existing evidence regarding the surgical management of JMG, including the benefits of surgical compared to medical therapy, important considerations when evaluating surgical candidacy and determining optimal timing of intervention. In addition, we provide an overview of the open, thoracoscopic and robotic surgical approaches available for thymectomy and compare the existing data to characterize optimal surgical management. Methods: A thorough literature review was conducted for full length research articles, including systematic reviews, retrospective cohort studies and case series, published between January 2000 and July 2023 regarding open, thoracoscopic or robotic thymectomy for management of JMG. Reference lists of the identified articles were manually searched for additional studies. Evidence was summarized in a narrative fashion with the incorporation of the authors' knowledge gained through clinical experience. Key Content and Findings: Although data specific to JMG are limited to small retrospective cohort studies, available evidence supports equal to greater disease control following thymectomy versus pharmacologic management. Furthermore, outcomes may be optimized when surgery is performed earlier in the disease course, particularly for patients who are post-pubertal with generalized or severe disease and those necessitating high-dose steroid administration thereby limiting its metabolic and growth inhibitory effects. Open transsternal resection is the historic gold-standard; however, as surgeons become more comfortable with thoracoscopic and robotic-assisted thymectomy, an increasing proportion of patients are expected to undergo thymectomy. At present, the data available is unable to support conclusions regarding which surgical approach is superior; however, minimally invasive approaches may be non-inferior while offering superior cosmesis and decreased morbidity. Conclusions: Higher-level investigation through the use of multi-institutional databases and randomized prospective trials is warranted in order to understand which child warrants thymectomy, at what point in their disease course and their development, and which surgical approach will optimize postoperative outcomes.

11.
PLoS One ; 19(6): e0304426, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38875222

RESUMO

Science education reform has been underway for almost a century with the general aim to engage students and train scientists needed to find solutions to global challenges, and also ensure a general public well disposed towards science. In an effort to aid science reform, more recently, colleges and universities have been augmenting their academic workforce by embedding education-focused science faculty into science departments. However, little research has investigated how this approach, and the identity of these faculty, may be changing over time. Here we investigate how conceptualizations of professional identities of these faculty across the United States have changed over the last two decades. We found three professional identities amongst these faculty: Science Faculty with Education Specialties (SFES), Discipline-Based Education Researchers (DBER), and faculty who identify as both SFES and DBER. Evidence indicates this is a maturing field within higher-education science departments, with more direct hiring and training pathways, but with potentially diminishing agency. Finally, data reveal resilience and perseverance despite negative biases from peers and college administrators, especially at PhD-granting institutions.


Assuntos
Docentes , Ciência , Estados Unidos , Docentes/psicologia , Humanos , Ciência/educação , Universidades , Feminino , Masculino
12.
bioRxiv ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38826196

RESUMO

Cryptococcus is a genus of saprophytic fungi with global distribution. Two species complexes, C. neoformans and C. gattii, pose health risks to humans and animals. Cryptococcal infections result from inhalation of aerosolized spores and/or desiccated yeasts from terrestrial reservoirs such as soil, trees, and avian guano. More recently, C. gattii has been implicated in infections in marine mammals, suggesting that inhalation of liquid droplets or aerosols from the air-water interface is also an important, yet understudied, mode of respiratory exposure. Water transport has also been suggested to play a role in the spread of C. gattii from tropical to temperate environments. However, the dynamics of fungal survival, persistence, and transport via water have not been fully studied. The size of the cryptococcal capsule was previously shown to reduce cell density and increase buoyancy. Here, we demonstrate that cell buoyancy is also impacted by the salinity of the media in which cells are suspended, with formation of a halocline interface significantly slowing the rate of settling of cryptococcal cells through water, resulting in persistence of C. neoformans within 1 cm of the air-water interface for over 60 min and C. gattii for 4-6 h. Our data also showed that during culture in yeast peptone dextrose media (YPD), polysaccharide accumulating in the supernatant formed a raft that augmented buoyancy and further slowed settling of cryptococcal cells. These findings illustrate new mechanisms by which cryptococcal cells may persist in aquatic environments, with important implications for aqueous transport and pathogen exposure.

13.
Fam Process ; 2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38852939

RESUMO

Research clearly demonstrates that conflictual interparental relationship dynamics can create a family context that contributes to child emotional insecurity and psychopathology. Significantly less research has examined familial factors that contribute to maladaptive conflict between parents. Scholars have alluded to the disruptive impacts of parenting a child with certain temperamental characteristics (e.g., negative emotionality). Yet, there is a lack of empirical research examining if and how child temperament contributes to later interparental conflict. Using an established multi-informant, multi-method sample of 150 families first assessed during pregnancy, and again when the child was 1, 2, and 3.5 years of age, the present study aimed to test an integrated conceptual model examining whether infants' negative emotionality assessed at age 1 predicts interparental conflict at age 3.5, as mediated through destructive coparenting dynamics in toddlerhood, and identifying prenatal protective factors mitigating this maladaptive pathway. Findings suggest that greater infant negative emotionality predicts worse interparental conflict management during preschool age by undermining the mother's (but not the father's) report of coparenting relationship quality during toddlerhood. However, these results were significant only to the extent that parents were lacking certain prenatal regulatory resources (i.e., low paternal self-compassion; less secure relationship between parents). Importantly, results point to the need for intervention and prevention efforts during pregnancy that might disrupt the deleterious impacts of parenting a child who is more reactive and prone to expressing negative emotions.

