Impact of COVID-19 on Dental Care Utilization and Oral Health Conditions in the United States.

PURPOSE: We aim to understand the impact of the COVID-19 on health care utilization and oral health conditions of patients at federally qualified health centers (FQHCs), where patients are disproportionately low income, publicly insured, or uninsured. METHODS: Using deidentified electronic health records of patients at FQHCs in the United States from January 2019 through December 2020 (n = 431,509), variations in health care utilization since the COVID-19 outbreak were observed by procedure types and patient characteristics. Changes in dental utilization and oral health conditions were characterized using mixed-effect negative binomial and logistic regression models. RESULTS: Dental utilization decreased more drastically than medical utilization during shelter-in-place periods in 2020 and rebounded more slowly after the reopening. Greater demands for oral surgery and teledentistry and less demands for preventive services were observed in 2020. As compared to 2019, patients experienced more psychological stress-related dental conditions with odds ratios of 1.52 (95% confidence interval [CI], 1.31-1.76) for uninsured, 1.48 (95% CI, 1.07-2.02) for Medicaid enrollees, and 2.38 (95% CI, 1.68-3.40) for private insurance beneficiaries. CONCLUSION: As a result of COVID-19, patients received more invasive dental procedures due to delayed treatment and experienced a higher risk of psychological stress-related dental conditions. Continued support for statewide policies to expand access to oral health care and oral health promotion strategies for the vulnerable populations would be encouraged. KNOWLEDGE TRANSFER STATEMENT: Our study describes the impact of COVID-19 on dental care use and oral health conditions at Federally Qualified Health Centers, targeted to provide care for some of the most vulnerable populations in the United States. The results of this retrospective cohort study can be used by clinicians and policymakers on understanding the clinical needs of the vulnerable populations after the pandemic. It highlights the need for continued support to expand access to oral health care and oral health promotion to these populations.

Modeling the Impact of COVID-19 on Dental Insurance Coverage and Utilization.

Unemployment rates in the United States are rapidly increasing as a result of the COVID-19 pandemic and attendant economic disruption. As employees lose their jobs, many will lose their employer-sponsored dental insurance (ESDI). Changes in insurance coverage are directly related to the oral health of the population, with many at risk of losing access to dental care. We assessed the impact of recent unemployment rates on insurance coverage and dental utilization. We estimated changes in dental insurance coverage at the state level, using previously applied econometric estimates. Expected changes in types of dental procedures performed at dental practices nationwide were assessed using a microsimulation model, using national practice survey data. Changes in emergency department (ED) visits for dental problems were estimated by fitting trendlines to ED visit patterns by payer type. Sensitivity analyses were conducted to assess how variations in unemployment rates and rates of ESDI in response to unemployment could alter the results. Since March 2020, the national unemployment rate has increased by 8.40 percentage points, an increase expected to result in more than 16 million individuals losing ESDI in the United States. Of these individuals, 45.0% are likely to enroll in their state's Medicaid and Children's Health Insurance Program, and 47.0% are expected to become uninsured. With these expected changes in dental insurance coverage, the average dental practice would experience decreases in routine checkup visits but increases in tooth extraction, a procedure that is highly used by publicly insured or uninsured patients. In addition, dental-related ED visits would be expected to grow by 4.0%. Losses of employment caused by the COVID-19 in the United States can have countervailing effects on people's health by impeding access to dental care. Lack of dental insurance is expected to be more pronounced in states that have not expanded Medicaid or do not provide Medicaid dental benefits for adults.

Clinical Significance of Macrophage Polarization in Antibody-Mediated Rejection of Renal Allograft.

BACKGROUND: The significance of proinflammatory M1 (classically activated) and profibrotic M2 (alternatively activated) macrophages in antibody-mediated rejection (ABMR) after kidney transplantation has not been investigated. METHODS: Fifty-five biopsy-confirmed ABMR samples were stained with MRP 8/14 (a marker of M1 macrophages) and CD163 (a marker of M2 macrophages), and positive cells were counted in glomeruli and the tubulointerstitium, respectively. Patients were classified into M1 and M2 polarization groups according to the glomerular and tubulointerstitial M1:M2 ratio, and the results were compared with Banff scores, serum creatinine level, estimated glomerular filtration rate (eGFR), and graft survival. RESULTS: The glomerular M2 polarization group showed significantly higher chronic glomerulopathy scores, serum creatinine levels, and lower eGFR at the time of biopsy (P = .019 and P = .015, respectively) and 3-month postbiopsy (P = .016 and P = .032, respectively) than the M1 polarization group. The tubulointerstitial M2 polarization group had significantly lower glomerulitis, arteritis, peritubular capillaritis, and glomerulitis + peritubular capillaritis scores than the M1 polarization group, but there was no significant difference in renal function. Long-term graft survival was not associated with macrophage polarization. CONCLUSION: Glomerular M2 polarization in ABMR biopsy samples is associated with chronic glomerular injury and poorer graft function, but without graft survival.

