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A 78-year-old man presented with acute-onset left temporal pain, eyelid swelling, and double vision. Computed tomography (CT) demonstrated a left sphenoid wing mass with extra-osseous intra-orbital and intracranial extension, thought to be a typical sphenoid wing meningioma by the primary team. The patient was admitted for an urgent craniotomy, which was planned for the following day. However, upon consultation with ophthalmic plastic surgery, concern was raised for an alternative diagnosis given the atypical timeline, inflammatory changes, and uncharacteristic imaging findings of mixed lytic and sclerotic bony changes without hyperostosis on CT and extensive peri-lesional dural thickening and enhancement on magnetic resonance imaging. A serum prostate-specific antigen was elevated to 206 ng/mL. Subsequent positron emission tomography (PET)/CT using 18F-fluorodeoxyglucose radiotracer was negative for metastatic disease. A prostate-specific membrane antigen (PSMA) PET/CT was then obtained and demonstrated extensive metastases. An orbital biopsy revealed poorly differentiated prostatic adenocarcinoma. The significant incongruence between the standard PET/CT and PSMA PET/CT highlights the value of this novel advanced radiographic modality in narrowing the differential diagnosis and determining the extent of disease. Findings of widespread metastasis on the PSMA PET/CT ultimately helped to avoid a large, morbid neurosurgical intervention in this patient, allowing for a minimally invasive orbital biopsy to characterize the tumor for therapeutic targeting.
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Yeast vacuoles are acidified by the v-type H+-ATPase (V-ATPase) that is comprised of the membrane embedded VO complex and the soluble cytoplasmic V1 complex. The assembly of the V1-VO holoenzyme on the vacuole is stabilized in part through interactions between the VO a-subunit ortholog Vph1 and the lipid phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2). PI(3,5)P2 also affects vacuolar Ca2+ release through the channel Yvc1 and uptake through the Ca2+ pump Pmc1. Here, we asked if H+ and Ca2+ transport activities were connected through PI(3,5)P2. We found that overproduction of PI(3,5)P2 by the hyperactive fab1T2250A mutant augmented vacuole acidification, whereas the kinase-inactive fab1EEE mutant attenuated the formation of a H+ gradient. Separately, we tested the effects of excess Ca2+ on vacuole acidification. Adding micromolar Ca2+ blocked vacuole acidification, whereas chelating Ca2+ accelerated acidification. The effect of adding Ca2+ on acidification was eliminated when the Ca2+/H+ antiporter Vcx1 was absent, indicating that the vacuolar H+ gradient can collapse during Ca2+ stress through Vcx1 activity. This, however, was independent of PI(3,5)P2, suggesting that PI(3,5)P2 plays a role in submicromolar Ca2+ flux but not under Ca2+ shock. To see if the link between Ca2+ and H+ transport was bidirectional, we examined Ca2+ transport when vacuole acidification was inhibited. We found that Ca2+ transport was inhibited by halting V-ATPase activity with Bafilomycin or neutralizing vacuolar pH with chloroquine. Together, these data show that Ca2+ transport and V-ATPase efficacy are connected but not necessarily through PI(3,5)P2.
