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The superconformal index of half-BPS states in N=4 supersymmetric Yang-Mills with gauge group U(N) admits an expansion in terms of giant gravitons, I_{N}(q)=I_{∞}(q)∑_{m=0}^{∞}q^{mN}I[over ^]_{m}(q), where m is the number of giant gravitons and I_{∞}(q) is the graviton index. The expansion can be viewed as the implementation of trace relations for finite N. We derive this expansion directly in supergravity from the class of half-BPS solutions due to Lin, Lunin, and Maldacena in type IIB supergravity. The moduli space of these configurations can be quantized using covariant quantization methods. We show how this quantization leads to the precise expression for the expansion in terms of giant gravitons. Our proposal provides a derivation of the giant graviton expansion directly in terms of quantized supergravity degrees of freedom, and it recovers discrete data via quantum geometries that are classically nonsmooth.
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Increasingly long and complex informed consents have yielded studies demonstrating comparatively low participant comprehension and satisfaction with traditional face-to-face approaches. In parallel, interest in electronic consents for clinical and research genomics has steadily increased, yet limited data are available for trio-based genomic discovery studies. We describe the design, development, implementation, and validation of an electronic iConsent application for trio-based genomic research deployed to support genomic studies of cerebral palsy. iConsent development incorporated stakeholder perspectives including researchers, patient advocates, institutional review board members, and genomic data-sharing considerations. The iConsent platform integrated principles derived from prior electronic consenting research and elements of multimedia learning theory. Participant comprehension was assessed in an interactive teachback format. The iConsent application achieved nine of ten proposed desiderata for effective patient-focused electronic consenting for genomic research. Overall, participants demonstrated high comprehension and retention of key human subjects' considerations. Enrollees reported high levels of satisfaction with the iConsent, and we found that participant comprehension, iConsent clarity, privacy protections, and study goal explanations were associated with overall satisfaction. Although opportunities exist to optimize iConsent, we show that such an approach is feasible, can satisfy multiple stakeholder requirements, and can realize high participant satisfaction and comprehension while increasing study reach.
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BACKGROUND: During the COVID-19 pandemic, novel nanoparticle-based mRNA vaccines were developed. A small number of individuals developed allergic reactions to these vaccines although the mechanisms remain undefined. METHODS: To understand COVID-19 vaccine-mediated allergic reactions, we enrolled 19 participants who developed allergic events within 2 h of vaccination and 13 controls, nonreactors. Using standard hemolysis assays, we demonstrated that sera from allergic participants induced stronger complement activation compared to nonallergic subjects following ex vivo vaccine exposure. RESULTS: Vaccine-mediated complement activation correlated with anti-polyethelyne glycol (PEG) IgG (but not IgM) levels while anti-PEG IgE was undetectable in all subjects. Depletion of total IgG suppressed complement activation in select individuals. To investigate the effects of vaccine excipients on basophil function, we employed a validated indirect basophil activation test that stratified the allergic populations into high and low responders. Complement C3a and C5a receptor blockade in this system suppressed basophil response, providing strong evidence for complement involvement in vaccine-mediated basophil activation. Single-cell multiome analysis revealed differential expression of genes encoding the cytokine response and Toll-like receptor (TLR) pathways within the monocyte compartment. Differential chromatin accessibility for IL-13 and IL-1B genes was found in allergic and nonallergic participants, suggesting that in vivo, epigenetic modulation of mononuclear phagocyte immunophenotypes determines their subsequent functional responsiveness, contributing to the overall physiologic manifestation of vaccine reactions. CONCLUSION: These findings provide insights into the mechanisms underlying allergic reactions to COVID-19 mRNA vaccines, which may be used for future vaccine strategies in individuals with prior history of allergies or reactions and reduce vaccine hesitancy.
