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Metal halide perovskite solar cells have achieved tremendous progress and have attracted enormous research and development efforts since the first report of demonstration in 2009. Due to fabrication versatility, many heat treatment methods can be utilized to achieve perovskite film crystallization. Herein, 10.6 µm carbon dioxide laser process is successfully developed for the first time for perovskite film crystallization. In addition, this is the first time formamidinium lead triiodide solar cells by laser annealing under ambient are demonstrated. The champion cell produces a power conversion efficiency of 21.8%, the highest for laser-annealed perovskite cells. And this is achieved without any additive, passivation, or post-treatment.
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An open-label, single-center, phase I study was conducted to determine the absolute bioavailability and absorption, distribution, metabolism, and excretion of capivasertib-a potent, selective AKT serine/threonine kinase inhibitor-in healthy males. In part 1, six participants received a single oral dose of capivasertib (400 mg; tablets) followed by a [14C]-radiolabeled intravenous microdose of capivasertib (100 µg). After a 14-day washout, five of the participants proceeded to part 2 and received a single oral dose of [14C]capivasertib (400 mg; solution). In part 1, median time of maximum observed concentration for capivasertib was 1.7 hours, geometric mean terminal elimination half-life was 12.9 hours, and absolute bioavailability was estimated at 28.6% (90% confidence interval, 23.9 to 34.2). In part 2, a high proportion of the administered radioactivity was recovered over the 168-hour sampling period [mean recovery: 95.1% (feces, 50.4%; urine, 44.7%)]. Unchanged capivasertib in urine accounted for 7.4% of the total dose and 21.1% of the systemically available drug. Geometric mean renal clearance was 8.3 L/h, suggesting active tubular secretion. Twelve metabolites were identified in plasma. M11 (AZ14102143)-the glucuronide conjugate of capivasertib, inactive as an AKT serine/threonine kinase inhibitor-was the most abundant, accounting for a mean 78.4% of the plasma drug-related area under the curve. Of 22 metabolites identified in excreta, M11 was the most abundant (mean 28.2% of administered dose), indicating direct glucuronidation as one of the major routes of metabolism. No new safety concerns were identified. SIGNIFICANCE STATEMENT: This study provides characterization of the pharmacokinetics of capivasertib-a potent, selective AKT serine/threonine kinase (AKT) inhibitor-including absolute bioavailability, mass balance, and metabolic fate in humans; the findings are being used to inform further clinical development. Absolute bioavailability was estimated at 28.6%, and mean recovery of the administered dose in excreta over 168 hours was 95.1%. M11 (AZ14102143)-the glucuronide conjugate, inactive as an AKT inhibitor-was the most abundant identified metabolite in plasma and excreta.
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Disponibilidad Biológica , Voluntarios Sanos , Humanos , Masculino , Adulto , Adulto Joven , Administración Oral , Inhibidores de Proteínas Quinasas/farmacocinética , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/sangre , Distribución Tisular , Pirroles/farmacocinética , Pirroles/administración & dosificación , Pirroles/metabolismo , Pirroles/orina , Pirroles/sangre , Persona de Mediana Edad , Semivida , Heces/química , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Pirimidinas/farmacocinética , Pirimidinas/sangre , Pirimidinas/administración & dosificaciónRESUMEN
As part of a medicinal chemistry program aimed at discovering a mineralocorticoid receptor modulator for treatment of kidney and cardiovascular indications, multiple labeled versions of the lead compound, balcinrenone (AZD9977), were prepared. Four stable isotope labeled versions of the compound were prepared for clinical bioanalysis and biological investigations. Three of these stable isotope labeled compounds were tritiated as well as the parent for biology applications and DMPK investigations. They were prepared using a standard iodination-tritiodehalogentation approach. Finally, AZD9977 was prepared in carbon-14 labeled form for preclinical and clinical applications.
