Tag: nevin manimala

Se Pu. 2020 Sep 8;38(9):993-998. doi: 10.3724/SP.J.1123.2020.05001.

ABSTRACT

This study aims to understand nanopore technology from the standpoint of capillary electrophoresis separation. The nanopore electrochemical measurements could be regarded as “single molecule electrophoresis”. Similar to the case of capillary electrophoresis, the single target molecules migrate inside a nanopore under an external electric field. The recognition ability of the nanopore mainly depends on the charge, shape, and size of the target molecules under the electric force. The confined space of an Aerolysin nanopore matches the size of single biomolecule, while the amino acid residues along the inner wall of the nanopore facilitate electrokinetic regulation inside the nanopore. Under the applied voltage, each molecule enters the nanopore, generating the characteristic migration velocity and trajectory. Therefore, statistical analysis of the current amplitude, duration, frequency, and shape of the electrochemical signals would help differentiate and identify a single analyte from the mixture. Herein, we used an Aerolysin nanopore for identifying the oligonucleotides of 5′-CAA-3′ (CA₂), 5′-CAAA-3′ (CA₃), and 5′-CAAAA-3′ (CA₄), which differ in length only by one nucleotide, as the model system to demonstrate single-molecule electrophoresis. The diameter of the Aerolysin nanopore is around 1 nm, and the pore length is approximately 10 nm. Under an applied voltage of 80 mV, the nanopore experiences a high electric field strength of about 80 kV/cm. The phosphate groups of the nucleotides carry negative charges in an electrolyte buffer solution of 1.0 mol/L KCl, at pH 8. Therefore, CA₂, CA₃, and CA₄ carry 2, 3, and 4 negative charges, respectively. During nanopore sensing, CA₂, CA₃, and CA₄ are subjected to electrophoretic forces and thus move inside the nanopore. Because the Aerolysin nanopore is anion selective, the direction of electroosmotic flow through the nanopore is consistent with the anion flow direction. Under the combined effects of the electrophoretic force and electroosmotic flow, CA₂, CA₃, CA₄ will transverse through the Aerolysin nanopore at different migration velocities. Note that the oligonucleotide shows strong electrostatic interaction with the two sensitive regions of Aerolysin, which comprises polar amino acids around R220 and K238. The strong interaction between the sensitive region of Aerolysin and the analyte would further modulate the translocation of oligonucleotides. Therefore, each oligonucleotide follows a different migration trajectory as it individually transverses through the nanopore. The migration speed and migration trajectory are recorded as ionic blockages in nanopore electrochemistry. The scatter plots of the blockage current and blockage duration of the mixed sample of CA₂, CA₃, and CA₄ show three characteristic distributions assigned to each type of oligonucleotide. Since the net charge increases with increasing length of the oligonucleotide, CA₃ and CA₄ experience a stronger electrophoretic force than does CA₂ inside the nanopore, leading to higher migration velocity. Therefore, the blockage duration of CA₃ and CA₄ is 5 times longer than that of CA₂. By Gaussian fitting, the fitted blockage currents of CA₂, CA₃, and CA₄ are 20.7, 15.7, and 12.7 pA, respectively. Similar to our previous results, the blockage current increases with the chain length when the oligonucleotides comprise not more than 14 nucleotides. Therefore, nanopore-based single-molecule electrophoresis allows for the electrochemical identification of CA₂, CA₃, and CA₄ that differ in a length by only one nucleotide. Understanding the “single-molecule electrophoresis” concept would promote the application of electrochemically confined effects in single-molecule electrophoresis separation. The combination of single-molecule electrophoresis with a microfluidic system and a nanopore array is expected to aid the separation and identification of single molecules.

PMID:34213265 | DOI:10.3724/SP.J.1123.2020.05001

Se Pu. 2020 Sep 8;38(9):1013-1021. doi: 10.3724/SP.J.1123.2020.02025.

