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1.
Article in English | MEDLINE | ID: mdl-39019584

ABSTRACT

Two critical components of patient support systems for people with TB are regular counseling and locally managed nutritional support. As part of an ongoing differentiated TB care initiative called Tamil Nadu Kasanoi Erappila Thittam (meaning TB death-free initiative in Tamil, TN-KET) to reduce TB deaths, adults with TB with very severe undernutrition, respiratory insufficiency, or poor performance status are identified at diagnosis (triage-positive) and prioritized for referral, comprehensive clinical assessment, and inpatient care. Between January and June 2023, in 6 districts, a pilot exercise was conducted in which trained TB survivors, known as TB champions, provided baseline counseling and additional counseling (if required) to triage-positive people with TB at diagnosis. Additionally, people with TB with severe undernutrition were prioritized for nutritional supplementation for at least 3 months. Among 652 people with TB who were triage-positive at diagnosis, the program staff shared details of 145 (22%), and all were counseled by TB champions (baseline counseling). Program staff identified 74 (11%) triage-positive people with TB who required additional counseling (i.e., those refusing referral or admission or continued admission), and 71 (96%) were counseled by TB champions. Among these, 54 (76%) were admitted or readmitted and successfully discharged. In addition, among 1,042 people with TB with severe undernutrition, program staff shared details of 390 (38%), of which 60% received nutritional supplementation through the efforts of TB champions. We conclude that TB champions were able to provide quality and timely peer support through direct counseling and by mobilizing local resources for nutritional support. The engagement of TB champions can be further strengthened by establishing robust coordination mechanisms with the TB program. Lessons from this pilot will contribute to the Tamil Nadu State TB Cell's plans to expand the role of TB champions and enhance community participation to end TB in India.

2.
Public Health Action ; 14(1): 3-6, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38798777

ABSTRACT

To reduce TB deaths, Tamil Nadu, a southern Indian state, implemented the first state-wide differentiated TB care strategy starting April 2022. Triage-positive severely ill patients are prioritised for comprehensive assessment and inpatient care. Routine program data during October-December 2022 revealed that documentation of total score after comprehensive assessment was available in only 39%, possibly indicating poor quality of comprehensive assessment. We confirmed this using operational research. The case record form to record comprehensive assessment was used only in 26% and among these, the completeness and correctness in filling out the form were sub-optimal. There is a clear need to enhance the quality of comprehensive assessments.


Depuis avril 2022, le Tamil Nadu, un État du sud de l'Inde, a mis en œuvre la première stratégie de soins différenciés pour la TB à l'échelle de l'État afin de réduire le nombre de décès dus à la TB. Les personnes gravement malades ayant obtenu un résultat positif au triage sont prioritaires pour une évaluation complète et des soins hospitaliers. Les données du programme de routine entre octobre et décembre 2022 ont révélé que la documentation du score total après l'évaluation complète n'était disponible que dans 39% des cas, ce qui pourrait indiquer une mauvaise qualité de l'évaluation complète. Nous l'avons confirmé par le biais d'une recherche opérationnelle. Le formulaire de dossier pour enregistrer l'évaluation complète n'a été utilisé que dans 26% des cas et, parmi ceux-ci, l'exhaustivité et l'exactitude du remplissage du formulaire n'étaient pas optimales. Il est manifestement nécessaire d'améliorer la qualité de l'évaluation complète.