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Benzoatos , Isótopos , Oxazinas , Radioisótopos de Carbono/química , Marcaje IsotópicoRESUMEN
Inappropriate diets cause many of the health problems commonly reported in parrots by psittaculturists and veterinarians. The dietary management of captive parrots would benefit from information derived from studies of dietary habits of wild parrots; however, it is unclear how complete this body of knowledge is at this time. Documentation of parrots' dietary habits appears to have grown dramatically over the past century. Reports of parrots consuming a number of foodstuffs beyond the reproductive parts of plants (alternate foodstuffs) have increased. The extent of alternate foodstuffs in parrot diets is currently unknown. We used Google search engines (ie, Scholar, Videos, Images) to determine how well psittaciform dietary habits have been studied to date and to quantify reports of alternate foodstuffs consumption among genera of Psittaciformes. We found that the dietary habits of over 43% of parrot species are poorly resolved. The dietary habits of 71.5% of parrot species classified by the International Union for Conservation of Nature as at risk of extinction are not well resolved. Parrots' consumption of alternate foodstuffs occurred at the following rates at the genus level: 91.2% foliage, 76.9% terrestrial invertebrates and fine earthen materials, 74.7% wood, 44% pure minerals, 34.1% vertebrates (9.9% dung), 29.7% sap, 19.8% roots, 17.6% charcoal, 18.7% epiphytes, 16.5% coarse earthen materials, 8.8% algae, and 6.6% aquatic invertebrates. Of these reports, 79.1% involved observations of wild parrots. Many parrot species may be more omnivorous than previously realized. Alternate foodstuffs are generally absent from current veterinary-based dietary recommendations for captive parrots. Future studies are needed to determine whether providing alternate foodstuffs to captive parrots can be used as a means to improve their diets and thus their health, welfare, and reproductive success.
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Dieta , Loros , Animales , Dieta/veterinariaRESUMEN
INTRODUCTION: Functional MRI with spatial resolution in the submillimeter domain enables measurements of activation across cortical layers in humans. This is valuable as different types of cortical computations, e.g., feedforward versus feedback related activity, take place in different cortical layers. Laminar fMRI studies have almost exclusively employed 7T scanners to overcome the reduced signal stability associated with small voxels. However, such systems are relatively rare and only a subset of those are clinically approved. In the present study, we examined if the feasibility of laminar fMRI at 3T could be improved by use of NORDIC denoising and phase regression. METHODS: 5 healthy subjects were scanned on a Siemens MAGNETOM Prisma 3T scanner. To assess across-session reliability, each subject was scanned in 3-8 sessions on 3-4 consecutive days. A 3D gradient echo EPI (GE-EPI) sequence was used for BOLD acquisitions (voxel size 0.82 mm isotopic, TR = 2.2 s) using a block design finger tapping paradigm. NORDIC denoising was applied to the magnitude and phase time series to overcome limitations in temporal signal-to-noise ratio (tSNR) and the denoised phase time series were subsequently used to correct for large vein contamination through phase regression. RESULTS AND CONCLUSION: NORDIC denoising resulted in tSNR values comparable to or higher than commonly observed at 7T. Layer-dependent activation profiles could thus be extracted robustly, within and across sessions, from regions of interest located in the hand knob of the primary motor cortex (M1). Phase regression led to substantially reduced superficial bias in obtained layer profiles, although residual macrovascular contribution remained. We believe the present results support an improved feasibility of laminar fMRI at 3T.
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Mano , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Reproducibilidad de los Resultados , Relación Señal-Ruido , Extremidad Superior , Mapeo Encefálico/métodos , EncéfaloRESUMEN
Hereditary multiple exostoses (HME), also known as hereditary multiple osteochondroma (HMO), is an autosomal dominant disorder caused by pathogenic variants in exostosin-1 or -2 (EXT1 or EXT2). It is characterized by the formation of multiple benign growing osteochondromas (exostoses) that most commonly affect the long bones; however, it may also occur throughout the body. Although many of these lesions are clinically asymptomatic, some can lead to chronic pain and skeletal deformities and interfere with adjacent neurovascular structures. Here, we report two unrelated probands that presented with a clinical and molecular diagnosis of HME with venous malformation, a clinical feature not previously reported in individuals with HME.