N-Cadherin modified lipid bilayers promote neural network formation and circuitry.

Neural adhesion, maturation, and the correct wiring of the brain to establish each neuron's intended connectivity are controlled by complex interactions of bioactive molecules such as ligands, growth factors, or enzymes. The correct pairing of adjacent neurons is thought to be highly regulated by ligand-mediated cell-cell adhesion proteins, which are known to induce signaling activities. We developed a new platform consisting of supported lipid bilayers incorporated with Fc-chimera synaptic proteins like ephrinA5 or N-cadherin. We extensively characterized their function employing a quartz crystal microbalance with dissipation (QCM-D), calcium imaging, and immunofluorescence analysis. Our biomimetic platform has been shown to promote neural cell adhesion and to improve neural maturation at day in vitro 7 (DIV7) as indicated by an elevated expression of synaptophysin.

A Study on CYP2C19 and CYP2D6 Polymorphic Effects on Pharmacokinetics and Pharmacodynamics of Amitriptyline in Healthy Koreans.

We performed a double-blinded, genotype-based stratification study to explore the pharmacokinetics and pharmacodynamics of amitriptyline according to CYP2C19 and CYP2D6 genotype in Korean subjects. Twenty-four healthy adults were grouped by genotype of CYP2C19 and CYP2D6. After a single dose of 25 mg of amitriptyline, blood samples were collected and anticholinergic effects were measured. The extent of N-demethylation of amitriptyline significantly decreased in subjects carrying two nonfunctional alleles of CYP2C19. The extent of hydroxylation of amitriptyline or nortriptyline was significantly reduced in subjects carrying two CYP2D6 decreased functional alleles compared with those with no or one decreased functional allele. The overall metabolic pathway of amitriptyline was more likely to be dominated by CYP2C19 than CYP2D6. The gene variations of CYP2C19 and CYP2D6 did not change the pharmacodynamic effect. The findings of this study will provide useful information on individualized drug treatment with amitriptyline considering both CYP2D6 and CYP2C19 gene variations.

Reconstitution of Fusion Proteins in Supported Lipid Bilayers for the Study of Cell Surface Receptor-Ligand Interactions in Cell-Cell Contact.

Bioactive molecules such as adhesion ligands, growth factors, or enzymes play an important role in modulating cell behavior such as cell adhesion, spreading, and differentiation. Deciphering the mechanism of ligand-mediated cell adhesion and associated signaling is of great interest not only for fundamental biophysical investigations but also for applications in medicine and biotechnology. In the presented work, we developed a new biomimetic platform that enables culturing primary neurons and testing cell surface-receptor ligand interactions in cell-cell contacts as, e.g., in neuronal synapses. This platform consists of a supported lipid bilayer modified with incorporated neuronal adhesion proteins conjugated with the Fc-domain of IgG (ephrin A5 Fc-chimera). We extensively characterized properties of these protein containing bilayers using fluorescence recovery after photobleaching (FRAP), quartz crystal microbalance with dissipation (QCM-D), and immunostaining. We conclude that the Fc-domain is the part responsible for the incorporation of the protein into the bilayer. The biomimetic platform prepared by this new approach was able to promote neuronal cell adhesion and maintain growth as well as facilitate neuronal maturation as shown by electrophysiological measurements. We believe that our approach can be extended to insert other proteins to create a general culture platform for neurons and other cell types.

The rate of and risk factors for frequent hospitalization in systemic lupus erythematosus: results from the Korean lupus network registry.