ABSTRACT

Capillary electrophoresis-mass spectrometry (CE-MS) has the advantages of higher sensitivity, higher efficiency, and less sample consumption. Moreover, it possesses obvious advantages during the analysis of strongly charged and highly polar samples. CE-MS has been widely applied in life sciences, medicine, and pharmacology. In the past ten years, the main factors affecting its application were system stability, reproducibility, and data accuracy. In order to solve the existing problems of CE-MS, researchers have invested significant effort in technology innovation to further expand CE-MS application. In the fields of medicine and analytical chemistry, substantial research indicates that CE-MS is superior compared to other metabolomic and proteomic approaches. This study aims at reviewing the latest methods and applications developed in the fields of medicine and analytical chemistry since 2015. Furthermore, it also aims at enhancing the technology development-related application value of CE-MS and serving as a reference for future development. Further development of the CE-MS technology is discussed from the aspects of coating-sample interaction, interface types, and data processing methods. Concerning the coating types, neutral coatings had been applied extensively in CE-MS and there should be no limitation to the charge of the analyte. The coating decreased sample adsorption on the inner wall by covering the surface charge, greatly reducing the electroosmotic flow (EOF). A charged capillary coating could modify such an EOF direction. The cationic coating could reduce the hydrophobic interaction between the sample and the capillary column, resulting in higher EOF. If it is applied to the sheathless interface, the resolution could be improved by extending the capillary length. Anionic coatings are predominant among the anionic compounds, shortening the separation time by reducing the interaction between the anionic compounds and the capillary. The coating type should be chosen relative to the analyte characteristics. Concerning the interface technology, all interfaces should be simple, practical, and non-dependent on sheath liquid and background electrolytes. As far as data processing methods are concerned, it is necessary to design and develop a practical method for span space data comparison and processing. The optimized experimental conditions have effectively improved separation efficiency and data comparison analysis. Furthermore, they established a solid foundation for its application development. CE-MS analysis of complex samples in the fields of metabolomics and proteomics (e. g., of tissues, cells, body fluids, etc.) could provide a visualization method for future clinical analysis. It contributes to the development of cancer pathological analysis, drug development, disease surveillance, etc. The characteristic analysis of small molecule metabolites and protein biomarkers directly reflects on enzymatic activity in the biological systems. It could be associated with the development of various diseases/complications. Omics analysis also has an important directive to disease detection and surveillance with obvious advantages in disease diagnosis, staged treatment, drug development, and patient treatment progress. CE-MS is useful in detecting complications and promoting personalized medicine. It provides technical support for future clinical developments. In addition to a comprehensive review of the recent advances of CE-MS research, this paper also indicates the development directions of CE-MS. In order to avoid the problem of omics analysis and obtain the optimized analysis results, future analysis should be improved from the following three aspects:(i) The analysis conditions should be optimized concerning sample preparation methods and separation techniques. (ii) The analytic techniques should be supported to adjust to capillary coating and interface technology. (iii) New ideas should be developed in the fields of clinical research and statistical analysis.

PMID:34213267 | DOI:10.3724/SP.J.1123.2020.02025

J Esthet Restor Dent. 2021 Jul 2. doi: 10.1111/jerd.12799. Online ahead of print.

ABSTRACT

PURPOSE: The objective of this systematic review was to describe studies that report on whether surface characteristics such as electrostatic charge, surface free energy, and surface topography promote influence on bacterial adhesion on ceramic surfaces.

MATERIAL AND METHOD: Searches in the SCOPUS, PubMed/Medline, Web of Science, EMBASE, and Google Scholar databases were performed between December 2020 and January 2021 and updated in March 2021. In addition, a manual search of reference lists from relevant retrieved articles was performed. The criteria included: studies that evaluated ceramic surfaces, which described factors such as surface free energy, electrostatic charges, roughness, zeta potential, and their relationship with bacteria.

RESULTS: Database search resulted in 348 papers. Of the 24 studies selected for full reading, 17 articles remained in this systematic review. Another five studies were found in references of articles included, totaling 22 studies. These had a high heterogeneity making it difficult to perform statistical analysis, so a descriptive analysis was performed.

CONCLUSIONS: For dental ceramics, not enough results were found to demonstrate the influence of the electrostatic condition, and its relationship with bacterial adhesion. However, studies of this review show that there is a correlation between bacterial adhesion, surface free energy, and topography.

CLINICAL SIGNIFICANCE: The knowledge of ceramics with repulsive physical-chemical interactions would allow an environment suggestive of non-adhesion of pathogenic biofilm.