3.
J Clin Transl Sci ; 8(1): e71, 2024.
Article in English | MEDLINE | ID: mdl-38690226

ABSTRACT

Introduction: Addressing social determinants of health (SDOH) is fundamental to improving health outcomes. At a student-run free clinic, we developed a screening process to understand the SDOH needs and resource utilization of Milwaukee's uninsured population. Methods: In this cross-sectional study, we screened adult patients without health insurance (N = 238) for nine traditional SDOH needs as well as their access to dental and mental health care between October 2021 and October 2022. Patients were surveyed at intervals greater than or equal to 30 days. We assessed correlations between SDOH needs and trends in patient-reported resource usefulness. Results: Access to dental care (64.7%) and health insurance (51.3%) were the most frequently endorsed needs. We found significant correlations (P ≤ 0.05) between various SDOH needs. Notably, mental health access needs significantly correlated with dental (r = 0.41; 95% CI = 0.19, 0.63), medications (r = 0.51; 95% CI = 0.30, 0.72), utilities (r = 0.39; 95% CI = 0.17, 0.61), and food insecurity (r = 0.42; 95% CI = 0.19, 0.64). Food-housing (r = 0.55; 95% CI = 0.32, 0.78), housing-medications (r = 0.58; 95% CI = 0.35, 0.81), and medications-food (r = 0.53; 95% CI = 0.32, 0.74) were significantly correlated with each other. Longitudinal assessment of patient-reported usefulness informed changes in the resources offered. Conclusions: Understanding prominent SDOH needs can inform resource offerings and interventions, addressing root causes that burden under-resourced patients. In this study, patient-reported data about resource usefulness prompted the curation of new resources and volunteer roles. This proof-of-concept study shows how longitudinally tracking SDOH needs at low-resource clinics can inform psychosocial resources.

5.
Med Sci Educ ; 33(5): 1155-1163, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37886297

ABSTRACT

Introduction: Medical trainees do not have many opportunities to develop communication skills with patients. We established the voluntary "My Life, My Story" (MLMS) program at the Clement J. Zablocki VAMC in Milwaukee, WI, to determine if this pilot narrative medicine program enhanced trainee interpersonal skills and improved patient-centered care. Methods: Trainees at the Medical College of Wisconsin conducted in-person or virtual interviews of Veterans receiving care at the Milwaukee VAMC about their meaningful life experiences. Post-interview, trainees wrote a short first-person narrative in the Veteran's voice, which, after the Veteran's approval, was added to the electronic medical record and made available to the patient's care team. Trainees, Veterans, and health professionals completed post-interview surveys, from which we conducted descriptive statistics and qualitatively analyzed the text-based feedback. Results: Between 2020 and 2021, 24 medical trainees participated in our pilot implementation of the MLMS program, conducting a total of 32 interviews. All trainees reported a meaningful personal impact and found the pilot to be "valuable" and "rewarding." Both trainees and health professionals believed that the MLMS program improved "rapport building" with Veterans. Nearly all Veterans (n = 25, 93%) believed that their medical care team would be able to provide better care after reading their life story. Conclusions: Narrative medicine initiatives like the MLMS program may enable value-added education for trainees. Future research will allow us to better understand and maximize specific educational gains, while further enhancing patient care. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-023-01854-4.

6.
Crit Rev Biomed Eng ; 51(6): 1-16, 2023.
Article in English | MEDLINE | ID: mdl-37824331

ABSTRACT

Respiratory diseases are a major cause of death worldwide, affecting a significant proportion of the population with lung function abnormalities that can lead to respiratory illnesses. Early detection and prevention are critical to effective management of these disorders. Deep learning algorithms offer a promising approach for analyzing complex medical data and aiding in early disease detection. While transformer-based models for sequence classification have proven effective for tasks like sentiment analysis, topic classification, etc., their potential for respiratory disease classification remains largely unexplored. This paper proposes a classifier utilizing the transformer-encoder block, which can capture complex patterns and dependencies in medical data. The proposed model is trained and evaluated on a large dataset from the International Conference on Biomedical Health Informatics 2017, achieving state-of-the-art results with a mean sensitivity of 70.53%, mean specificity of 84.10%, mean average score of 77.32%, and mean harmonic score of 76.10%. These results demonstrate the model's effectiveness in diagnosing respiratory diseases while taking up minimal computational resources.


Subject(s)
Respiratory Sounds , Respiratory Tract Diseases , Humans , Respiratory Sounds/diagnosis , Algorithms , Auscultation , Lung
7.
Crit Rev Biomed Eng ; 51(3): 1-19, 2023.
Article in English | MEDLINE | ID: mdl-37560877

ABSTRACT

Nailfold capillaroscopy is a tool which is non-invasive in nature and can be useful for diagnosis, research, therapeutic study and prognosis. Research shows that specific capillary morphology patterns are identified for diabetic subjects, hypertensive subjects and normal controls. In this study, we have proposed RATHEW approach of classifying these three classes of subjects. RATHEW approach employs a three step process for classifying nailfold images: one, identify six abnormality parameters from the image dataset; two, score these abnormality parameters based on the defined scoring rules; and three, combine them mathematically to segregate them into three classes. This technique can be further enhanced to grade the severity of disease and organ involvement. This can bring in a paradigm shift to the disease detection and therapeutic study mechanism.