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Exostosis Múltiple Hereditaria , Humanos , Exostosis Múltiple Hereditaria/diagnóstico , Exostosis Múltiple Hereditaria/genética , N-Acetilglucosaminiltransferasas/genética , MutaciónRESUMEN
PURPOSE: To assess the responsiveness, defined as the ability to detect change in a patient's health or function, of the Patient-Reported Outcome Measure for Vascular Malformation (PROVAM) questionnaire in a cohort of patients with low-flow vascular malformations (VMs). MATERIALS AND METHODS: PROVAM was previously developed to assess symptoms, functional limitations, and social/emotional effects experienced by patients with VMs. This is a prospective cohort study of 56 patients with venous and lymphatic VMs who completed at least 2 PROVAM questionnaires, of whom 43 had undergone treatment with sclerotherapy in the interim between questionnaires. External responsiveness was assessed using a receiver operating characteristic (ROC) curve to ascertain whether a change in the total PROVAM score predicts whether patients reported symptom improvement and by correlating the change in the total PROVAM score and change in symptoms reported during clinic visit. Internal responsiveness was evaluated using Wilcoxon signed rank test, Cohen d effect size (ESp), and standard response mean difference (SRM). RESULTS: The total PROVAM score demonstrated excellent discrimination for symptom improvement with an area under the ROC curve of 0.856. There was a statistically significant, moderate positive correlation between the change in the total PROVAM score and the change in patient symptoms as determined from clinical visits (Spearman correlation coefficient [rs] = 0.67, P < .001). The total PROVAM score and all subdomain scores improved significantly after treatment (all P < .05). ESp and SRM were 0.80 and 0.83, respectively. CONCLUSIONS: PROVAM is responsive to improvement after treatment and may be useful to assess health-related quality of life in patients treated for VMs.
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Calidad de Vida , Malformaciones Vasculares , Humanos , Calidad de Vida/psicología , Estudios Prospectivos , Encuestas y Cuestionarios , Medición de Resultados Informados por el Paciente , Malformaciones Vasculares/diagnóstico por imagen , Malformaciones Vasculares/terapia , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate whether intraoperative neuromonitoring (IONM), including pre-embolization lidocaine injection challenge ("provocative testing") is associated with reduced risk of irreversible nerve injury during embolization of peripheral arteriovenous malformations (AVMs). MATERIALS AND METHODS: Medical records of patients with peripheral AVMs who underwent embolotherapy with IONM with provocative testing between 2012 and 2021 were reviewed retrospectively. Data collected included patient demographic characteristics, AVM location and size, embolic agent used, IONM signal changes after lidocaine and embolic agent injections, postprocedural adverse events, and clinical outcomes. Decisions regarding whether embolization would proceed at specific locations were based on IONM findings after the lidocaine challenge and as embolization proceeded. RESULTS: A cohort of 17 patients (mean age, 27 years ± 19; 5 women) who underwent 59 image-guided embolization procedures with adequate IONM data was identified. No permanent neurologic deficits occurred. Transient neurologic deficits were observed in 3 patients (4 sessions), comprising skin numbness (2 patients), extremity weakness (1 patient), and extremity weakness and numbness (1 patient). All neurologic deficits resolved by postoperative day 4 without additional treatment. CONCLUSIONS: IONM, including provocative testing, during AVM embolization may minimize potential nerve injury.
