Antidepressant Augmentation versus Switch in Treatment-Resistant Geriatric Depression.

BACKGROUND: The benefits and risks of augmenting or switching antidepressants in older adults with treatment-resistant depression have not been extensively studied. METHODS: We conducted a two-step, open-label trial involving adults 60 years of age or older with treatment-resistant depression. In step 1, patients were randomly assigned in a 1:1:1 ratio to augmentation of existing antidepressant medication with aripiprazole, augmentation with bupropion, or a switch from existing antidepressant medication to bupropion. Patients who did not benefit from or were ineligible for step 1 were randomly assigned in step 2 in a 1:1 ratio to augmentation with lithium or a switch to nortriptyline. Each step lasted approximately 10 weeks. The primary outcome was the change from baseline in psychological well-being, assessed with the National Institutes of Health Toolbox Positive Affect and General Life Satisfaction subscales (population mean, 50; higher scores indicate greater well-being). A secondary outcome was remission of depression. RESULTS: In step 1, a total of 619 patients were enrolled; 211 were assigned to aripiprazole augmentation, 206 to bupropion augmentation, and 202 to a switch to bupropion. Well-being scores improved by 4.83 points, 4.33 points, and 2.04 points, respectively. The difference between the aripiprazole-augmentation group and the switch-to-bupropion group was 2.79 points (95% CI, 0.56 to 5.02; P = 0.014, with a prespecified threshold P value of 0.017); the between-group differences were not significant for aripiprazole augmentation versus bupropion augmentation or for bupropion augmentation versus a switch to bupropion. Remission occurred in 28.9% of patients in the aripiprazole-augmentation group, 28.2% in the bupropion-augmentation group, and 19.3% in the switch-to-bupropion group. The rate of falls was highest with bupropion augmentation. In step 2, a total of 248 patients were enrolled; 127 were assigned to lithium augmentation and 121 to a switch to nortriptyline. Well-being scores improved by 3.17 points and 2.18 points, respectively (difference, 0.99; 95% CI, -1.92 to 3.91). Remission occurred in 18.9% of patients in the lithium-augmentation group and 21.5% in the switch-to-nortriptyline group; rates of falling were similar in the two groups. CONCLUSIONS: In older adults with treatment-resistant depression, augmentation of existing antidepressants with aripiprazole improved well-being significantly more over 10 weeks than a switch to bupropion and was associated with a numerically higher incidence of remission. Among patients in whom augmentation or a switch to bupropion failed, changes in well-being and the occurrence of remission with lithium augmentation or a switch to nortriptyline were similar. (Funded by the Patient-Centered Outcomes Research Institute; OPTIMUM ClinicalTrials.gov number, NCT02960763.).

Enhanced Photocatalytic Activities of Sodium Borohydride-Calcined Magnetic Manganese Ferrite Nanoparticles.

The synthesis, enhancement, and maintenance of magnetite-based catalyst nanoparticles (NPs) are important for photocatalytic activity and recovery rates. We used a sodium borohydride (NaBH4) calcination method to modify MnFe2O4 nanoparticles to optimize their performance in the photocatalytic oxidation of 2,5-hydroxymethylfurfural. The results indicated a 94% increase in photocatalytic efficiency, while magnetic assessments performed using a vibrating sample magnetometer showed an 8.9% improvement in magnetic properties without degradation. These findings show the dual benefits of increased photocatalytic performance with strong magnetic properties, which are important for the application and reusability of photocatalysts. The recycling of these photocatalysts reduces secondary pollution and increases the process cost-effectiveness. These results contribute to the solution of problems with the use of photocatalytic materials.

Safety and efficacy of IV theophylline for regadenoson-associated side effect reversal.

BACKGROUND: Aminophylline injection has been on an intermittent nation-wide shortage due to manufacturing delays leaving a need for an alternative reversal agent for regadenoson-associated side effects. Intravenous theophylline should be a logical acceptable pharmacological alternative; however, data regarding its safety and efficacy as a reversal agent are lacking. METHODS: Utilizing electronic medical records at the University of Colorado hospital, we identified patients ≥ 18 years of age who had a pharmacologic stress test using regadenoson during periods of aminophylline shortage (3/1/2013 to 5/31/2013 and 4/1/2018 to 8/30/2018) in which theophylline was used as an alternative antidote for side effect reversal. Intravenous theophylline was prepared by the inpatient pharmacy to a concentration of 0.8 mg/mL in a total volume of 100 mL D5W. Specific side effects and side effect resolution were evaluated. RESULTS: Of the 122 patients evaluated, theophylline was administered in doses ranging from 40 to 75 mg with the majority receiving 40 mg. Complete resolution of regadenoson side effects occurred in 98 patients with 12 experiencing partial resolution and 1 without resolution. No adverse effects or events were reported. CONCLUSION: Due to limited availability of aminophylline, theophylline may be a safe and effective alternative to reverse regadenoson-associated side effects.

Performance Promotion of Multipurpose Catalysts Using Increased Oxygen Vacancy Amounts by Charge-Mismatched Doping.