Objectives The survival rate of patients with systemic lupus erythematosus has improved in the last few decades, but the rate of hospitalization and health care costs for these patients remain higher than in the general population. Thus, we evaluated the rate of hospitalization and associated risk factors in an inception cohort of Korean patients with lupus. Methods Of the 507 patients with systemic lupus erythematosus enrolled in the KORean lupus NETwork, we investigated an inception cohort consisting of 196 patients with systemic lupus erythematosus presenting within 6 months of diagnosis based on the American College of Rheumatology classification criteria. We evaluated the causes of hospitalization, demographic characteristics, and laboratory and clinical data at the time of systemic lupus erythematosus diagnosis of hospitalized patients and during a follow-up period. We calculated the hospitalization rate as the number of total hospitalizations divided by the disease duration, and defined "frequent hospitalization" as hospitalization more than once per year. Results Of the 196 patients, 117 (59.6%) were admitted to hospital a total of 257 times during the 8-year follow-up period. Moreover, 22 (11.2%) patients were hospitalized frequently. The most common reasons for hospitalization included disease flares, infection, and pregnancy-related morbidity. In the univariate regression analysis, malar rash, arthritis, pericarditis, renal involvement, fever, systemic lupus erythematosus disease activity index > 12, hemoglobin level < 10 mg/dl, albumin level < 3.5 mg/dl, and anti-Sjögren's syndrome A positivity were associated with frequent hospitalization. Finally, multivariate analysis showed that arthritis, pericarditis, and anti-Sjögren's syndrome A antibody positivity at the time of diagnosis were risk factors for frequent hospitalization. Conclusions Our results showed that frequent hospitalization occurred in 11.2% of hospitalized patients and arthritis, pericarditis, and anti-Sjögren's syndrome A antibody positivity at the time of diagnosis were risk factors for frequent hospitalization.

Extracellular visfatin activates gluconeogenesis in HepG2 cells through the classical PKA/CREB-dependent pathway.

Adipokines reportedly affect hepatic gluconeogenesis, and the adipokine visfatin is known to be related to insulin resistance and type 2 diabetes. However, whether visfatin contributes to hepatic gluconeogenesis remains unclear. Visfatin, also known as nicotinamide phosphoribosyltransferase (NAMPT), modulates sirtuin1 (SIRT1) through the regulation of nicotinamide adenine dinucleotide (NAD). Therefore, we investigated the effect of extracellular visfatin on glucose production in HepG2 cells, and evaluated whether extracellular visfatin affects hepatic gluconeogenesis via an NAD+-SIRT1-dependent pathway. Treatment with visfatin significantly increased glucose production and the mRNA expression and protein levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) in HepG2 cells in a time- and concentration-dependent manner. Knockdown of SIRT1 had no remarkable effect on the induction of gluconeogenesis by visfatin. Subsequently, we evaluated if extracellular visfatin stimulates the production of gluconeogenic enzymes through the classical protein kinase A (PKA)/cyclic AMP-responsive element (CRE)-binding protein (CREB)-dependent process. The phosphorylation of CREB and PKA increased significantly in HepG2 cells treated with visfatin. Additionally, knockdown of CREB and PKA inhibited visfatin-induced gluconeogenesis in HepG2 cells. In summary, extracellular visfatin modulates glucose production in HepG2 cells through the PKA/CREB pathway, rather than via SIRT1 signaling.

Gene expression profiling of allogeneic islet grafts in an experimental mouse model before rejection or tolerance phenotypes arise.

BACKGROUND: It has been reported that an HY antigen-mismatched islet transplantation can induce peripheral tolerance. However, the factors that initiate the peripheral tolerance are not clear. This study was designed to examine which genes were most important for the induction of peripheral tolerance. METHODS: Islets from female Balb/c and male C57BL/6 mice were transplanted underneath the left perirenal capsule of female C57BL/6 recipient mice rendered diabetic by intraperitoneal injection of streptozotocin. Before rejection or tolerance phenotypes arose, we harvested islet grafts for cDNA microarray analysis. RESULTS: Minor antigen-mismatched islets transplanted into recipient mice showed no rejection or tolerance phenotypes until 12 days posttransplantation. When we confirmed, decreased functional islet grafts and increased inflammatory cell infiltration. Gene expression profiles revealed differences in expression among groups. Major histocompatibility complex-mismatched islets induced upregulation of 209 genes and downregulation of 10 genes compared with the HY antigen-mismatched islet (2-fold; P < .05). Of these, 3 genes exhibited significant changes in expression levels in Balb/c donor islet grafts compared with C57BL/6 donor islet grafts: Gad1, Gdf10, and Scg2 (P < .01). CONCLUSIONS: The present study suggested that 3 genes showed a significant relationship to protection against graft rejection. The identification of these genes may help to understand signaling pathways, involved in the communication between transplanted islet grafts and recipients in vivo.

Health-care utilization and respiratory morbidities in preterm infants with pulmonary hypertension.

OBJECTIVE: To assess health-care utilization and risk of respiratory morbidities in preterm infants with bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH). STUDY DESIGN: Retrospective data were obtained from subjects (n=109) attending a BPD clinic. Subjects were stratified by the presence or absence of PH before and after 2 months of age. Analytic methods included t-tests, χ(2) tests and regression. RESULT: Subjects with BPD and PH present after 2 months of age were hospitalized for 2.2 months longer than those without PH (P=0.02). These subjects were 4.5 times more likely to receive home supplemental oxygen or mechanical ventilation (P=0.03). No difference in the risk of respiratory morbidities after initial hospital discharge was seen with PH. CONCLUSION: PH in preterm infants is associated with longer initial hospitalizations and a higher likelihood of requiring home respiratory support. This has implications for counseling families and reducing the medical, psychosocial, and economic burden of BPD and PH.

