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1.
Med Phys ; 2024 May 06.
Article En | MEDLINE | ID: mdl-38710222

BACKGROUND: Preclinical low-count positron emission tomography (LC-PET) imaging offers numerous advantages such as facilitating imaging logistics, enabling longitudinal studies of long- and short-lived isotopes as well as increasing scanner throughput. However, LC-PET is characterized by reduced photon-count levels resulting in low signal-to-noise ratio (SNR), segmentation difficulties, and quantification uncertainties. PURPOSE: We developed and evaluated a novel deep-learning (DL) architecture-Attention based Residual-Dilated Net (ARD-Net)-to generate standard-count PET (SC-PET) images from LC-PET images. The performance of the ARD-Net framework was evaluated for numerous low count realizations using fidelity-based qualitative metrics, task-based segmentation, and quantitative metrics. METHOD: Patient Derived tumor Xenograft (PDX) with tumors implanted in the mammary fat-pad were subjected to preclinical [18F]-Fluorodeoxyglucose (FDG)-PET/CT imaging. SC-PET images were derived from a 10 min static FDG-PET acquisition, 50 min post administration of FDG, and were resampled to generate four distinct LC-PET realizations corresponding to 10%, 5%, 1.6%, and 0.8% of SC-PET count-level. ARD-Net was trained and optimized using 48 preclinical FDG-PET datasets, while 16 datasets were utilized to assess performance. Further, the performance of ARD-Net was benchmarked against two leading DL-based methods (Residual UNet, RU-Net; and Dilated Network, D-Net) and non-DL methods (Non-Local Means, NLM; and Block Matching 3D Filtering, BM3D). The performance of the framework was evaluated using traditional fidelity-based image quality metrics such as Structural Similarity Index Metric (SSIM) and Normalized Root Mean Square Error (NRMSE), as well as human observer-based tumor segmentation performance (Dice Score and volume bias) and quantitative analysis of Standardized Uptake Value (SUV) measurements. Additionally, radiomics-derived features were utilized as a measure of quality assurance (QA) in comparison to true SC-PET. Finally, a performance ensemble score (EPS) was developed by integrating fidelity-based and task-based metrics. Concordance Correlation Coefficient (CCC) was utilized to determine concordance between measures. The non-parametric Friedman Test with Bonferroni correction was used to compare the performance of ARD-Net against benchmarked methods with significance at adjusted p-value ≤0.01. RESULTS: ARD-Net-generated SC-PET images exhibited significantly better (p ≤ 0.01 post Bonferroni correction) overall image fidelity scores in terms of SSIM and NRMSE at majority of photon-count levels compared to benchmarked DL and non-DL methods. In terms of task-based quantitative accuracy evaluated by SUVMean and SUVPeak, ARD-Net exhibited less than 5% median absolute bias for SUVMean compared to true SC-PET and lower degree of variability compared to benchmarked DL and non-DL based methods in generating SC-PET. Additionally, ARD-Net-generated SC-PET images displayed higher degree of concordance to SC-PET images in terms of radiomics features compared to non-DL and other DL approaches. Finally, the ensemble score suggested that ARD-Net exhibited significantly superior performance compared to benchmarked algorithms (p ≤ 0.01 post Bonferroni correction). CONCLUSION: ARD-Net provides a robust framework to generate SC-PET from LC-PET images. ARD-Net generated SC-PET images exhibited superior performance compared other DL and non-DL approaches in terms of image-fidelity based metrics, task-based segmentation metrics, and minimal bias in terms of task-based quantification performance for preclinical PET imaging.

2.
Microbiol Spectr ; : e0421323, 2024 May 03.
Article En | MEDLINE | ID: mdl-38700324

A US collection of invasive Escherichia coli serotype O1 bloodstream infection (BSI) isolates were assessed for genotypic and phenotypic diversity as the basis for designing a broadly protective O-antigen vaccine. Eighty percent of the BSI isolate serotype O1 strains were genotypically ST95 O1:K1:H7. The carbohydrate repeat unit structure of the O1a subtype was conserved in the three strains tested representing core genome multi-locus sequence types (MLST) sequence types ST95, ST38, and ST59. A long-chain O1a CRM197 lattice glycoconjugate antigen was generated using oxidized polysaccharide and reductive amination chemistry. Two ST95 strains were investigated for use in opsonophagocytic assays (OPA) with immune sera from vaccinated animals and in murine lethal challenge models. Both strains were susceptible to OPA killing with O1a glycoconjugate post-immune sera. One of these, a neonatal sepsis strain, was found to be highly lethal in the murine challenge model for which virulence was shown to be dependent on the presence of the K1 capsule. Mice immunized with the O1a glycoconjugate were protected from challenges with this strain or a second, genotypically related, and similarly virulent neonatal isolate. This long-chain O1a CRM197 lattice glycoconjugate shows promise as a component of a multi-valent vaccine to prevent invasive E. coli infections. IMPORTANCE: The Escherichia coli serotype O1 O-antigen serogroup is a common cause of invasive bloodstream infections (BSI) in populations at risk such as newborns and the elderly. Sequencing of US BSI isolates and structural analysis of O polysaccharide antigens purified from strains that are representative of genotypic sub-groups confirmed the relevance of the O1a subtype as a vaccine antigen. O polysaccharide was purified from a strain engineered to produce long-chain O1a O-antigen and was chemically conjugated to CRM197 carrier protein. The resulting glycoconjugate elicited functional antibodies and was protective in mice against lethal challenges with virulent K1-encapsulated O1a isolates.

