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Chronic active lesions (CAL) are an important manifestation of chronic inflammation in multiple sclerosis (MS) and have implications for non-relapsing biological progression. In recent years, the discovery of innovative magnetic resonance imaging (MRI) and PET derived biomarkers has made it possible to detect CAL, and to some extent quantify them, in the brain of persons with MS, in vivo. Paramagnetic rim lesions on susceptibility-sensitive MRI sequences, MRI-defined slowly expanding lesions on T1-weighted (T1-w) and T2-w scans, and 18-kDa translocator protein-positive lesions on PET are promising candidate biomarkers of CAL. While partially overlapping, these biomarkers do not have equivalent sensitivity and specificity to histopathological CAL. Standardization in the use of available imaging measures for CAL identification, quantification, and monitoring is lacking. To fast-forward clinical translation of CAL, the North American Imaging in Multiple Sclerosis Cooperative developed a Consensus Statement, which provides guidance for the radiological definition and measurement of CAL. The proposed manuscript presents this Consensus Statement, summarizes the multistep process leading to it, and identifies the remaining major gaps in knowledge.
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Although 7 T MRI research has contributed much to our understanding of multiple sclerosis (MS) pathology, most prior data has come from small, single-center studies with varying methods. In order to truly know if such findings have widespread applicability, multicenter methods and studies are needed. To address this, members of the North American Imaging in MS (NAIMS) Cooperative worked together to create a multicenter collaborative study of 7 T MRI in MS. In this manuscript, we describe the methods we have developed for the purpose of pooling together a large, retrospective dataset of 7 T MRIs acquired in multiple MS studies at five institutions. To date, this group has contributed five-hundred and twenty-eight 7 T MRI scans from 350 individuals with MS to a common data repository, with plans to continue to increase this sample size in the coming years. We have developed unified methods for image processing for data harmonization and lesion identification/segmentation. We report here our initial observations on intersite differences in acquisition, which includes site/device differences in brain coverage and image quality. We also report on the development of our methods and training of image evaluators, which resulted in median Dice Similarity Coefficients for trained raters' annotation of cortical and deep gray matter lesions, paramagnetic rim lesions, and meningeal enhancement between 0.73 and 0.82 compared to final consensus masks. We expect this publication to act as a resource for other investigators aiming to combine multicenter 7 T MRI datasets for the study of MS, in addition to providing a methodological reference for all future analysis projects to stem from the development of this dataset.
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Imagen por Resonancia Magnética , Esclerosis Múltiple , Humanos , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/normas , Adulto , Femenino , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
OBJECTIVES: To define consensus entrustable professional activities (EPAs) for neurocritical care (NCC) advanced practice providers (APPs), establish validity evidence for the EPAs, and evaluate factors that inform entrustment expectations of NCC APP supervisors. DESIGN: A three-round modified Delphi consensus process followed by application of the EQual rubric and assessment of generalizability by clinicians not affiliated with academic medical centers. SETTING: Electronic surveys. SUBJECTS: NCC APPs ( n = 18) and physicians ( n = 12) in the United States with experience in education scholarship or APP program leadership. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The steering committee generated an initial list of 61 possible EPAs. The panel proposed 30 additional EPAs. A total of 47 unique nested EPAs were retained by consensus opinion. The steering committee defined six core EPAs addressing medical knowledge, procedural competencies, and communication proficiency which encompassed the nested EPAs. All core EPAs were retained and subsequently met the previously described cut score for quality and structure using the EQual rubric. Most clinicians who were not affiliated with academic medical centers rated each of the six core EPAs as very important or mandatory. Entrustment expectations did not vary by prespecified groups. CONCLUSIONS: Expert consensus was used to create EPAs for NCC APPs that reached a predefined quality standard and were important to most clinicians in different practice settings. We did not identify variables that significantly predicted entrustment expectations. These EPAs may aid in curricular design for an EPA-based assessment of new NCC APPs and may inform the development of EPAs for APPs in other critical care subspecialties.