Dose-related effect of urinary cotinine levels on bone mineral density among Korean females.

UNLABELLED: To evaluate the dose-dependent relationship between smoking and bone mineral density (BMD), the present study used the BMD dataset of the Korean National Health and Nutrition Examination Survey IV (KNHANES IV). The linearity of BMD for urinary cotinine levels was demonstrated with statistical significance in postmenopausal females. INTRODUCTION: It is well established that smoking is an important lifestyle risk factor for bone health (bone loss, osteoporosis, and fracture). However, several studies demonstrated conflicting evidence for a dose-dependent relationship between smoking and bone health. To evaluate the dose-dependent relationship between smoking and BMD, the present study estimated dose-related effects of smoking (urinary cotinine level) on BMD at various sites (femur neck, total femur, and lumbar spine) in females with controlling menopausal status. METHODS: The present study used the BMD dataset of the KNHANES IV, which was performed in 2008 and 2009. A total of 4,260 pre- and postmenopausal females were included in the present study. Dose-response relationships between BMD and urinary cotinine levels were estimated using analysis of covariance in pre-menopausal females and postmenopausal females, respectively. RESULTS: In postmenopausal females, the regression coefficients for BMD with urinary cotinine levels were -0.006, -0.006, and -0.008 (g/cm2 per ng/ml) at femur neck, total femur, and lumbar spine, respectively (p value<0.05). Thus, the linearity of BMD for urinary cotinine levels was demonstrated with statistical significance in postmenopausal females. CONCLUSION: Our findings suggested a significant dose-related effect of urinary cotinine level with BMD at femur neck, total femur, and lumbar spine among postmenopausal females.

Antibacterial activity of bark of Alnus pendula against methicillin-resistant Staphylococcus aureus.

BACKGROUND AND OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) infections are a rapidly growing health problem around the globe. Recently, there has been considerable interest in the use of plant materials as an alternative method to control pathogenic microorganisms. In this study we evaluated the antibacterial activity of bark of Alnus pendula against MRSA. MATERIALS AND METHODS: The MIC determination was done using the microdilution broth method and bacterial growth was determined by measuring optical density using spectrophotometer. RESULTS: Alnus pendula bark EtOH extract and fractions (F-1, -2, -3 and -4) were investigated against MRSA. The most active fractions (F-3 and F-4) led to the isolation of oregonin (ORE) and hirsutanone (HIR). These compounds were active against MRSA strains with minimum inhibitory concentrations (MICs) ranging from 31.25 to 250 microg/ml MIC and 2 MIC of HIR completely inhibited the growth of MRSA. CONCLUSIONS: The bark EtOH extract of Alnus Pendula has potent antibacterial activity against MRSA.

Artificial neural network weights of residues for the serological specificities of HLA.

New human leucocyte antigen (HLA) alleles are assigned largely based on their sequence homologies due to lack of information on the serological reactivities. Artificial neural networks (ANNs) have been tested as a possible tool for helping to predict the serology of new alleles in the absence of serological information. However, an ANN analysis per se imparts no information regarding which residues are important in determining serological specificity. To address this issue, we extracted ANN weights of HLA residues. The ANN was trained using 139 HLA-A, 302 HLA-B and 136 HLA-DRB1 alleles, for which serological specificities were assigned in the 2004 Nomenclature Report. When the trained ANN was evaluated using alleles that were contained in the HLA Dictionary 2008 but had not been employed in the training set, the accuracy was 91% (29/32) for HLA-A, 91% (40/44) for HLA-B and 90% (9/10) for HLA-DR. Finally, ANN residue weights were extracted by summing the weights of directly connected ANN nodes. When we assessed the significance of the ANN residue weights by comparing our data with the results of epitope studies conducted by El-Awar and colleagues, we found that the ANN weights tended to be high at the epitopes described by El-Awar et al. Furthermore, the ANN weights extracted in this work could be used to explain ambiguous characteristics of serological specificities to some extent. Our data are thus considered to support the results of the epitope studies conducted by El-Awar and advance our understanding of the ambiguous serological specificities of some alleles.

Anthropological analysis of Koreans using HLA class II diversity among East Asians.

