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The acidity of atmospheric aerosols influences fundamental physicochemical processes that affect climate and human health. We recently developed a novel and facile water-probe-based method for directly measuring of the pH for micrometer-size droplets, providing a promising technique to better understand aerosol acidity in the atmosphere. The complex chemical composition of fine particles in the ambient air, however, poses certain challenges to using a water-probe for pH measurement, including interference from interactions between compositions and the influence of similar compositions on water structure. To explore the universality of our method, it was employed to measure the pH of ammonium, nitrate, carbonate, sulfate, and chloride particles. The pH of particles covering a broad range (0-14) were accurately determined, thereby demonstrating that our method can be generally applied, even to alkaline particles. Furthermore, a standard spectral library was developed by integrating the standard spectra of common hydrated ions extracted through the water-probe. The library can be employed to identify particle composition and overcome the spectral overlap problem resulting from similar effects. Using the spectral library, all ions were identified and their concentrations were determined, in turn allowing successful pH measurement of multicomponent (ammonium-sulfate-nitrate-chloride) particles. Insights into the synergistic effect of Cl-, NO3-, and NH4+ depletion obtained with our approach revealed the interplay between pH and volatile partitioning. Given the ubiquity of component partitioning and pH variation in particles, the water probe may provide a new perspective on the underlying mechanisms of aerosol aging and aerosol-cloud interaction.
Subject(s)
Aerosols , Environmental Monitoring , Spectrum Analysis, Raman , Water , Hydrogen-Ion Concentration , Spectrum Analysis, Raman/methods , Water/chemistry , Environmental Monitoring/methods , Aerosols/analysis , Air Pollutants/analysis , Air Pollutants/chemistry , Atmosphere/chemistry , Particulate Matter/analysisABSTRACT
Formic and acetic acids are the most abundant gaseous organic acids and play the key role in the atmospheric chemistry. In iodine-adduct chemical ionization mass spectrometry (CIMS), the low utilization efficiency of methyl iodide and humidity interference are two major issues of the vacuum ultraviolet (VUV) lamp initiated CIMS for on-line gaseous formic and acetic acids analysis. In this work, we present a new CIMS based on VUV lamp, and the ion-molecular reactor is separated into photoionization and chemical ionization zones by a reducer electrode. Acetone was added to the photoionization zone, and the VUV photoionization acetone provided low-energy electrons for methyl iodide to generate I-, and the addition of acetone reduced the amount of methyl iodide by 2/3. In the chemical ionization zone, a headspace vial containing ultrapure water was added for humidity calibration, and the vial changes the sensitivity as a function of humidity from ambiguity to well linear correlation (R2 > 0.95). With humidity calibration, the CIMS can quantitatively measure formic and acetic acids in the humidity range of 0%-88% RH. In this mode, limits of detection of 10 and 50 pptv are obtained for formic and acetic acids, respectively. And the relative standard deviation (RSD) of quantitation stability for 6 days were less than 10.5%. This CIMS was successfully used to determine the formic and acetic acids in the underground parking and ambient environment of the Shandong University campus (Qingdao, China). In addition, we developed a simple model based formic acid concentration to assess vehicular emissions.