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BACKGROUND AND OBJECTIVES: Giant pituitary adenomas (GPAs) are a challenging clinical entity, composing 5% to 15% of all pituitary adenomas. While the endoscopic endonasal transsphenoidal (EET) approach has surpassed the microsurgical transsphenoidal (MT) and transcranial (TC) approaches as the first-line surgical modality in most institutions, a systematic review comparing the 3 approaches has not been undertaken since 2012. Given growing adoption of EET and development of novel operative techniques over the past decade, an updated comparison of GPA surgical modalities is warranted. METHODS: We identified all studies related to the surgical management of GPAs in PubMed, Embase, and Web of Science from inception to December 31, 2021. End points assessed included gross total resection (GTR) rates, postoperative visual improvement, mortality, and perioperative complications. RESULTS: After screening of 1701 studies, we identified 45 studies on the surgical management of GPAs for meta-analysis. Thirty-one used the EET approach (n = 1413), 11 studies used the MT approach (n = 601), and 10 used the TC approach (n = 416). The cumulative number of patients treated by EET did not exceed that of patients treated by the TC or MT approaches until 2014 and 2015, respectively. Despite patients undergoing EET having the highest average tumor diameter, pooled rates for GTR were significantly higher for EET (42%) than MT (33%, P < .001) and TC (8%, P < .001) and EET similarly exhibited superior rates of visual improvement (85%) than MT (73%, P < .001) and TC (56%, P < .001). Mortality rates were comparable between EET (0.6%) and MT (1.6%), but EET had significantly lower mortality than TC (2.7%, P < .001). Compared with MT, EET had lower rates of hypopituitarism (8.5% vs 14.9%, P = .012) but higher rates of diabetes insipidus (3.1% vs 0.5%, P = .001). CONCLUSION: In an updated meta-analysis of 1413 patients with GPA, EET resection conferred significantly higher rates of visual improvement and GTR, when compared with the MT and TC approaches.
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The objective of this case report is to describe and document a case of respiratory syncytial virus (RSV) in a pediatric patient with Dravet syndrome (DS), also known as severe myoclonic epilepsy of infancy. Febrile seizures are often a complication in a patient with DS and can lead to status epilepticus, necessitating measures to prevent triggers such as fever, electrolyte imbalance, or dehydration. An increased awareness and understanding of DS can facilitate the identification of warning signs. A two-year-old female with a past medical history of DS with focal and generalized features presented to the pediatric emergency department (ED) with a five-day history of cough, fever, and decreased oral intake. The patient's parents accompanied her and expressed concerns regarding the risk of seizures associated with a rise in body temperature, as they had been alternating between acetaminophen and ibuprofen to manage her fever with a maximum recorded temperature of 101.5â. She exhibited signs of increased work of breathing, necessitating the administration of supplemental oxygen via nasal cannula. Blood samples were obtained and resulted in the development of metabolic acidosis. A respiratory panel confirmed the presence of an RSV infection, promoting the administration of breathing treatment with albuterol and ipratropium bromide. The patient was admitted for dehydration and was started on ½ normal saline/potassium chloride 20 mEq at 40 mL/hr. Additionally, her home medication regimen was resumed to minimize the risk of seizures. Given the patient's complications and increased risk of seizure, she was transferred to higher-level care where her status improved after the placement of a percutaneous endoscopic gastrostomy (PEG). This case underscores the complexities involved in managing patients with DS, particularly when complicated by respiratory illness and electrolyte imbalances that can lower the seizure threshold. This patient received a combination of diet and medications to prevent seizures, as well as allow for recovery and correction of the underlying metabolic acidosis. The transfer to a higher level of care in this case was necessary to allow for the specialized resources and expertise needed to handle this case.
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Dry hitting, a phenomenon produced by e-cigarettes with refillable cartridges when the liquid in the coil is low, is a common occurrence among regular vapers despite being an unintended consequence of the device. This phenomenon's hazard to public health is still unknown and needs further investigation. Lung cells cultured at the air-liquid interface were exposed to vaped aerosol consisting of 3â¯% w/v ethyl maltol in propylene glycol for three-second puffs every 30â¯seconds for 80 total puffs with either dry hit or saturated conditions. Cytotoxicity was measured colorimetrically. The thermal degradation of the heating coils and wicks was visualized using scanning electron microscopy. The chemical byproducts in the aerosol were analyzed using proton nuclear magnetic resonance and inductively coupled plasma mass spectrometry. The results revealed a highly significant increase in cytotoxicity from dry hit treatments. Imaging showed thermal decomposition of the cotton wick after dry hitting, which was confirmed by energy dispersive x-ray spectroscopy with less oxygen in the dry hit cotton. Chemical byproducts were found via unique peaks in the dry hit condensate in the aromatic and alkene regions. Saturated condensate showed higher concentrations of detected metal species than dry-hit condensate. E-cigarette users should avoid dry hitting by refilling tanks or cartridges preemptively or by using disposable coils to avoid increased toxicity during vaping.