Human leukocyte antigens (HLAs) are useful markers for anthropological investigations because the allele and haplotype distributions at these loci vary widely among ethnic groups. HLA frequencies in Koreans, however, have not previously been analyzed on a phylogenetic basis. We determined the allele frequencies of four HLA class II (HLA-DRB1, -DQA1, -DQB1, and -DPB1) loci in 149 unrelated Korean individuals using a sequence-based typing method. A total of 29 HLA-DRB1, 17 HLA-DQA1, 16 HLA-DQB1, and 15 HLA-DPB1 alleles were identified. The most common allele at each locus was DRB1*0901, DQA1*0102, DQB1*0301, and DPB1*0501, respectively. Four-locus allelic association analysis showed the existence of 25 DRB1-DQA1-DQB1-DPB1 haplotypes with a frequency greater than 0.010. A dataset comprising ethnicity-specific information from published literature and the dbMHC database, as well as the allele frequencies determined in this study, was subjected to phylogenetic analysis. The analysis showed that Koreans are most closely related to Japanese and Han Chinese from Shandong province. Correspondence analyses showed that the current Korean population is located in a position intermediate between the northern and southern East Asian groups, supporting the theory of a bi- and/or multidirectional route of migration of early Korean settlers. This report can be used for anthropological studies, and may also be of use in the International Hematopoietic Stem Cell Sharing program.

MICA polymorphisms and haplotypes with HLA-B and HLA-DRB1 in Koreans.

Major histocompatibility complex (MHC) class I chain-related gene A (MICA) is located within the human MHC, centromeric to HLA-B and telomeric to HLA-DRB1. The location of MICA in the MHC indicates the presence of linkage disequilibrium with human leukocyte antigen (HLA). Like HLA, MICA is highly polymorphic; however, the information available for MICA polymorphisms is not as comprehensive as that for HLA polymorphisms. We estimated the allelic frequencies of MICA and haplotypes with HLA-B and HLA-DRB1 at high-resolution in a population of 139 unrelated Korean individuals by applying the newly developed method of sequence-based typing (SBT). A total of 17 MICA alleles were identified. The most frequent allele was MICA*010 (19.4%), followed by alleles *00201 (17.6%), *00801 (14.7%), *01201 (9.4%), *004 (8.3%) and *049 (7.9%). The most common two- and three-locus haplotypes were HLA-B*1501-MICA*010 (10.4%), MICA*010-HLA-DRB1*0406 (5.8%) and HLA-B*1501-MICA*010-HLA-DRB1*0406 (5.8%). This is the first study to provide such high-resolution information on the distribution of haplotypes comprising MICA, HLA-B and HLA-DRB1 in Korean individuals, a level of resolution made possible by use of the SBT method. The results of this study should help determine the mechanisms underlying diseases associated with MICA polymorphisms in Korean individuals.

Effective screening of informative single nucleotide polymorphisms using the novel method of restriction fragment mass polymorphism.

Restriction fragment mass polymorphism (RFMP) was applied to pooled DNA for selecting informative single nucleotide polymorphisms (SNPs). A total of 225 coding non-synonymous SNPs (cnSNPs) from immunomodulating genes known to be involved in the pathogenesis of asthma were selected from the National Center for Biotechnology Information's (NCBI) SNP database (dbSNP). DNA samples from 200 healthy Koreans were pooled, amplified by polymerase chain reaction, digested with restriction enzymes and the fragments analysed by mass spectrometry. Only 30 of the 225 cnSNPs (13.3%) were informative, i.e.had a minor allele frequency>10%. The percentage of informative cnSNPs varied according to the validation status of the dbSNP, being 42.3% (22/52) when validated by multiple submissions and frequency data, 8.7% (2/23) when validated by multiple submissions alone and 9.1% (3/33) when validated by frequency data alone. Most of the 112 unvalidated cnSNPs were not informative. In conclusion, the RFMP method using pooled DNA is useful in selecting informative SNPs, as also is validation status in the dbSNP.

Near-field imaging of surface plasmon on gold nano-dots fabricated by scanning probe lithography.

We obtained scanning near-field optical microscopy images to study the excitation of surface plasmons on metallic dots fabricated using scanning probe lithography. Gold nano-dots were fabricated by applying electric voltages to conducting probes installed in an atomic force microscope using the mechanism of field-induced diffusion and nano-oxidation plus Au-coating. High spatial resolution of scanning near-field optical microscopy revealed a 'bifold' pattern of surface plasmon mode on fabricated Au dots in the polarization direction of incident light. We found that scanning near-field optical microscopy imaging combined with scanning probe lithography is able to provide a systematic study of surface plasmon excitation on nano-metallic structures.