Subject(s)
Mass Spectrometry , Mass Spectrometry/methods , Air Pollutants/analysis , Iodides/analysis , Iodides/chemistry , Ultraviolet Rays , Formates/analysis , Formates/chemistry , Atmosphere/chemistry , Environmental Monitoring/methods , Photochemical Processes , Acetic Acid/analysis , Acetic Acid/chemistry , Hydrocarbons, Iodinated/analysis , Hydrocarbons, Iodinated/chemistryABSTRACT
Purpose: Use of mechanical imaging (MI) as complementary to digital mammography (DM), or in simultaneous digital breast tomosynthesis (DBT) and MI - DBTMI, has demonstrated the potential to increase the specificity of breast cancer screening and reduce unnecessary biopsies compared with DM. The aim of this study is to investigate the increase in the radiation dose due to the presence of an MI sensor during simultaneous image acquisition when automatic exposure control is used. Approach: A radiation dose study was conducted on clinically available breast imaging systems with and without an MI sensor present. Our estimations were based on three approaches. In the first approach, exposure values were compared in paired clinical DBT and DBTMI acquisitions in 97 women. In the second approach polymethyl methacrylate (PMMA) phantoms of various thicknesses were used, and the average glandular dose (AGD) values were compared. Finally, a rectangular PMMA phantom with a 45 mm thickness was used, and the AGD values were estimated based on air kerma measurements with an electronic dosemeter. Results: The relative increase in exposure estimated from digital imaging and communications in medicine headers when using an MI sensor in clinical DBTMI was 11.9 % ± 10.4 . For the phantom measurements of various thicknesses of PMMA, the relative increases in the AGD for DM and DBT measurements were, on average, 10.7 % ± 3.1 and 11.4 % ± 3.0 , respectively. The relative increase in the AGD using the electronic dosemeter was 11.2 % ± < 0.001 in DM and 12.2 % ± < 0.001 in DBT. The average difference in dose between the methods was 11.5 % ± 3.3 . Conclusions: Our measurements suggest that the use of simultaneous breast radiography and MI increases the AGD by an average of 11.5 % ± 3.3 . The increase in dose is within the acceptable values for mammography screening recommended by European guidelines.
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Accurate measurement of the size of lesions or distances between any two points during endoscopic examination of the gastrointestinal tract is difficult owing to the fisheye lens used in endoscopy. To overcome this issue, we developed a phase-shift method to measure three-dimensional (3D) data on a curved surface, which we present herein. Our system allows the creation of 3D shapes on a curved surface by the phase-shift method using a stripe pattern projected from a small projecting device to an object. For evaluation, 88 measurement points were inserted in porcine stomach tissue, attached to a half-pipe jig, with an inner radius of 21 mm. The accuracy and precision of the measurement data for our shape measurement system were compared with the data obtained using an Olympus STM6 measurement microscope. The accuracy of the path length of a simulated protruded lesion was evaluated using a plaster model of the curved stomach and graph paper. The difference in height measures between the measurement microscope and measurement system data was 0.24 mm for the 88 measurement points on the curved surface of the porcine stomach. The error in the path length measurement for a lesion on an underlying curved surface was <1% for a 10-mm lesion. The software was developed for the automated calculation of the major and minor diameters of each lesion. The accuracy of our measurement system could improve the accuracy of determining the size of lesions, whether protruded or depressed, regardless of the curvature of the underlying surface.
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BACKGROUND: Cochlear dimension measurements are critical in diagnosing and managing congenital sensorineural hearing loss. OBJECTIVES: To evaluate the feasibility and reliability of an automated landmark approach for measuring cochlear dimensions (A-, B- and H-values). MATERIAL AND METHODS: Cochlear parameters from 100 patients were measured by MPR, manual three-dimensional and ALPACA. We assessed intra- and inter-observer reliability as well as inter-method reliability. Statistical analyses were conducted to detect differences between the right and left ears, as well as to assess the relevance of the values obtained using ALPACA. RESULTS: All A-, B-, and H-values measured by the various methods showed a high intra-observer reliability with intra-class correlation coefficients (ICC) ranging from 0.70 to 0.99, and values gained by ALPACA reaching the highest ICC. Inter-method reliability was at a good level with ICC ranging from 0.51 to 0.86. There were no significant differences between the right and left ears' measured values. Obvious positive correlations existed among cochlear dimensions measured by ALPACA. CONCLUSIONS AND SIGNIFICANCE: The ALPACA method can be used to measure cochlear dimensions. Values obtained by the method demonstrate high reliability and consistency with a significant reduction in intra-observer variability compared to results from conventional MPR and manual 3D measurements.
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Introduction: Formula feeding is the only viable nutrition alternative for infants 0-6mos who cannot breastfeed. Among the drawbacks of formula feeding, however, is potential dilution or concentration errors in the formula during preparation that may lead to infant health issues. The present study aimed to investigate the accuracy of caregiver measurements as they prepared infant formula under multiple conditions, compared with manufacturer specifications. Methods: A diverse sample of caregivers (N = 84) participated in this cross-over experimental study. Participants hand-scooped infant formula powder and poured water to prepare 4oz. and 7oz. feedings, using both a standardized set of infant formula products and participants' own products. Linear mixed effects models were used to estimate fixed effects of target amount (4oz. versus 7oz) and products (participant versus researcher) on mean absolute percent error (MAPE) of measurement. Results: Across all conditions MAPE was significantly greater for measuring powder than for water (9.0% vs. 4.4%; p < 0.001) with a combined powder and water MAPE at 13.0%. Greater measurement error was associated with the odd-sized 7oz. preparation and participants' own products. Discussion: We observed considerable variability and substantial error during infant formula preparation, particularly for hand-scooping of powder, which tended toward higher values than the theoretical gold standard.
