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1.
Nature ; 630(8018): 866-871, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38839964

RESUMO

Membranes are widely used for separation processes in applications such as water desalination, batteries and dialysis, and are crucial in key sectors of our economy and society1. The majority of technologically exploited membranes are based on solid polymers and function as passive barriers, whose transport characteristics are governed by their chemical composition and nanostructure. Although such membranes are ubiquitous, it has proved challenging to maximize selectivity and permeability independently, leading to trade-offs between these pertinent characteristics2. Self-assembled biological membranes, in which barrier and transport functions are decoupled3,4, provide the inspiration to address this problem5,6. Here we introduce a self-assembly strategy that uses the interface of an aqueous two-phase system to template and stabilize molecularly thin (approximately 35 nm) biomimetic block copolymer bilayers of scalable area that can exceed 10 cm2 without defects. These membranes are self-healing, and their barrier function against the passage of ions (specific resistance of approximately 1 MΩ cm2) approaches that of phospholipid membranes. The fluidity of these membranes enables straightforward functionalization with molecular carriers that shuttle potassium ions down a concentration gradient with exquisite selectivity over sodium ions. This ion selectivity enables the generation of electric power from equimolar solutions of NaCl and KCl in devices that mimic the electric organ of electric rays.

2.
Nat Methods ; 18(6): 604-617, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34099939

RESUMO

Single-cell profiling methods have had a profound impact on the understanding of cellular heterogeneity. While genomes and transcriptomes can be explored at the single-cell level, single-cell profiling of proteomes is not yet established. Here we describe new single-molecule protein sequencing and identification technologies alongside innovations in mass spectrometry that will eventually enable broad sequence coverage in single-cell profiling. These technologies will in turn facilitate biological discovery and open new avenues for ultrasensitive disease diagnostics.


Assuntos
Análise de Sequência de Proteína/métodos , Imagem Individual de Molécula/métodos , Espectrometria de Massas/métodos , Nanotecnologia , Proteínas/química , Proteômica/métodos , Análise de Sequência de RNA/métodos , Análise de Célula Única/métodos
3.
Nano Lett ; 23(8): 3251-3258, 2023 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-37053043

RESUMO

Ferritin is a protein that stores and releases iron to prevent diseases associated with iron dysregulation in plants, animals, and bacteria. The conversion between iron-loaded holo-ferritin and empty apo-ferritin is an important process for iron regulation. To date, studies of ferritin have used either ensemble measurements to quantify the characteristics of a large number of proteins or single-molecule approaches to interrogate labeled or modified proteins. Here we demonstrate the first real-time study of the dynamics of iron ion loading and biomineralization within a single, unlabeled ferritin protein. Using optical nanotweezers, we trapped single apo- and holo-ferritins indefinitely, distinguished one from the other, and monitored their structural dynamics in real time. The study presented here deepens the understanding of the iron uptake mechanism of ferritin proteins, which may lead to new therapeutics for iron-related diseases.


Assuntos
Ferritinas , Ferro , Animais , Ferro/química , Ferritinas/química , Transporte Biológico
4.
Nature ; 552(7684): 214-218, 2017 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-29239354

RESUMO

Progress towards the integration of technology into living organisms requires electrical power sources that are biocompatible, mechanically flexible, and able to harness the chemical energy available inside biological systems. Conventional batteries were not designed with these criteria in mind. The electric organ of the knifefish Electrophorus electricus (commonly known as the electric eel) is, however, an example of an electrical power source that operates within biological constraints while featuring power characteristics that include peak potential differences of 600 volts and currents of 1 ampere. Here we introduce an electric-eel-inspired power concept that uses gradients of ions between miniature polyacrylamide hydrogel compartments bounded by a repeating sequence of cation- and anion-selective hydrogel membranes. The system uses a scalable stacking or folding geometry that generates 110 volts at open circuit or 27 milliwatts per square metre per gel cell upon simultaneous, self-registered mechanical contact activation of thousands of gel compartments in series while circumventing power dissipation before contact. Unlike typical batteries, these systems are soft, flexible, transparent, and potentially biocompatible. These characteristics suggest that artificial electric organs could be used to power next-generation implant materials such as pacemakers, implantable sensors, or prosthetic devices in hybrids of living and non-living systems.