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Embolización Terapéutica , Malformaciones Arteriovenosas Intracraneales , Humanos , Femenino , Adulto , Malformaciones Arteriovenosas Intracraneales/diagnóstico por imagen , Malformaciones Arteriovenosas Intracraneales/terapia , Malformaciones Arteriovenosas Intracraneales/etiología , Hipoestesia/etiología , Hipoestesia/terapia , Estudios Retrospectivos , Embolización Terapéutica/efectos adversos , Embolización Terapéutica/métodos , Inyecciones , Resultado del TratamientoRESUMEN
BACKGROUND: Liver biopsy and hepatic venous pressure gradient (HVPG), the gold standard for assessing advanced fibrosis (AF) and clinically significant portal hypertension (CSPH), are invasive, costly, and time-consuming. GOAL: We investigated if the combination of fibrosis index based on 4 factors (FIB-4) and liver stiffness measure (LSM) can identify AF and more importantly, CSPH. PATIENTS AND METHODS: Patients with chronic liver disease referred for transjugular liver biopsy were analyzed retrospectively. FIB-4 and LSM were compared with liver histology for diagnosing AF. FIB-4, LSM, and platelet count were compared with HVPG for diagnosing CSPH. Optimal cutoffs for predicting CSPH were determined by grid search. A composite log-odds to predict CSPH was derived from logistic regression using LSM, FIB-4, and gender. Internal bootstrap validation and external validation were performed. RESULTS: A total of 142 patients were included in the derivation; 42.3% had AF, and 11.3% had CSPH using the current gold standards. The area under the receiver operating characteristic curve (AUROC) for LSM, FIB-4, and their combination to predict AF were 0.7550, 0.7049, and 0.7768, respectively. LSM, FIB-4, and platelet count predicted CSPH with AUROC 0.6818, 0.7532, and 0.7240, respectively. LSM plus FIB-4 showed the best performance in predicting CSPH with AUROC 0.8155. Based on LSM, FIB-4, and gender, a novel model-the Portal Hypertension Assessment Tool (PHAT)-was developed to predict CSPH. PHAT score ≥-2.76 predicted CSPH with sensitivity 94%, specificity 67%, positive predictive value 27%, negative predictive value 99%, and accuracy 70%. In internal and external validation, AUROCs for the model were 0.8293 and 0.7899, respectively. CONCLUSION: A model consisting of FIB-4, LSM, and gender can identify CSPH among patients with chronic liver disease.
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Diagnóstico por Imagen de Elasticidad , Hipertensión Portal , Humanos , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/patología , Estudios Retrospectivos , Hipertensión Portal/diagnóstico , Hipertensión Portal/patología , HígadoRESUMEN
BACKGROUND. Endovascular embolization of pulmonary arteriovenous malformations (PAVMs) was historically performed with embolic coils. The Amplatzer Vascular Plug device (AVP) was introduced for this purpose in 2007 and the Micro Vascular Plug device (MVP) in 2013. OBJECTIVE. The purpose of this study was to compare coils, AVPs, and MVPs in terms of risk of persistence after PAVM embolization by use of propensity score weighting to account for biases in device selection. METHODS. This retrospective study included 112 patients (78 women and girls, 34 men and boys; mean age, 45 years) who underwent embolization of 393 PAVMs with a single device type (coil, MVP, or AVP) from January 2003 to January 2020. Persistence was defined as less than 70% reduction in PAVM sac size or contrast enhancement of the sac on follow-up pulmonary CTA. A Cox proportional hazards regression model was used to assess associations between embolic device selection and PAVM persistence. Inverse propensity score weighting was used to account for differences in embolic device selection based on patient and PAVM characteristics. RESULTS. The median postembolization follow-up period was 1.5 years (IQR, 0.3-5.6 years). Persistence was found in 10% (41/393) of PAVMs, including 16% (34/207) of those treated with coils, 8% (7/88) of those treated with AVPs, and 0% (0/98) of those treated with MVPs. Variables associated with embolization device (p < .25) were age, sex, pediatric versus adult status, smoking status, PAVM complexity, PAVM laterality, number of feeding arteries, and feeding artery diameter. The Cox regression model incorporated inverse propensity score weighting to account for the differences between treatment groups in these variables and incorporated feeding artery diameter because of imbalance remaining after weighting. With coils as the referent, MVPs had a hazard ratio for persistence of less than 0.01 (95% CI, < 0.01 to < 0.01; p < .001), and AVPs had a hazard ratio of 0.37 (95% CI, 0.16-0.90; p = .03). CONCLUSION. The risk of persistence after PAVM embolization was significantly lower for MVPs alone than for coils or AVPs alone. In addition, the risk of persistence was lower for AVPs than for coils. CLINICAL IMPACT. The findings support the clinical use of MVPs as the preferred device for PAVM embolization over coils and polytetrafluoroethylene-covered plugs.