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Proteínas de Saccharomyces cerevisiae , ATPasas de Translocación de Protón Vacuolares , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Fosfatidilinositoles , Vacuolas/metabolismo , ATPasas de Translocación de Protón Vacuolares/genética , ATPasas de Translocación de Protón Vacuolares/metabolismo , ATPasas Transportadoras de Calcio de la Membrana Plasmática , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismoRESUMEN
BACKGROUND: Validated methods to identify neuro-ophthalmologists in administrative data do not exist. The development of such method will facilitate research on the quality of neuro-ophthalmic care and health care utilization for patients with neuro-ophthalmic conditions in the United States. METHODS: Using nationally representative, 20% sample from Medicare carrier files from 2018, we identified all neurologists and ophthalmologists billing at least 1 office-based evaluation and management (E/M) outpatient visit claim in 2018. To isolate neuro-ophthalmologists, the National Provider Identifier numbers of neuro-ophthalmologists in the North American Neuro-Ophthalmology Society (NANOS) directory were collected and linked to Medicare files. The proportion of E/M visits with International Classification of Diseases-10 diagnosis codes that best distinguished neuro-ophthalmic care ("neuro-ophthalmology-specific codes" or NSC) was calculated for each physician. Multiple logistic regression models assessed predictors of neuro-ophthalmology specialty designation after accounting for proportion of ophthalmology, neurology, and NSC claims and primary specialty designation. Sensitivity, specificity, and positive predictive value (PPV) for varying proportions of E/M visits with NSC were calculated. RESULTS: We identified 32,293 neurologists and ophthalmologists who billed at least 1 outpatient E/M visit claim in 2018 in Medicare. Of the 472 NANOS members with a valid individual National Provider Identifier, 399 (84.5%) had a Medicare outpatient E/M visit in 2018. The model containing only the proportion of E/M visits with NSC best predicted neuro-ophthalmology specialty designation (odds ratio 1.05 [95% confidence interval 1.04, 1.05]; P < 0.001; area under the receiver operating characteristic [AUROC] = 0.91). Model predictiveness for neuro-ophthalmology designation was maximized when 6% of all billed claims were for NSC (AUROC = 0.89; sensitivity: 84.0%; specificity: 93.9%), but PPV was low (14.9%). The threshold was unchanged when limited only to neurologists billing ≥1% ophthalmology claims or ophthalmologists billing ≥1% neurology claims, but PPV increased (33.3%). CONCLUSIONS: Our study provides a validated method to identify neuro-ophthalmologists who can be further adapted for use in other administrative databases to facilitate future research of neuro-ophthalmic care delivery in the United States.
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Neurología , Oftalmólogos , Oftalmología , Anciano , Humanos , Estados Unidos , Medicare , Atención a la SaludRESUMEN
BACKGROUND: Neuro-ophthalmologists have expertise in rare and complex disorders, but the ability of patients to access neuro-ophthalmic care has not been examined at a nationwide level. METHODS: Using the 2020 directory of all 502 members of the North American Neuro-Ophthalmology Society as a reference, we found the practice locations of 461 confirmed practicing members and converted each street address to latitude and longitude coordinates. We calculated the travel distance and time from each census tract to the nearest practice location and calculated population-weighted averages by state, region, and other prespecified factors. Choropleth maps were used to visualize the distribution of travel distances and times across the United States. RESULTS: California had the most practicing neuro-ophthalmologists out of any state (50), whereas 4 states (DE, MT, SD, and WY) had none. Washington, DC and MA had the most neuro-ophthalmologists per capita. The average travel distance and time to the nearest neuro-ophthalmologists were found to be 40.90 miles and 46.50 minutes, respectively, although a large portion of western plains and mountain regions had travel times of over 120 minutes. Patients in rural areas had longer travel times than those in urban areas, and Native American patients had the longest travel times of any racial or ethnic group. CONCLUSION: The travel time to see a neuro-ophthalmologist varies widely by state, region, and rurality, with Native American patients and rural patients being disproportionately affected. By identifying the areas with the greatest travel burdens, future policies can work to alleviate these potential barriers to care.
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Oftalmólogos , Estados Unidos/epidemiología , Humanos , Accesibilidad a los Servicios de Salud , Viaje , Factores de Tiempo , Población RuralRESUMEN
Eukaryotic cells are compartmentalized into membrane-bound organelles, allowing each organelle to maintain the specialized conditions needed for their specific functions. One of the features that change between organelles is lumenal pH. In the endocytic and secretory pathways, lumenal pH is controlled by isoforms and concentration of the vacuolar-type H+-ATPase (V-ATPase). In the endolysosomal pathway, copies of complete V-ATPase complexes accumulate as membranes mature from early endosomes to late endosomes and lysosomes. Thus, each compartment becomes more acidic as maturation proceeds. Lysosome acidification is essential for the breakdown of macromolecules delivered from endosomes as well as cargo from different autophagic pathways, and dysregulation of this process is linked to various diseases. Thus, it is important to understand the regulation of the V-ATPase. Here we describe a high-throughput method for screening inhibitors/activators of V-ATPase activity using Acridine Orange (AO) as a fluorescent reporter for acidified yeast vacuolar lysosomes. Through this method, the acidification of purified vacuoles can be measured in real-time in half-volume 96-well plates or a larger 384-well format. This not only reduces the cost of expensive low abundance reagents, but it drastically reduces the time needed to measure individual conditions in large volume cuvettes.