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Aerossóis , Sobrevivência Celular , Sistemas Eletrônicos de Liberação de Nicotina , Humanos , Sobrevivência Celular/efeitos dos fármacos , Vaping/efeitos adversos , Pulmão/efeitos dos fármacosRESUMO
BACKGROUND AND IMPORTANCE: Surgery of jugular foramen tumors (JFTs) often requires vascular control by means of ligating the internal jugular vein and sigmoid sinus (SS) to allow intrabulbar access. Occlusion of the SS traditionally involves presigmoid and retrosigmoid durotomies allowing introduction of ligature devices, predisposing to cerebrospinal fluid (CSF) leakage and pseudomeningoceles. We describe a simple and novel endoluminal sigmoid sinus occlusion (ESSO) technique with Gelfoam that is entirely extradural. CLINICAL PRESENTATION: An extended anterolateral infralabyrinthine approach with ESSO was performed in 33 patients with JFTs. After ligating the internal jugular vein, the SS is opened and Gelfoam is placed endoluminally into the proximal SS. Care is taken to avoid occlusion of the venous outflow of the vein of Labbe to avoid temporal lobe venous infarction. Hemostatic gelatin matrix is injected distally to stop venous backflow from the inferior petrosal sinus. The jugular venous system is isolated, and the outer jugular wall can be opened to expose the JFT for resection. There were no complications of temporal lobe venous infarction or postoperative hematoma observed. Four patients with intradural tumor extension developed pseudomeningoceles. For patients with purely extradural JFTs, none developed postoperative incisional CSF leaks and one had pseudomeningocele. CONCLUSION: This ESSO technique is fast and effective, permitting occlusion of the SS during JFT surgery. It has the advantage of being entirely extradural, avoiding durotomy which can result in postoperative CSF leak. It is important to keep the Gelfoam distal to the transverse-sigmoid junction to avoid occlusion of the vein of Labbe inlet and temporal lobe venous infarction.
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Purpose: To describe a case of intraocular lens (IOL) tilt following transscleral IOL fixation with the Yamane technique and subsequent correction of tilt using 810-nm endoscopic diode laser. Observations: Our patient required lens exchange and secondary IOL implantation due to a dislocated 1-piece IOL in the bag causing iris chafe. After routine IOL fixation with the Yamane technique and a Zeiss CT Lucia 602 lens, the IOL tilted significantly in the immediate postoperative period. The lens tilt was subsequently corrected in the operating room using endolaser to melt and reshape (cure) the optic-haptic junction. Conclusions: IOL tilt is a known complication associated with the Yamane technique, which has seen increasing reports with the Zeiss CT Lucia 602 lens. Using endolaser to reconfigure the tilted optic into the desired orientation is a more novel procedure that can correct the lens tilt without the need for IOL exchange.
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OBJECTIVE: Evaluation of the demographic and academic characteristics of current neurosurgery residents may provide prospective students with insight into factors that affect research output. Therefore, this study aimed to evaluate the research output among neurosurgery residents. METHODS: US neurosurgery residency programs were abstracted from the American Association of Neurological Surgeons website. Demographic data on 1690 current residents across 119 programs were collected using publicly available institutional websites, Doximity, and LinkedIn. The h-index of each resident was recorded using Scopus and exported into the NIH iCite tool to determine the weighted relative citation ratio (w-RCR) and mean relative citation ratio (m-RCR). The total number of publications, h-index, and w-RCR were used as a proxy for research output, while m-RCR was used to measure research impact. One-way ANOVA and Kruskal-Wallis H-tests were used to assess the statistical significance of relationships between demographic data and measures of research activity. RESULTS: A total of 1690 residents (25.4% female), representing 119 programs, were evaluated. Neurosurgery residents had an average of 17 publications, h-index of 5.5, m-RCR of 1.4, and w-RCR of 16.9, with an upward trend of research activity by postgraduate year (PGY) class. Male residents on average had a greater total number of publications (p < 0.001), higher h-index (p < 0.001), and higher w-RCR (p = 0.002) compared with their female peers. Significant differences in research activity were also observed by degree (Doctor of Medicine [MD], Doctor of Osteopathy [DO], or other), where those with MD and other degrees had higher metrics than those with DO degrees. International medical graduates (IMGs) also had higher research output than American medical graduates (AMGs) (p < 0.001). Differences in all measures of research activity except impact were also observed in research activity when pre-residency medical school ranks were compared. CONCLUSIONS: The authors observed overall high research activity among neurosurgery residents. Factors such as gender, degree, PGY, IMG/AMG status, and medical school rank may therefore be related to the success of matching within neurological surgery. Although large disparities in gender representation have been identified in neurosurgery, newer classes are trending toward shrinking the gap. These data may be used by prospective residents to gauge changes and progress occurring in the neurosurgery match.