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Competencia Clínica , Cuidados Críticos , Técnica Delphi , Humanos , Cuidados Críticos/normas , Consenso , Estados Unidos , Asistentes Médicos/educaciónRESUMEN
BACKGROUND: Paramagnetic rim lesions (PRLs) are associated with chronic inflammation in multiple sclerosis (MS). 7-Tesla (7T) magnetic resonance imaging (MRI) can evaluate the integrity of the blood-brain barrier (BBB) in addition to the tissue myelination status and cell loss. PURPOSE: To use MRI metrics to investigate underlying physiology and clinical importance of PRLs. STUDY TYPE: Prospective. SUBJECTS: Thirty-six participants (mean-age 47, 23 females, 13 males) of mixed MS subtypes. FIELD STRENGTH/SEQUENCE: 7T, MP2RAGE, MULTI-ECHO 3D-GRE, FLAIR. ASSESSMENT: Lesion heterogeneity; longitudinal changes in lesion counts; comparison of T1, R2*, and χ; association between baseline lesion types and disease progression (2-3 annual MRI visits with additional years of annual clinical follow-up). STATISTICAL TESTS: Two-sample t-test, Wilcoxon Rank-Sum test, Pearson's chi-square test, two-group comparison with linear-mixed-effect model, mixed-effect ANOVA, logistic regression. P-values <0.05 were considered significant. RESULTS: A total of 58.3% of participants had at least one PRL at baseline. Higher male proportion in PRL+ group was found. Average change in PRL count was 0.20 (SD = 2.82) for PRLs and 0.00 (SD = 0.82) for mottled lesions. Mean and median pre-/post-contrast T1 were longer in PRL+ than in PRL-. No differences in mean χ were seen for lesions grouped by PRL (P = 0.310, pre-contrast; 0.086, post-contrast) or PRL/M presence (P = 0.234, pre-contrast; 0.163, post-contrast). Median χ were less negative in PRL+ and PRL/M+ than in PRL- and PRL/M-. Mean and median pre-/post-contrast R2* were slower in PRL+ compared to PRL-. Mean and median pre-/post-contrast R2* were slower in PRL/M+ than in PRL/M-. PRL presence at baseline was associated with confirmed EDSS Plus progression (OR 3.75 [1.22-7.59]) and PRL/M+ at baseline with confirmed EDSS Plus progression (OR 3.63 [1.14-7.43]). DATA CONCLUSION: Evidence of BBB breakdown in PRLs was not seen. Quantitative metrics confirmed prior results suggesting greater demyelination, cell loss, and possibly disruption of tissue anisotropy in PRLs. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.
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Esclerosis Múltiple , Femenino , Humanos , Masculino , Esclerosis Múltiple/patología , Barrera Hematoencefálica/patología , Encéfalo/patología , Estudios Prospectivos , Imagen por Resonancia Magnética/métodosRESUMEN
Marine cloud brightening (MCB) is a potential intervention to mitigate the effects of climate change by increasing the reflectance of low-level maritime clouds, including those over the Great Barrier Reef. The technique involves dispersing a plume of submicrometer seawater droplets over the ocean, which evaporate, generating nanosized sea-salt aerosols (SSAs) that disperse through the atmosphere with some fraction incorporated into clouds. Droplet evaporation, which occurs in the immediate vicinity (meters to tens of meters) of the source, has been theorized to produce a negatively buoyant plume hindering the mixing of the sea-salt aerosol to cloud height and compromising the effectiveness of MCB. We characterized in situ for the first time the nearfield aerosol dispersion from a point source of atomized seawater produced using the effervescent technique. We observed consistent vertical mixing of the plume up to 150 ± 5 m height at 1 km downwind. The extent of vertical dispersion was influenced by wind velocity and atmospheric stability. We found no evidence that negative buoyancy due to the evaporation of the 0.068 kg/s water fraction significantly suppressed vertical mixing. Our results can be attributed to the small droplet sizes generated by the effervescent spray technology and associated low flow rates required to generate around 1014 droplets s-1. We estimate that, for a hypothetical implementation producing up to 1016 s-1 similarly sized SSAs, evaporative cooling is unlikely to significantly suppress the vertical dispersion of aerosol for MCB.