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Naranja de Acridina , ATPasas de Translocación de Protón Vacuolares , Vacuolas , Endosomas/metabolismo , Saccharomyces cerevisiae/metabolismo , Lisosomas/metabolismo , Concentración de Iones de HidrógenoRESUMEN
BACKGROUND: Appropriate evaluation of diplopia requires separating serious from benign causes. If providers are not adept in this task, diagnosis of critical conditions may be delayed and unnecessary testing may result. METHODS: We studied the records of 100 consecutive patients who presented to an emergency department between 2010 and 2020 with diplopia as a prominent symptom. We rated the performance of emergency medicine physicians (EMPs) and consulting neurologists (CNs) in the examination, diagnosis, and ordering of diagnostic tests according to standards based on neuro-ophthalmologic consultation and the neuro-ophthalmologic literature. RESULTS: EMPs made no diagnosis or an incorrect diagnosis in 88 (88%) of 100 encounters. They ordered 14 unindicated and 12 incorrect studies, mostly noncontrast computed tomography scans. CNs made an incorrect diagnosis in 13 (31%) encounters. They ordered 6 unindicated and 2 incorrect studies. The total charge for unindicated and incorrect studies ordered by EMPs and CNs was $119,950. CONCLUSIONS: EMPs and CNs made frequent errors in the examination, diagnosis, and ordering of diagnostic studies, leading to inefficient care and unnecessary testing. EMPs largely delegated the evaluation of diplopia to their consultants. If such consultative support were not available, the care of diplopic patients would be delayed. CNs performed more complete examinations, but rarely enough to allow appreciation of the pattern of ocular misalignment, contributing to misdiagnoses and ordering errors. The identification of these provider errors allows for more targeted teaching in the evaluation of diplopia.
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Medicina de Emergencia , Médicos , Diplopía/diagnóstico , Diplopía/etiología , Humanos , Neurólogos , Derivación y ConsultaRESUMEN
PURPOSE: Evidence suggests that fruit and vegetable consumptions may improve mental health among general population. However, their associations among breast cancer survivors are unclear. We planned to investigate this association via a nationwide survey in the USA. METHODS: We identified 7988 breast cancer survivors from 2009 Behavioral Risk Factor Surveillance System (BRFSS). Fruit juice, fruit, and vegetable consumptions were categorized as ordinal variables to approximate tertiles. Survivors who were mentally unhealthy for at least 14 days in the past 30 days were defined as having frequent mental distress (FMD). Multivariable logistic regression treating FMD as the outcome was used to calculate adjusted odd ratios (aORs) and 95% confidence intervals (CIs) for exposures. Quadratic model was used to depict the dose-response pattern in primary analysis. Subgroup analyses by adverse lifestyle behaviors were conducted; Wald tests were used to examine if there were interactions between these factors and exposures in relation to FMD. RESULTS: Overall, 825 (10.3%) survivors had FMD. Mean age was 67.2 years, and 89.7% of survivors were white. Juice showed non-significant associations with FMD. Moderate (aOR = 0.81, 95% CI = 0.68-0.98) and high (aOR = 0.79, 95% CI = 0.63-0.98) fruit consumptions, as well as moderate vegetable consumption (aOR = 0.78, 95% CI = 0.64-0.94), were significantly and inversely associated with FMD. The dose-response curves were consistent with results in primary analysis. No interaction was identified for adverse lifestyle behaviors. CONCLUSION: Fruit and vegetable, but not fruit juice, show potential preventive effects against FMD among breast cancer survivors. The conclusion should be verified by studies with clear temporality in future.