3.
J Med Internet Res ; 26: e50629, 2024 Mar 29.
Article En | MEDLINE | ID: mdl-38442238

BACKGROUND: Increasing health care expenditure in the United States has put policy makers under enormous pressure to find ways to curtail costs. Starting January 1, 2021, hospitals operating in the United States were mandated to publish transparent, accessible pricing information online about the items and services in a consumer-friendly format within comprehensive machine-readable files on their websites. OBJECTIVE: The aims of this study are to analyze the available files on hospitals' websites, answering the question-is price transparency (PT) information as provided usable for patients or for machines?-and to provide a solution. METHODS: We analyzed 39 main hospitals in Florida that have published machine-readable files on their website, including commercial carriers. We created an Excel (Microsoft) file that included those 39 hospitals along with the 4 most popular services-Current Procedural Terminology (CPT) 45380, 29827, and 70553 and Diagnosis-Related Group (DRG) 807-for the 4 most popular commercial carriers (Health Maintenance Organization [HMO] or Preferred Provider Organization [PPO] plans)-Aetna, Florida Blue, Cigna, and UnitedHealthcare. We conducted an A/B test using 67 MTurkers (randomly selected from US residents), investigating the level of awareness about PT legislation and the usability of available files. We also suggested format standardization, such as master field names using schema integration, to make machine-readable files consistent and usable for machines. RESULTS: The poor usability and inconsistent formats of the current PT information yielded no evidence of its usefulness for patients or its quality for machines. This indicates that the information does not meet the requirements for being consumer-friendly or machine readable as mandated by legislation. Based on the responses to the first part of the experiment (PT awareness), it was evident that participants need to be made aware of the PT legislation. However, they believe it is important to know the service price before receiving it. Based on the responses to the second part of the experiment (human usability of PT information), the average number of correct responses was not equal between the 2 groups, that is, the treatment group (mean 1.23, SD 1.30) found more correct answers than the control group (mean 2.76, SD 0.58; t65=6.46; P<.001; d=1.52). CONCLUSIONS: Consistent machine-readable files across all health systems facilitate the development of tools for estimating customer out-of-pocket costs, aligning with the PT rule's main objective-providing patients with valuable information and reducing health care expenditures.


Delivery of Health Care , Health Expenditures , United States , Humans , Costs and Cost Analysis , Florida , Hospitals
4.
J Cardiopulm Rehabil Prev ; 44(1): 40-48, 2024 Jan 01.
Article En | MEDLINE | ID: mdl-37285601

PURPOSE: The aim of this study was to evaluate the effects of a mobile health (mHealth) intervention, HerBeat, compared with educational usual care (E-UC) for improving exercise capacity (EC) and other patient-reported outcomes at 3 mo among women with coronary heart disease. METHODS: Women were randomized to the HerBeat group (n = 23), a behavior change mHealth intervention with a smartphone, smartwatch, and health coach or to the E-UC group (n = 24) who received a standardized cardiac rehabilitation workbook. The primary endpoint was EC measured with the 6-min walk test (6MWT). Secondary outcomes included cardiovascular disease risk factors and psychosocial well-being. RESULTS: A total of 47 women (age 61.2 ± 9.1 yr) underwent randomization. The HerBeat group significantly improved on the 6MWT from baseline to 3 mo ( P = .016, d = .558) while the E-UC group did not ( P = .894, d =-0.030). The between-group difference of 38 m at 3 mo was not statistically significant. From baseline to 3 mo, the HerBeat group improved in anxiety ( P = .021), eating habits confidence ( P = .028), self-efficacy for managing chronic disease ( P = .001), diastolic blood pressure ( P = .03), general health perceptions ( P = .047), perceived bodily pain ( P = .02), and waist circumference ( P = .008) while the E-UC group showed no improvement on any outcomes. CONCLUSIONS: The mHealth intervention led to improvements in EC and several secondary outcomes from baseline to 3 mo while the E-UC intervention did not. A larger study is required to detect small differences between groups. The implementation and outcomes evaluation of the HerBeat intervention was feasible and acceptable with minimal attrition.