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Malformaciones Arteriovenosas , Embolización Terapéutica , Venas Pulmonares , Adulto , Masculino , Humanos , Femenino , Niño , Persona de Mediana Edad , Estudios Retrospectivos , Puntaje de Propensión , Resultado del Tratamiento , Malformaciones Arteriovenosas/diagnóstico por imagen , Malformaciones Arteriovenosas/terapia , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/anomalías , Venas Pulmonares/diagnóstico por imagen , Venas Pulmonares/anomalías , Embolización Terapéutica/métodosRESUMEN
OBJECTIVE: To examine differences in surgical practices between salaried and fee-for-service (FFS) surgeons for two common degenerative spine conditions. Surgeons may offer different treatments for similar conditions on the basis of their compensation mechanism. METHODS: The study assessed the practices of 63 spine surgeons across eight Canadian provinces (39 FFS surgeons and 24 salaried) who performed surgery for two lumbar conditions: stable spinal stenosis and degenerative spondylolisthesis. The study included a multicenter, ambispective review of consecutive spine surgery patients enrolled in the Canadian Spine Outcomes and Research Network registry between October 2012 and July 2018. The primary outcome was the difference in type of procedures performed between the two groups. Secondary study variables included surgical characteristics, baseline patient factors, and patient-reported outcome. RESULTS: For stable spinal stenosis (n = 2234), salaried surgeons performed statistically fewer uninstrumented fusion (p < 0.05) than FFS surgeons. For degenerative spondylolisthesis (n = 1292), salaried surgeons performed significantly more instrumentation plus interbody fusions (p < 0.05). There were no statistical differences in patient-reported outcomes between the two groups. CONCLUSIONS: Surgeon compensation was associated with different approaches to stable lumbar spinal stenosis and degenerative lumbar spondylolisthesis. Salaried surgeons chose a more conservative approach to spinal stenosis and a more aggressive approach to degenerative spondylolisthesis, which highlights that remuneration is likely a minor determinant in the differences in practice of spinal surgery in Canada. Further research is needed to further elucidate which variables, other than patient demographics and financial incentives, influence surgical decision-making.
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Fusión Vertebral , Estenosis Espinal , Espondilolistesis , Cirujanos , Humanos , Estenosis Espinal/cirugía , Estenosis Espinal/complicaciones , Espondilolistesis/cirugía , Espondilolistesis/complicaciones , Vértebras Lumbares/cirugía , Canadá , Fusión Vertebral/efectos adversos , Resultado del TratamientoRESUMEN
Despite the emergence of promising therapeutic approaches in preclinical studies, the failure of large-scale clinical trials leaves clinicians without effective treatments for acute spinal cord injury (SCI). These trials are hindered by their reliance on detailed neurological examinations to establish outcomes, which inflate the time and resources required for completion. Moreover, therapeutic development takes place in animal models whose relevance to human injury remains unclear. Here, we address these challenges through targeted proteomic analyses of cerebrospinal fluid and serum samples from 111 patients with acute SCI and, in parallel, a large animal (porcine) model of SCI. We develop protein biomarkers of injury severity and recovery, including a prognostic model of neurological improvement at 6 months with an area under the receiver operating characteristic curve of 0.91, and validate these in an independent cohort. Through cross-species proteomic analyses, we dissect evolutionarily conserved and divergent aspects of the SCI response and establish the cerebrospinal fluid abundance of glial fibrillary acidic protein as a biochemical outcome measure in both humans and pigs. Our work opens up new avenues to catalyze translation by facilitating the evaluation of novel SCI therapies, while also providing a resource from which to direct future preclinical efforts.