Assuntos
Órgãos Artificiais , Biomimética/métodos , Fontes de Energia Elétrica , Electrophorus , Hidrogéis/química , Animais , Órgão Elétrico/fisiologia , Electrophorus/fisiologia , Microfluídica/instrumentação , Impressão Tridimensional/instrumentação , Próteses e Implantes
5.
J Chem Phys ; 158(1): 014901, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36610969

RESUMO

This paper presents a theoretical investigation of the design of a new actuator type made of anisotropic colloidal particles grafted with stimuli-responsive polymer chains. These artificial muscles combine the osmotic actuation principle of stimuli-responsive hydrogels with the structural alignment of colloidal liquid crystals to achieve directional motion. The solubility of the stimuli-responsive polymer in the neutral state, its degree of polymerization, the salt concentration, and the grafting density of the polymer chains on the surface of the colloidal particles are investigated and identified as important for actuator performance and tunability. The computational results suggest that the proposed mechanically active material matches or exceeds the performances of natural muscles and provide the guidelines for the realization of artificial muscles with predetermined actuation properties.


Assuntos
Nanocompostos , Polímeros Responsivos a Estímulos , Polímeros/química , Hidrogéis/química
6.
Eur Spine J ; 32(3): 867-873, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36633691

RESUMO

PURPOSE: Posterior instrumentation is the state-of-the-art surgical treatment for fractures of the thoracic and lumbar spine. Options for pedicle screw placement comprise open or minimally invasive techniques. Open instrumentation causes large approach related muscle detachment, which minimally invasive techniques aim to reduce. However, concerns of accurate pedicle screw placement are still a matter of debate. Beside neurological complications due to pedicle screw malplacement, also affection of the facet joints and thus motion dependent pain is known as a complication. The aim of this study was to assess accuracy of pedicle screw placement concerning facet joint violation (FJV) after open- and minimally invasive posterior instrumentation. METHODS: A retrospective data analysis of postoperative computer tomographic scans of 219 patients (1124 pedicle screws) was conducted. A total of 116 patients underwent open screw insertion (634 screws) and 103 patients underwent minimally invasive, percutaneous screw insertion (490 screws). RESULTS: In the lumbar spine (segments L3, L4, L5), there were significantly more and higher grade (open = 0.55 vs. percutaneous = 1.2; p = 0.001) FJV's after percutaneously compared to openly inserted screws. In the thoracic spine, no significant difference concerning rate and grade of FJV was found (p > 0.56). CONCLUSION: FJV is more likely to occur in percutaneously placed pedicle screws. Additionally, higher grade FJV's occur after percutaneous instrumentation. However, in the thoracic spine we didn't find a significant difference between open and percutaneous technique. Our results suggest a precise consideration concerning surgical technique according to the fractured vertebrae in the light of the individual anatomic structures in the preop CT.


Assuntos
Parafusos Pediculares , Fraturas da Coluna Vertebral , Fusão Vertebral , Articulação Zigapofisária , Humanos , Articulação Zigapofisária/diagnóstico por imagem , Articulação Zigapofisária/cirurgia , Estudos Retrospectivos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia , Parafusos Pediculares/efeitos adversos , Fusão Vertebral/efeitos adversos
7.
Eur Spine J ; 32(1): 368-373, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36416969

RESUMO

PURPOSE: Measurement of neck rotation is currently reliant on radiologic imaging. Given the radiation exposure for CT imaging and the additional inconvenience for the patients, an alternative assessment is needed. Goniometers are comfortably to use and easy to access, also for private consulting. The aim of this study was the assessment of whether a handheld goniometer can be used for accurately measuring the rotation of C1-C2. METHODS: Clinical measurement of rotation was taken in flexed position of the neck. As comparison functional MRI was used. The measured rotation of C1-C2 was compared to identify the accuracy of the goniometer, in comparison to functional MRI scan. RESULTS: Analysis of accuracy using a goniometer and dynamic MRI to assess C1-2 axial rotation showed significant differences for absolute values, but not regarding the percentage of rotation compared to total neck rotation. CONCLUSION: The goniometer is exact to impartially determine the percentage contribution of C1-2 rotation to total neck rotation.