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Neoplasias de la Mama/psicología , Supervivientes de Cáncer/psicología , Conducta Alimentaria/psicología , Frutas , Distrés Psicológico , Verduras , Adulto , Anciano , Anciano de 80 o más Años , Mama/patología , Femenino , Conductas Relacionadas con la Salud , Humanos , Estilo de Vida , Modelos Logísticos , Trastornos Mentales , Salud Mental , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
Direct oral anticoagulant (DOAC) starter packs are designed for unique treatment dosing for acute venous thromboembolism (VTE). Inappropriate use of 30-day DOAC starter packs in patients with atrial fibrillation (AF) may increase the risk for bleeding events given higher dosing in the first 1-3 weeks of treatment. A retrospective analysis of medical and outpatient pharmacy claims data from 2015 to 2018 in Optum's De-identified Clinformatics® Data Mart was performed. Patients greater than 18 years of age with AF and a new prescription of apixaban or rivaroxaban were included. Patients with an acute VTE were excluded. The main outcome of interest was adverse events (emergency department [ED] visits, hospitalizations, and deaths within 90 days after prescription fill date) associated with inappropriate DOAC starter pack prescription. A total of 90,950 DOAC-treated patients with AF were identified. The mean age was 74.5 years (SD 10.0) and 42,717 (47.0%) were female. Inappropriate starter packs were used by 117 (0.1%) patients, who were younger than non-starter pack patients (71.3 years vs. 74.5 years). Patients who received an inappropriate DOAC prescription were more likely to identify as Black (12.0% vs. 8.8%). Rates of ED visits, hospitalizations, and deaths overall were numerically lower in patients with starter pack compared to non-starter pack DOAC prescriptions. In contrast, rates of ED visits and hospitalizations related to significant bleeding were numerically higher in patients with starter pack compared to non-starter pack DOAC prescriptions. Among patients with AF but no VTE, those who received an inappropriate DOAC starter pack had numerically higher rates of severe bleeding leading to ED visits and hospitalizations compared to those prescribed an appropriate non-starter pack DOAC anticoagulant.
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Fibrilación Atrial , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Tromboembolia Venosa , Administración Oral , Anciano , Anticoagulantes/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Femenino , Hemorragia/inducido químicamente , Hemorragia/tratamiento farmacológico , Humanos , Prescripciones , Estudios Retrospectivos , Rivaroxabán/uso terapéutico , Tromboembolia Venosa/tratamiento farmacológicoRESUMEN
BACKGROUND: To describe the clinical course of an active solitary idiopathic choroiditis (focal scleral nodule) that nearly resolved over six weeks without intervention. CASE PRESENTATION: An 18-year-old man presented to the emergency department with headaches and new onset central scotoma in the right eye. Visual acuity was 20/20 in both eyes. Fundus examination revealed an amelanotic choroidal lesion with associated shallow subretinal fluid. It measured 6.1 × 6.3 × 1.4mm on A- and B-scan. Evaluation for systemic inflammatory and infectious diseases was negative. A week later, the lesion remained stable, and a month later, there was improvement of the lesion with a decrease in size on OCT and exam and resolution of the subretinal fluid suggesting that the lesion had become inactive. CONCLUSIONS: Solitary idiopathic choroiditis (Focal scleral nodule) is a rare condition characterized by inflammatory granulomatous reaction. This case report sheds light on the unknown natural course of a solitary idiopathic choroiditis (focal scleral nodule).
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Coroiditis , Tomografía de Coherencia Óptica , Adolescente , Coroides , Coroiditis/diagnóstico , Angiografía con Fluoresceína , Fondo de Ojo , Humanos , MasculinoRESUMEN
Soluble IL-13 receptor-α1, or sIL13rα1, is a soluble protein that binds to interleukin-13 (IL-13) that has been previously described in mice. The function of sIL13rα1 remains unclear, but it has been hypothesized to act as a decoy receptor for IL-13. Recent studies have identified a role for IL-13 in glucose metabolism, suggesting that a decoy receptor for IL-13 might increase circulating glucose levels. Here, we report that delivery of sIL13rα1 to mice by either gene transfer or recombinant protein decreases blood glucose levels. Surprisingly, the glucose-lowering effect of sIL13rα1 was preserved in mice lacking IL-13, demonstrating that IL-13 was not required for the effect. In contrast, deletion of IL-4 in mice eliminated the hypoglycemic effect of sIL13rα1. In humans, endogenous blood levels of IL13rα1 varied substantially, although there were no differences between diabetic and nondiabetic patients. There was no circadian variation of sIL13rα1 in normal human volunteers. Delivery of sIL13rα1 fused to a fragment crystallizable (Fc) domain provided sustained glucose lowering in mice on a high-fat diet, suggesting a potential therapeutic strategy. These data reveal sIL13rα1 as a circulating human protein with an unexpected role in glucose metabolism.