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Atmósfera , Agua de Mar , Agua , Viento , Aerosoles/análisisRESUMEN
The ability to synthetically tune the ligand frameworks of redox-active molecules is of critical importance to the economy of solar fuels because manipulating their redox properties can afford control over the operating potentials of sustained electrocatalytic or photoelectrocatalytic processes. The electronic and steric properties of 2,2':6',2â³-terpyridine (Terpy) ligand frameworks can be tuned by functional group substitution on ligand backbones, and these correlate strongly to their Hammett parameters. The synthesis of a new series of tridentate meridional ligands of 2,4,6-trisubstituted pyridines that engineers the ability to finely tune the redox potentials of cobalt complexes to more positive potentials than that of their Terpy analogs is achieved by aryl-functionalizing at the four-position and by including isoquinoline at the two- and six-positions of pyridine (Aryl-DiQ). Their cobalt complex syntheses, their electronic properties, and their catalytic activity for carbon dioxide (CO2) reduction are reported and compared to their Terpy analogs. The cobalt derivatives generally experience a positive shift in their redox features relative to the Terpy-based analogs, covering a complementary potential range. Although those evaluated fail to produce any quantifiable products for the reduction of CO2 and suffer from long-term instability, these results suggest possible alternate strategies for stabilizing these compounds during catalysis. We speculate that lower equilibrium association constants to the cobalt center are intrinsic to these ligands, which originate from a steric interaction between protons on the pyridine and isoquinoline moieties. Nevertheless, the new Aryl-DiQ ligand framework has been engineered to selectively tune homoleptic cobalt complexes' redox potentials.
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Central neurocytoma is the most common primary intraventricular tumor in adults being classified by the World Health Organization (WHO) as a benign grade II tumor with a good prognosis. Given the recent advances with regard to this tumor, a bibliometric analysis was due to study the future direction of research for neurocytomas. A comprehensive Elsevier's Scopus database search was performed to capture all published and indexed studies to date relevant to neurocytoma. A discrete set of validated bibliometric parameters were extracted and analyzed on R v4.1.3. A total of 1002 documents were included in our analysis covering a period between 1910 and 2021 (111 years). Around 98.5% of the documents were multi-author publications with a collaboration index (CI) of 4.21. Acta Neuropathologica, The American Journal of Surgical Pathology, and Cancer were the journals to include the highest number of top ten cited articles (2 out of 10 most cited articles, 20%). Switzerland (4 out of 10, 40%) accounted for the country to have the highest number of top 10 most cited articles with the USA (5588 out of 16,395 citations, 34.1%) having the greatest number of citations. Lastly, our analysis reported an annual growth rate of 6.9% for the number of papers produced by year. This is the first bibliometric analysis to study the top 10 most cited articles with regard to neurocytomas. A shift from histopathologic and clinical symptoms towards the treatment and management of the tumor was observed in our analysis.