Assuntos
Articulação Atlantoaxial , Vértebras Cervicais , Humanos , Vértebras Cervicais/diagnóstico por imagem , Rotação , Articulação Atlantoaxial/diagnóstico por imagem , Imageamento por Ressonância Magnética , Amplitude de Movimento Articular , Fenômenos Biomecânicos
8.
Curr Cardiol Rep ; 25(10): 1165-1174, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37610597

RESUMO

PURPOSE OF REVIEW: In this article, we discuss the relationship between emotional distress and common cardiovascular disease condition, including coronary artery disease, atrial fibrillation, congestive heart failure, mechanical circulatory support, and heart transplant. We review screening measures that have been studied and used in clinical practice for each condition, as well as priorities for future research. RECENT FINDINGS: Studies consistently demonstrate failing to identify and treat emotional distress in patients with cardiovascular disease is associated with adverse outcomes. However, routine emotional distress screening is not formally recommended for all cardiovascular disease conditions and is limited to depression screening in select patient populations. Future research should focus on evaluating the validity and reliability of standardized screening measures across the scope of emotional distress in patients with or at risk for cardiovascular disease. Other areas of future research include implementation of evidence-based pharmaceutical treatments and integrated behavioral health approaches and interventions.


Assuntos
Fibrilação Atrial , Doenças Cardiovasculares , Angústia Psicológica , Humanos , Doenças Cardiovasculares/diagnóstico , Reprodutibilidade dos Testes , Emoções , Fibrilação Atrial/diagnóstico
9.
Nanotechnology ; 33(27)2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35320779

RESUMO

Resistive pulses generated by nanoparticles that translocate through a nanopore contain multi-parametric information about the physical properties of those particles. For example, non-spherical particles sample several different orientations during translocation, producing fluctuations in blockade current that relate to their shape. Due to the heterogenous distribution of electric field from the center to the wall of a nanopore while a particle travels through the pore, its radial position influences the blockade current, thereby affecting the quantification of parameters related to the particle's characteristics. Here, we investigate the influence of these off-axis effects on parameters estimated by performing finite element simulations of dielectric particles transiting a cylindrical nanopore. We varied the size, ellipsoidal shape, and radial position of individual particles, as well as the size of the nanopore. As expected, nanoparticles translocating near the nanopore wall produce increase current blockades, resulting in overestimates of particle volume. We demonstrated that off-axis effects also influence estimates of shape determined from resistive pulse analyses, sometimes producing a multiple-fold deviation in ellipsoidal length-to-diameter ratio between estimates and reference values. By using a nanopore with the minimum possible diameter that still allows the particle to rotate while translocating, off-axis effects on the determination of both volume and shape can be minimized. In addition, tethering the nanoparticles to a fluid coating on the nanopore wall makes it possible to determine an accurate particle shape with an overestimated volume. This work provides a framework to select optimal ratios of nanopore to nanoparticle size for experiments targeting free translocations.

10.
Geophys Res Lett ; 49(10): e2022GL097885, 2022 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-35859720

RESUMO

In order to explore temporal changes of predictability of El Niño Southern Oscillation (ENSO), a novel set of global biennial climate reforecasts for the historical period 1901-2010 has been generated using a modern initialized coupled forecasting system. We find distinct periods of enhanced long-range skill at the beginning and at the end of the twentieth century, and an extended multi-decadal epoch of reduced skill during the 1930s-1950s. Once the forecast skill extends beyond the first spring barrier, the predictability limit is much enhanced and our results provide support for the feasibility of skillful ENSO forecasts up to 18 months. Changes in the mean state, variability (amplitude), persistence, seasonal cycle and predictability suggest that multi-decadal variations in the dynamical characteristics of ENSO rather than the data coverage and quality of the observations have primarily driven the reported non-monotonic skill modulations.