Modulating the oxygen vacancy (V0) in nanostructures has opened a new avenue for efficient catalyst design, facilitating biomass oxidation reactions and electrocatalytic properties. In this study, we have investigated the properties of NiO-based catalysts with varying degrees of V0 achieved through ion doping of the catalyst with cations of different oxidation states (TM3+) or the same valence state (TM2+) as Ni2+ in the NiO matrix. By introducing charge-mismatched dopants, we enhanced the concentration of V0 in the NiO catalyst, resulting in remarkable selectivity (∼50%) for the conversion of 2,5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA), as well as a lower overpotential in the oxygen evolution reaction (OER). We believe that charge-mismatched doping offers a novel avenue for optimizing defect engineering in oxide-based catalysts, which can enable more efficient biomass conversion and water splitting. These findings have made a significant contribution to the field of multipurpose catalysis and hold the potential to inspire new catalyst designs that would usher in a more sustainable future.

Revealing Photocatalytic Performance of ZnxCd1-xS Nanoparticles Depending on the Irradiation Wavelength.

Photocatalysts are useful for various applications, including the conservation and storage of energy, wastewater treatment, air purification, semiconductors, and production of high-value-added products. Herein, ZnxCd1-xS nanoparticle (NP) photocatalysts with different concentrations of Zn2+ ions (x = 0.0, 0.3, 0.5, or 0.7) were successfully synthesized. The photocatalytic activities of ZnxCd1-xS NPs varied with the irradiation wavelength. X-ray diffraction, high-resolution transmission electron microscopy, energy-dispersive X-ray spectroscopy, and ultraviolet-visible spectroscopy were used to characterize the surface morphology and electronic properties of the ZnxCd1-xS NPs. In addition, in situ X-ray photoelectron spectroscopy was performed to investigate the effect of the concentration of Zn2+ ions on the irradiation wavelength for photocatalytic activity. Furthermore, wavelength-dependent photocatalytic degradation (PCD) activity of the ZnxCd1-xS NPs was investigated using biomass-derived 2,5-hydroxymethylfurfural (HMF). We observed that the selective oxidation of HMF using ZnxCd1-xS NPs resulted in the formation of 2,5-furandicarboxylic acid via 5-hydroxymethyl-2-furancarboxylic acid or 2,5-diformylfuran. The selective oxidation of HMF was dependent on the irradiation wavelength for PCD. Moreover, the irradiation wavelength for the PCD depended on the concentration of Zn2+ ions in the ZnxCd1-xS NPs.

Enhancement of Sulfur Source-Dependent Zn Vacancies in Different Photocatalytic Performances of ZnIn2S4 Nanoparticles.

This study focuses on the synthesis and investigation of ZnIn2S4 nanoparticle (NP) photocatalysts treated with different sulfur sources, thioacetamide (TAA), or thiourea (TU), to explore their wavelength-dependent photocatalytic activity. The research aims to understand the impact of Zn vacancies present on the surface of ZnIn2S4 NPs. The investigation involves electron spin resonance and in situ X-ray photoelectron spectroscopy to study the photocatalytic activity of ZnIn2S4-TU and ZnIn2S4-TAA NPs, following the characterization of surface morphology and electronic properties using high-resolution transmission electron microscopy and X-ray diffraction. Additionally, the study delves into the wavelength-dependent photocatalytic degradation (PCD) activity of the ZnIn2S4 NPs using 2,5-hydroxymethylfurfural (HMF) across a wide range. Notably, the selective oxidation of HMF using ZnIn2S4-TU NPs resulted in the formation of 2,5-furandicarboxylic acid (FDCA) via 2,5-diformylfuran, with an efficiency exceeding 40% over the broad wavelength range. The research demonstrates that the irradiation wavelength for PCD is influenced by the number of defect structures introduced into the ZnIn2S4 NPs through the sulfur source.

A General Autofluorescence Method to Characterize Polymerization Progress.

An autofluorescence technique to characterize polymerization progress in real time/in line was developed, which functioned in the absence of typical fluorogenic groups on the monomer or polymer. The monomer dicyclopentadiene and polymer polydicyclopentadiene are hydrocarbons that lack traditional functional groups for fluorescence spectroscopy. Here, the autofluorescence of formulations containing this monomer and polymer during ruthenium-catalyzed ring-opening metathesis polymerization (ROMP) was harnessed for reaction monitoring. The methods fluorescence recovery after photobleaching (FRAP) and here-developed fluorescence lifetime recovery after photobleaching (FLRAP) characterized polymerization progress in these native systems-without requiring exogenous fluorophore. (Auto)fluorescence lifetime recovery changes during polymerization correlated linearly to degree of cure, providing a quantitative link with reaction progress. These changing signals also provided relative rates of background polymerization, enabling comparison of 10 different catalyst-inhibitor-stabilized formulations. Multiple-well analysis demonstrated suitability for future high-throughput evaluation of formulations for thermosets. The central concept of the combined autofluorescence and FLRAP/FRAP method may be extendable to monitoring other polymerization reactions previously overlooked for lack of an obvious fluorescence handle.