Coronary Disease , Telemedicine , Humans , Female , Middle Aged , Aged , Pilot Projects , Chronic Disease , Health Behavior
5.
Int J Appl Basic Med Res ; 13(2): 124-128, 2023.
Article En | MEDLINE | ID: mdl-37614843

Lymphoma in the jaw bone is a rare malignant neoplasm with heterogeneous nature diagnosis of which requires utmost knowledge of cellular morphology and tissue architecture. The lineage of the neoplastic lymphocytes, whether it is B- or T-cell or mixed in nature, is designated by cluster of differentiation numbers. Broad classification of malignant lymphoma includes Hodgkin's and non-Hodgkin's lymphoma which have various subtypes. An unusual case of a B-cell lymphoma in the mandible in a middle-aged male patient is presented herewith clinicopathological and immunohistochemical features.

6.
J Med Internet Res ; 25: e44307, 2023 05 11.
Article En | MEDLINE | ID: mdl-37166952

BACKGROUND: While there is high-quality online health information, a lot of recent work has unfortunately highlighted significant issues with the health content on social media platforms (eg, fake news and misinformation), the consequences of which are severe in health care. One solution is to investigate methods that encourage users to post high-quality content. OBJECTIVE: Incentives have been shown to work in many domains, but until recently, there was no method to provide financial incentives easily on social media for users to generate high-quality content. This study investigates the following question: What effect does the provision of incentives have on the creation of social media health care content? METHODS: We analyzed 8328 health-related posts from an incentive-based platform (Steemit) and 1682 health-related posts from a traditional platform (Reddit). Using topic modeling and sentiment analysis-based methods in machine learning, we analyzed these posts across the following 3 dimensions: (1) emotion and language style using the IBM Watson Tone Analyzer service, (2) topic similarity and difference from contrastive topic modeling, and (3) the extent to which posts resemble clickbait. We also conducted a survey using 276 Amazon Mechanical Turk (MTurk) users and asked them to score the quality of Steemit and Reddit posts. RESULTS: Using the Watson Tone Analyzer in a sample of 2000 posts from Steemit and Reddit, we found that more than double the number of Steemit posts had a confident language style compared with Reddit posts (77 vs 30). Moreover, 50% more Steemit posts had analytical content and 33% less Steemit posts had a tentative language style compared with Reddit posts (619 vs 430 and 416 vs 627, respectively). Furthermore, more than double the number of Steemit posts were considered joyful compared with Reddit posts (435 vs 200), whereas negative posts (eg, sadness, fear, and anger) were 33% less on Steemit than on Reddit (384 vs 569). Contrastive topic discovery showed that only 20% (2/10) of topics were common, and Steemit had more unique topics than Reddit (5 vs 3). Qualitatively, Steemit topics were more informational, while Reddit topics involved discussions, which may explain some of the quantitative differences. Manual labeling marked more Steemit headlines as clickbait than Reddit headlines (66 vs 26), and machine learning model labeling consistently identified a higher percentage of Steemit headlines as clickbait than Reddit headlines. In the survey, MTurk users said that at least 57% of Steemit posts had better quality than Reddit posts, and they were at least 52% more likely to like and comment on Steemit posts than Reddit posts. CONCLUSIONS: It is becoming increasingly important to ensure high-quality health content on social media; therefore, incentive-based social media could be important in the design of next-generation social platforms for health information.


Motivation , Social Media , Humans , Sentiment Analysis , Emotions , Fear
7.
Med Biol Eng Comput ; 61(10): 2581-2591, 2023 Oct.
Article En | MEDLINE | ID: mdl-37233860

Mandible subcondylar fractures have very high complication rate, yet there is no consensus on suitable plate design for optimal patient outcomes. Our study is aimed at comparing single mini, trapezoid, lambda, strut and double mini plates. A finite-element (FE) model of intact mandible was developed based on healthy CT-scan data, which was further virtually osteotomized and fixated with plates. The cortical and cancellous bones were assigned region-specific orthotropic and heterogenous isotropic material properties respectively. The models were subjected to six load cases representing the mastication cycle. Under opposite lateralities, the tensile and compressive mandibular strain distributions were found as the opposite, with tensile strains at the posterior border under ipsilateral molar clenching (RMOL) resulting in lesser mandibular strain in reconstructed mandible with single mini plate under RMOL but highest mandibular strain under the contralateral molar clenching (LMOL). Owing to the reduced mandibular strains under LMOL than RMOL, the contralateral chewing is preferred during the immediate post-surgery period for patients. Under LMOL, the peak von Mises stresses in the plate decreased with increase in the number of screws. Furthermore, the presence of two arms in double mini and trapezoid plates seems beneficial to neutralise the tensile and compressive strains across load cases.