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Glucosa/metabolismo , Subunidad alfa1 del Receptor de Interleucina-13/fisiología , Adolescente , Adulto , Anciano , Animales , Metabolismo de los Hidratos de Carbono/efectos de los fármacos , Metabolismo de los Hidratos de Carbono/genética , Femenino , Humanos , Hipoglucemiantes/uso terapéutico , Subunidad alfa1 del Receptor de Interleucina-13/genética , Subunidad alfa1 del Receptor de Interleucina-13/uso terapéutico , Interleucina-4/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Persona de Mediana Edad , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacología , Proteínas Recombinantes/uso terapéutico , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Adulto JovenRESUMEN
Cell-free DNA (cfDNA) released from dead cells could be a player in some autoimmune disorders by activating Toll-like receptor 9 (TLR9) and inducing proinflammatory cytokines. Cationic nanoparticles (cNPs) address cfDNA clearance, yet challenges persist, including toxicity, low specificity and ineffectiveness against endocytosed cfDNA. This study introduced pH-sensitive cNPs, reducing off-target effects and binding cfDNA at inflammatory sites. This unique approach inhibits the TLR9 pathway, offering a novel strategy for inflammation modulation. Synthesized cNPs, with distinct cationic moieties, exhibit varied pKa values, enhancing cfDNA binding. Comprehensive studies elucidate the mechanism, demonstrating minimal extracellular binding, enhanced endosomal DNA binding, and optimal tumor necrosis factor-α suppression. In a traumatic brain injury mice model, pH-sensitive cNPs effectively suppress inflammatory cytokines, highlighting their potential in acute inflammation regulation.
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Cationes , Ácidos Nucleicos Libres de Células , Endosomas , Inflamación , Ratones Endogámicos C57BL , Nanopartículas , Receptor Toll-Like 9 , Animales , Nanopartículas/administración & dosificación , Nanopartículas/química , Concentración de Iones de Hidrógeno , Endosomas/metabolismo , Inflamación/tratamiento farmacológico , Receptor Toll-Like 9/metabolismo , Masculino , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Ratones , Citocinas/metabolismo , Humanos , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND AND OBJECTIVE: Epiretinal membrane (ERM) formation, a common complication following pars plana vitrectomy (PPV) for primary rhegmatogenous retinal detachment (RRD) repair, is associated with vision loss and metamorphopsias. Although laser retinopexy is generally associated with ERM formation, the correlation between the extent of laser treatment and ERM formation during PPV is not well established. The aim of this study was to identify risk factors associated with ERM formation including extend of endolaser retinopexy after PPV for primary RRD. PATIENTS AND METHODS: A retrospective, observational case series of 181 consecutive patients (185 eyes) who underwent PPV for primary RRD repair by a single surgeon was performed. Charts were reviewed by two independent reviewers, and de-identified data including patient characteristics and intraoperative findings such as number of laser spots placed were recorded. RESULTS: Postoperative ERM formation occurred in 75 eyes (40.5%) of which 68 (90.6%) were Stage 1, two (2.6%) were Stage 2, three (4%) were Stage 3, and two (2.6%) were Stage 4. Only one patient required secondary PPV for visually significant ERM. Patients with ERM had significantly more laser spots compared with patients with no ERM, with a mean of 807 and 519 laser spots respectively (95% CI: 387.6 to -187.3; P < 0.0001). Univariable analysis identified ≥750 endolaser spots (odds ratio [OR] = 4.0, 95% CI: 2.0 to 8.4; P < 0.0001), ≥4 retinal tears (OR = 2.8, 95%: CI 1.4 to 6.4; P = 0.005), and female sex (OR = 2.0, 95% CI: 1.1 to 3.7; P = 0.02) as significantly associated factors. After adjusting for potential confounding factors (ie, age, sex, macula status, lattice degeneration, length of symptoms, vitreous hemorrhage, number of endolaser spots, number of retinal tears) in multivariable logistic regression, ≥ 750 endolaser spots (OR = 2.4; P = 0.04) and female sex (OR = 2.4; P = 0.03) persisted as significant independent factors. CONCLUSIONS: Our study identified ≥ 750 laser spots and female sex as independent risk factors for ERM formation following PPV for RRD with an OR of 2.4 each. Although the incidence of ERM formation was generally high (40.5%), only one case required secondary PPV with ERM peeling, and visual outcomes were comparable between patients with and without ERM at final follow up. While endolaser photocoagulation is critical for successful RRD repair, consideration of the risk of ERM formation with extensive laser exposure is warranted. [Ophthalmic Surg Lasers Imaging Retina 2024;55:326-333.].