Subject(s)
Capillaries , Nails , Humans , Nails/diagnostic imaging , Nails/blood supply , Capillaries/diagnostic imaging , Microscopic Angioscopy/methods
8.
Am J Physiol Heart Circ Physiol ; 325(1): H149-H162, 2023 07 01.
Article in English | MEDLINE | ID: mdl-37204873

ABSTRACT

Patients with two congenital heart diseases (CHDs), Ebstein's anomaly (EA) and left ventricular noncompaction (LVNC), suffer higher morbidity than either CHD alone. The genetic etiology and pathogenesis of combined EA/LVNC remain largely unknown. We investigated a familial EA/LVNC case associated with a variant (p.R237C) in the gene encoding Kelch-like protein 26 (KLHL26) by differentiating induced pluripotent stem cells (iPSCs) generated from affected and unaffected family members into cardiomyocytes (iPSC-CMs) and assessing iPSC-CM morphology, function, gene expression, and protein abundance. Compared with unaffected iPSC-CMs, CMs containing the KLHL26 (p.R237C) variant exhibited aberrant morphology including distended endo(sarco)plasmic reticulum (ER/SR) and dysmorphic mitochondria and aberrant function that included decreased contractions per minute, altered calcium transients, and increased proliferation. Pathway enrichment analyses based on RNASeq data indicated that the "structural constituent of muscle" pathway was suppressed, whereas the "ER lumen" pathway was activated. Taken together, these findings suggest that iPSC-CMs containing this KLHL26 (p.R237C) variant develop dysregulated ER/SR, calcium signaling, contractility, and proliferation.NEW & NOTEWORTHY We demonstrate here that iPSCs derived from patients with Ebstein's anomaly and left ventricular noncompaction, when differentiated into cardiomyocytes, display significant structural and functional changes that offer insight into disease pathogenesis, including altered ER/SR and mitochondrial morphology, contractility, and calcium signaling.


Subject(s)
Ebstein Anomaly , Induced Pluripotent Stem Cells , Humans , Ebstein Anomaly/genetics , Ebstein Anomaly/metabolism , Ebstein Anomaly/pathology , Induced Pluripotent Stem Cells/metabolism , Myocytes, Cardiac/metabolism , Cell Differentiation , Calcium Signaling
9.
Glob Health Sci Pract ; 11(2)2023 04 28.
Article in English | MEDLINE | ID: mdl-37116929

ABSTRACT

To reduce TB deaths in resource-limited settings, a differentiated care strategy can be used to triage patients with high risk of severe illness (i.e., those with very severe undernutrition, respiratory insufficiency, or inability to stand without support) at diagnosis and refer them for comprehensive assessment and inpatient care. Globally, there are few examples of implementing this type of strategy in routine program settings. Beginning in April 2022, the Indian state of Tamil Nadu implemented a differentiated care strategy called Tamil Nadu-Kasanoi Erappila Thittam (TN-KET) for all adults aged 15 years and older with drug-susceptible TB notified by public facilities. Before evaluating the impact on TB deaths, we sought to understand the retention and delays in the care cascade as well as predictors of losses. During April-June 2022, 14,961 TB patients were notified and 11,599 (78%) were triaged. Of those triaged, 1,509 (13%) were at high risk of severe illness; of these, 1,128 (75%) were comprehensively assessed at a nodal inpatient care facility. Of 993 confirmed as severely ill, 909 (92%) were admitted, with 8% unfavorable admission outcomes (4% deaths). Median admission duration was 4 days. From diagnosis, the median delay in triaging and admission of severely ill patients was 1 day each. Likelihood of triaging decreased for people with extrapulmonary TB, those diagnosed in high-notification districts or teaching hospitals, and those transferred out of district. Predictors of not being comprehensively assessed included: aged 25-34 years, able to stand without support, and diagnosis at a primary or secondary-level facility. Inability to stand without support was a predictor of unfavorable admission outcomes. To conclude, the first quarter of implementation suggests that TN-KET was feasible to implement but could be improved by addressing predictors of losses in the care cascade and increasing admission duration.