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Biallelic pathogenic variants in the PNPLA6 gene cause a broad spectrum of disorders leading to gait disturbance, visual impairment, anterior hypopituitarism and hair anomalies. PNPLA6 encodes neuropathy target esterase (NTE), yet the role of NTE dysfunction on affected tissues in the large spectrum of associated disease remains unclear. We present a systematic evidence-based review of a novel cohort of 23 new patients along with 95 reported individuals with PNPLA6 variants that implicate missense variants as a driver of disease pathogenesis. Measuring esterase activity of 46 disease-associated and 20 common variants observed across PNPLA6-associated clinical diagnoses unambiguously reclassified 36 variants as pathogenic and 10 variants as likely pathogenic, establishing a robust functional assay for classifying PNPLA6 variants of unknown significance. Estimating the overall NTE activity of affected individuals revealed a striking inverse relationship between NTE activity and the presence of retinopathy and endocrinopathy. This phenomenon was recaptured in vivo in an allelic mouse series, where a similar NTE threshold for retinopathy exists. Thus, PNPLA6 disorders, previously considered allelic, are a continuous spectrum of pleiotropic phenotypes defined by an NTE genotype:activity:phenotype relationship. This relationship, and the generation of a preclinical animal model, pave the way for therapeutic trials, using NTE as a biomarker.
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Fenótipo , Animais , Feminino , Humanos , Masculino , Camundongos , Aciltransferases , Hidrolases de Éster Carboxílico/genética , Mutação de Sentido Incorreto , Fosfolipases/genética , Doenças Retinianas/genéticaRESUMO
Surface-functionalized cellulose materials are developed for various purposes, including food additives and food contact materials. A new biologically relevant testing strategy has been developed based on guidance from the European Food Safety Authority to demonstrate the safety of several next-generation surface-functionalized cellulose materials. This strategy involves a complex three-stage simulated digestion to compare the health effects of thirteen novel different types of cellulose. The physical and chemical properties of surface-functionalized fibrillated celluloses differed depending on the type, amount, and location of functional groups such as sulfonate, TEMPO-oxidized carboxy, and periodate-chlorite oxidized dicarboxylic acid celluloses. Despite exposure to gastrointestinal fluids, the celluloses maintained their physicochemical properties, such as negative surface charges and high length-to-width/thickness aspect ratios. An established intestinal co-culture model was used to measure cytotoxicity, barrier integrity, oxidative stress, and pro-inflammatory response to create a toxicological profile for these unique materials. We conclude that the C6 carboxylated cellulose nanofibrils by TEMPO-oxidation induced the most toxicity in the biological model used in this study and that the observed effects were most prominent at the 4-hour post-exposure time point.