Mandible , Mandibular Fractures , Humans , Finite Element Analysis , Mandible/surgery , Mandibular Fractures/surgery , Tomography, X-Ray Computed/methods , Fracture Fixation, Internal/methods , Bone Plates , Biomechanical Phenomena , Stress, Mechanical
8.
Med Eng Phys ; 111: 103941, 2023 01.
Article En | MEDLINE | ID: mdl-36792242

Mandibles with odontogenic tumors are often partially reconstructed with a metallic bone graft analogue with dental roots, crowns, along with a customized plate fixed with monocortical or bicortical screws, following resection of the tumor. In this study, two different designs of patient specific customized Ti reconstruction plates, solid and plate with holes, were considered. Fixation through both bicortical and monocortical screw types were investigated. FE models of the reconstructed mandibles were developed to analyse the influence of the plate-screw type combination on the load transfer across the mandibles under a mastication cycle. The effective homogenized orthotropic material properties of the lattice structures with 0.6 mm fibre diameter with 0.5 mm inter-fibre space were assigned to material properties for the bone graft analogue. The study shows that the combination of plate and screw types influences the state of stresses in the reconstructed mandible. Based on the results of this patient specific study, following resection of the tumor, either solid Ti plate with bicortical screws or Ti plate with holes along with monocortical screws may be used for partial mandibulectomy. It should also be noted that stresses in none of the plates or screws exceeded the yield limit for Ti under the mastication cycle indicating that the components are safe for mandibular reconstruction. However, the choice of this combination of reconstruction plates and screws is dependant on the condition and severity of the tumor in the diseased mandible.


Mandibular Reconstruction , Plastic Surgery Procedures , Humans , Mandibular Reconstruction/methods , Bone Screws , Bone Transplantation , Mandible/surgery , Bone Plates , Biomechanical Phenomena
9.
Nanomedicine (Lond) ; 18(2): 109-123, 2023 01.
Article En | MEDLINE | ID: mdl-36853798

Aim: The functionalization and characterization of antibacterial nanoceria with folic acid (FA) and elucidation of their in vivo wound-healing application. Materials & methods: Functionalization of nanoceria were done with FA using a chemical method and their antibacterial activity, cellular biocompatibility and in vivo wound-healing application were evaluated. Results: The functionalization of nanoceria with FA was done with 10-20 nm size and -20.1 mV zeta potential. The nanoformulation showed a bacteriostatic effect along with biocompatibility to different cell lines; 0.1% w/v spray of FA-nanoceria demonstrated excellent wound-healing capacity within 14 days in a Wister rat model. Conclusion: The antioxidant and reactive oxygen species scavenging activity of the FA-nanoceria make it a promising therapeutic agent as a unique spray formulation in wound-healing applications.


The emergence of chronic wounds is a main reason for mortality in patients with diabetes and other severe pathological complications. Advances in the use of nanotechnology have resulted in beneficial technology for tailoring of pharmacokinetic properties of different drug-delivery vehicles for different biomedical applications. In this study, folic acid (FA) functionalized nanoceria (FA-nanoceria) were formulated and their potential efficacy in the wound-healing process was explored. The nanoformulation showed a remarkable bacteriostatic effect on both Gram-negative and Gram-positive bacteria. In vitro cell line studies showed satisfactory biocompatibility in three different types of cell lines. In addition, a 0.1% w/v spray of FA-nanoceria was applied to full-thickness wounds in an in vivo mice model where it demonstrated excellent wound-healing capacity within 14 days. The combined antioxidant and reactive oxygen species scavenging activity of both the FA and nanoceria makes FA-nanoceria a promising therapeutic agent as a unique spray formulation in wound-healing applications.


Antioxidants , Folic Acid , Rats , Animals , Folic Acid/chemistry , Rats, Wistar , Antioxidants/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry
10.
J Immunol ; 210(6): 764-773, 2023 03 15.
Article En | MEDLINE | ID: mdl-36723033

Implementation of conjugate vaccine technology revolutionized the ability to effectively elicit long-lasting immune responses to bacterial capsular polysaccharides. Although expansion of conjugate vaccine serotype coverage is designed to target residual disease burden to pneumococcal serotypes not contained in earlier vaccine versions, details of polysaccharide Ag structure, heterogeneity, and epitope structure components contributing to vaccine-mediated immunity are not always clear. Analysis of Streptococcus pneumoniae serotype 12F polysaccharide by two-dimensional nuclear magnetic resonance spectroscopy and mass spectrometry revealed a partial substitution of N-acetyl-galactosamine by the keto sugar 2-acetamido-2,6-dideoxy-xylo-hexos-4-ulose (Sug) in up to 25% of the repeat units. This substitution was not described in previous published structures for 12F. Screening a series of contemporary 12F strains isolated from humans (n = 17) identified Sug incorporation at varying levels in all strains examined. Thus, partial Sug substitution in S. pneumoniae serotype 12F may have always been present but is now detectable by state-of-the-art analytical techniques. During the steps of conjugation, the serotype 12F Sug epitope is modified by reduction, and both polysaccharide PPSV23 and conjugate PCV20 vaccines contain 12F Ags with little to no Sug epitope. Both PCV20 and PPSV23 vaccines were evaluated for protection against circulating 12F strains with varying amounts of Sug in their repeat unit based on an opsonophagocytic killing assay involving HL-60 cells and rabbit complement. Both vaccines elicited human-derived neutralizing Abs against serotype 12F, independent of Sug level between ∼2 and 25 mol%. These findings suggest that the newly identified serotype 12F Sug epitope is likely not an essential epitope for vaccine-elicited protection.