Subject(s)
Malnutrition , Adult , Humans , India/epidemiology
10.
Glob Health Action ; 16(1): 2161231, 2023 12 31.
Article in English | MEDLINE | ID: mdl-36621943

ABSTRACT

Due to the workload and lack of a critical mass of trained operational researchers within their ranks, health systems and programmes may not be able to dedicate sufficient time to conducting operational research (OR). Hence, they may need the technical support of operational researchers from research/academic organisations. Additionally, there is a knowledge gap regarding implementing differentiated tuberculosis (TB) care in programme settings. In this 'how we did it' paper, we share our experience of implementing a differentiated TB care model along with an inbuilt OR component in Tamil Nadu, a southern state in India. This was a health system initiative through a collaboration of the State TB cell with the Indian Council of Medical Research institutes and the World Health Organisation country office in India. The learnings are in the form of eleven tips: four broad principles (OR on priority areas and make it a health system initiative, implement simple and holistic ideas, embed OR within routine programme settings, aim for long-term engagement), four related to strategic planning (big team of investigators, joint leadership, decentralised decision-making, working in advance) and three about implementation planning (conducting pilots, smart use of e-tools and operational research publications at frequent intervals). These may act as a guide for other Indian states, high TB burden countries that want to implement differentiated care, and for operational researchers in providing technical assistance for strengthening implementation and conducting OR in health systems and programmes (TB or other health programmes). Following these tips may increase the chances of i) an enriching engagement, ii) policy/practice change, and iii) sustainable implementation.


Subject(s)
Biomedical Research , Tuberculosis , Humans , India , Tuberculosis/prevention & control , Government Programs , Organizations
11.
J Cardiovasc Dev Dis ; 9(4)2022 Apr 13.
Article in English | MEDLINE | ID: mdl-35448091

ABSTRACT

Traditional definitions of Ebstein's anomaly (EA) and left ventricular noncompaction (LVNC), two rare congenital heart defects (CHDs), confine disease to either the right or left heart, respectively. Around 15-29% of patients with EA, which has a prevalence of 1 in 20,000 live births, commonly manifest with LVNC. While individual EA or LVNC literature is extensive, relatively little discussion is devoted to the joint appearance of EA and LVNC (EA/LVNC), which poses a higher risk of poor clinical outcomes. We queried PubMed, Medline, and Web of Science for all peer-reviewed publications from inception to February 2022 that discuss EA/LVNC and found 58 unique articles written in English. Here, we summarize and extrapolate commonalities in clinical and genetic understanding of EA/LVNC to date. We additionally postulate involvement of shared developmental pathways that may lead to this combined disease. Anatomical variation in EA/LVNC encompasses characteristics of both CHDs, including tricuspid valve displacement, right heart dilatation, and left ventricular trabeculation, and dictates clinical presentation in both age and severity. Disease treatment is non-specific, ranging from symptomatic management to invasive surgery. Apart from a few variant associations, mainly in sarcomeric genes MYH7 and TPM1, the genetic etiology and pathogenesis of EA/LVNC remain largely unknown.

12.
Crit Rev Biomed Eng ; 48(1): 17-28, 2020.
Article in English | MEDLINE | ID: mdl-32749117

ABSTRACT

We sort human emotions using Russell's circumplex model of emotion by classifying electroencephalogram (EEG) signals from 25 subjects into four discrete states, namely, happy, sad, angry, and relaxed. After acquiring signals, we use a standard database for emotion analysis using physiological EEG signals. Once raw signals are pre-processed in an EEGLAB, we perform feature extraction using Matrix Laboratory and apply discrete wavelet transform. Before classifying we optimize extracted features with particle swarm optimization. The acquired set of EEG signals are validated after finding average classification accuracy of 75.25%, average sensitivity of 76.8%, and average specificity of 91.06%.