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Celulose , Digestão , Celulose/química , Humanos , Propriedades de Superfície , Trato Gastrointestinal/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Modelos Biológicos , Células CACO-2 , Nanofibras/químicaRESUMO
Immunosuppressive macrophages restrict anti-cancer immunity in glioblastoma (GBM). Here, we studied the contribution of microglia (MGs) and monocyte-derived macrophages (MDMs) to immunosuppression and mechanisms underlying their regulatory function. MDMs outnumbered MGs at late tumor stages and suppressed T cell activity. Molecular and functional analysis identified a population of glycolytic MDM expressing GLUT1 with potent immunosuppressive activity. GBM-derived factors promoted high glycolysis, lactate, and interleukin-10 (IL-10) production in MDMs. Inhibition of glycolysis or lactate production in MDMs impaired IL-10 expression and T cell suppression. Mechanistically, intracellular lactate-driven histone lactylation promoted IL-10 expression, which was required to suppress T cell activity. GLUT1 expression on MDMs was induced downstream of tumor-derived factors that activated the PERK-ATF4 axis. PERK deletion in MDM abrogated histone lactylation, led to the accumulation of intratumoral T cells and tumor growth delay, and, in combination with immunotherapy, blocked GBM progression. Thus, PERK-driven glucose metabolism promotes MDM immunosuppressive activity via histone lactylation.
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Glioblastoma , Glucose , Histonas , Macrófagos , Glioblastoma/imunologia , Glioblastoma/metabolismo , Glioblastoma/patologia , Animais , Histonas/metabolismo , Camundongos , Macrófagos/imunologia , Macrófagos/metabolismo , Glucose/metabolismo , Humanos , Linhagem Celular Tumoral , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Transportador de Glucose Tipo 1/metabolismo , Transportador de Glucose Tipo 1/genética , Interleucina-10/metabolismo , Glicólise , Microglia/metabolismo , Microglia/imunologia , Camundongos Endogâmicos C57BL , Linfócitos T/imunologia , Linfócitos T/metabolismo , Tolerância ImunológicaRESUMO
This case report describes necrotizing enterocolitis (NEC) in an infant with a history of twin-twin transfusion syndrome (TTTS). TTTS is a volume imbalance where the anastomosis at the vascular equator between the two placentae shifts from the donor to the recipient twin. This causes a higher risk for NEC, a marked inflammation caused by bacterial infection into the intestinal wall, from prematurity and intestinal hypoperfusion. Complications include sepsis, bowel necrosis, perforation, peritonitis, and death. NEC is a leading cause of morbidity in preterm infants. A 3-month-old female with a history of TTTS and prematurity presented with her mother to the pediatric emergency department (ED) for bloody diarrhea, emesis, lack of appetite, and lethargy for 4 days. The pediatrician changed the formula due to a possible milk allergy, however, she continued to have bloody diarrhea. Over the 2 days, the patient had nonbilious and non-bloody emesis and couldn't tolerate oral intake. In the ED, labs showed neutropenia and sepsis. She had a positive fecal occult blood test (FOBT) and an abdominal x-ray that revealed dilated loops of bowel and pneumatosis intestinalis. She was started on intravenous (IV) fluids for maintenance of hydration. She was started on broad-spectrum antibiotics including intravenous (IV) vancomycin and meropenem, and had her feedings temporarily stopped. The patient was transferred to the pediatric intensive care unit (PICU) at a tertiary care/children's hospital that evening where she had a laparotomy performed to resect the diseased intestine. She was discharged 10 days after the surgery for home recovery with clinical follow-up.
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Background: Glioblastoma exhibits aggressive growth and poor outcomes despite treatment, and its marked variability renders therapeutic design and prognostication challenging. The Oncology Research Information Exchange Network (ORIEN) database contains complementary clinical, genomic, and transcriptomic profiling of 206 glioblastoma patients, providing opportunities to identify novel associations between molecular features and clinical outcomes. Methods: Survival analyses were performed using the Logrank test, and clinical features were evaluated using Wilcoxon and chi-squared tests with q-values derived via Benjamini-Hochberg correction. Mutational analyses utilized sample-level enrichments from whole exome sequencing data, and statistical tests were performed using the one-sided Fisher Exact test with Benjamini-Hochberg correction. Transcriptomic analyses utilized a student's t-test with Benjamini-Hochberg correction. Expression fold changes were processed with Ingenuity Pathway Analysis to determine pathway-level alterations between groups. Results: Key findings include an association of MUC17, SYNE1, and TENM1 mutations with prolonged overall survival (OS); decreased OS associated with higher epithelial growth factor receptor (EGFR) mRNA expression, but not with EGFR amplification or mutation; a 14-transcript signature associated with OSâ >â 2 years; and 2 transcripts associated with OSâ <â 1 year. Conclusions: Herein, we report the first clinical, genomic, and transcriptomic analysis of ORIEN glioblastoma cases, incorporating sample reclassification under updated 2021 diagnostic criteria. These findings create multiple avenues for further investigation and reinforce the value of multi-institutional consortia such as ORIEN in deepening our knowledge of intractable diseases such as glioblastoma.