PMID:34213078 | DOI:10.1111/jerd.12799

Hum Brain Mapp. 2021 Jul 2. doi: 10.1002/hbm.25575. Online ahead of print.

ABSTRACT

Type 2 diabetes mellitus (T2DM) is associated with cognitive impairment and may progress to dementia. However, the brain functional mechanism of T2DM-related dementia is still less understood. Recent resting-state functional magnetic resonance imaging functional connectivity (FC) studies have proved its potential value in the study of T2DM with cognitive impairment (T2DM-CI). However, they mainly used a mass-univariate statistical analysis that was not suitable to reveal the altered FC “pattern” in T2DM-CI, due to lower sensitivity. In this study, we proposed to use high-order FC to reveal the abnormal connectomics pattern in T2DM-CI with a multivariate, machine learning-based strategy. We also investigated whether such patterns were different between T2DM-CI and T2DM without cognitive impairment (T2DM-noCI) to better understand T2DM-induced cognitive impairment, on 23 T2DM-CI and 27 T2DM-noCI patients, as well as 50 healthy controls (HCs). We first built the large-scale high-order brain networks based on temporal synchronization of the dynamic FC time series among multiple brain region pairs and then used this information to classify the T2DM-CI (as well as T2DM-noCI) from the matched HC based on support vector machine. Our model achieved an accuracy of 79.17% in T2DM-CI versus HC differentiation, but only 59.62% in T2DM-noCI versus HC classification. We found abnormal high-order FC patterns in T2DM-CI compared to HC, which was different from that in T2DM-noCI. Our study indicates that there could be widespread connectivity alterations underlying the T2DM-induced cognitive impairment. The results help to better understand the changes in the central neural system due to T2DM.

PMID:34213081 | DOI:10.1002/hbm.25575

Microsc Res Tech. 2021 Jul 2. doi: 10.1002/jemt.23857. Online ahead of print.

ABSTRACT

The aim of this study was to investigate human dental enamel surfaces using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), Raman spectroscopy, and small angle X-ray scattering (SAXS) techniques concerning differences between the demineralized enamel surface and remineralized enamel surface by casein phosphopeptide amorphous calcium phosphate, Tooth mousse® (CPP-ACP) and remineralizing oral care systems (ROCS®) agents within the same tooth. For this purpose, 20 freshly extracted human maxillary central incisors without caries and defects were used. Labial surfaces of each of the teeth were divided into four sections, which were marked as follows: Group 1, normal enamel; Group 2, demineralized enamel with demineralization solution; Group 3, demineralized enamel + remineralization agent (ROCS for 10 teeth, CPP-ACP for 10 teeth); and Group 4, remineralization agent (ROCS for 10 teeth, CPP-ACP for 10 teeth). To describe the changes in tooth enamel, the phosphate group concentration within enamel was used as an indicator of the degree of mineralization. The phosphate and carbonate bands in the FTIR and Raman spectra were used to investigate the structural changes in the demineralized and remineralized enamel. Spectroscopic data were statistically analyzed in terms of CPP-ACP and ROCS using one-way analysis of variance. The carbonate content of demineralized enamel was higher than the carbonate content in the other groups (p < .03). The apatite carbonate-phosphate balance in the samples with only remineralizing agent-especially ROCS applied-changed significantly (p < .05) compared to the normal group. The average FTIR spectra of the groups were subjected to multivariate hierarchical cluster analysis (HCA) conducted with the use of the OPUS 5.5 software. Nanosized surface morphologies of the samples were compared using pair distance distributions obtained through SAXS analyses. According to the SAXS analyses, applications of CCP + ACP and ROCS agents were effective on nanostructures for all groups.

PMID:34213062 | DOI:10.1002/jemt.23857

HIV Med. 2021 Jul 1. doi: 10.1111/hiv.13126. Online ahead of print.