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BACKGROUND: Improving the quality of breastfeeding counselling delivered by primary care providers can improve breastfeeding outcomes and ultimately reduce mortality and morbidity of children and mothers. Accurate data on coverage and quality of primary care breastfeeding counselling is essential for monitoring progress; however, global and national indicators are limited. To help address this gap, this study validated indicators of receipt and quality of breastfeeding counselling during routine consultations for infant care at seven primary health facilities across Kosovo. METHODS: Mothers' reports of breastfeeding counselling received during routine consultations for their infants (0-12 months of age) were collected by exit interview in 2019 and 2021 (n = 609). Responses were compared against direct observation of their consultation using a structured checklist (reference standard) by a trained third-party observer at the primary care facility. We assessed 13 indicators; ten were related to the receipt and content of breastfeeding counselling, and three were specific to the provider's interpersonal skills. We calculated sensitivity, specificity, and area under the receiver operating curve (AUC) to determine individual-level reporting accuracy. RESULTS: Ten indicators had an agreement rate above 70% and seven indicators had high overall individual-level validity (AUC ≥ 0.7). High prevalence indicators recorded high sensitivity and low specificity, and the inverse for low prevalence indicators. More subjective indicators were less reliable, e.g., mothers over-reported the prevalence of all three indicators related to providers' interpersonal skills. CONCLUSIONS: This study offers evidence on breastfeeding counselling quality by validating maternal reports of whether a provider discussed breastfeeding, the clinical content of that counselling, and how it was delivered. It is also situated in a primary care setting within a fragile state of which there is limited evidence. We observed that mothers reported accurately when asked directly to recall breastfeeding counselling services received. However, there is a need to further validate subjective questions about interpersonal skills and other measures for the 'experience of care' quality dimension.
Subject(s)
Breast Feeding , Counseling , Mothers , Primary Health Care , Humans , Breast Feeding/statistics & numerical data , Female , Counseling/methods , Kosovo , Adult , Mothers/psychology , Infant , Infant, Newborn , Reproducibility of Results , Young AdultABSTRACT
BACKGROUND: Traditional plaster-cast fabrication of an ankle-foot orthosis (AFO), although robust, is time-consuming and cumbersome. 3D scanning is quickly gaining attention as an alternative to plaster casting the foot and ankle region for AFO fabrication. The aim of this study was to assess the accuracy and speed of two high-performing 3D scanners compared with plaster casting in pediatric patients requiring an AFO. METHODS: Ten participants (mean age 10.0 ± 3.9 years) prescribed AFOs for a movement disorder were 3D scanned with the high-cost Artec Eva (Eva) and low-cost Structure Sensor II (SSII) using one-person (1p) and two-person (2p) protocols. Accuracy and speed for both 3D scanners were compared with corresponding plaster cast measures (≤5% acceptable difference). Bland and Altman plots were generated to show mean bias and limits of agreement. RESULTS: Overall, Eva and SSII were accurate for foot, ankle, and lower leg key clinical landmarks (Eva-1p: 4.4 ± 7.3%; Eva-2p: 3.2 ± 7.5%; SSII-1p: 0.6 ± 7.4%; SSII-2p: 0.7 ± 8.2%). Bland and Altman plots for the SSII demonstrated lower biases for 1p (bias 0.5 mm, LoA: -12.4-13.5 mm) and 2p (0.4 mm, LoA: -11.4-12.2 mm) protocols compared with Eva for 1p (bias 2.3 mm, LoA: -8.0-12.7 mm) and 2p (1.8 mm, LoA: -10.7-14.3 mm) protocols. The SSII 2p protocol was the fastest 3D scanning method (26.4 ± 11.1 s). CONCLUSIONS: The high-cost Eva and low-cost SSII 3D scanners using the 1p and 2p protocols produced comparable accuracy and faster capture of key clinical landmarks compared with plaster cast measures for the fabrication of AFOs in pediatric patients.
