RESUMEN
BACKGROUND: Visual snow syndrome (VSS) is associated with functional connectivity (FC) dysregulation of visual networks (VNs). We hypothesized that mindfulness-based cognitive therapy, customized for visual symptoms (MBCT-vision), can treat VSS and modulate dysfunctional VNs. METHODS: An open-label feasibility study for an 8-week MBCT-vision treatment program was conducted. Primary (symptom severity; impact on daily life) and secondary (WHO-5; CORE-10) outcomes at Week 9 and Week 20 were compared with baseline. Secondary MRI outcomes in a subcohort compared resting-state functional and diffusion MRI between baseline and Week 20. RESULTS: Twenty-one participants (14 male participants, median 30 years, range 22-56 years) recruited from January 2020 to October 2021. Two (9.5%) dropped out. Self-rated symptom severity (0-10) improved: baseline (median [interquartile range (IQR)] 7 [6-8]) vs Week 9 (5.5 [3-7], P = 0.015) and Week 20 (4 [3-6], P < 0.001), respectively. Self-rated impact of symptoms on daily life (0-10) improved: baseline (6 [5-8]) vs Week 9 (4 [2-5], P = 0.003) and Week 20 (2 [1-3], P < 0.001), respectively. WHO-5 Wellbeing (0-100) improved: baseline (median [IQR] 52 [36-56]) vs Week 9 (median 64 [47-80], P = 0.001) and Week 20 (68 [48-76], P < 0.001), respectively. CORE-10 Distress (0-40) improved: baseline (15 [12-20]) vs Week 9 (12.5 [11-16.5], P = 0.003) and Week 20 (11 [10-14], P = 0.003), respectively. Within-subject fMRI analysis found reductions between baseline and Week 20, within VN-related FC in the i) left lateral occipital cortex (size = 82 mL, familywise error [FWE]-corrected P value = 0.006) and ii) left cerebellar lobules VIIb/VIII (size = 65 mL, FWE-corrected P value = 0.02), and increases within VN-related FC in the precuneus/posterior cingulate cortex (size = 69 mL, cluster-level FWE-corrected P value = 0.02). CONCLUSIONS: MBCT-vision was a feasible treatment for VSS, improved symptoms and modulated FC of VNs. This study also showed proof-of-concept for intensive mindfulness interventions in the treatment of neurological conditions.
Asunto(s)
Terapia Cognitivo-Conductual , Atención Plena , Trastornos de la Percepción , Trastornos de la Visión , Humanos , Masculino , Estudios de Factibilidad , Imagen por Resonancia Magnética , Resultado del TratamientoRESUMEN
PURPOSE: A challenging clinical scenario is distinguishing between normal tension glaucoma (NTG) and non-glaucomatous optic neuropathies (NGON). The key to the assessment remains identifying the presence of optic nerve head cupping. Recent optical coherence tomography (OCT) measurements now allow objective assessment of cupping by minimum rim width at Bruch's membrane opening (MRW-BMO). This study assessed the hypothesis that the MRW-BMO measurement quantifies cupping and therefore can differentiate between NTG and NGON. DESIGN: Diagnostic evaluation with area under the curve. METHODS: Setting: multicenter tertiary hospitals and outpatient clinics. PATIENT POPULATION: 81 eyes of 81 patients were enrolled, 27 with NTG and 54 with NGON, including ischemic optic neuropathy, previous optic neuritis, and compressive and inherited optic neuropathies. All NGON patients with intraocular pressure >21 mm Hg, narrow drainage angles, or a family history of glaucoma were excluded. Observational procedure: optic disc OCT images were obtained of both the retinal nerve fiber layer thickness and the MRW-BMO. MAIN OUTCOME MEASUREMENTS: the utility of the MRW-BMO in differentiating GON from NGON was assessed using the area under the curve (AUC) estimated from a logistic regression model. RESULTS: The 5-fold cross-validated AUC for glaucoma versus nonglaucoma from logistic regression models using MRW-BMO values from all sectors was 0.95 (95% confidence interval: 0.86-1.00). CONCLUSIONS: The measurement of MRW-BMO effectively differentiates between NTG and NGON with a high level of sensitivity and specificity. Incorporating this measurement into routine glaucoma assessment may provide a robust method of assisting clinicians to improve diagnosis and therefore treatment of optic nerve diseases.