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Membrana Epirretinal , Desprendimiento de Retina , Agudeza Visual , Vitrectomía , Humanos , Desprendimiento de Retina/cirugía , Desprendimiento de Retina/etiología , Desprendimiento de Retina/diagnóstico , Vitrectomía/efectos adversos , Vitrectomía/métodos , Estudios Retrospectivos , Femenino , Membrana Epirretinal/cirugía , Masculino , Persona de Mediana Edad , Anciano , Factores de Riesgo , Complicaciones Posoperatorias/etiología , Adulto , Terapia por Láser/métodos , Terapia por Láser/efectos adversos , Anciano de 80 o más Años , Tomografía de Coherencia Óptica/métodosRESUMEN
PURPOSE: To compare operative time and case characteristics of primary rhegmatogenous retinal detachment (RRD) repairs between academic and community vitreoretinal surgeons. DESIGN: A retrospective, observational clinical study. SUBJECTS: Patients who underwent primary RRD repair surgeries at Massachusetts Eye and Ear between 2019 and 2021. METHODS: A random sample of 20 vitreoretinal surgeons distributed evenly among the academic or community setting was selected. Fifteen consecutive cases of primary RRD repair surgeries were included from each surgeon. A cost analysis was performed for the teaching modifier for the physician fee and for hospital costs. MAIN OUTCOME MEASURES: Length of surgery. RESULTS: Of 300 primary RRD repairs, fellows were present in 75%, which comprised all academic surgeon cases and 50% of community surgeon cases, P < 0.001. Mean operation length was shorter for community surgeon cases without fellows (55.0 ± 24.1) than either academic (73.0 ± 30.8) or community surgeon cases with fellows (75.7 ± 32.5) (P < 0.001). There was a higher percentage of macula-off RRDs in academic versus community surgeon cases (52.7% vs. 38.0%, P = 0.002) and higher rates of combined scleral buckle (SB)/pars plana vitrectomy (PPV) repairs (14% vs. 3%, P < 0.001). When excluding combined SB/PPV cases, there was no difference in operative time between academic and community surgeon cases. Among RRDs repaired by PPV only, there was a 31.4% (16.6 minutes) greater procedure duration in cases with fellows compared with cases without fellows (P < 0.001). Covariates associated with greater surgery time: addition of an SB (ß = 32.6), membrane peel (ß = 18.5), presence of a fellow (ß = 14.5), proliferative vitreoretinopathy (ß = 12.8), and greater number of retinal breaks (ß = 2.4). The teaching modifier adds 16% extra reimbursement ($184.16) to the physician fee, which is 50.9% of what is necessary to cover the percentage increase in surgeon time (31.4%). Using a time-driven activity-based costing for hospital costs, the extra 16.6 minutes leads to an additional $1038.00, which is 5.6 times more than the reimbursement for the modifier. CONCLUSIONS: Retinal detachment repair cases performed by academic surgeons are more likely to be macula-off and include the addition of an SB, which drive longer operative times. Medicare's reimbursement of the assistant modifier in a teaching facility significantly undercompensates the time-driven activity-based costing of trainee participation. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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A new serine protease with fibrinolytic activity from a marine invertebrate, Urechis unicinctus, was purified to electrophoretic homogeneity using column chromatography. SDS-PAGE of the purified enzyme showed a single polypeptide chain with MW ~20.8 kDa. Its N-terminal sequence was IIGGSQAAITSY. The purified enzyme, UFEIII, was stable at pH 6-10 below 60 °C with an optimum pH of 8.5 at approx. 55 °C. The enzyme activity was significantly inhibited by PMSF and SBTI suggesting that it was a serine protease. In fibrin plate assays, UFEIII was contained 1.46 × 10(3 )U (urokinase units) mg(-1) total fibrinolytic activity, which consisted of 692 U mg(-1) direct fibrinolytic activity and 769 U mg(-1) plasminogen-activator activity. Km and Vmax values for azocasein were 1 mg ml(-1) and 43 µg min(-1) ml(-1), respectively.