Subject(s)
Ankle , Casts, Surgical , Foot Orthoses , Foot , Imaging, Three-Dimensional , Humans , Child , Casts, Surgical/economics , Female , Male , Foot/physiopathology , Foot/diagnostic imaging , Adolescent , Imaging, Three-Dimensional/methods , Leg/diagnostic imagingABSTRACT
Among older adults, depression is a common, morbid, and costly disorder. Older adults with depression are overwhelmingly treated by primary care providers with poor rates of remission and treatment response, despite attempts to improve care delivery through behavioral health integration and care management models. Given one in 10 older adults in primary care settings meet criteria for depression, there is a pressing need to improve the efficacy of depression treatment among affected individuals. Measurement-based care (i.e., the incorporation of systematic measurement of patient outcomes into treatment) for depressed older adults in primary care has had poor uptake, which at least partly underlies the limited efficacy of depression treatments. In this perspective, we discuss the proposal that ecological momentary assessment (EMA) may increase uptake of measurement-based care for depression in primary care, enhance the quality of clinical depression data, and lead to improvements in treatment efficacy without adding to providers' burden. We describe key issues related to EMA implementation and application in routine settings for depressed older adults, along with potential pitfalls and future research directions.
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Photoacoustics can provide a direct measurement of light absorption by microalgae depending on the photosynthesis pigment within them. In this study, we have performed photoacoustic flowmetry on living microalgae cells to measure their flow characteristics, which include flow speed, flow angle, flow direction, and, more importantly, the photoacoustic absorption spectrum, all by observing the photoacoustic Doppler power spectra during their flowing state. A supercontinuum pulsed laser with a high repetition frequency is used as the light source: through intensity modulation at a specified frequency, it can provide wavelength-selectable excitation of a photoacoustic signal centered around this frequency. Our approach can be useful to simultaneously measure the flow characteristics of microalgae and easily discriminate their different species with high accuracy in both static and dynamic states, thus facilitating the study of their cultivation and their role in our ecosystem.
Subject(s)
Microalgae , Photoacoustic Techniques , PhotosynthesisABSTRACT
The clinical significance of measuring vessel wall thickness is widely acknowledged. Recent advancements have enabled high-resolution 3D scans of arteries and precise segmentation of their lumens and outer walls; however, most existing methods for assessing vessel wall thickness are 2D. Despite being valuable, reproducibility and accuracy of 2D techniques depend on the extracted 2D slices. Additionally, these methods fail to fully account for variations in wall thickness in all dimensions. Furthermore, most existing approaches are difficult to be extended into 3D and their measurements lack spatial localization and are primarily confined to lumen boundaries. We advocate for a shift in perspective towards recognizing vessel wall thickness measurement as inherently a 3D challenge and propose adapting the Laplacian method as an outstanding alternative. The Laplacian method is implemented using convolutions, ensuring its efficient and rapid execution on deep learning platforms. Experiments using digital phantoms and vessel wall imaging data are conducted to showcase the accuracy, reproducibility, and localization capabilities of the proposed approach. The proposed method produce consistent outcomes that remain independent of centerlines and 2D slices. Notably, this approach is applicable in both 2D and 3D scenarios. It allows for voxel-wise quantification of wall thickness, enabling precise identification of wall volumes exhibiting abnormal wall thickness. Our research highlights the urgency of transitioning to 3D methodologies for vessel wall thickness measurement. Such a transition not only acknowledges the intricate spatial variations of vessel walls, but also opens doors to more accurate, localized, and insightful diagnostic insights.