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Neurocitoma , Humanos , Estados Unidos , Neurocitoma/cirugía , Bibliometría , Publicaciones , Suiza , Bases de Datos FactualesRESUMEN
While magnetic resonance imaging (MRI) is the current standard imaging method for diagnosing and localizing corticotropinomas in Cushing disease, it can fail to detect adenomas in up to 40% of cases. Recently, positron emission tomography (PET) has shown promise as a diagnostic tool to detect pituitary adenomas in Cushing disease. We perform a scoping review to characterize the uses of PET in diagnosing Cushing disease, with a focus on describing the types of PET investigated and defining PET-positive disease. A scoping review was conducted following the PRISMA-ScR guidelines. Thirty-one studies fulfilled our inclusion criteria, consisting of 10 prospective studies, 8 retrospective studies, 11 case reports, and 2 illustrative cases with a total of 262 patients identified. The most commonly utilized PET modalities in prospective/retrospective studies were FDG PET (n = 5), MET PET (n = 5), 68 Ga-DOTATATE PET (n = 2), 13N-ammonia PET (n = 2), and 68 Ga-DOTA-CRH PET (n = 2). MRI positivity ranged from 13 to 100%, while PET positivity ranged from 36 to 100%. In MRI-negative disease, PET positivity ranged from 0 to 100%. Five studies reported the sensitivity and specificity of PET, which ranged from 36 to 100% and 50 to 100%, respectively. PET shows promise in detecting corticotropinomas in Cushing disease, including MRI-negative disease. MET PET has been highly investigated and has demonstrated excellent sensitivity and specificity. However, preliminary studies with FET PET and 68 Ga-DOTA-CRH PET show promise for achieving high sensitivity and specificity and warrant further investigation.
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Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT) , Humanos , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/diagnóstico por imagen , Radioisótopos de Nitrógeno , Estudios Prospectivos , Estudios Retrospectivos , Tomografía de Emisión de PositronesRESUMEN
Despite more than six decades of extensive research, the etiology of moyamoya disease (MMD) remains unknown. Inflammatory or autoimmune (AI) processes have been suggested to instigate or exacerbate the condition, but the data remains mixed. The objective of the present systematic review was to summarize the available literature investigating the association of MMD and AI conditions as a means of highlighting potential treatment strategies for this subset of moyamoya patients. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the PubMed, Embase, Scopus, Web of Science, and Cochrane databases were queried to identify studies describing patients with concurrent diagnoses of MMD and AI disease. Data were extracted on patient demographics, clinical outcomes, and treatment. Stable or improved symptoms were considered favorable outcomes, while worsening symptoms and death were considered unfavorable. Quantitative pooled analysis was performed with individual patient-level data. Of 739 unique studies identified, 103 comprising 205 unique patients (80.2% female) were included in the pooled analysis. Most patients (75.8%) identified as Asian/Pacific Islanders, and the most commonly reported AI condition was Graves' disease (57.6%), with 55.9% of these patients presenting in a thyrotoxic state. Of the 148 patients who presented with stroke, 88.5% of cases (n = 131) were ischemic. Outcomes data was available in 152 cases. There were no significant baseline differences between patients treated with supportive therapy alone and those receiving targeted immunosuppressant therapy. Univariable logistic regression showed that surgery plus medical therapy was more likely than medical therapy alone to result in a favorable outcome. On subanalysis of operated patients, 94.1% of patients who underwent combined direct and indirect bypass reported favorable outcomes, relative to 76.2% of patients who underwent indirect bypass and 82% who underwent direct bypass (p < 0.05). On univariable analysis, the presence of multiple AI disorders was associated with worse outcomes relative to having a single AI disorder. Autoimmune diseases have been uncommonly reported in patients with MMD, but the presence of multiple AI comorbidities portends poorer prognosis. The addition of surgical intervention appears to improve outcomes and for patients deemed surgical candidates, combined direct and indirect bypass appears to offer better outcomes that direct or indirect bypass alone.