11.
Nervenarzt ; 93(5): 450-458, 2022 May.
Artigo em Alemão | MEDLINE | ID: mdl-34905064

RESUMO

OBJECTIVE: To investigate whether implementation recommendations derived from the German guidelines "Prevention of coercion" can be implemented on acute psychiatric wards by means of implementation consultants into ward work and if this contributes to an increased level of adherence to guideline intervention recommendations approved by the DGPPN (Deutsche Gesellschaft für Psychiatrie und Psychotherapie, Psychosomatik und Nervenheilkunde)? MATERIAL AND METHODS: Two medical or nursing experts advised ward teams on the implementation of three individually selected recommendations from the guidelines in a structured consulting process over 6 months. The degree of implementation of the recommendations was assessed before and after the intervention by the ward teams together with the implementation consultants using a tool developed for this purpose (PreVCo rating tool). RESULTS: A total of five wards responsible for compulsorily admitted patients took part in the pilot study; three of them completed the intervention. On all three wards, implementation of the guideline recommendations improved for both selected and unselected recommendations. The strategy of using implementation consultants as well as the application of the PreVCo rating tool were well accepted and considered feasible by both the treatment teams and the implementation consultants. CONCLUSION: This pilot study showed that an implementation of recommendations on psychiatric wards derived from the German guidelines "Prevention of coercion" supported by implementation consultants is feasible, well acceptable among treatment teams and can lead to positive changes. The sample of five wards with diverse patient profiles was convincing. The efficacy in terms of reduction of coercive measures is currently being investigated in a randomized controlled trial on 55 psychiatric wards in different parts of Germany, with an intervention based on this pilot study.


Assuntos
Coerção , Unidade Hospitalar de Psiquiatria , Adulto , Agressão , Alemanha , Humanos , Projetos Piloto
12.
Analyst ; 146(3): 997-1003, 2021 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-33295341

RESUMO

Bearing multiple functionalities dramatically increases nanomaterial capabilities to enhance analytical assays by improving sensitivity, selectivity, sample preparation, or signal read-out strategies. Magnetic properties are especially desirable for nanoparticles and nanovesicles as they assist in negating diffusion limitations and improving separation capabilities. Here, we propose a microfluidic method that reliably labels functional nanovesicles while avoiding the risk of crosslinking that would lead to large conglomerates as typically observed in bulk reactions. Thus, the carboxy groups of bi-functional biotinylated fluorescent liposomes were activated in bulk. They were then covalently bound to amino group presenting magnetic beads immobilized through a magnetic field within microfluidic channels. Microfluidic design and coupling strategy optimization led to a 62% coupling efficiency when using 1 µm magnetic beads. The yield dropped to 13% with 30 nm magnetic nanoparticles (MNPs) likely due to crowding of the MNPs on the magnet. Finally, both populations of these tri-functional liposomes were applied to a biological binding assay demonstrating their superior performance under the influence of a magnetic field. The microfluidic functionalization strategy lends itself well for massively parallelized production of larger volumes and can be applied to micro- and nanosized vesicles and particles.


Assuntos
Técnicas Analíticas Microfluídicas , Microfluídica , Separação Imunomagnética , Magnetismo , Imãs
13.
Chem Rev ; 119(13): 7996-8027, 2019 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-31070892

RESUMO

The Internet of Things (IoT) is a megatrend that cuts across all scientific and engineering disciplines and establishes an integrating technical evolution to improve production efficiencies and daily human life. Linked machines and sensors use decision-making routines to work toward a common product or solution. Expanding this technical revolution into the value chain of complex areas such as agriculture, food production, and healthcare requires the implementation and connection of sophisticated (bio)analytical methods. Today, wearable sensors, monitors, and point-of-care diagnostic tests are part of our daily lives and improve patients' medical progression or athletes' monitoring capabilities that are already beyond imagination. Also, early contributions toward sensor networks and finally the IT revolution with wireless data collection and transmission via Bluetooth or smartphones have set the foundation to connect remote sensors and distributed analytical chemical services with centralized laboratories, cloud storage, and cloud computing. Here, we critically review those biosensor and chemosensor technologies and concepts used in an IoT setting or considered IoT-ready that were published in the period 2013-2018, while also pointing to those foundational concepts and ideas that arose over the last two decades. We focus on these sensors due to their unique ability to be remotely stationed and that easily function in networks and have made the greatest progress toward IoT integration. Finally, we highlight requirements and existing and future challenges and provide possible solutions important toward the vision of a seamless integration into a global analytical concept, which includes many more analytical techniques than sensors and includes foremost next-generation sequencing and separation principles coupled with MS detection.