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This paper illustrates a rigorous approach to the initial phases of scale development when evaluating an existing construct, dyadic efficacy, in a new population. Cancer-related dyadic efficacy represents a couples' confidence in their conjoint abilities to manage the effects of cancer. Two samples of individuals diagnosed with cancer and their partners, along with a professional panel, contributed lay and content expertise, respectively. Thematic analysis was used to describe cancer-related dyadic efficacy and identify content domains. Cancer-related dyadic efficacy was conceptualized as multidimensional, consistent with relational functioning, and distinct from self-efficacy. A pool of 50 items was developed to assess eight content domains grouped into three main themes: dyadic efficacy for managing (a) illness intrusions, (b) emotional responses and (c) communication and care for children. This paper responds to calls for more rigorous reporting of the qualitative procedures required to establish a conceptual grounding for a new scale.
Subject(s)
Neoplasms , Humans , Neoplasms/psychology , Female , Male , Adult , Middle Aged , Self EfficacyABSTRACT
BACKGROUND: This scoping review summarizes the tasks and outcomes in dynamic and functional balance assessments of individuals with chronic ankle instability, focusing on the physiological and biomechanical characteristics. METHOD: A comprehensive literature search was conducted in PubMed, Scopus, Web of Science, and MEDLINE databases in September 2023 and revised in April 2024. Studies evaluating dynamic and functional balance in chronic ankle instability using clinical tests, as well as biomechanical and physiological outcomes, were included. RESULTS: Out of 536 publications, 31 met the screening criteria. A history of ankle sprain was the main focus of the inclusion criteria (28 articles, 90%). The star excursion balance test, emphasizing maximum reach distance, was the most common quantitative task (12 articles, 66%). Physiological data mainly came from electromyography studies (7 articles, 23%), while biomechanical variables were often assessed through center of pressure studies using force plates (17 articles, 55%). CONCLUSIONS: The preferred quantitative clinical assessment was the star excursion balance test, focusing on normalized reach outcomes. Qualitative functional balance assessments emphasize landing activities and center of pressure displacement. Electromyography is commonly used to analyze the tibialis anterior and peroneus longus muscles. However, there is a lack of qualitative data on dynamic balance control, including morphological characteristics and the center of mass adaptation.
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INTRODUCTION: Medical education has been changing, and the evaluation strategies that make it possible to address not only theoretical knowledge but also clinical skills. In Mental Health, these skills play a central role. The Objective Structured Clinical Examination (OSCE) is one of the evaluations that could assess clinical skills. This article describes the implementation and performance for the evaluation of undergraduate students since the OSCE's introduction in 2015. METHODS: An explanation of the implementation is made, and a description of the OSCEs carried out to undergraduate medical students in the second semester of mental health, using the databases of the final practical examinations during those years. The perception of mental health teachers is also described. RESULTS: The mental health OSCE implemented in 2015-2, is developed in the Simulated Hospital of the University and has five stations (interview, mental examination, diagnosis, treatment and information to the family and ethics). Between 2016-2 and 2019-2, 486 students performed OSCE with an average score of 3.85 (scale 0-5). It was observed that the grade obtained when evaluating anxiety disorders was below average, that of affective disorders above average, while that of psychotic disorders was within the average. The professors highlight the versatility, the comprehensive objective evaluation of the practical and theoretical aspects, and the possibility of comparison between the different groups. CONCLUSIONS: The OSCE is an examination that provides the possibility to evaluate the competences in psychiatry of medical students and allows the identification of the aspects to be improved in the teaching learning process.
Subject(s)
Clinical Competence , Education, Medical, Undergraduate , Educational Measurement , Psychiatry , Students, Medical , Humans , Psychiatry/education , Educational Measurement/methods , Education, Medical, Undergraduate/methodsABSTRACT
Background and Aims: We aimed to test the performance of the Fibroscan-aspartate aminotransferase (FAST) score, a noninvasive test, to identify nonalcoholic steatohepatitis (NASH) and significant fibrosis (NASH + ≥F2) in a cohort of patients with a histological diagnosis of NASH, using a cutoff of ≥0.35 as a rule in factor. We also compared performance to liver stiffness measurement (LSM) ≥8 kPa and the fibrosis-4 index (FIB-4) ≥1.3 and attempted to identify risk factors to develop a model for improving diagnostic accuracy. Methods: Patients with histologically confirmed NASH were identified from 2020-2021. Demographic information, laboratory data, and LSM were collected. The FAST score and FIB-4 were calculated. Univariate and backward entry multivariate logistic regression analyses were performed to identify risk factors in addition to the FAST score ≥0.35 that are associated with an accurate histological diagnosis of NASH + ≥F2. Discrimination and overall accuracy were assessed using area under receiver operating characteristic curves. Results: Using a rule in cutoff of ≥0.35, the FAST score performed with a sensitivity, specificity, negative predictive value, and positive predictive value of 96.4%, 36.8%, 77.7%, and 81.8%, respectively. Age (P = .05) and FAST ≥0.35 (P = .001) correctly identified histologically confirmed NASH + ≥F2. The FAST + age model outperformed FAST ≥0.35 (0.70, confidence interval [CI]: 0.55-0.84), LSM ≥8 kPa (0.72, CI: 0.59-0.85), and FIB-4 ≥1.3 (0.73, CI: 0.59-0.87) with a c-statistic of 0.78 (CI: 0.64-0.92). Conclusion: A FAST score with a rule cutoff of ≥0.35 performed well (c-statistic: 0.70) and was superior to LSM and FIB-4 when age was incorporated into the model (0.78) in detecting NASH + ≥F2 fibrosis in the real world.