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Enfermedades Autoinmunes , Enfermedad de Moyamoya , Accidente Cerebrovascular , Humanos , Femenino , Masculino , Enfermedad de Moyamoya/complicaciones , Enfermedad de Moyamoya/epidemiología , Enfermedad de Moyamoya/cirugía , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/epidemiología , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Bases de Datos FactualesRESUMEN
BACKGROUND AND PURPOSE: Meningeal lymphatic vessels (MLVs) along the dural venous sinuses are suspected to be important in connecting the glymphatic and peripheral lymphatic system. Understanding the topography of MLVs may clarify the role of the glymphatic system in neurological diseases. The aim of this analysis was to use high resolution pre- and post-contrast FLAIR 7T MRI to identify and characterize the morphology of MLV in a cohort of healthy volunteers. MATERIALS AND METHODS: MRI examinations of seventeen healthy volunteers enrolled as controls in a larger 7T MRI study were reviewed. Pre- and post-contrast 3-D FLAIR subtractions and MP2RAGE sequences were spatially normalized and reviewed for signal intensity and enhancement patterns within putative MLVs along pre-determined dural and venous structures. Frequency of occurrence of MLVs at the above-described locations and patterns of their enhancement were analyzed. RESULTS: Putative MLVs are commonly located along the superior sagittal sinus (SSS) and cortical veins. A "fixed enhancement" signal pattern was more frequent at these locations (p<.05). The morphology of MLVs along the SSS qualitatively changes in an antero-posterior direction. Lack of signal was more frequent along the straight and transverse sinuses (p<.05). CONCLUSION: Putative MLVs in healthy individuals are concentrated along the SSS and cortical veins. FLAIR signal and enhancement characteristics suggest these structures may transport proteinaceous fluid. Pathways connecting MLVs to cervical lymph nodes however remain unclear.
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Sistema Glinfático , Meninges , Humanos , Adulto , Meninges/diagnóstico por imagen , Meninges/patología , Imagen por Resonancia Magnética/métodos , Senos CranealesRESUMEN
BACKGROUND: Retinal atrophy in multiple sclerosis (MS) as measured by optical coherence tomography (OCT) correlates with demyelinating lesions and brain atrophy, but its relationship with cortical lesions (CLs) and meningeal inflammation is not well known. OBJECTIVES: To evaluate the relationship of retinal layer atrophy with leptomeningeal enhancement (LME) and CLs in MS as visualized on 7 Tesla (7T) magnetic resonance imaging (MRI). METHODS: Forty participants with MS underwent 7T MRI of the brain and OCT. Partial correlation and mixed-effects regression evaluated relationships between MRI and OCT findings. RESULTS: All participants had CLs and 32 (80%) participants had LME on post-contrast MRI. Ganglion cell/inner plexiform layer (GCIPL) thickness correlated with total CL volume (r =-0.45, p < 0.01). Participants with LME at baseline had thinner macular retinal nerve fiber layer (mRNFL; p = 0.01) and GCIPL (p < 0.01). Atrophy in various retinal layers was faster in those with certain patterns of LME. For example, mRNFL declined -1.113 (-1.974, -0.252) µm/year faster in those with spread/fill-pattern LME foci at baseline compared with those without (p = 0.01). CONCLUSION: This study associates MRI findings of LME and cortical pathology with thinning of retinal layers as measured by OCT, suggesting a common link between meningeal inflammation, CLs, and retinal atrophy in MS.
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Esclerosis Múltiple , Degeneración Retiniana , Atrofia/patología , Humanos , Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología , Retina/diagnóstico por imagen , Retina/patología , Degeneración Retiniana/patología , Tomografía de Coherencia ÓpticaRESUMEN
Although multiple sclerosis has traditionally been considered a white matter disease, extensive research documents the presence and importance of grey matter injury including cortical and deep regions. The deep grey matter exhibits a broad range of pathology and is uniquely suited to study the mechanisms and clinical relevance of tissue injury in multiple sclerosis using magnetic resonance techniques. Deep grey matter injury has been associated with clinical and cognitive disability. Recently, MRI characterization of deep grey matter properties, such as thalamic volume, have been tested as potential clinical trial end points associated with neurodegenerative aspects of multiple sclerosis. Given this emerging area of interest and its potential clinical trial relevance, the North American Imaging in Multiple Sclerosis (NAIMS) Cooperative held a workshop and reached consensus on imaging topics related to deep grey matter. Herein, we review current knowledge regarding deep grey matter injury in multiple sclerosis from an imaging perspective, including insights from histopathology, image acquisition and post-processing for deep grey matter. We discuss the clinical relevance of deep grey matter injury and specific regions of interest within the deep grey matter. We highlight unanswered questions and propose future directions, with the aim of focusing research priorities towards better methods, analysis, and interpretation of results.