Immunogenicity, Vaccine , Streptococcus pneumoniae , Humans , Serogroup , Vaccines, Conjugate , Magnetic Resonance Spectroscopy
11.
Infect Immun ; 90(4): e0002222, 2022 04 21.
Article En | MEDLINE | ID: mdl-35311580

Multivalent O-antigen polysaccharide glycoconjugate vaccines are under development to prevent invasive infections caused by pathogenic Enterobacteriaceae. Sequence type 131 (ST131) Escherichia coli of serotype O25b has emerged as the predominant lineage causing invasive multidrug-resistant extraintestinal pathogenic E. coli (ExPEC) infections. We observed the prevalence of E. coli O25b ST131 among a contemporary collection of isolates from U.S. bloodstream infections from 2013 to 2016 (n = 444) and global urinary tract infections from 2014 to 2017 (n = 102) to be 25% and 24%, respectively. To maximize immunogenicity of the serotype O25b O antigen, we investigated glycoconjugate properties, including CRM197 carrier protein cross-linking (single-end versus cross-linked "lattice") and conjugation chemistry (reductive amination chemistry in dimethyl sulfoxide [RAC/DMSO] versus ((2-((2-oxoethyl)thio)ethyl)carbamate [eTEC] linker). Using opsonophagocytic assays (OPAs) to measure serum functional antibody responses to vaccination, we observed that higher-molecular-mass O25b long-chain lattice conjugates showed improved immunogenicity in mice compared with long- or short-chain O antigens conjugated via single-end attachment. The lattice conjugates protected mice from lethal challenge with acapsular O25b ST131 strains as well as against hypervirulent O25b isolates expressing K5 or K100 capsular polysaccharides. A single 1-µg dose of long-chain O25b lattice conjugate constructed with both chemistries also elicited robust serum IgG and OPA responses in cynomolgus macaques. Our findings show that key properties of the O-antigen carrier protein conjugate such as saccharide epitope density and degree of intermolecular cross-linking can significantly enhance functional immunogenicity.


Escherichia coli Infections , O Antigens , Animals , Carrier Proteins , Escherichia coli , Escherichia coli Infections/prevention & control , Glycoconjugates , Mice
12.
Cancers (Basel) ; 13(15)2021 Jul 28.
Article En | MEDLINE | ID: mdl-34359696

Preclinical magnetic resonance imaging (MRI) is a critical component in a co-clinical research pipeline. Importantly, segmentation of tumors in MRI is a necessary step in tumor phenotyping and assessment of response to therapy. However, manual segmentation is time-intensive and suffers from inter- and intra- observer variability and lack of reproducibility. This study aimed to develop an automated pipeline for accurate localization and delineation of TNBC PDX tumors from preclinical T1w and T2w MR images using a deep learning (DL) algorithm and to assess the sensitivity of radiomic features to tumor boundaries. We tested five network architectures including U-Net, dense U-Net, Res-Net, recurrent residual UNet (R2UNet), and dense R2U-Net (D-R2UNet), which were compared against manual delineation by experts. To mitigate bias among multiple experts, the simultaneous truth and performance level estimation (STAPLE) algorithm was applied to create consensus maps. Performance metrics (F1-Score, recall, precision, and AUC) were used to assess the performance of the networks. Multi-contrast D-R2UNet performed best with F1-score = 0.948; however, all networks scored within 1-3% of each other. Radiomic features extracted from D-R2UNet were highly corelated to STAPLE-derived features with 67.13% of T1w and 53.15% of T2w exhibiting correlation ρ ≥ 0.9 (p ≤ 0.05). D-R2UNet-extracted features exhibited better reproducibility relative to STAPLE with 86.71% of T1w and 69.93% of T2w features found to be highly reproducible (CCC ≥ 0.9, p ≤ 0.05). Finally, 39.16% T1w and 13.9% T2w features were identified as insensitive to tumor boundary perturbations (Spearman correlation (-0.4 ≤ ρ ≤ 0.4). We developed a highly reproducible DL algorithm to circumvent manual segmentation of T1w and T2w MR images and identified sensitivity of radiomic features to tumor boundaries.