14.
bioRxiv ; 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38895476

RESUMO

If two haplotypes share the same alleles for an extended gene tract, these haplotypes are likely to derive identical-by-descent from a recent common ancestor. Identity-by-descent segment lengths are correlated via unobserved tree and recombination processes, which commonly presents challenges to the derivation of theoretical results in population genetics. Under interpretable regularity conditions, we show that the proportion of detectable identity-by-descent segments at a locus is normally distributed for large sample size and large scaled population size. We use efficient and exact simulations to study the distributional behavior of the detectable identity-by-descent rate in finite samples. One consequence of non-normality in finite samples is that genome-wide scans based on identity-by-descent rates may be subject to anti-conservative Type 1 error control. Highlights: We show the asymptotic normality of the identity-by-descent rate, a mean of correlated binary random variables that arises in population genetics studies.We describe an efficient algorithm capable of simulating long identity-by-descent segments around a locus in large sample sizes.In enormous simulation studies, we use this algorithm to characterize the distributional properties of the identity-by-descent rate.In finite samples, we reject the null hypothesis of normality more often than the nominal significance level, indicating that genome-wide scans based on identity-by-descent rates may be anti-conservative.

15.
Sci Rep ; 14(1): 14665, 2024 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918510

RESUMO

Delivery of therapeutic stem cells to treat bone tissue damage is a promising strategy that faces many hurdles to clinical translation. Among them is the design of a delivery vehicle which promotes desired cell behavior for new bone formation. In this work, we describe the use of an injectable microporous hydrogel, made of crosslinked gelatin microgels, for the encapsulation and delivery of human mesenchymal stem cells (MSCs) and compared it to a traditional nonporous injectable hydrogel. MSCs encapsulated in the microporous hydrogel showed rapid cell spreading with direct cell-cell connections whereas the MSCs in the nonporous hydrogel were entrapped by the surrounding polymer mesh and isolated from each other. On a per-cell basis, encapsulation in microporous hydrogel induced a 4 × increase in alkaline phosphatase (ALP) activity and calcium mineral deposition in comparison to nonporous hydrogel, as measured by ALP and calcium assays, which indicates more robust osteogenic differentiation. RNA-seq confirmed the upregulation of the genes and pathways that are associated with cell spreading and cell-cell connections, as well as the osteogenesis in the microporous hydrogel. These results demonstrate that microgel-based injectable hydrogels can be useful tools for therapeutic cell delivery for bone tissue repair.


Assuntos
Diferenciação Celular , Hidrogéis , Células-Tronco Mesenquimais , Osteogênese , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Humanos , Hidrogéis/química , Porosidade , Fosfatase Alcalina/metabolismo , Células Cultivadas , Encapsulamento de Células/métodos , Transplante de Células-Tronco Mesenquimais/métodos , Injeções
16.
J Proteome Res ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38836855

RESUMO

Sleep is regulated via circadian mechanisms, but effects of sleep disruption on physiological rhythms, in particular metabolic cycling, remain unclear. To examine this question, we probed diurnal metabolic alterations of two Drosophila short sleep mutants, fumin and sleepless. Samples were collected with high temporal sampling (every 2 h) over 24 h under a 12:12 light:dark cycle, and profiling was done using an ion-switching LCMS/MS method. Fewer metabolites with 24 h oscillations were noted with short sleep (50 and 46 in fumin and sleepless, BH. Q < 0.2 by RAIN analysis) compared to a wild-type control (iso31, 63 with BH. Q < 0.2), and peak phases of the sleep mutants were consolidated into two major phase peaks at mid-day and middle of night. Overall, altered nicotinate/nicotinamide, alanine/aspartate/glutamate, acetylcholine, glyoxylate/dicarboxylate, and TCA cycle metabolism were observed in the short sleep mutants, indicative of increased energetic demand and oxidative stress compared to wild type. Both changes in cycling and discriminant models suggest unique alterations in the dark period indicative of constrained metabolic networks. Thus, we conclude that sleep loss alters metabolic function uniquely throughout the day, and further examination of specific mechanisms is warranted.