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Fibrinolíticos/aislamiento & purificación , Proteínas del Helminto/aislamiento & purificación , Poliquetos/enzimología , Serina Proteasas/aislamiento & purificación , Animales , Cromatografía Liquida , Electroforesis en Gel de Poliacrilamida , Estabilidad de Enzimas , Fibrinolíticos/química , Proteínas del Helminto/química , Concentración de Iones de Hidrógeno , Cinética , Peso Molecular , Serina Proteasas/química , TemperaturaRESUMEN
The current recommendation system predominantly relies on evidential factors such as behavioral outcomes and purchasing history. However, limited research has been conducted to explore the use of psychological data in these algorithms, such as consumers' self-perceived identities. Based on the gap identified and the soaring significance of levering the non-purchasing data, this study presents a methodology to quantify consumers' self-identities to help examine the relationship between these psychological cues and decision-making in an e-commerce context, focusing on the projective self, which has been overlooked in previous research. This research is expected to contribute to a better understanding of the cause of inconsistency in similar studies and provide a basis for further exploration of the impact of self-concepts on consumer behavior. The coding method in grounded theory, in conjunction with the synthesis of literature analysis, was employed to generate the final approach and solution in this study as they provide a robust and rigorous basis for the findings and recommendations presented in this study.
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In glioma modeling, existing organoid protocols lack the ability to replicate glioma cell invasion and interaction with normal brain tissue. Here, we present a protocol for generating in vitro brain disease models using human-induced pluripotent- or embryonic-stem-cell-derived cerebral organoids (COs). We describe steps for forming glioma organoids by co-culturing forebrain organoids with U-87 MG cells. We also detail vibratome sectioning of COs to prevent cell death and enhance contact between U-87 MG cells and cerebral tissues.
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Glioma , Células Madre Pluripotentes Inducidas , Humanos , Organoides , Prosencéfalo , Glioma/metabolismoRESUMEN
Purpose: To evaluate the safety, efficacy, and efficiency of the Ngenuity 3-dimensional (3D) heads-up display (HUD) visualization system for primary rhegmatogenous retinal detachment (RRD) repair at a large academic medical center in the United States. Methods: This retrospective review comprised consecutive patients aged 18 years or older who had primary RRD repair (pars plana vitrectomy [PPV] alone or combined PPV and scleral buckle) performed by the same fellowship-trained vitreoretinal surgeon using the 3D visualization system and a traditional standard operating microscope (SOM) at Massachusetts Eye and Ear from June 2017 to December 2021. The minimum follow-up was 90 days. Results: The 3D HUD group comprised 50 eyes of 47 patients and the SOM group, 138 eyes of 136 patients. There were no between-group differences in single surgery anatomic success rates at 3 months (98% HUD vs 99% SOM; P = 1.00) or at the last follow-up (94% HUD vs 98% SOM; P = .40). The rate of postoperative proliferative vitreoretinopathy was similar between the 2 groups (3 months: 3% HUD vs 5% SOM, P = .94; last follow-up, 2% HUD vs 3% SOM, P = .93). There was no difference in the mean duration of surgery (57.4 ± 28.9 minutes HUD vs 59.4 ± 29.9 minutes SOM; P = .68). Conclusions: Anatomic and functional outcomes, in addition to surgical efficiency, of noncomplex primary RRD repair with a 3D HUD system were similar to those of surgery performed with an SOM.
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The cortical organoid is an efficient model for studying human brain neurodevelopment and neurological disease. However, its three-dimensional structure limits real-time observation of internal physiological changes. Here, we present a protocol for an air-liquid interface attachment culture for cortical organoids. We describe steps for transplanting cortical organoid slices and generating the air-liquid interface. We then detail calcium imaging on organoid external neural networks and immunohistochemical staining on confocal plates.
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Encéfalo , Organoides , Humanos , CabezaRESUMEN
Purpose: To report 2 cases of persistent inflammation associated with human leukocyte antigen-B27 (HLA-B27) after pars plana vitrectomy (PPV) with scleral buckling. Methods: Two cases were analyzed. Results: A 47-year-old man had pars plana vitrectomy (PPV), scleral buckle (SB) placement, and endolaser for a macula-on rhegmatogenous retinal detachment (RRD). A 61-year-old man also had uneventful PPV, SB placement, and endolaser for a macula-off RRD. Postoperatively, both patients reported eye pain and had persistent intraocular inflammation. Both were found to be HLA-B27 positive despite having no previous signs or symptoms that would warrant HLA-B27 testing. Conclusions: Discovering the source of prolonged postoperative inflammation is critical in initiating the correct treatment and removing suspicion of infection. Although intraocular inflammation associated with HLA-B27 does not often present initially after surgery, HLA-B27 testing should be considered in cases of persistent, unexpected postoperative inflammation.