Subject(s)
Electroencephalography/methods , Emotions/physiology , Signal Processing, Computer-Assisted , Support Vector Machine , Wavelet Analysis , Adolescent , Adult , Algorithms , Deep Learning , Electrodes , Female , Humans , Male , Pattern Recognition, Automated , Recognition, Psychology , Reproducibility of Results , Young Adult
13.
Front Cell Dev Biol ; 8: 440, 2020.
Article in English | MEDLINE | ID: mdl-32656206

ABSTRACT

Hypoplastic left heart syndrome (HLHS) is a clinically and anatomically severe form of congenital heart disease; however, its etiology remains largely unknown. We previously demonstrated that genetic variants in the MYH6 gene are significantly associated with HLHS. Additionally, induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) from an HLHS-affected family trio (affected parent, unaffected parent, affected proband) carrying an MYH6-R443P head domain variant demonstrated dysmorphic sarcomere structure and increased compensatory MYH7 expression. Analysis of iPSC-CMs derived from the HLHS trio revealed that only beta myosin heavy chain expression was observed in CMs carrying the MYH6-R443P variant after differentiation day 15 (D15). Functional assessments performed between D20-D23 revealed that MYH6-R443P variant CMs contracted more slowly (40 ± 2 vs. 47 ± 2 contractions/min, P < 0.05), shortened less (5.6 ± 0.5 vs. 8.1 ± 0.7% of cell length, P < 0.05), and exhibited slower shortening rates (19.9 ± 1.7 vs. 28.1 ± 2.5 µm/s, P < 0.05) and relaxation rates (11.0 ± 0.9 vs. 19.7 ± 2.0 µm/s, P < 0.05). Treatment with isoproterenol had no effect on iPSC-CM mechanics. Using CRISPR/Cas9 gene editing technology, introduction of the R443P variant into the unaffected parent's iPSCs recapitulated the phenotype of the proband's iPSC-CMs, and conversely, correction of the R443P variant in the proband's iPSCs rescued the cardiomyogenic differentiation, sarcomere organization, slower contraction (P < 0.05) and decreased velocity phenotypes (P < 0.0001). This is the first report to identify that cardiac tissues from HLHS patients with MYH6 variants can exhibit sarcomere disorganization in atrial but not ventricular tissues. This new discovery was not unexpected, since MYH6 is expressed predominantly in the postnatal atria in humans. These findings demonstrate the feasibility of employing patient-derived iPSC-CMs, in combination with patient cardiac tissues, to gain mechanistic insight into how genetic variants can lead to HLHS. Results from this study suggest that decreased contractility of CMs due to sarcomere disorganization in the atria may effect hemodynamic changes preventing development of a normal left ventricle.

14.
Mol Genet Genomic Med ; 8(4): e1152, 2020 04.
Article in English | MEDLINE | ID: mdl-31985165

ABSTRACT

BACKGROUND: Ebstein's anomaly (EA) is a rare congenital heart disease of the tricuspid valve and right ventricle. Patients with EA often manifest with left ventricular noncompaction (LVNC), a cardiomyopathy. Despite implication of cardiac sarcomere genes in some cases, very little is understood regarding the genetic etiology of EA/LVNC. Our study describes a multigenerational family with at least 10 of 17 members affected by EA/LVNC. METHODS: We performed echocardiography on all family members and conducted exome sequencing of six individuals. After identifying candidate variants using two different bioinformatic strategies, we confirmed segregation with phenotype using Sanger sequencing. We investigated structural implications of candidate variants using protein prediction models. RESULTS: Exome sequencing analysis of four affected and two unaffected members identified a novel, rare, and damaging coding variant in the Kelch-like family member 26 (KLHL26) gene located on chromosome 19 at position 237 of the protein (GRCh37). This variant region was confirmed by Sanger sequencing in the remaining family members. KLHL26 (c.709C > T p.R237C) segregates only with EA/LVNC-affected individuals (FBAT p < .05). Investigating structural implications of the candidate variant using protein prediction models suggested that the KLHL26 variant disrupts electrostatic interactions when binding to part of the ubiquitin proteasome, specifically Cullin3 (CUL3), a component of E3 ubiquitin ligase. CONCLUSION: In this familial case of EA/LVNC, we have identified a candidate gene variant, KLHL26 (p.R237C), which may have an important role in ubiquitin-mediated protein degradation during cardiac development.