18.
J Physiol ; 602(12): 2917-2930, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38758592

RESUMO

Fluid intelligence (Gf) involves rational thinking skills and requires the integration of information from different cortical regions to resolve novel complex problems. The effects of non-invasive brain stimulation on Gf have been studied in attempts to improve Gf, but such studies are rare and the few existing have reached conflicting conclusions. The parieto-frontal integration theory of intelligence (P-FIT) postulates that the parietal and frontal lobes play a critical role in Gf. To investigate the suggested role of parietal cortices, we applied high-definition transcranial direct current stimulation (HD-tDCS) to the left and right parietal cortices of 39 healthy adults (age 19-33 years) for 20 min in three separate sessions (left active, right active and sham). After completing the stimulation session, the participants completed a logical reasoning task based on Raven's Progressive Matrices during magnetoencephalography. Significant neural responses at the sensor level across all stimulation conditions were imaged using a beamformer. Whole-brain, spectrally constrained functional connectivity was then computed to examine the network-level activity. Behaviourally, we found that participants were significantly more accurate following left compared to right parietal stimulation. Regarding neural findings, we found significant HD-tDCS montage-related effects in brain networks thought to be critical for P-FIT, including parieto-occipital, fronto-occipital, fronto-parietal and occipito-cerebellar connectivity during task performance. In conclusion, our findings showed that left parietal stimulation improved abstract reasoning abilities relative to right parietal stimulation and support both P-FIT and the neural efficiency hypothesis. KEY POINTS: Abstract reasoning is a critical component of fluid intelligence and is known to be served by multispectral oscillatory activity in the fronto-parietal cortices. Recent studies have aimed to improve abstract reasoning abilities and fluid intelligence overall through behavioural training, but the results have been mixed. High-definition transcranial direct-current stimulation (HD-tDCS) applied to the parietal cortices modulated task performance and neural oscillations during abstract reasoning. Left parietal stimulation resulted in increased accuracy and decreased functional connectivity between occipital regions and frontal, parietal, and cerebellar regions. Future studies should investigate whether HD-tDCS alters abstract reasoning abilities in those who exhibit declines in performance, such as healthy ageing populations.


Assuntos
Inteligência , Lobo Parietal , Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Adulto , Lobo Parietal/fisiologia , Masculino , Feminino , Inteligência/fisiologia , Adulto Jovem , Rede Nervosa/fisiologia , Magnetoencefalografia/métodos
19.
Methods Mol Biol ; 2775: 239-255, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38758322

RESUMO

One of the standard assays for the fungal pathogen Cryptococcus neoformans is the glucuronoxylomannan (GXM) ELISA. This assay utilizes monoclonal antibodies targeted against the critical virulence factor, the polysaccharide (PS) capsule. GXM ELISA is one of the most used assays in the field used for diagnosis of cryptococcal infection, quantification of PS content, and determination of binding specificity for antibodies. Here we present three variations of the GXM ELISA used by our group-indirect, capture, and competition ELISAs. We have also provided some history, perspective, and notes on these methods, which we hope will help the reader choose, and implement, the best assay for their research.While it has long been referred to as the GXM ELISA, we also suggest a name update to better reflect our updated understanding of the polysaccharide antigens targeted by this assay. The Cryptococcal PS ELISA is a more accurate description of this set of methodologies and the antigens they measure. Finally, we discuss the limitations of this assay and put forth future plans for expanding the antigens assayed by ELISA.


Assuntos
Criptococose , Cryptococcus neoformans , Ensaio de Imunoadsorção Enzimática , Polissacarídeos , Ensaio de Imunoadsorção Enzimática/métodos , Cryptococcus neoformans/imunologia , Criptococose/diagnóstico , Criptococose/microbiologia , Criptococose/imunologia , Polissacarídeos/análise , Polissacarídeos/imunologia , Humanos , Antígenos de Fungos/imunologia , Antígenos de Fungos/análise , Polissacarídeos Fúngicos/imunologia , Polissacarídeos Fúngicos/análise , Anticorpos Monoclonais/imunologia , Anticorpos Antifúngicos/imunologia
20.
Clin Shoulder Elb ; 27(2): 141-148, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38738328

RESUMO

BACKGROUND: Radial head arthroplasty allows a high degree of customizability, and implant polarity has emerged as an important variable. The purpose of this meta-analysis was to evaluate differences in functional and clinical outcomes between patients receiving monopolar and bipolar radial head prosthetic implants. METHODS: A systematic review and meta-analysis were employed, and 65 articles were identified in three databases. Twelve articles contained non-English or insufficient text and were consequently excluded, and 20 others did not contain sufficient data or follow-up. The remaining 33 articles were qualitatively and quantitatively reviewed. RESULTS: In total, 33 populations were identified, with 809 unduplicated patients: 565 with monopolar and 244 with bipolar implants. In these respective patients, the mean follow-up was 40.2 and 56.9 months. Average Mayo Elbow Performance Score were 86.7 and 87.4 (P=0.80), respectively; average Disability of the Arm, Shoulder, and Hand scores were 17.9 and 14.7 (P=0.47), and average final flexion/extension arcs were 119.4° and 118.7° (P=0.48). Revision rates were 4.07% and 6.56%, while complication rates were 19.65% and 20.08% in the respective monopolar and bipolar patients. These increased relative risks associated with bipolar implants were not significant. CONCLUSIONS: Radial head implant polarity does not appear to affect functional outcomes. While bipolar prosthetic design may increase the risks of revision and complications, the increases were not significant. Level of evidence: IV.

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