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Proteína Ácida Fibrilar de la Glía/sangre , Proteína Ácida Fibrilar de la Glía/líquido cefalorraquídeo , Traumatismos de la Médula Espinal/sangre , Traumatismos de la Médula Espinal/líquido cefalorraquídeo , Animales , Femenino , Humanos , Proteómica , Médula Espinal/patología , Traumatismos de la Médula Espinal/patología , PorcinosRESUMEN
OBJECTIVE: This study sought to (1) collate the experiences of university students with concussion history and academic stakeholders through interviews and (2) develop concussion management recommendations for institutions of higher learning using a multidisciplinary Delphi procedure. SETTING: Remote semistructured interviews and online surveys. PARTICIPANTS: The first aim of this study included undergraduate university students with concussion history who did not participate in varsity athletics ( n = 21; 57.1% female), as well as academic faculty/staff with experience assisting university students with their postconcussion academic needs ( n = 7; 71.4% female). The second aim enrolled 22 participants (54.5% female) to serve on the Delphi panel including 9 clinicians, 8 researchers, and 5 academic faculty/staff. DESIGN: An exploratory-sequential mixed-methods approach. MAIN MEASURES: Semistructured interviews were conducted to unveil barriers regarding the return-to-learn (RTL) process after concussion, with emergent themes serving as a general framework for the Delphi procedure. Panelists participated in 3 stages of a modified Delphi process beginning with a series of open-ended questions regarding postconcussion management in higher education. The second stage included anonymous ratings of the recommendations, followed by an opportunity to review and/or modify responses based on the group's consensus. RESULTS: The results from the semistructured interviews indicated students felt supported by their instructors; however, academic faculty/staff lacked information on appropriate academic supports and/or pathways to facilitate the RTL process. Of the original 67 statements, 39 achieved consensus (58.2%) upon cessation of the Delphi procedure across 3 main categories: recommendations for discharge documentation (21 statements), guidelines to facilitate a multidisciplinary RTL approach (10 statements), and processes to obtain academic supports for students who require them after concussion (8 statements). CONCLUSIONS: These findings serve as a basis for future policy in higher education to standardize RTL processes for students who may need academic supports following concussion.
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Conmoción Encefálica , Deportes , Humanos , Femenino , Masculino , Universidades , Alta del Paciente , Conmoción Encefálica/diagnóstico , Conmoción Encefálica/terapia , EstudiantesRESUMEN
STUDY DESIGN: An ambispective review of consecutive cervical spine surgery patients enrolled in the Canadian Spine Outcomes and Research Network (CSORN) between January 2015 and September 2019. PURPOSE: To compare complication rates of degenerative cervical spine surgery over time between older (> 65) and younger age groups (< 65). More elderly people are having spinal surgery. Few studies have examined the temporal nature of complications of cervical spine surgery by patient age groups. METHODS: Adverse events were collected prospectively using adverse event forms. Binary logistic regression analysis was utilized to assess associations between risk modifiers and adverse events at the intra-, peri-operative and 3 months post-surgery. RESULTS: Of the 761 patients studied (age < 65, n = 581 (76.3%) and 65 + n = 180 (23.7%), the intra-op adverse events were not significantly different; < 65 = 19 (3.3%) vs 65 + = 11 (6.1%), p < 0.087. Peri-operatively, the < 65 group had significantly lower percentage of adverse events (65yrs (11.2%) vs. 65 + = (26.1%), p < 0.001). There were no differences in rates of adverse events at 3 months post-surgery (< 65 = 39 (6.7%) vs. 65 + = 12 (6.7%), p < 0.983). Less blood loss (OR = 0.99, p < 0.010) and shorter length of hospital stay (OR = 0.97, p < 0.025) were associated with not having intra-op adverse events. Peri-operatively, > 1 operated level (OR = 1.77, p < 0.041), shorter length of hospital stay (OR = 0.86, p < 0.001) and being younger than 65 years (OR = 2.11, p < 0.006) were associated with not having adverse events. CONCLUSION: Following degenerative cervical spine surgery, the older and younger age groups had significantly different complication rates at peri-operative time points, and the intra-operative and 3-month post-operative complication rates were similar in the groups.
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Enfermedades de la Columna Vertebral , Humanos , Anciano , Canadá , Enfermedades de la Columna Vertebral/epidemiología , Enfermedades de la Columna Vertebral/cirugía , Enfermedades de la Columna Vertebral/complicaciones , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Sistema de Registros , Vértebras Cervicales/cirugía , Estudios RetrospectivosRESUMEN
Acro-osteolysis is the osseous destruction of the hand or foot distal phalanges. The categories of the disease include terminal tuft, midshaft, or mixed types. Recognition of acro-osteolysis is straightforward on radiographs, but providing an accurate differential diagnosis and appropriately recommending advanced imaging or invasive tissue diagnosis can be more elusive. A radiologist's ability to provide advanced assessment can greatly aid clinicians in expedient diagnosis and management of the array of diseases presenting with acro-osteolysis.