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Environmental contaminants are ubiquitous in the air we breathe and can potentially cause adverse immunological outcomes such as respiratory sensitization, a type of immune-driven allergic response in the lungs. Wood dust, latex, pet dander, oils, fragrances, paints, and glues have all been implicated as possible respiratory sensitizers. With the increased incidence of exposure to chemical mixtures and the rapid production of novel materials, it is paramount that testing regimes accounting for sensitization are incorporated into development cycles. However, no validated assay exists that is universally accepted to measure a substance's respiratory sensitizing potential. The lungs comprise various cell types and regions where sensitization can occur, with the gas-exchange interface being especially important due to implications for overall lung function. As such, an assay that can mimic the alveolar compartment and assess sensitization would be an important advance for inhalation toxicology. Some such models are under development, but in-depth transcriptomic analyses have yet to be reported. Understanding the transcriptome after sensitizer exposure would greatly advance hazard assessment and sustainability. We tested two known sensitizers (i.e., isophorone diisocyanate and ethylenediamine) and two known non-sensitizers (i.e., chlorobenzene and dimethylformamide). RNA sequencing was performed in our in vitro alveolar model, consisting of a 3D co-culture of epithelial, macrophage, and dendritic cells. Sensitizers were readily distinguishable from non-sensitizers by principal component analysis. However, few differentially regulated genes were common across all pair-wise comparisons (i.e., upregulation of genes SOX9, UACA, CCDC88A, FOSL1, KIF20B). While the model utilized in this study can differentiate the sensitizers from the non-sensitizers tested, further studies will be required to robustly identify critical pathways inducing respiratory sensitization.
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Perfilação da Expressão Gênica , Transcriptoma , Transcriptoma/genética , Pulmão , Alérgenos/toxicidadeRESUMO
OBJECTIVE: Ethmoidal dural arteriovenous fistulas (DAVFs) are often associated with cortical venous drainage (CVD) and a higher incidence of hemorrhage compared with DAVFs in other locations. They may be treated with open surgical disconnection or with endovascular treatment (EVT). In this systematic review and meta-analysis, the authors compare the outcomes of ethmoidal DAVFs treated with open microsurgery versus EVT and report four additional cases of ethmoidal DAVFs treated with open microsurgery in their institution. METHODS: A literature search of the PubMed and Scopus databases was conducted between December 2021 and May 2022 to identify relevant articles published between 1990 and 2021 using the PRISMA guidelines. References were reviewed and screened by two authors independently, and disagreements were resolved through consensus. Exclusion criteria included non-English-language studies, those with an incorrect study design, those reporting DAVFs in a nonethmoidal location, and studies whose outcomes were not stratified based on DAVF location. Inclusion criteria were any studies reporting on ethmoidal DAVFs treated by either microsurgery or EVT. A risk of bias assessment was performed using the Newcastle-Ottawa Scale. The authors performed a pooled proportional meta-analysis to compare patient outcomes. RESULTS: Twenty studies were included for analysis. Of 224 patients, 142 were treated with surgery, while 103 were treated with EVT. Seventy percent (148/210) of the patients were symptomatic at presentation, with hemorrhage being the most common presentation (48%). CVD was present in 98% of patients and venous ectasia in 61%. The rates of complete DAVF obliteration with surgery and EVT were 89% and 70%, respectively (95% CI -30% to -10%, p < 0.03). Twenty percent (21/103) of endovascularly treated fistulas required subsequent surgery. Procedure-related complications occurred in 10% of the surgical cases, compared with 13% of the EVT cases. The authors' case series included 4 patients with ethmoidal DAVFs treated surgically with complete obliteration, without any postoperative complications. CONCLUSIONS: The complete obliteration rates of ethmoidal DAVF appear to be higher and more definitive with microsurgical intervention than with EVT. While complication rates between the two procedures seem similar, patients treated with EVT may require further interventions for definitive treatment. The limitations of this study include its retrospective nature, the quality of studies included, and the continued evolving technologies of EVT. Future studies should focus on the association between venous drainage pattern and the proclivity toward venous ectasia or rate of hemorrhage at presentation.