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Encéfalo/patología , Sustancia Gris/patología , Esclerosis Múltiple/patología , HumanosRESUMEN
Millipedes (Diplopoda) are well known for their toxic or repellent defensive secretions. Here, we describe (6aR,10aS,10bR)-8,8-dimethyldodecahydropyrrolo[2,1-a]isoquinoline [trans-anti-trans-deoxybuzonamine (1a)] and (rel-6aR,10aR,10bR)-8,8-dimethyldodecahydropyrrolo[2,1-a]isoquinoline [trans-syn-cis-deoxybuzonamine (1b)], two isomers of deoxybuzonamine found in the chemical defense secretions of the millipede Brachycybe lecontii Wood (Colobognatha, Platydesmida, Andrognathidae). The carbon-nitrogen skeleton of these compounds was determined from their MS and GC-FTIR spectra obtained from the MeOH extract of whole millipedes, along with a subsequent selective synthesis. Their structures were established from their 1D (1H, 13C) and 2D NMR (COSY, NOESY, multiplicity-edited HSQC, HSQC-TOCSY, HMBC) spectra. Additionally, computational chemistry (DFT and DP4) was used to identify the relative configurations of 1a and 1b by comparing predicted 13C data to their experimental values, and the absolute configuration of 1a was determined by comparing its experimental specific rotation with that of the computationally calculated value. This is the first report of dodecahydropyrrolo[2,1-a]isoquinoline alkaloids from a platydesmidan millipede.
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Artrópodos , Animales , Artrópodos/química , Isomerismo , Espectroscopía de Resonancia Magnética , Estructura MolecularRESUMEN
BACKGROUND: Pilocytic astrocytomas are the most common low-grade glioma of the central nervous system that typically occurs in children, and much research has been dedicated to characterizing their molecular features and clinical courses. We provide an overview of the current literature through the use of a bibliometric analysis of the top 100 most cited publications discussing pilocytic astrocytomas. METHODS: We identified the top 100 most cited publications discussing pilocytic astrocytomas. Articles were ranked based on the number of citations. Descriptive statistics and univariate analysis were used to determine any trends or significant differences in the data. RESULTS: Of the top 100 articles, 50 were basic science (50%), 34 were clinical (34%), and 16 were review (16%). The number of citations ranged from 79 to 921, with 123 being the median. The US had the most first authors and principal authors (n = 53 and n = 54, respectively). Years of publication had a left-skewed distribution and peaked during 2011 with 12 articles published in that year. Sixty percent of basic science articles investigated BRAF/MAPK pathways, while 67.6% of clinical articles focused on evaluating treatment options for pilocytic astrocytomas. Compared to basic science and clinical articles, review articles were published more recently (p < 0.001), had fewer authors (p = 0.025) and were published in journals with higher impact factors (p = 0.022). CONCLUSION: Research regarding pilocytic astrocytomas has increased over the past three decades. Future directions of research point towards employing targeted therapies and discovering additional cellular pathways contributing to disease pathogenesis.