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Acroosteólisis , Falanges de los Dedos de la Mano , Osteólisis , Humanos , Diagnóstico Diferencial , Acroosteólisis/diagnóstico por imagen , Falanges de los Dedos de la Mano/diagnóstico por imagen , Mano/diagnóstico por imagen , Radiografía , Osteólisis/diagnóstico por imagenRESUMEN
OBJECTIVES: To systematically review the scientific literature regarding the acute assessment of sport-related concussion (SRC) and provide recommendations for improving the Sport Concussion Assessment Tool (SCAT6). DATA SOURCES: Systematic searches of seven databases from 2001 to 2022 using key words and controlled vocabulary relevant to concussion, sports, SCAT, and acute evaluation. ELIGIBILITY CRITERIA: (1) Original research articles, cohort studies, case-control studies, and case series with a sample of >10; (2) ≥80% SRC; and (3) studies using a screening tool/technology to assess SRC acutely (<7 days), and/or studies containing psychometric/normative data for common tools used to assess SRC. DATA EXTRACTION: Separate reviews were conducted involving six subdomains: Cognition, Balance/Postural Stability, Oculomotor/Cervical/Vestibular, Emerging Technologies, and Neurological Examination/Autonomic Dysfunction. Paediatric/Child studies were included in each subdomain. Risk of Bias and study quality were rated by coauthors using a modified SIGN (Scottish Intercollegiate Guidelines Network) tool. RESULTS: Out of 12 192 articles screened, 612 were included (189 normative data and 423 SRC assessment studies). Of these, 183 focused on cognition, 126 balance/postural stability, 76 oculomotor/cervical/vestibular, 142 emerging technologies, 13 neurological examination/autonomic dysfunction, and 23 paediatric/child SCAT. The SCAT discriminates between concussed and non-concussed athletes within 72 hours of injury with diminishing utility up to 7 days post injury. Ceiling effects were apparent on the 5-word list learning and concentration subtests. More challenging tests, including the 10-word list, were recommended. Test-retest data revealed limitations in temporal stability. Studies primarily originated in North America with scant data on children. CONCLUSION: Support exists for using the SCAT within the acute phase of injury. Maximal utility occurs within the first 72 hours and then diminishes up to 7 days after injury. The SCAT has limited utility as a return to play tool beyond 7 days. Empirical data are limited in pre-adolescents, women, sport type, geographical and culturally diverse populations and para athletes. PROSPERO REGISTRATION NUMBER: CRD42020154787.
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Conmoción Encefálica , Deportes , Niño , Humanos , Adolescente , Adulto , Femenino , Conmoción Encefálica/diagnóstico , Atletas , Estudios de Casos y Controles , CogniciónRESUMEN
Kappa opioid receptors (KOPr) are involved in the response to stress. KOPr are also targets for the treatment of stress-related psychiatric disorders including depression, anxiety, and addiction although effects of KOPr are often sex-dependent. Here we investigated c-Fos expression in a range of brain regions in male and female mice following an acute stressor, and a single injection of KOPr agonist. Using adult C57BL/6 c-Fos-GFP transgenic mice and quantitative fluorescence microscopy, we identified brain regions activated in response to a challenge with the KOPr agonist U50,488 (20 mg/kg) or an acute stress (15 min forced swim stress, FSS). In male mice, U50,488 increased expression of c-Fos in the prelimbic area of the prefrontal cortex (PFCx), nucleus accumbens (NAcc), and basolateral nuclei of the amygdala (BLA). In contrast, in female mice U50,488 only activated the BLA but not the PFCx or the NAcc. FSS increased activation of PFCx, NAcc, and BLA in males while there was no activation of the PFCx in female mice. In both sexes, the KOPr antagonist norBNI significantly blocked U50,488-induced, but not stress-induced activation of brain regions. In separate experiments, activated cells were confirmed as non-GABAergic neurons in the PFCx and NAcc. Together these data demonstrate sex differences in activation of brain regions that are key components of the 'reward' circuitry. These differential responses may contribute to sex differences in stress-related psychiatric disorders and in the treatment of depression, anxiety, and addiction.
