Modeling the Construction of Polymeric Adsorbent Media: Effects of Counter-Ions on Ligand Immobilization and Pore Structure

Molecular dynamics modeling and simulations are employed to study the effects of counter-ions on the dynamic spatial density distribution and total loading of immobilized ligands as well as on the pore structure of the resultant ion exchange chromatography adsorbent media. The results show that the porous adsorbent media formed by polymeric chain molecules involve transport mechanisms and steric resistances which cause the charged ligands and counter-ions not to follow stoichiometric distributions so that (i) a gradient in the local nonelectroneutrality occurs, (ii) non-uniform spatial density distributions of immobilized ligands and counter-ions are formed, and (iii) clouds of counter-ions outside the porous structure could be formed. The magnitude of these counter-ion effects depends on several characteristics associated with the size, structure, and valence of the counter-ions. Small spherical counter-ions with large valence encounter the least resistance to enter a porous structure and their effects result in the formation of small gradients in the local nonelectroneutrality, higher ligand loadings, and more uniform spatial density distributions of immobilized ligands, while the formation of exterior counter-ion clouds by these types of counter-ions is minimized. Counter-ions with lower valence charges, significantly larger sizes, and elongated shapes, encounter substantially greater steric resistances in entering a porous structure and lead to the formation of larger gradients in the local nonelectroneutrality, lower ligand loadings, and less uniform spatial density distributions of immobilized ligands, as well as substantial in size exterior counter-ion clouds. The effects of lower counter-ion valence on pore structure, local nonelectroneutrality, spatial ligand density distribution, and exterior counter-ion cloud formation are further enhanced by the increased size and structure of the counter-ion. Thus, the design, construction, and functionality of polymeric porous adsorbent media will significantly depend, for a given desirable ligand to be immobilized and represent the adsorption active sites, on the type of counter-ion that is used during the ligand immobilization process. Therefore, the molecular dynamics modeling and simulation approach presented in this work could contribute positively by representing an engineering science methodology to the design and construction of polymeric porous adsorbent media which could provide high intraparticle mass transfer and adsorption rates for the adsorbate biomolecules of interest which are desired to be separated by an adsorption process

A Molecular Dynamics Study on the Transport of a Charged Biomolecule in a Polymeric Adsorbent Medium and Its Adsorption onto a Charged Ligand

The transport of a charged adsorbate biomolecule in a porous polymeric adsorbent medium and its adsorption onto the covalently immobilized ligands have been modeled and investigated using molecular dynamics modeling and simulations as the third part of a novel fundamental methodology developed for studying ion-exchange chromatography based bioseparations. To overcome computational challenges, a novel simulation approach is devised where appropriate atomistic and coarse grain models are employed simultaneously and the transport of the adsorbate is characterized through a number of locations representative of the progress of the transport process. The adsorbate biomolecule for the system studied in this work changes shape, orientation, and lateral position in order to proceed toward the site where adsorption occurs and exhibits decreased mass transport coefficients as it approaches closer to the immobilized ligand. Furthermore, because the ligands are surrounded by counterions carrying the same type of charge as the adsorbate biomolecule, it takes the biomolecule repeated attempts to approach toward a ligand in order to displace the counterions in the proximity of the ligand and to finally become adsorbed. The formed adsorbate-ligand complex interacts with the counterions and polymeric molecules and is found to evolve slowly and continuously from one-site (monovalent) interaction to multisite (multivalent) interactions. Such a transition of the nature of adsorption reduces the overall adsorption capacity of the ligands in the adsorbent medium and results in a type of surface exclusion effect. Also, the adsorption of the biomolecule also presents certain volume exclusion effects by not only directly reducing the pore volume and the availability of the ligands in the adjacent regions, but also causing the polymeric molecules to change to more compact structures that could further shield certain ligands from being accessible to subsequent adsorbate molecules. These findings have significant practical implications to the design and construction of polymeric porous adsorbent media for effective bioseparations and to the synthesis and operation of processes employed in the separation of biomolecules. The modeling and analysis methods presented in this work could also be suitable for the study of biocatalysis where an enzyme is immobilized on the surface of the pores of a porous medium

Volumetric facial contour changes of immediately placed implants with and without immediate provisionalization