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Malformações Vasculares do Sistema Nervoso Central , Embolização Terapêutica , Humanos , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Malformações Vasculares do Sistema Nervoso Central/cirurgia , Malformações Vasculares do Sistema Nervoso Central/complicações , Dilatação Patológica/complicações , Dilatação Patológica/terapia , Embolização Terapêutica/métodos , Hemorragia , Resultado do Tratamento , MicrocirurgiaRESUMO
As environmental air quality worsens and respiratory health injuries and diseases increase, it is essential to enhance our ability to develop better methods to identify potential hazards. One promising approach in emerging toxicology involves the utilization of lung surfactant as a model that addresses the limitations of conventional in vitro toxicology methods by incorporating the biophysical aspect of inhalation. This study employed a constrained drop surfactometer to assess 20 chemicals for potential surfactant inhibition. Of these, eight were identified as inhibiting lung surfactant function: 1-aminoethanol, bovine serum albumin, maleic anhydride, propylene glycol, sodium glycocholate, sodium taurocholate, sodium taurodeoxycholate, and Triton X-100. These results are consistent with previously reported chemical-induced acute lung dysfunction in vivo. The study provides information on each chemical's minimum and maximum surface tension conditions and corresponding relative area and contact angle values. Isotherms and box plots are reported for selected chemicals across doses, and vector plots are used to summarize and compare the results concisely. This lung surfactant bioassay is a promising non-animal model for hazard identification, with broader implications for developing predictive modeling and decision-making tools.
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Ensaios de Triagem em Larga Escala , Surfactantes Pulmonares , Ensaios de Triagem em Larga Escala/métodos , Tensão Superficial/efeitos dos fármacos , Animais , Benchmarking , Humanos , Relação Dose-Resposta a DrogaRESUMO
Spinal subdural haemorrhage or haematoma (SSDH) is a rare condition that is often overlooked and missed on initial presentation due to its non-specific features that may mimic other more common pathologies. It is associated with high morbidity and mortality rates, with few evidence-based management principles, particularly during the subacute stages of recovery. In this report, we detail a case of SSDH associated with exercise and anticoagulation therapy, which was complicated by acute ischaemic stroke. SSDH should be suspected in cases of acute back pain without a clear alternative cause, particularly in coagulopathic individuals. Following treatment, early recommencement of anticoagulation therapy may be justified in certain cases where indicated, after careful consideration of the affected individual's risk profile.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Varfarina/efeitos adversos , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Hemorragia , Hematoma Subdural , Anticoagulantes/efeitos adversosRESUMO
OBJECTIVE: The aim of this study was to examine the distribution of olfactory filaments (OFs) in the nasal mucosa to facilitate preservation of olfactory function in endonasal approaches and preparation of a nasoseptal flap. METHODS: One formalin-fixed and 9 fresh cadaveric silicone-injected specimens with 20 total sides were studied to measure the distance of the OFs to the anatomical landmarks and compare the OF presence in the nasal septum mucosa (NSM) and ethmoidal mucosa (EM). RESULTS: The mean distance from the first to the last OF was 19.37 ± 2.16 mm in the NSM and 23.44 ± 5.42 mm in the EM. The NSM had a mean of 7.55 ± 1.31 OFs and the EM had 14.3 ± 1.78. Average OF lengths were measured at 6.44 ± 1.48 (range 3.75-12.40) mm in the NSM and 8.05 ± 1.76 (range 4.14-13.20) mm in the EM. The mean values of the EM measurements were compared with those of the NSM; the number of OFs, the distance between the first and last OF, the average OF length, and the number of OFs between anterior and posterior ethmoidal arteries in the NSM were significantly less (p < 0.05) than those in the EM. The distance between the first OF to the nasal bone on the NSM was greater than on the EM. CONCLUSIONS: Compared with the EM, the OFs are significantly fewer in number and smaller in size in the NSM. The uppermost edge of the nasoseptal flap incision in the NSM might be safer to start below 12 mm from the cribriform plate for OF protection.