Subject(s)
Ebstein Anomaly/genetics , Heart Defects, Congenital/genetics , Loss of Function Mutation , Adult , Binding Sites , Child , Child, Preschool , Cullin Proteins/metabolism , Ebstein Anomaly/pathology , Female , Genetic Testing , Heart Defects, Congenital/pathology , Humans , Infant, Newborn , Male , Middle Aged , Pedigree , Protein Binding
15.
J Mol Recognit ; 33(1): e2812, 2020 01.
Article in English | MEDLINE | ID: mdl-31531903

ABSTRACT

Polyphenols are secondary plant metabolites, which have received much attention because of their potential health benefits. Silibinin (SIL) is a well-known naturally occurring flavonolignan, which is extensively used in treating a wide variety of diseases as a dietary supplement as well as a prescribed drug. The mechanism of binding of SIL to calf thymus DNA (ctDNA) was investigated by employing multispectroscopic techniques, viz., absorption, fluorescence, and circular dichroism besides viscosity measurements and docking studies. Analysis of fluorescence results indicated that SIL has interacted with ctDNA and quenched its intensity through static quenching mechanism. The binding constant at room temperature was found to be 2.48×104 mol-1 , suggesting moderate binding affinity between SIL and ctDNA. The hypochromicity observed in the absorption spectra of ctDNA in the presence of SIL revealed the intercalation of SIL into ctDNA base pairs. Further, the intercalative mode of binding between SIL and ctDNA was confirmed by viscosity measurements and molecular docking studies. The outcome of present study helps to decipher the interaction mechanism between SIL and DNA at physiological pH, which further assists in the design of a new analogue for better therapeutic effects.


Subject(s)
Base Pairing/drug effects , DNA/metabolism , Flavonoids/metabolism , Intercalating Agents/metabolism , Silybin/metabolism , Circular Dichroism , Hydrogen Bonding , Molecular Docking Simulation/methods , Viscosity/drug effects
16.
J Pharm Anal ; 9(4): 274-283, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31452966

ABSTRACT

Repaglinide (RPG) regulates the amount of glucose by stimulating the pancreas to release insulin in the blood. In view of its biological importance, we have examined the interaction between RPG and a model protein, bovine serum albumin (BSA) employing various spectroscopic, electrochemical and molecular docking methods. Fluorescence spectra of BSA were recorded in the presence and absence of RPG in phosphate buffer of pH 7.4. Fluorescence intensity of BSA was decreased upon the addition of increased concentrations of RPG, indicating the interaction between RPG and BSA. Stern-Volmer quenching analysis results revealed that RPG quenched the intensity of BSA through dynamic quenching mechanism. This was further confirmed from the time-resolved fluorescence measurements. The binding constant as calculated from the spectroscopic and voltammetric results was observed to be in the order of 104 M-1 at 298 K, suggesting the moderate binding affinity between RPG and BSA. Competitive experimental results revealed that the primary binding site for RPG on BSA was site II. Absorption and circular dichroism studies indicated the changes in the secondary structure of BSA upon its interaction with RPG. Molecular simulation studies pointed out that RPG was bound to BSA in the hydrophobic pocket of site II.

17.
J Pharm Bioallied Sci ; 11(Suppl 2): S112-S125, 2019 May.
Article in English | MEDLINE | ID: mdl-31198322

ABSTRACT

BACKGROUND: Methyl methacrylate monomer of denture base resins was modified with several monomers to achieve better physico-mechanical properties without compromising the biocompatibility. However, there are no consensuses on the best strategy to achieve best modified monomer. PURPOSE: To identify and evaluate the differences in the properties between conventional and modified monomers and to verify the influence of several variables on the properties of denture base acrylic resin. MATERIALS AND METHODS: This study was executed by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. In-vitro studies that investigated the properties of conventional and modified monomers were selected. Searches were carried out in the Ebscohost, PubMed, Semantic scholar and J-stage databases. The search commenced from the year 1995 and the last search was done till November 2018. A comparison was performed between modified and unmodified monomers. The analyses were carried out using fixed-effect models. RESULTS: The meta-analysis results showed high heterogeneity in all aspects, and higher flexural strength for monomers modified with 20% methacrylic acid. CONCLUSION: Although the articles included in this meta-analysis showed high heterogeneity and high risk of bias, the in-vitro literature seems to suggest that use of modified monomers could improve the properties of denture base resins. Other variants of monomer modifications and their tested parameters were discussed in this systematic review as well. Dimensional accuracy is an unexplored variable to be evaluated extensively in the future researches.