Assuntos
Técnicas Biossensoriais/tendências , Técnicas de Química Analítica/tendências , Internet das Coisas/tendências , Animais , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Técnicas de Química Analítica/instrumentação , Técnicas de Química Analítica/métodos , Humanos , Sistemas Automatizados de Assistência Junto ao Leito/tendências
14.
Eur Spine J ; 30(3): 788-796, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33409729

RESUMO

INTRODUCTION: Correction of severe idiopathic scoliosis poses surgical challenges. Treatment options entail anterior and/or posterior release, Halo-gravity traction (HGT) and three-column osteotomies (3CO). The authors report results with a novel technique of temporary short-term magnetically controlled growing rod (MCGR) as part of a posterior-only strategy to treat severe idiopathic major thoracic curves (MTC). METHODS: Seven patients with MTC > 100° treated with temporary MCGR were included. Mean age was 15 years. Preoperative MTC was av. 118° and TC-flexibility av. 19.8%. Patients underwent posterior instrumentation, periapical release using advanced Ponte osteotomies, segmental insertion of pedicle screws and a single MCGR. After av. 14 days, the second surgery was performed with removal of MCGR and final correction and fusion. The spinal height from lowest instrumented vertebra (LIV) to T1 was measured. MTC-correction and scoliosis correction index (SCI) were calculated. RESULTS: No patient suffered a major complication or neurologic deficit. Instrumentation was from T2 to L3 or L4. This kind of staged surgery achieved a correction of postop MTC to av. 39°, MTC-correction 67% and SCI of av. 4.3. Spinal height T1-LIV increased from preoperative av. 288 mm to postoperative av. 395 mm indicating an increase of > 10 cm. CONCLUSION: This is the first series of AIS patients that had temporary MCGR to treat severe thoracic scoliosis. A staged protocol including internal temporary distraction with MCGR after posterior release and definitive correction resulted in large MTC-correction and restoration of trunk height. Results indicate that technique has the potential to reduce the necessity for HGT and high-risk 3CO for the correction of severe scoliosis.


Assuntos
Cifose , Escoliose , Fusão Vertebral , Adolescente , Humanos , Estudos Retrospectivos , Vértebras Torácicas , Resultado do Tratamento
15.
Eur J Nucl Med Mol Imaging ; 47(7): 1678-1687, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31734781

RESUMO

AIMS: To investigate the benefit of utilizing 18F-sodium fluoride (NaF) PET/CT over calcium and Framingham scoring for potential preventative coronary artery disease (CAD) intervention. METHODS AND RESULTS: This retrospective study included 136 participants (ages 21-75, BMI 18-43 kg/m2): 86 healthy controls and 50 patients. CT heart segmentations were superimposed onto PET images and standard uptake values (SUV) were calculated by a semi-auto segmentation method of drawing volumes of interest around the heart. Intergroup comparisons were made matching 37 patient/control pairs based on age, gender, and BMI. ROC curves were generated to determine how well SUV and Framingham methods predicted patient status. Regressions including all 136 participants were performed between SUV, age, and BMI. Patients exhibited higher average SUV (SUVmean; P = 0.006) and Framingham scores (P = 0.02) than controls. However, ROC curves indicated that SUVmean could discriminate patients from controls (AUC = 0.63, P = 0.049), but Framingham scores could not (AUC = 0.44, P = 0.38). Calcium scores and maximum SUV (SUVmax) did not differ between patients and controls. SUVmean correlated with age and BMI among females (age, partial R2 = 0.16, P = 0.001; BMI, partial R2 = 0.12, P = 0.004) and males (age, partial R2 = 0.28, P < 0.0001; BMI, partial R2 = 0.22, P < 0.0001). CONCLUSION: Unlike calcium scores, NaF PET/CT-derived values differed between patients and controls. Framingham risk score patterns echoed those of SUVmean, but were not sensitive enough to predict patient status. SUVmean values increased with age and BMI. Therefore, incorporation of NaF PET/CT into routine prognostic CAD assessment might prove beneficial for assessing early stage plaque calcification in coronary arteries. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01724749).