Selective Oxidation of Biomass Molecules via ZnO Nanoparticles Modified Using Charge Mismatch of the Doped Co ions.

A charge mismatch between transition-metal-ion dopants and metal oxide nanoparticles (MO NPs) within an engineered complex engenders a significant number of oxygen vacancies (VO) on the surface of the MO NP construct. To elucidate in-depth the mechanism of this tendency, Co ions with different charge states (Co3+ and Co2+) were doped into ZnO NPs, and their atomic structural changes were correlated with their photocatalytic efficiency. We ascertained that the increase of the Zn-O bond distances was distinctly affected by Co3+-ion doping, and, subsequently, the number of VO was noticeably increased. We further investigated the mechanistic pathways of the photocatalytic oxidation of 2,5-hydroxymethylfurfural (HMF), which have been widely investigated as biomass derivatives because of their potential use as precursors for the synthesis of sustainable alternatives to petrochemical substances. To identify the reaction products in each oxidation step, selective oxidation products obtained from HMF in the presence of pristine ZnO NPs, Co3+- and Co2+-ion-doped ZnO NPs were evaluated. We confirmed that Co3+-ion-doped ZnO NPs can efficiently and selectively oxidize HMF with a good conversion rate (∼40%) by converting HMF to 2,5-furandicarboxylic acid (FDCA). The present study demonstrates the feasibility of improving the production efficiency of FDCA (an alternative energy material) by using enhanced photocatalytic MO NPs with the help of the charge mismatch between MO and metal-ion dopants.

Ecological Momentary Assessment of Real-World Functional Behaviors in Individuals With Stroke: A Longitudinal Observational Study.

OBJECTIVE: To validate and characterize real-world functional behaviors in individuals after stroke. DESIGN: Longitudinal observational study using ecological momentary assessment (EMA) as a real-time assessment of functional behaviors in natural contexts. Wilcoxon rank-sum tests, Fisher exact tests, and Spearman correlations were used to analyze data. SETTING: Community. PARTICIPANTS: Individuals with mild to moderate stroke (N=212). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Individuals were assessed 5 times daily for 14 days with EMA surveys to determine what, with whom, and where individuals were doing activities and appraise mental, somatic, and cognitive symptoms. Individuals also completed standardized assessments during laboratory visits, including Lawton Instrumental Activities of Daily Living Scale, Activity Card Sort, Patient-Reported Outcome Measurement Information System, and Quality of Life in Neurological Disorders. RESULTS: Most individuals (median age, 60 years; 55% male) were ischemic stroke (90%) and had mild stroke severity (median National Institutes of Health Stroke Scale, 2). A total of 14,140 EMA surveys were analyzed. Individuals were home 78% of the time; primarily participated in passive, unproductive activities (27%), especially watching television and resting; and participated least in physical activities (4%). EMA was sensitive to indicators of poststroke disability; unemployed individuals reported fewer vocational activities but more activities of daily living (ADL) and passive activities than employed counterparts. Users of mobility devices and individuals with cognitive problems spent significantly less time on vocational activities and more on ADL than nonusers and those without cognitive problems. Our data supported the validity of EMA methods in stroke, with small to moderate correlations of EMA with in-laboratory measures of daily functioning (r=-0.30 to 0.35, P<.05) and very large correlations between EMA and in-laboratory measures of symptoms, especially those measuring same constructs (r=-0.64 to 0.79, P<.0001). CONCLUSIONS: Our findings reveal that EMA tracked poststroke functioning precisely. EMA may be beneficial in examining poststroke functional recovery, in monitoring patients for home-based interventions, and for longitudinal research.

Comparison between Nanoparticle Encapsulation and Surface Loading for Lysosomal Enzyme Replacement Therapy.

Poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) enhance the delivery of therapeutic enzymes for replacement therapy of lysosomal storage disorders. Previous studies examined NPs encapsulating or coated with enzymes, but these formulations have never been compared. We examined this using hyaluronidase (HAse), deficient in mucopolysaccharidosis IX, and acid sphingomyelinase (ASM), deficient in types A−B Niemann−Pick disease. Initial screening of size, PDI, ζ potential, and loading resulted in the selection of the Lactel II co-polymer vs. Lactel I or Resomer, and Pluronic F68 surfactant vs. PVA or DMAB. Enzyme input and addition of carrier protein were evaluated, rendering NPs having, e.g., 181 nm diameter, 0.15 PDI, −36 mV ζ potential, and 538 HAse molecules encapsulated per NP. Similar NPs were coated with enzyme, which reduced loading (e.g., 292 HAse molecules/NP). NPs were coated with targeting antibodies (> 122 molecules/NP), lyophilized for storage without alterations, and acceptably stable at physiological conditions. NPs were internalized, trafficked to lysosomes, released active enzyme at lysosomal conditions, and targeted both peripheral organs and the brain after i.v. administration in mice. While both formulations enhanced enzyme delivery compared to free enzyme, encapsulating NPs surpassed coated counterparts (18.4- vs. 4.3-fold enhancement in cells and 6.2- vs. 3-fold enhancement in brains), providing guidance for future applications.