19.
J Pharm Bioallied Sci ; 9(Suppl 1): S154-S160, 2017 Nov.
Article in English | MEDLINE | ID: mdl-29284956

ABSTRACT

BACKGROUND: Masticatory forces cause fatigue to the dental luting agents, adversely affecting the retention of these cement-retained crowns. Sandblasting (SB) and diamond abrading the abutment surface improves the bond strength of luting agents. However, the effect of acid etching (AE) on the implant abutment surface and the effect of other surface modifications under masticatory load are yet to be documented. PURPOSE: The aim of the study was to evaluate the effect of abutment surface modifications on the retention of cement-retained restorations subjected to cyclic fatigue loads. MATERIALS AND METHODS: Forty Ni-Cr copings were made on Cp-titanium laboratory analogs. The specimens were divided into two groups as Group I: Uniaxial tensile loading (UTL) and Group II: Offaxial cyclic loading followed by uniaxial tensile loading [CTL]. Further subgrouped as, subgroup I: Control (C), subgroup II: SB, subgroup III: AE, and subgroup IV: SB + AE. The copings were luted with Zn2(PO4)3 and subjected to uniaxial tensile loading. Copings were recemented, and CTL was conducted. Two-way analysis of variance was used as the statistical test of significance. RESULTS: In relation to the subgroups, the bond strength of Zn2(PO4)3 was higher in Group I than in Group II. The bond strength in subgroup IV was superior in both Group I and Group II (547.170 N ± 5.752 and 531.975 N ± 6.221 respectively). CONCLUSIONS: For both UTL and CTL, abutment SB + AE elicited maximum coping retention followed by AE. Off-axial cyclic loading adversely affected the retention irrespective of the surface modifications.

20.
Anal Bioanal Chem ; 409(27): 6325-6335, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28852787

ABSTRACT

Bosutinib (BST) and imatinib mesylate (IMT) are tyrosine kinase inhibitors (TKIs). In view of the importance of these inhibitors in cancer treatment, we investigated the mechanism of interaction between BST/IMT and bovine serum albumin (BSA) using various spectroscopic and molecular docking methods. Fluorescence studies indicated that BST/IMT interacted with BSA without affecting the microenvironment around the residue Trp213 of BSA. The quenching mechanism associated with the BST-BSA and IMT-BSA interactions was determined by performing fluorescence measurements at different temperatures. These results suggested that BST and IMT quenched the fluorescence intensity of BSA through static and dynamic processes, respectively, which was confirmed by time-resolved fluorescence measurements. Evaluation of the thermodynamic parameters ∆H°, ∆S°, and ∆G° suggested that hydrophobic and electrostatic interactions played significant roles in the BST-BSA interaction, while IMT-BSA was stabilized by hydrophobic forces. Competitive experimental results revealed that the primary binding sites for BST and IMT on BSA were sites II and I, respectively. This was supported by the results of molecular docking and dynamic simulation studies. The change in the secondary structure of BSA upon binding with BST/IMT was investigated by 3D fluorescence, absorption, and CD spectroscopic studies. In addition, the influences of ß-cyclodextrin and metal ions (Cu2+ and Zn2+) on the binding affinities of BST and IMT to BSA were examined. Graphical abstract Binding of BST and IMT in BSA at site II and site I respectively.


Subject(s)
Aniline Compounds/metabolism , Antineoplastic Agents/metabolism , Imatinib Mesylate/metabolism , Nitriles/metabolism , Protein Kinase Inhibitors/metabolism , Quinolines/metabolism , Serum Albumin, Bovine/metabolism , Animals , Cattle , Hydrophobic and Hydrophilic Interactions , Molecular Docking Simulation , Molecular Dynamics Simulation , Protein Binding , Protein Conformation/drug effects , Serum Albumin, Bovine/chemistry , Spectrometry, Fluorescence , Spectrophotometry, Ultraviolet , Thermodynamics
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