13.
Mol Pharm ; 18(3): 889-897, 2021 03 01.
Article En | MEDLINE | ID: mdl-33470823

Antibody-drug conjugates (ADCs) consist of a target-specific antibody that is covalently conjugated to a drug via a linker. ADCs are designed to deliver cytotoxic drugs (payloads), specifically to cancer cells, while minimizing systemic toxicity. Conventional cysteine conjugation typically results in the formation of ADC molecules containing a heterogeneous mixture of 2, 4, 6, and 8 drug-loaded species. The drug-to-antibody ratio (DAR) of the mixture represents the weighted average of these species. In this report, we have investigated the impact of the hydrophobicity of payloads and the overall drug loading on the in vitro binding and cytotoxicity of ADC species. Several ADCs were prepared by conventional cysteine conjugation using different payloads. ADC species with different DAR values were purified from the ADC mixture and characterized by standard analytical techniques. These ADC species were evaluated for target antigen binding using an immunoassay, enzyme-linked immunosorbent assay (ELISA). The potency was assessed using a cell-based cytotoxicity assay. These structure-function studies lead to a better understanding of factors that impact the in vitro target binding and cytotoxicity of ADC species. ADC species containing hydrophobic payloads with high DAR were found to have lower target binding by ELISA compared to that of the unconjugated antibody or the heterogeneous reference ADC with DAR ∼4. Under similar assay conditions, the ADCs conjugated to hydrophilic payloads did not show a significant impact on the target binding. The cytotoxic potency of ADC species increased with increasing level of drug loading in the cell-based cytotoxicity assay.


Antigens/chemistry , Antineoplastic Agents/chemistry , Cysteine/chemistry , Cytotoxins/chemistry , Immunoconjugates/chemistry , Antibodies, Monoclonal/chemistry , Cell Line, Tumor , Humans , Hydrophobic and Hydrophilic Interactions/drug effects , Immunoassay/methods
14.
JMIR Form Res ; 4(6): e16420, 2020 Jun 03.
Article En | MEDLINE | ID: mdl-32348270

BACKGROUND: Coronary heart disease (CHD) is the leading cause of death and disability among American women. The prevalence of CHD is expected to increase by more than 40% by 2035. In 2015, the estimated cost of caring for patients with CHD was US $182 billion in the United States; hospitalizations accounted for more than half of the costs. Compared with men, women with CHD or those who have undergone coronary revascularization have up to 30% more rehospitalizations within 30 days and up to 1 year. Center-based cardiac rehabilitation is the gold standard of care after an acute coronary event, but few women attend these valuable programs. Effective home-based interventions for improving cardiovascular health among women with CHD are vital for addressing this gap in care. OBJECTIVE: The ubiquity of mobile phones has made mobile health (mHealth) behavioral interventions a viable option to improve healthy behaviors of both women and men with CHD. First, this study aimed to examine the usability of a prototypic mHealth intervention designed specifically for women with CHD (herein referred to as HerBeat). Second, we examined the influence of HerBeat on selected health behaviors (self-efficacy for diet, exercise, and managing chronic illness) and psychological (perceived stress and depressive symptoms) characteristics of the participants. METHODS: Using a single-group, pretest, posttest design, 10 women participated in the 12-week usability study. Participants were provided a smartphone and a smartwatch on which the HerBeat app was installed. Using a web portal dashboard, a health coach monitored participants' ecological momentary assessment data, their behavioral data, and their heart rate and step count. Participants then completed a 12-week follow-up assessment. RESULTS: All 10 women (age: mean 64.4 years, SD 6.3 years) completed the study. The usability and acceptability of HerBeat were good, with a mean system usability score of 83.60 (SD 16.3). The participants demonstrated statistically significant improvements in waist circumference (P=.048), weight (P=.02), and BMI (P=.01). Furthermore, depressive symptoms, measured with the Patient Health Questionnaire-9, significantly improved from baseline (P=.04). CONCLUSIONS: The mHealth prototype was feasible and usable for women with CHD. Participants provided data that were useful for further development of HerBeat. The mHealth intervention is expected to help women with CHD self-manage their health behaviors. A randomized controlled trial is needed to further verify the findings.