BackgroundWhether immediate provisionalization can preserve facial tissue contour remains undetermined. The goal of this 12- month randomized controlled clinical trial was to compare three- dimensional (3D) ridge changes after immediate implant placement with and without immediate provisionalization.MethodsForty participants with an unrestorable maxillary anterior or premolar tooth were randomized to receive either a provisional crown (test) or standard healing abutment (control) after immediate implant placement. In each participant, three digital models taken before implant surgery, final crown delivery (4 months), and final follow- up (12 months) were registered to analyze linear deviation in 3D and volume changes of ridge contour at the implant site.ResultsThe mean value of mid- facial linear 3D spatial resorption ranged from 0.1 to 0.7 mm. Significant difference of linear changes of facial contour was noted over time and not between the groups. Facial volume changes at 12 months remained significantly higher in the control group than in the test group (17.4% versus 11.9%, P = 0.04).ConclusionsLinear changes of facial soft- tissue resorption at immediately placed implants were independent of immediate provisionalization. However, immediate provisionalization showed better volume preservation at the esthetic concern area (mid- facial margin and 2 to 6 mm above) at the final 12- month follow- up.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156220/2/jper10486_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156220/1/jper10486.pd

Association between periodontitis and systemic medication intake: A case- control study

BackgroundTo investigate the frequency of systemic drugs taken by elderly patients with or without periodontitis and the possible association between medication consumption and the severity of periodontitis.MethodsA total of 1221 patients, including 608 with generalized moderate to severe periodontitis (periodontitis group) and 613 age- and gender- matched individuals with healthy periodontium (healthy group) were selected. Systemic conditions, medications and periodontal status were recorded. Medication intake frequency (%) was compared using unconditional logistic regression.ResultsThe top three most common medications were angiotensin- converting enzyme (ACE) inhibitors (17.9%), antidepressants (17.8%), and lipid- lowering medications (16.5%). Both ACE inhibitors and antidepressants showed statistically higher intake frequency in the periodontitis group relative to healthy controls (21.5% versus 14.4%; odds ratio [OR] = 1.64), (21.1% versus 14.5%, OR = 1.57) (P < 0.01). Additionally, intake of oral hypoglycemic agents, calcium channel blockers (CCB), insulin, and diuretics were significantly higher in the periodontitis group with OR = 2.49, 2.32, 2.08 and 1.79, respectively (P < 0.05). Several medications demonstrated a disease severity- dependent association comparing generalized severe periodontitis with moderate periodontitis and healthy group: oral hypoglycemic agents (17.4% versus 16.8% versus 8.0%), CCB (14.8% versus 14.4% versus 8.0%) and anticonvulsants (13.4% versus 7.7% versus 6.4%) with OR of 2.43, 1.99, and 2.28 (severe periodontitis versus healthy group), respectively.ConclusionThere was a significantly higher frequency of medication intake related to cardiovascular disease and diabetes in patients with periodontitis. A disease severity- dependence with medication intake frequency was also noted. This study provides indirect evidence for the possible relationship between systemic diseases and periodontitis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163409/2/jper10532_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163409/1/jper10532.pd

Using Technology-Supported Enrichment Activities to Extend Student Learning in a Chinese as a Foreign Language Classroom

The purpose of this study was to investigate whether exposing middle school students to content above their ability level produced significant differences in students’ confidence in their Chinese as a foreign language competence in each of the following four areas: reading, listening, speaking, and learning vocabulary. Participants (N = 30) were sixth and seventh graders. Results of paired t-test analyses indicated that there was no significant difference in student confidence in Chinese reading competence, t(30) = 0.78, p = 0.22; in Chinese speaking competence, t(30) = -0.50, p = 0.31; or to learn Chinese vocabulary, t(30) = -0.80, p = 0.21. However, there was a significant difference in student confidence in ability to learn Chinese listening, t(30) = -1.78, p \u3c 0.05. It is suggested that exposing students to content well above their ability level can increase their confidence in ability to learn Chinese listening