Assuntos
Vasos Coronários , Radioisótopos de Flúor , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Calcificação Vascular , Adulto , Idoso , Cálcio , Vasos Coronários/diagnóstico por imagem , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fluoreto de Sódio , Calcificação Vascular/diagnóstico por imagem , Adulto Jovem
16.
Eur Spine J ; 29(4): 813-820, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31797134

RESUMO

PURPOSE: Proximal junctional kyphosis (PJK) in adult spinal deformity (ASD) surgery patients is a severe complication with potential need for revision surgery. While thoracic kyphosis (TK) is known to influence PJK, the role of TK flexibility is still unknown. We analyzed the influence of TK flexibility to predict postoperative sagittal alignment. METHODS: Patients with ASD, ≥ 2-year follow-up, and upper-most instrumented vertebra (UIV) including and below T10 were included in this retrospective study. TK flexibility, defined as > 10° difference of the TK in standing and supine imaging, was analyzed. Patient characteristics like age, sex, weight, total hip arthroplasty, and sagittal alignment parameters were studied. RESULTS: Sixty-five patients aged 66 ± 8 years were included in the study. Lowest instrumented vertebra was S1 or the ilium in 85% of them; the number of levels being fused averaged 7. Flexible TK was present in 31% (n = 20). These patients had a larger preoperative TK (p < 0.01), but no PJK was found (p = 0.04). In contrast, patients who underwent revision surgery had a decreased TK flexibility (p = 0.04) and increased PJK angle at follow-up (p = 0.01). In the non-flexible patients, the PJK was found in 14% of patients. CONCLUSIONS: Based on our retrospective data, TK flexibility influences the outcome of ASD surgery. In patients demonstrating no TK flexibility, a more cephalad UIV-level should be considered because spontaneous curve correction in the sagittal plane might be low in these patients. This new parameter should be included in future prediction models. These slides can be retrieved under Electronic Supplementary Material.


Assuntos
Cifose , Fusão Vertebral , Idoso , Humanos , Cifose/diagnóstico por imagem , Cifose/cirurgia , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Coluna Vertebral
17.
Allergy Asthma Proc ; 41(4): 265-270, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32393418

RESUMO

Background: Intranasal antihistamines and steroids should be delivered in a volume and with a technique that allow for optimal drug retention within the entire nasal cavity, maximize local absorption by the nasal mucosa, and, subsequently, increase the potential for the most desirable local availability and therapeutic effect. Objective: This in vitro evaluation simulated nasal medication deposition and evaluated the extent of runoff. MP-AzeFlu, a novel intranasal formulation of azelastine hydrochloride (AZE) plus fluticasone propionate (FP), was compared with sequential sprays of available commercial products with the individual medication components. Methods: A model of a normal adult human nasal cavity was used to visualize deposition of nasal spray products. A single spray of MP-AzeFlu (0.137 mL [137 µg of AZE/50 µg of FP]) or single sequential sprays of AZE nasal spray (0.137 mL [137 µg]) followed by brand name or generic FP nasal spray (0.100 mL [50 µg]) were manually actuated into the model. The interior was coated with a water-sensitive dye that changes to magenta when exposed to aqueous-based formulations. A slight vacuum was applied during spray delivery to simulate sniffing. The results were photographed by using anterior and lateral views. Results: Three replicates of MP-AzeFlu showed no dripping from the front of the nostril or backflow from the nasal cavity. However, three replicates of AZE nasal spray, followed by a brand name or generic FP nasal spray, showed significant dripping from the front of the nostril and backflow from the nasal cavity. Conclusion: A single spray of MP-AzeFlu resulted in no runoff compared with sequential dosing of the two other therapeutic products. Product runoff is likely due to the volume exceeding the capacity of the nasal cavity model. Furthermore, the common clinical dosing regimen of two sprays per nostril of each of the individual components would promote even greater increased undesirable flooding and leakage.