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Osteoarthritis (OA) is a common chronic disease largely driven by mechanical factors, causing significant health and economic burdens worldwide. Early detection is challenging, making animal models a key tool for studying its onset and mechanically-relevant pathogenesis. This review evaluate current use of preclinical in vivo models and progressive measurement techniques for analysing biomechanical factors in the specific context of the clinical OA phenotypes. It categorizes preclinical in vivo models into naturally occurring, genetically modified, chemically-induced, surgically-induced, and non-invasive types, linking each to clinical phenotypes like chronic pain, inflammation, and mechanical overload. Specifically, we discriminate between mechanical and biological factors, give a new explanation of the mechanical overload OA phenotype and propose that it should be further subcategorized into two subtypes, post-traumatic and chronic overloading OA. This review then summarises the representative models and tools in biomechanical studies of OA. We highlight and identify how to develop a mechanical model without inflammatory sequelae and how to induce OA without significant experimental trauma and so enable the detection of changes indicative of early-stage OA in the absence of such sequelae. We propose that the most popular post-traumatic OA biomechanical models are not representative of all types of mechanical overloading OA and, in particular, identify a deficiency of current rodent models to represent the chronic overloading OA phenotype without requiring intraarticular surgery. We therefore pinpoint well standardized and reproducible chronic overloading models that are being developed to enable the study of early OA changes in non-trauma related, slowly-progressive OA. In particular, non-invasive models (repetitive small compression loading model and exercise model) and an extra-articular surgical model (osteotomy) are attractive ways to present the chronic natural course of primary OA. Use of these models and quantitative mechanical behaviour tools such as gait analysis and non-invasive imaging techniques show great promise in understanding the mechanical aspects of the onset and progression of OA in the context of chronic knee joint overloading. Further development of these models and the advanced characterisation tools will enable better replication of the human chronic overloading OA phenotype and thus facilitate mechanically-driven clinical questions to be answered.
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OBJECTIVE: To investigate the anatomical indexes and anatomical positional indexes of the atlantoaxial synchondroses in normal Chinese Han children aged 1-6 years, and to analyze the changing law of the atlantoaxial cartilage union with the growth and development of age and its influence on the atlantoaxial ossification in children. METHODS: A retrospective collection of CT imaging of 160 cases of normal cervical spine in children aged 1 to 6 years old was conducted. The cases were divided into six age groups, with each group representing a one-year age range. Measure the morphological anatomical indicators and anatomical positional indicators of the atlantoaxial synchondroses. Record and statistically analyze the measurements of each indicator. RESULTS: Measurements were taken on various parameters of the atlantoaxial synchondroses. TD, SD, height, area, and perimeter all gradually decreased among the groups. Distance between bilateral atlantal anterolateral synchondroses increased gradually from Group A to Group F, while the angle formed along the long axis in the cross-section showed a decreasing trend. Distance between the axoid dentolateral synchondroses and between the neurocentral synchondroses increased gradually from Group A to Group F, with the angle value in the cross-section showing a gradual decrease, and distance from the odontoid apex increasing from Group A to Group F. CONCLUSIONS: The atlantoaxial synchondroses gradually decrease in size with age, and ossification levels increase with age, with faster ossification occurring during a 1-2 years-old period. The anterolateral synchondroses, dentolateral synchondroses, and neurocentral synchondroses all gradually ossify towards the lateral direction with increasing age.