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Lámina Basal de la Coroides/patología , Glaucoma de Baja Tensión/diagnóstico , Enfermedades del Nervio Óptico/diagnóstico , Adulto , Área Bajo la Curva , Lámina Basal de la Coroides/diagnóstico por imagen , Femenino , Humanos , Presión Intraocular/fisiología , Masculino , Persona de Mediana Edad , Fibras Nerviosas/patología , Curva ROC , Células Ganglionares de la Retina/patología , Sensibilidad y Especificidad , Tomografía de Coherencia Óptica , Tonometría Ocular , Campos VisualesRESUMEN
A study of single-laboratory validation (SLV) of a reversed-phase liquid chromatography (RP-LC) method was conducted for the determination of diester-diterpene Aconitum alkaloids, viz., aconitine, mesaconitine, and hypaconitine, in a variety of dietary supplements, including single- and multiple-ingredient dry powder extracts, pills, capsules, and raw materials. The Aconitum alkaloids in the samples were extracted by diethyl ether in the presence of ammonia. After cleanup with solid-phase extraction to remove the matrix interferences, the alkaloids were determined by RP-LC with UV detection at 235 nm, and the results were confirmed by tandem mass spectrometry. The linear responses for aconitine, mesaconitine, and hypaconitine based on the present LC system ranged from 0.5 to 200 microg/mL. Relative standard deviations of 2.0 to 6.9% were obtained from duplicate analysis of 6 test materials of different matrixes for the 3 Aconitum alkaloids performed by 2 analysts on 5 different days. The recoveries determined for supplements and raw materials spiked with 3 Aconitum alkaloids at levels of 2.5-10 microg/g were in the range of 86-99%. In view of the attainment of satisfactory results for accuracy, precision, and recovery in the SLV study, it is recommended that the method validation process proceed to a collaborative study.
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Aconitum/química , Alcaloides/análisis , Suplementos Dietéticos/análisis , Calibración , Cápsulas , Cromatografía Líquida de Alta Presión , Indicadores y Reactivos , Espectrometría de Masas , Extractos Vegetales/análisis , Estándares de Referencia , Reproducibilidad de los Resultados , Espectrofotometría Ultravioleta , ComprimidosRESUMEN
Streptavidin is a biotin-binding protein which has been widely used in many in vitro and in vivo applications. Because of the ease of protein recovery and availability of protease-deficient strains, the Bacillus subtilis expression-secretion system is an attractive system for streptavidin production. However, attempts to produce streptavidin using B. subtilis face the problem that cells overproducing large amounts of streptavidin suffer poor growth, presumably because of biotin deficiency. This problem cannot be solved by supplementing biotin to the culture medium, as this will saturate the biotin binding sites in streptavidin. We addressed this dilemma by engineering a B. subtilis strain (WB800BIO) which overproduces intracellular biotin. The strategy involves replacing the natural regulatory region of the B. subtilis chromosomal biotin biosynthetic operon (bioWAFDBIorf2) with an engineered one consisting of the B. subtilis groE promoter and gluconate operator. Biotin production in WB800BIO is induced by gluconate, and the level of biotin produced can be adjusted by varying the gluconate dosage. A level of gluconate was selected to allow enhanced intracellular production of biotin without getting it released into the culture medium. WB800BIO, when used as a host for streptavidin production, grows healthily in a biotin-limited medium and produces large amounts (35 to 50 mg/liter) of streptavidin, with over 80% of its biotin binding sites available for future applications.