15.
Proc Inst Mech Eng H ; 234(5): 486-495, 2020 May.
Article En | MEDLINE | ID: mdl-32022650

The extent to which load transfer in a diseased mandible with odontogenic tumour might influence the potential risk of pathological fracture has scarcely been investigated. The study sought to investigate the quantitative deviations in load transfer across healthy and cancer-affected (diseased) mandibles having odontogenic tumours. The effect of size of the tumours (small: 9 mm diameter, large: 19 mm diameter), and variation in bone mechanical (elastic) properties of the mandible on load transfer in cancer-affected mandibles during a mastication cycle have been investigated. Based on patient-specific computed tomography-scan datasets, detailed three-dimensional finite element models of healthy and diseased mandibles were developed. High stresses of 25-30 MPa and strains ∼700 µÎµ were observed in the healthy mandible during the right molar bite. However, marginal deviations were observed in principal stress distributions in the diseased mandibles with small- and large-sized tumours, as compared to the healthy mandible. Maximum principal strains of ∼1474 µÎµ were found in the body region adjacent to the symphysis region for small-sized tumour. Whereas for large-sized tumour, maximum strains of ∼2700 µÎµ were observed in the right buccal regions. Reduction in Young's modulus due to different stages of odontogenic tumours had a localised effect on the principal stress distributions, but triggered an abrupt increase in the principal tensile strains. It appears that there is a potential risk of pathological fracture for large-sized odontogenic tumour, owing to high tensile stresses and strains.


Mandible/physiopathology , Mastication , Odontogenic Tumors/physiopathology , Biomechanical Phenomena , Finite Element Analysis , Humans , Jaw/physiopathology , Stress, Mechanical , Weight-Bearing
16.
J Indian Soc Pedod Prev Dent ; 37(2): 120-126, 2019.
Article En | MEDLINE | ID: mdl-31249173

CONTEXT: The primary tooth has numerous functions and is important in a child's development. Pediatric endodontic treatment has a very important role in maintaining oral health of the child. However, the morphology of root canals in deciduous teeth usually leads to complications in root canal therapy. To improve the success in endodontic, a thorough knowledge of the root canal morphology is essential. AIMS: The aim of this study is to determine the thorough in vitro, morphological evaluation of root canal system of human primary molars using multidetector computed tomography. SETTINGS AND DESIGN: A total of 64 human primary maxillary and mandibular molars without any macroscopic root resorption were selected and divided into four groups. The samples were arranged in wax block, and the scanning was done on the computed tomography scanne (GE light speed 16 slice CT). SUBJECTS AND METHODS: The images were grabbed by the computer as a raw image and reformatted in a GE Advantage workstation version 4.2 (GE healthcare) with the help of Denta Scan (GE healthcare) software and volume rendering was done. STATISTICAL ANALYSIS USED: Descriptive statistical analysis (Student's t-test) was performed to calculate the means with corresponding standard deviations. A value of P ≤ 0.05 was taken to be statistically significant. RESULTS: It enlightens the clinicians view to access the morphological variations of the root canals for the effective pediatric endodontic treatment. CONCLUSIONS: The images showed the complexity of the root canals of the primary mandibular molars and also the several capabilities of the CT scan in advance endodontic research in primary teeth were observed.


Dental Pulp Cavity , Tooth Root , Child , Cone-Beam Computed Tomography , Humans , Molar , Multidetector Computed Tomography , Root Canal Therapy , Tooth, Deciduous
17.
J Indian Prosthodont Soc ; 18(3): 263-270, 2018.
Article En | MEDLINE | ID: mdl-30111916

CONTEXT: Determination of horizontal condylar guidance (HCG) by various clinical and radiographic methods was performed by several investigators. If a correlation between HCG values using lateral radiographic tracing and protrusive interocclusal records can be established, the necessity of performing elaborate recording procedures can be eliminated. AIMS: The aim of this study is to evaluate and to compare the correlation between HCG values in edentulous people using the protrusive interocclusal records mounted on a semi-adjustable articulator with the manual tracing of panoramic radiograph and lateral cephalogram. MATERIALS AND METHODS: A total of 20 completely edentulous individuals of either sex from 45 to 75 years (mean age 63.15 years) fulfilling the inclusion criteria were included in this in vivo study. In all the participants, HCG angles were determined clinically using protrusive interocclusal records and semi-adjustable articulator after intraoral gothic arch tracing. Radiographically, it was obtained by cephalometric tracing of panoramic radiograph and lateral cephalogram. RESULTS: The present study shows mean HCG ± standard deviation (SD) of 28.17° ± 5.99° for interocclusal protrusive record while cephalometric tracing method yielded HCG ± SD of 38.95° ± 4.77° and 35.2° ± 4.94° for lateral cephalogram and orthopantomogram, respectively. A statistically significant positive correlation (P < 0.0001) was found among these three methods. CONCLUSION: HCG can be successfully determined in edentulous participants by using three aforementioned methods. HCG values from cephalometric tracing of diagnostic radiographs can be used as an adjunct to the clinical method but cannot be used independently for programming a semi-adjustable articulator.