Assuntos
Antiasmáticos/administração & dosagem , Fluticasona/administração & dosagem , Modelos Anatômicos , Cavidade Nasal , Sprays Nasais , Ftalazinas/administração & dosagem , Administração Intranasal , Humanos , Técnicas In Vitro
18.
Anal Chem ; 91(20): 13080-13087, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31524378

RESUMO

Luminol is a major probe for chemiluminescence (CL) and electrochemiluminescence (ECL) detection technologies in (bio)analysis. Surfactants are added to ECL assay cocktails to enhance signals or are present, owing to given bioassay protocols, yet little is known regarding their effects on luminol ECL. In-depth understanding is provided here through a broad study with bioanalytically relevant surfactants (cationic, anionic, and nonionic), four common electrode materials, and two luminol derivatives. Naturally, in ECL, surface effects are dominant; however, bulk solution, diffusion, and luminescence-stabilization processes also contribute significantly to the overall reaction. It was found that in contrast to CL the effect surfactants have on luminol ECL cannot be linked to general surfactant characteristics such as ionic nature, hydrophilic lipophilic balance (HLB) value, and critical micellar concentration (CMC). Instead, surfactants act in an all-encompassing mechanism, including surface electrochemistry, their solution and interfacial phases, and the chemical luminescence pathway. This leads to dramatic differences in signals obtained, ranging from 5-fold increases to total quenching. Within this complexity, we defined six guiding principles that are extrapolated from the underlying mechanisms and selection guides for surfactant, electrode, and environmental condition combinations. Those will now assist in developing highly sensitive luminol-ECL-based bioassays, because the surfactant selection can be based not only on properties needed for the assay protocol but also on identifying the optimal electrode-surfactant pair to maximize detection efficiency.


Assuntos
Luminol/química , Tensoativos/química , Adsorção , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Eletrodos , Luminescência , Medições Luminescentes/métodos
19.
J Child Psychol Psychiatry ; 60(4): 427-429, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30919476

RESUMO

There is a growing interest in applying the conceptual and analytical frameworks of computational psychiatry to developmental populations. This is motivated by appreciation that psychiatric illness needs to be understood from a neurodevelopmental perspective. The target article by Hauser and colleagues highlights progress in applying the computational psychiatry perspectives to identifying the developmental mechanisms of mental illness. We share the enthusiasm and optimism for this venture, while recognizing the substantial theoretical and pragmatic challenges associated with applying computational frameworks to developing populations. In this commentary, we highlight the ways that taking a developmental perspective in this arena stretches beyond merely identifying age differences in a computational parameter of interest. These include the need for experimental and computational frameworks to recognize that developmental changes can be quantitative or qualitative in nature, the need to consider developmental stage beyond age groupings or even numerical age, and the need for large quantities of data to model age-related changes in a reproducible manner. In doing so, we hope to stimulate progress in uncovering the mechanisms of psychiatric illness in a way that is developmentally informed.


Assuntos
Transtornos Mentais , Psiquiatria , Humanos
20.
Nanotechnology ; 30(26): 265301, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-30849769

RESUMO

This paper presents a maskless method to manufacture fused silica chips for low-noise resistive-pulse sensing. The fabrication includes wafer-scale density modification of fused silica with a femtosecond-pulsed laser, low-pressure chemical vapor deposition (LPVCD) of silicon nitride (SiN x ) and accelerated chemical wet etching of the laser-exposed regions. This procedure leads to a freestanding SiN x window, which is permanently attached to a fused silica support chip and the resulting chips are robust towards Piranha cleaning at ∼80 °C. After parallel chip manufacturing, we created a single nanopore in each chip by focused helium-ion beam or by controlled breakdown. Compared to silicon chips, the resulting fused silica nanopore chips resulted in a four-fold improvement of both the signal-to-noise ratio and the capture rate for signals from the translocation of IgG1 proteins at a recording bandwidth of 50 kHz. At a bandwidth of ∼1 MHz, the noise from the fused silica nanopore chips was three- to six-fold reduced compared to silicon chips. In contrast to silicon chips, fused silica chips showed no laser-induced current noise-a significant benefit for experiments that strive to combine nanopore-based electrical and optical measurements.

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