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Proteínas Proto-Oncogénicas c-fos , Receptores Opioides kappa , Caracteres Sexuales , Animales , Femenino , Humanos , Masculino , Ratones , Encéfalo/metabolismo , Ratones Endogámicos C57BL , Corteza Prefrontal/metabolismo , Proteínas Proto-Oncogénicas c-fos/genética , Proteínas Proto-Oncogénicas c-fos/metabolismo , Receptores Opioides kappa/metabolismoRESUMEN
Polydopamine (PDA) is a synthetic model for melanin and has a wide range of opto-electronic properties that underpin its utility in applied and biological settings, from broadband light absorbance to possessing stable free radical species. Here, we show that PDA free radicals are photo-responsive under visible light irradiation, enabling PDA to serve as a photo-redox catalyst. Steady-state and transient electron spin resonance spectroscopy reveals a reversible amplification in semiquinone radical population within PDA under visible light. This photo-response modifies the redox potential of PDA and supports sensitisation of exogenous species via photoinduced electron transfer (PET). We demonstrate the utility of this discovery by employing PDA nanoparticles to photosensitise a common diaryliodonium photoinitiator and initiate free-radical polymerisation (FRP) of vinylic monomers. In situ 1 H nuclear magnetic resonance spectroscopy reveals an interplay between PDA-driven photosensitising and radical quenching during FRP under blue, green, and red light. This work provides crucial insights into the photoactive free radical properties of melanin-like materials and reveals a promising new application for polydopamine as a photosensitiser.
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Back-contact architectures offer a promising route to improve the record efficiencies of perovskite solar cells (PSCs) by eliminating parasitic light absorption. However, the performance of back-contact PSCs is limited by inadequate carrier diffusion in perovskite. Here, we report that perovskite films with a preferred out-of-plane orientation show improved carrier dynamic properties. With the addition of guanidine thiocyanate, the films exhibit carrier lifetimes and mobilities increased by 3-5â times, leading to diffusion lengths exceeding 7â µm. The enhanced carrier diffusion results from substantial suppression of nonradiative recombination and improves charge collection. Devices using such films achieve reproducible efficiencies reaching 11.2 %, among the best performances for back-contact PSCs. Our findings demonstrate the impact of carrier dynamics on back-contact PSCs and provide the basis for a new route to high-performance back-contact perovskite optoelectronic devices at low cost.
RESUMEN
Current vaccination against Streptococcus pneumoniae uses vaccines based on capsular polysaccharides from selected serotypes and has led to nonvaccine serotype replacement disease. We have investigated an alternative serotype-independent approach, using multiple-antigen vaccines (MAV) prepared from S. pneumoniae TIGR4 lysates enriched for surface proteins by a chromatography step after culture under conditions that induce expression of heat shock proteins (Hsp; thought to be immune adjuvants). Proteomics and immunoblot analyses demonstrated that, compared to standard bacterial lysates, MAV was enriched with Hsps and contained several recognized protective protein antigens, including pneumococcal surface protein A (PspA) and pneumolysin (Ply). Vaccination of rodents with MAV induced robust antibody responses to multiple serotypes, including nonpneumococcal conjugate vaccine serotypes. Homologous and heterologous strains of S. pneumoniae were opsonized after incubation in sera from vaccinated rodents. In mouse models, active vaccination with MAV significantly protected against pneumonia, while passive transfer of rabbit serum from MAV-vaccinated rabbits significantly protected against sepsis caused by both homologous and heterologous S. pneumoniae strains. Direct comparison of MAV preparations made with or without the heat shock step showed no clear differences in protein antigen content and antigenicity, suggesting that the chromatography step rather than Hsp induction improved MAV antigenicity. Overall, these data suggest that the MAV approach may provide serotype-independent protection against S. pneumoniae.