ABSTRACT

OBJECTIVES: South Africa has made remarkable progress in increasing the coverage of antiretroviral therapy (ART) among pregnant women; however, viral suppression among pregnant women receiving ART is reported to be low. Access to routine viral load testing is crucial to identify women with unsuppressed viral load early in pregnancy and to provide timely intervention to improve viral suppression. This study aimed to determine the coverage of maternal viral load monitoring nationally, focusing on viral load testing, documentation of viral load test results, and viral suppression (viral load < 50 copies/mL). At the time of this study, the first-line regimen for women initiating ART during pregnancy was non-nucleoside reverse transcriptase (NNRTI)-based regimen.

METHODS: Between 1 October and 15 November 2019, a cross-sectional survey was conducted among 15- to 49-year-old pregnant women attending antenatal care in 1589 nationally representative public health facilities. Data on ART status, viral load testing and viral load test results were extracted from medical records. Logistic regression was used to examine factors associated with coverage of viral load testing.

RESULTS: Of 8112 participants eligible for viral load testing, 81.7% received viral load testing, and 94.1% of the viral load test results were documented in the medical records. Of those who had viral load test results documented, 74.1% were virally suppressed. Women initiated on ART during pregnancy and who received ART for three months had lower coverage of viral load testing (73%) and viral suppression (56.8%) compared with women initiated on ART before pregnancy (82.8% and 76.1%, respectively). Initiating ART during pregnancy rather than before pregnancy was associated with a lower likelihood of receiving a viral load test during pregnancy (adjusted odds ratio = 1.6, 95% confidence interval: 1.4-1.8).

CONCLUSIONS: Viral load result documentation was high; viral load testing could be improved especially among women initiating ART during pregnancy. The low viral suppression among women who initiated ART during pregnancy despite receiving ART for three months highlights the importance of enhanced adherence counselling during pregnancy. Our finding supports the WHO recommendation that a Dolutegravir-containing regimen be the preferred regimen for women who are newly initiating ART during pregnancy for more rapid viral suppression.

PMID:34213065 | DOI:10.1111/hiv.13126

Vet Ophthalmol. 2021 Jul 2. doi: 10.1111/vop.12915. Online ahead of print.

ABSTRACT

OBJECTIVE: Identify ocular findings associated with blunt ocular trauma to aid in differentiation from other equine ocular diseases.

STUDY DESIGN: Retrospective case-control study.

METHODS: Medical records of horses at the Equine Clinic Munich-Riem, Munich, Germany and Auburn University, College of Veterinary Medicine were reviewed. Age, sex, breed, laterality, and clinical findings on ophthalmic examination, as well as an observed (confirmed) or unobserved (suspected) history of trauma, were recorded. Statistical analysis was performed to identify any correlation between clinical signs and blunt ocular trauma. Fifty-nine clinical signs were evaluated, and their association with blunt ocular trauma and non-traumatic uveitis was determined. The frequency of clinical signs associated with non-traumatic uveitis was also reported.

RESULTS: Fifty-five eyes affected with blunt trauma were included. The comparison group consisted of 233 eyes (168 horses) diagnosed with non-traumatic uveitis. The most frequent ocular findings after BOT included cataract (36/55, 65.5%), corneal edema (26/55, 47.2%), decreased intraocular pressure (23/55, 41.8%), aqueous flare (19/55, 34.5%), lens subluxation, luxation, or lens loss (18/55, 32.7%), fibrin in the anterior chamber (18/55, 32.7%), hyphema (16/55, 29.1%), peripapillary depigmentation (“butterfly lesion”) (16/55, 29.1%), conjunctival hyperemia (16/55, 29.1%), corneal fibrosis (15/55, 27.3%), corpora nigra avulsion (14/55, 25.5%), blepharospasm (13/55, 23.6%), and iridodialysis (11/55, 20.0%).

CONCLUSIONS: The characteristic pattern of ocular signs associated with blunt ocular trauma may assist in differentiation from other types of uveitis and may improve interpretation of ocular lesions identified during pre-purchase examinations. This study also represents the first peer-reviewed documented and photographed cases of iridodialysis in the horse.

PMID:34213057 | DOI:10.1111/vop.12915

Chemphyschem. 2021 Jul 2. doi: 10.1002/cphc.202100431. Online ahead of print.