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Plasticity of synaptic transmission underlies learning and memory. It is accompanied by changes in the density and size of synapses, collectively called structural plasticity. Therefore, understanding the mechanism of structural plasticity is critical for understanding the mechanism of synaptic plasticity. In this chapter, we describe the procedures and equipment required to image structural plasticity of a single dendritic spine, which hosts excitatory synapses in the central nervous system, and underlying molecular interactions/biochemical reactions using two-photon fluorescence lifetime microscopy (2P-FLIM) in combination with Förster resonance energy transfer (FRET)-based biosensors.
Subject(s)
Dendritic Spines , Fluorescence Resonance Energy Transfer , Microscopy, Fluorescence, Multiphoton , Neuronal Plasticity , Dendritic Spines/metabolism , Dendritic Spines/ultrastructure , Dendritic Spines/physiology , Neuronal Plasticity/physiology , Animals , Fluorescence Resonance Energy Transfer/methods , Microscopy, Fluorescence, Multiphoton/methods , Synapses/metabolism , Synapses/physiology , Mice , Biosensing Techniques/methodsABSTRACT
Cucurbit[n]urils (CB[n]s) are cyclic macrocycles with rich host-guest chemistry. In many cases, guest binding in CB[n]s results in structural deformations. Unfortunately, measuring such deformations remains a major challenge, with only a handful of manual estimations reported in the literature. To address this challenge, we have developed the public program ElliptiCB[n], which is available on GitHub, that provides a robust and automated method for measuring the elliptical deformations in CB[n] hosts. We outline the development and validation of this approach, apply ElliptiCB[n] to measure to the ellipticity of the 1113 available CB[n] structures from the Cambridge Structural Database (CSD), and directly investigate the structural deformations of CB[5], CB[6], CB[7], CB[8], and CB[10]. We also report the general landscape of accessible CB[n] elliptical deformations and compare ellipticity distributions across CB[n] hosts and host-guest complexes. We found that in almost all cases guest binding significant impacts the distribution of host ellipticity distributions and that ellipticity distributions are dissimilar across host-guest complexes of differently sized CB[n]s. We anticipate that this work will provide a useful approach for understanding of the flexibility of CB[n] hosts and will also enable future measurement and standardization of ellipticity measurements of CB[n]s.
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INTRODUCTION/AIMS: Myotonia is a key symptom of myotonic dystrophies (DM), and its quantification is challenging. This exploratory study evaluated the utility of tissue Doppler ultrasound (TDU) to assess myotonia in DM. METHODS: Twelve DM patients (seven type-1 DM [DM1] and five type-2 DM [DM2]) and 20 age-matched healthy subjects were included in this cross-sectional study. After measuring cross-sectional areas of the flexor digitorum superficialis (FDS) and extensor digitorum communis (EDC) muscles in a resting state, muscle contraction/relaxation time, time to peak tissue velocity, peak tissue velocity and velocity gradients of these muscles were measured via TDU while performing forced fist unclenching after fist closure. Additionally, grip strength, Medical Research Council Sum score and patient-reported myotonia severity scores were assessed. RESULTS: DM1 and DM2 patients had a lower grip strength than healthy subjects (p = .0001/p = .002). Patient-reported myotonia did not differ between DM1 and DM2 patients. DM1 patients revealed FDS and EDC atrophy compared to DM2 patients and healthy subjects (p = .003/p = .004). TDU revealed prolonged muscle contraction and relaxation times in both DM subtypes, with prolonged time to reach FDS peak relaxation velocity and altered peak FDS relaxation velocity only in DM1 patients (p = .03/p = .003). Peak FDS relaxation velocity correlated inversely with C(C)TG repeat numbers in DM patients. Sensitivity of TDU parameters to detect myotonic dystrophy varied between 50% and 75%, with a specificity of 95%. DISCUSSION: Our exploratory study suggests that TDU could serve as a novel tool to quantify myotonia in DM patients, but larger follow-up studies are warranted to validate its diagnostic accuracy.