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Astrocitoma , Glioma , Astrocitoma/patología , Astrocitoma/terapia , Bibliometría , Niño , Humanos , Proyectos de InvestigaciónRESUMEN
The literature has had some conflicting evidence regarding the effective management of lumbar spondylolisthesis (LS). Herein, we review active and prospective clinical trials to identify the emerging trends for the management of LS. A systematic search was conducted utilizing the NIH Clinical Trials database using the search term "lumbar spondylolisthesis" on February 2, 2022. Currently active and prospective clinical trials for LS were included and analyzed. All statistical analyses were performed on R 4.1.2. We identified 37 clinical trials. Nearly half the trials (n = 18, 48.6%) include novel technologies; 6 (16.2%) are comparing surgical approaches, of which 4 (67%) include decompression alone versus decompression with instrumented fusion; 6 (16.2%) are evaluating perioperative pain management protocols, of which 3 (50%) include bupivacaine or ropivacaine; 3 (8.1%) are evaluating alternative medicines in LS; 2 (5.4%) are observational studies about the natural history of LS; 1 (2.7%) involves surgical infection prophylaxis; and 1 (2.7%) is evaluating AK1320 microspheres. The 18 trials involving novel technologies include 3D-printed titanium cages (n = 3, 16.7%), interbody implants (n = 4, 22.2%), bone graft materials (n = 4, 22.2%), and miscellaneous intraoperative devices (n = 7, 38.9%). The top 3 outcomes measured were Oswestry Disability Index (n = 28, 75.7%), visual analog scale (n = 21, 56.7%), and postoperative radiographs (n = 16, 43.2%). Patient-reported outcome measures (PROMs) were included in 34 (91.9%) trials, while 23 (62.2%) trials included lumbar spine imaging. LS can often require a multifaceted approach. Novel technologies and utilization of PROMs appear to be a significant emerging trend in LS management.
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Fusión Vertebral , Espondilolistesis , Humanos , Espondilolistesis/cirugía , Fusión Vertebral/métodos , Estudios Prospectivos , Vértebras Lumbares/cirugía , Región Lumbosacra/cirugía , Resultado del TratamientoRESUMEN
Whilst 2- or 5-OMe groups on the bridging phenylene ring in [{Cp*(dppe)RuC≡C}2 (µ-1,3-C6 H4 )]+ have little influence on the electronic structure of this weakly coupled mixed-valence complex, a 4-OMe substituent enhances ground state electron delocalization, and increases the intensity of the IVCT transition. Vibrational frequency and TDDFT calculations (LH20t-D3(BJ), def2-SVP, COSMO (CH2 Cl2 )) on ([{Cp*(dppe)RuC≡C}2 (µ-1,3-C6 H3 -n-OMe)]+ (n=2, 4, 5) models are in excellent agreement with the experimental results. The stronger ground state coupling is attributed to the change in composition of the ß-HOSO brought about by the 4-OMe group, which is ortho or para to each of the metal fragments. The intensity of the IVCT transition increases with the greater overlap of the ß-HOSO and ß-LUSO, whilst the relative phases of the ß-HOSO and ß-LUSO in the 4-OMe substituted complex are consistent with predictions of constructive quantum interference from molecular circuit rules.
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BACKGROUND: Cortical demyelination is a relevant aspect of tissue damage in multiple sclerosis (MS). Microstructural changes may affect each layer in the cortex differently. OBJECTIVES: To evaluate the sensitivity of quantitative magnetic resonance imaging (qMRI) measurements on cortical layers as clinically accessible biomarkers of grey matter (GM) pathology. METHODS: Forty-five participants with MS underwent 7 T magnetic resonance imaging (MRI) of the brain. Magnetization prepared two rapid acquisition gradient echoes (MP2RAGE) was processed for T1-weighted images and a T1 map. Multi-echo gradient echo images were processed for quantitative susceptibility and R2* maps. Cortical GM volumes were segmented into four cortical layers, and relaxometry metrics were calculated within and between these layers. RESULTS: Significant correlations were found for disability scales and multi-layer metrics, for example, Expanded Disability Status Scale (EDSS) and peak height (PH) in the subpial (T1: ρ = -0.372, p < 0.050) and inner (R2*: ρ = -0.359, p < 0.050) cortical layers. Multivariate regression showed interdependency between atrophy and cortical metrics in some instances, but an independent relationship between cortical metrics and disability in others. CONCLUSION: Cortical layer 7 T qMRI analyses reveal layer-specific relationships with disability in MS and allow emergence of clinically relevant associations that are hidden when analysing the full cortex.