18.
J Biol Chem ; 293(12): 4555-4563, 2018 03 23.
Article En | MEDLINE | ID: mdl-29374059

Intrinsically disordered proteins (IDPs) play important roles in many biological systems. Given the vast conformational space that IDPs can explore, the thermodynamics of the interactions with their partners is closely linked to their biological functions. Intrinsically disordered regions of Phe-Gly nucleoporins (FG Nups) that contain multiple phenylalanine-glycine repeats are of particular interest, as their interactions with transport factors (TFs) underlie the paradoxically rapid yet also highly selective transport of macromolecules mediated by the nuclear pore complex. Here, we used NMR and isothermal titration calorimetry to thermodynamically characterize these multivalent interactions. These analyses revealed that a combination of low per-FG motif affinity and the enthalpy-entropy balance prevents high-avidity interaction between FG Nups and TFs, whereas the large number of FG motifs promotes frequent FG-TF contacts, resulting in enhanced selectivity. Our thermodynamic model underlines the importance of functional disorder of FG Nups. It helps explain the rapid and selective translocation of TFs through the nuclear pore complex and further expands our understanding of the mechanisms of "fuzzy" interactions involving IDPs.


Cell Nucleus/metabolism , Intrinsically Disordered Proteins/metabolism , Nuclear Pore Complex Proteins/metabolism , Nuclear Pore/physiology , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae/metabolism , Thermodynamics , Active Transport, Cell Nucleus , Crystallography, X-Ray , Glycine/chemistry , Intrinsically Disordered Proteins/chemistry , Nuclear Pore Complex Proteins/chemistry , Phenylalanine/chemistry , Protein Binding , Protein Transport , Saccharomyces cerevisiae Proteins/chemistry
19.
J Conserv Dent ; 20(2): 76-80, 2017.
Article En | MEDLINE | ID: mdl-28855751

AIM: Compare the measurement of working length with three different methods manual tactile sensation, digital radiography and Mutidetector computed tomography(MDCT). MATERIALS AND METHOD: 40 human premolar extracted for orthodontic purpose were selected. Teeth were store in sodium chloride (0.9%) during the study. Access cavity was prepared and canal patency was seen with no 10 file in each tooth. Manually no 15 K file was inserted from access cavity until the tip was visible at the foramen, a silicon stopper was adjusted to the corresponding buccal cusp tip and the root canal length was measured. After that in each tooth with no-15 K file inserted from access cavity with stop at tip of buccal cusp until tip appear at foramen and x-ray was taken with digital radiograph (RVG,Satelac) and canal length was measured. After that all teeth are mounted in wax block,MDCT scan was done and in the scan images of teeth, root canal length is measured from buccal cusp tip to root end. After taking measurement of working length with all three methods and the data was stastically analyzed with One Way Analysis of variance (ANOVA) followed by Turkey's Test. RESULTS: ANOVA and turkeys test showed that there was no significant difference in the measurements by the three procedures (p>0.05). CONCLUSION: Working length measurement with MDCT scan and other two conventional methods does not show significant difference in measurement. Use of newer 3D imaging technique is useful in root canal treatment for measuring working length.

20.
Indian J Orthop ; 51(3): 292-298, 2017.
Article En | MEDLINE | ID: mdl-28566781

BACKGROUND: Extraarticular distal tibial fractures are among the most challenging fractures encountered by an orthopedician for treatment because of its subcutaneous location, poor blood supply and decreased muscular cover anteriorly, complications such as delayed union, nonunion, wound infection, and wound dehiscence are often seen as a great challenge to the surgeon. Minimally invasive plate osteosynthesis (MIPO) and intramedullary interlocking nail (IMLN) are two well-accepted and effective methods, but each has been historically related to complications. This study compares clinical and radiological outcome in extraarticular distal tibia fractures treated by intramedullary interlocking nail (IMLN) and minimally invasive plate osteosynthesis (MIPO). MATERIALS AND METHODS: 42 patients included in this study, 21 underwent IMLN and 21 were treated with MIPO who met the inclusion criteria and operated between June 2014 and May 2015. Patients were followed up for clinical and radiological evaluation. RESULTS: In IMLN group, average union time was 18.26 weeks compared to 21.70 weeks in plating group which was significant (P < 0.0001). Average time required for partial and full weight bearing in the nailing group was 4.95 weeks and 10.09 weeks respectively which was significantly less (P < 0.0001) as compared to 6.90 weeks and 13.38 weeks in the plating group. Lesser complications in terms of implant irritation, ankle stiffness, and infection, were seen in interlocking group as compared to plating group. Average functional outcome according to American Orthopedic Foot and Ankle Society score was measured which came out to be 96.67. CONCLUSION: IMLN group was associated with lesser duration of surgery, earlier weight bearing and union rate, lesser incidence of infection and implant irritation which makes it a preferable choice for fixation of extra-articular distal tibial fractures. However, larger randomized controlled trials are required for confirming the results.

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