Relationship between Peri-implantitis and Cardiovascular Diseases

Objectives: The purpose of this study was to assess the relationship between peri-implantitis and cardiovascular diseases. Methods: A case-control design, cross-sectional study was conducted to evaluate the prevalence of peri-implantitis among individuals diagnosed with cardiovascular diseases (CVD). Health and CVD history were obtained through structured questionnaire. Participants who had at least one implant in function for more than 6 months were recruited. Individuals without CVD were grouped as "Control', and participants in the "Case" CVD group were recruited only when the dental implants were placed prior to CVD diagnosis. Among the "Case" group, individuals with peri-implantitis were included in the final analysis only when the per-implantitis onset was evidenced radiographically prior to the diagnosis of the CVD. Clinical and radiographic examinations were performed; samples of serum, peri-implant crevicular fluid (PICF), and gingival crevicular fluid (GCF) at the most severe diseased sites were collected to evaluate the pro-inflammatory cytokine profile. Subgingival plaque from the peri-implantitis sulci were analyzed using 16S rRNA next-generation sequencing and real-time qPCR technologies. Results: A higher prevalence of peri-implantitis (with detectable radiographic bone loss) in the CVD group (OR= 1.48, 95% CI= 0.71 to 3.11, p= 0.30) was found. Furthermore, moderate to severe peri-implantitis (radiographic bone loss ≥ 2mm) was significantly associated with cardiovascular diseases (OR= 2.18, 95% CI= 1.02 to 4.67, p=0.04), but was no longer observed after controlling for multiple significant confounding factors. The microbial community among the CVD group and peri-implantitis group demonstrated a more divergent profile compared to the control and healthy implant group. Predominantly anaerobic microorganisms at the peri-implantitis niche were associated with deeper pockets and severe bone loss. A higher bacterial counts (gene copies) of Prophylomonas gingivalis (P. gingivalis) was observed in the CVD group. Secondly, peri-implantitis pockets appeared to harbor higher Fusobacterium nucleatum (F. nucleatum) DNA in a dose-responsive relationship with the severity of peri-implant disease. Tannerella forsythia (T. forsythia) was significantly higher only in the severe peri-implantitis (radiographic bone loss> 4 mm). Serum fibrinogen was significantly higher in the CVD group and moderate to severe peri-implantitis (radiographic bone loss≥ 2mm) sites when compared to the control or healthy implant groups. A similar trend was observed in the serum interleukin (IL)-6, tumor necrosis factor (TNF-), and osteoprotegerin (OPG). PICF TNF- was predominantly higher in the CVD group. This coincided with the local peri-implant inflammation. Matrix metalloproteinase (MMP)-8, IL-1, and tissue inhibited metalloproteinase (TIMP)-2 displayed fair accuracy in predicting peri-implant disease. The sensitivity increased when combined with the bacterial concentration of T. forsythia and F. nucleatum. Finally, OPG appeared to be the only GCF biomarker correlated with peri-implant disease. Conclusions: Moderate to severe peri-implantitis (radiographic bone loss ≥ 2mm) was observed to be a mild associative positive risk factor for the development of cardiovascular disease. However, a significant association was not observed after multivariable adjustment. Low-grade chronic inflammation around diseased dental implants, especially when the disease severity and tissue destruction was increased, may be linked to atherosclerosis and cardiovascular disease by increasing the overall inflammation burden on patients at risk for CVD.Master of SciencePeriodonticsUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/165335/1/I-Ching_Wang_Thesis_Final_2020.pd

Validation of the Action Research Arm Test using item response theory in patients after stroke

Objective: To validate the unidimensionality of the Action Research Arm Test (ARAT) using Mokken analysis and to examine whether scores of the ARAT can be transformed into interval scores using Rasch analysis. Subjects and methods: A total of 351 patients with stroke were recruited from 5 rehabilitation departments located in 4 regions of Taiwan. The 19-item ARAT was administered to all the subjects by a physical therapist. The data were analysed using item response theory by non-parametric Mokken analysis followed by Rasch analysis. Results: The results supported a unidimensional scale of the 19-item ARAT by Mokken analysis, with the scalability coefficient H = 0.95. Except for the item pinch ball bearing 3rd finger and thumb'', the remaining 18 items have a consistently hierarchical order along the upper extremity function's continuum. In contrast, the Rasch analysis, with a stepwise deletion of misfit items, showed that only 4 items (grasp ball'', grasp block 5 cm(3)'', grasp block 2.5 cm(3)'', and grip tube 1 cm(3)'') fit the Rasch rating scale model's expectations. Conclusion: Our findings indicated that the 19-item ARAT constituted a unidimensional construct measuring upper extremity function in stroke patients. However, the results did not support the premise that the raw sum scores of the ARAT can be transformed into interval Rasch scores. Thus, the raw sum scores of the ARAT can provide information only about order of patients on their upper extremity functional abilities, but not represent each patient's exact functioning

Cell-Based Assays in High-Throughput Screening for Drug Discovery

Drug screening is a long and costly process confronted with low productivity and challenges in using animals, which limit the discovery of new drugs.  To improve drug screening efficacy and minimize animal testing, recent efforts have been dedicated to developing cell-based high throughput screening (HTS) platforms that can provide more relevant in vivo biological information than biochemical assays and thus reduce the number of animal tests and accelerate the drug discovery process. Today, cell-based assays are used in more than half of all high-throughput drug screenings for target validation and ADMET (absorption, distribution, metabolism, elimination and toxicity) in the early stage of drug discovery. In this review, we discuss the uses of different types of cells and cell culture systems, including 2D, 3D and perfusion cell cultures, in cell-based HTS for drug discovery. Optical and electrochemical methods for online, non-invasive detection and quantification of cells or cellular activities are discussed. Recent progresses and applications of 3D cultures and microfluidic systems for cell-based HTS are also discussed, followed with several successful examples of using cell-based HTS in commercial development of new drugs. Finally, a brief discussion on potential applications of cell-based HTS for screening phytochemicals and herbal medicines is provided in this review