ABSTRACT

In many experimental investigations of thermodynamic equilibrium or kinetic properties of series of similar reactions it is found that the enthalpies and entropies derived from van ‘t Hoff or Arrhenius plots exhibit a strong linear correlation. The origin of this Enthalpy-Entropy compensation, which is strongly related to the coalescence tendency of van ‘t Hoff or Arrhenius plots, is not necessarily due to a physical/chemical/biological process. It can also be a merely statistical artefact. A new method, called Combined K-CQF makes it possible both to quantify the degree of coalescence of experimental Van ‘t Hoff lines and to verify whether or not the Enthalpy-Entropy Compensation is of a statistical origin at a desired confidence level. The method is universal and can handle data sets with any degree of coalescence of Van ‘t Hoff (or Arrhenius) plots. The new method requires only a standard least square fit of the enthalpy ΔH versus entropy ΔS plot to determine the two essential dimensionless parameters K and CQF . The parameter K indicates the position (in inverse temperature) of the coalescence region of Van ‘t Hoff plots and CQF is a quantitative measure of the smallest spread of the Van ‘t Hoff plots. The position of the ( K, CQF) couple with respect to universal confidence contours determined from a large number of simulations of random Van ‘t Hoff plots indicates straightforwardly whether or not the ΔH-ΔS compensation is a statistical artefact.

PMID:34213060 | DOI:10.1002/cphc.202100431

Stat Med. 2021 Jul 2. doi: 10.1002/sim.9030. Online ahead of print.

ABSTRACT

Healthcare researchers are showing renewed interest in the utilization of N-of-1 clinical trials for the individualization of pharmacological treatments. Here, we propose a frequentist approach to conducting treatment individualization in N-of-1 trials that we call “partial empirical Bayes.” We infer the most beneficial treatment for the patient from combining the information provided by a previously conducted population crossover trial with individual patient data. We propose a method for estimating an optimal number of treatment cycles and investigate the statistical conditions under which N-of-1 trials are more beneficial than traditional clinical approaches. We represent the patient population with a random-coefficients linear model and calculate estimators of posttreatment individual disease severities. We show the estimators’ consistency under the most common N-of-1 designs and examine their prediction errors and performance with small numbers of patient’s responses. We demonstrate by simulating new patients that our approach is equivalent or superior to both the common clinical practice of recommending the on-average best treatment for all patients and the common individualization method that simply compares average responses to the tested treatments. We conclude that some situations exist in which individualization with N-of-1 trials is highly beneficial while other situations exist in which individualization may be unfruitful.

PMID:34213011 | DOI:10.1002/sim.9030

J Intellect Disabil Res. 2021 Jul 2. doi: 10.1111/jir.12865. Online ahead of print.

ABSTRACT

BACKGROUND: Deficits in executive functioning (EF) have been measured in individuals with developmental disabilities, such as autism spectrum disorder and attention-deficit/hyperactivity disorder, through the use of behaviour rating scales and performance-based assessment. Associations between EF and variables such as challenging and adaptive behaviour have been observed; however, limited research exists on EF profiles in children with heterogeneous developmental delay or with intellectual disability (ID) or the impact of EF on adaptive and challenging behaviour with this population.

METHODS: The present study sought to examine the EF profile of 93 children (75 male and 18 female) previously identified with developmental delay in early childhood. EF was assessed using the Behaviour Rating Inventory of Executive Function, Second Edition (BRIEF-2). Children were categorised into an ID group (n = 14) or no ID group (n = 79) based on scores from cognitive and adaptive behaviour assessments. EF profiles were investigated and compared by group. In addition, the impact of EF on both adaptive behaviour and challenging behaviour was measured using hierarchical linear regressions.

RESULTS: Statistically significant differences in caregiver-reported EF were not observed between groups; however, both the ID and the no ID group scores were elevated as reported by their caregivers. For the overall sample, caregiver-EF accounted for significant variance in both adaptive (22%) and challenging (68%) behaviour after accounting for child age and sex.

CONCLUSIONS: Results indicated deficits in EF for children with and without ID. The significance of EF was accounted for in both adaptive and challenging behaviour for all children in the sample. Future research could elucidate the role of adaptive and challenging behaviour in understanding EF variability among children with histories of developmental delay.

PMID:34213015 | DOI:10.1111/jir.12865