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Esclerosis Múltiple , Atrofia/patología , Encéfalo , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Humanos , Imagen por Resonancia Magnética , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patologíaRESUMEN
Homoleptic transition-metal complexes of 2,2':6',2â³-terpyridine (terpy) and substituted derivatives of the form [M(R-terpy)2]2+ display a wide range of redox potentials that correlate well to the Hammett parameter of the terpy substituents. Less is known about the impact of incorporating a phenyl spacer between the functional group responsible for controlling the electron density of terpy and how that translates to metal complexes of the form [M(4'-aryl-terpy)2]2+, where M = Mn, Fe, Co, Ni, and Zn. Herein, we report our studies on these complexes revealed a good correlation of redox potentials of both metal- and ligand-centered events with the Hammett parameters of the aryl substituents, regardless of aryl-substitution pattern (i.e., the presence of multiple functional groups, combinations of withdrawing and donating functional groups). The phenyl spacer results in 60-80% attenuation of electron density as compared to the 4'-substituted terpy analogue, depending on the metal and redox couple analyzed. Density functional theory calculations performed on a simple model system revealed a strong correlation between the Hammett parameters and lowest unoccupied molecular orbital energies of the corresponding substituted pyridine models, thus serving as an inexpensive predictive tool when coupled with electrochemical data. Overall, these data suggest that such ligand modifications may be used in combination with previous approaches to further fine-tune the redox potentials of homoleptic transition-metal complexes, which may have applications in photochemical and electrochemical catalytic processes.
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BACKGROUND: Autopsy data suggest a causative link between meningeal inflammation and cortical lesions (CLs) in multiple sclerosis (MS). OBJECTIVE: To use leptomeningeal enhancement (LME) and CLs on 7-Tesla (7T) magnetic resonance imaging (MRI) to investigate associations between meningeal inflammation and cortical pathology. METHODS: Forty-one participants with MS underwent 7T MRI of the brain. CLs and foci of LME were quantified. RESULTS: All MS participants had CLs; 27 (65.8%) had >1 focus of LME. Except for hippocampal CL count (ρ = 0.32 with spread/fill-sulcal pattern LME, p = 0.042), no significant correlations were seen between LME and CLs. Mean cortical thickness correlated with the number of LME foci (ρ = -0.43, p = 0.005). Participants with relapsing-remitting multiple sclerosis (RRMS) showed no correlation with neocortical CLs, but significant correlations were seen between LME and hippocampal lesion count (ρ = 0.39, p = 0.030), normalized cortical gray matter (GM) volume (ρ = -0.49, p = 0.005), and mean cortical thickness (ρ = -0.59, p < 0.001). CONCLUSION: This study supports a relationship between LME and cortical GM atrophy but does not support an association of LME and neocortical CLs. This may indicate that meningeal inflammation is involved with neurodegenerative inflammatory processes, rather than focal lesion development.
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Encéfalo/diagnóstico por imagen , Encéfalo/patología , Meninges/diagnóstico por imagen , Meninges/patología , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología , Adulto , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Neuroimagen/métodosRESUMEN
Millipedes (Diplopoda) are well known for their toxic or repellent defensive secretions. Here we describe gosodesmine (1), 7-(4-methylpent-3-en-1-yl)-1,2,3,5,8,8a-hexahydroindolizine, a unique alkaloid with some terpene character found in the chemical defense secretions of the millipede Gosodesmus claremontus Chamberlin (Colobognatha, Platydesmida, Andrognathidae). The structure of 1 was suggested by its mass spectra and GC-FTIR spectra and established from its 1H, 13C, and 2D NMR spectra and 1D NOE studies. The 7-substituted indolizidine carbon skeleton of 1 was confirmed by unambiguous synthesis. This is the first report of an alkaloid from a platydesmid millipede and the first report of a 7-substituted indolizidine from an arthropod.