Comparison of Retinal Structural and Neurovascular Changes between Patients with and without Amyloid Pathology.

To evaluate whether an impaired anterior visual pathway (retinal structures with microvasculature) is associated with underlying beta-amyloid (Aß) pathologies in patients with Alzheimer's disease dementia (ADD) and mild cognitive impairment (MCI), we compared retinal structural and vascular factors in each subgroup with positive or negative amyloid biomarkers. Twenty-seven patients with dementia, thirty-five with MCI, and nine with cognitively unimpaired (CU) controls were consecutively recruited. All participants were divided into positive Aß (A+) or negative Aß (A-) pathology based on amyloid positron emission tomography or cerebrospinal fluid Aß. The retinal circumpapillary retinal nerve fiber layer thickness (cpRNFLT), macular ganglion cell/inner plexiform layer thickness (mGC/IPLT), and microcirculation of the macular superficial capillary plexus were measured using optical coherence tomography (OCT) and OCT angiography. One eye of each participant was included in the analysis. Retinal structural and vascular factors significantly decreased in the following order: dementia < MCI < CU controls. The A+ group had significantly lower microcirculation in the para- and peri-foveal temporal regions than did the A-. However, the structural and vascular parameters did not differ between the A+ and A- with dementia. The cpRNFLT was unexpectedly greater in the A+ than in the A- with MCI. mGC/IPLT was lower in the A+ CU than in the A- CU. Our findings suggest that retinal structural changes may occur in the preclinical and early stages of dementia but are not highly specific to AD pathophysiology. In contrast, decreased temporal macula microcirculation may be used as a biomarker for the underlying Aß pathology.

Face Biometric Spoof Detection Method Using a Remote Photoplethysmography Signal.

Spoofing attacks in face recognition systems are easy because faces are always exposed. Various remote photoplethysmography-based methods to detect face spoofing have been developed. However, they are vulnerable to replay attacks. In this study, we propose a remote photoplethysmography-based face recognition spoofing detection method that minimizes the susceptibility to certain database dependencies and high-quality replay attacks without additional devices. The proposed method has the following advantages. First, because only an RGB camera is used to detect spoofing attacks, the proposed method is highly usable in various mobile environments. Second, solutions are incorporated in the method to obviate new attack scenarios that have not been previously dealt with. In this study, we propose a remote photoplethysmography-based face recognition spoofing detection method that improves susceptibility to certain database dependencies and high-quality replay attack, which are the limitations of previous methods without additional devices. In the experiment, we also verified the cut-off attack scenario in the jaw and cheek area where the proposed method can be counter-attacked. By using the time series feature and the frequency feature of the remote photoplethysmography signal, it was confirmed that the accuracy of spoof detection was 99.7424%.

Serum progranulin is not associated with rs5848 polymorphism in Korean patients with neurodegenerative diseases.

Low serum progranulin (PGRN) is known to be associated with granulin (GRN) gene mutation and T alleles of GRN rs5848 polymorphism. However, there have been only a few Asian studies exploring these. We investigated the serum PGRN levels, rs5848 genotypes, and their relations with cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers in the Korean population. Serum PGRN levels, GRN rs5848 polymorphism, and GRN mutations were evaluated in 239 participants (22 cognitively unimpaired participants and 217 patients with neurodegenerative diseases). CSF AD biomarkers were also evaluated in 214 participants. There was no significant difference in the serum PGRN levels among the diagnostic groups. We could not find any GRN mutation carrier in our sample. The differences in the frequencies of the rs5848 genotypes among the clinical groups or the effects of the rs5848 genotypes on serum PGRN were not observed. There was no correlation between the serum PGRN level or rs5848 genotype and CSF AD biomarkers. Neither the T allele nor the TT genotype had an effect on the development of AD. Our results showed that serum PGRN levels were not associated with rs5848 genotypes, indicating that multiple single nucleotide polymorphisms might affect PGRN concentrations in an ethnicity-specific manner.

Induction of Anti-Aquaporin 5 Autoantibody Production by Immunization with a Peptide Derived from the Aquaporin of Prevotella melaninogenica Leads to Reduced Salivary Flow in Mice.

Sjögren's syndrome (SS) is an autoimmune disease characterized by dryness of the mouth and eyes. The glandular dysfunction in SS involves not only T cell-mediated destruction of the glands but also autoantibodies against the type 3 muscarinic acetylcholine receptor or aquaporin 5 (AQP5) that interfere with the secretion process. Studies on the breakage of tolerance and induction of autoantibodies to these autoantigens could benefit SS patients. To break tolerance, we utilized a PmE-L peptide derived from the AQP5-homologous aquaporin of Prevotella melaninogenica (PmAqp) that contained both a B cell "E" epitope and a T cell epitope. Repeated subcutaneous immunization of C57BL/6 mice with the PmE-L peptide efficiently induced the production of Abs against the "E" epitope of mouse/human AQP5 (AQP5E), and we aimed to characterize the antigen specificity, the sequences of AQP5E-specific B cell receptors, and salivary gland phenotypes of these mice. Sera containing anti-AQP5E IgG not only stained mouse Aqp5 expressed in the submandibular glands but also detected PmApq and PmE-L by immunoblotting, suggesting molecular mimicry. Characterization of the AQP5E-specific autoantibodies selected from the screening of phage display Ab libraries and mapping of the B cell receptor repertoires revealed that the AQP5E-specific B cells acquired the ability to bind to the Ag through cumulative somatic hypermutation. Importantly, animals with anti-AQP5E Abs had decreased salivary flow rates without immune cell infiltration into the salivary glands. This model will be useful for investigating the role of anti-AQP5 autoantibodies in glandular dysfunction in SS and testing new therapeutics targeting autoantibody production.

Diagnostic ability of salivary matrix metalloproteinase-9 lateral flow test point-of-care test for periodontitis.

AIM: This cross-sectional study aimed to examine the diagnostic ability of salivary matrix metalloproteinase (MMP)-9 lateral flow test (LFT) point-of-care (POC) kit and develop an algorithm for diagnosis of periodontitis. MATERIALS AND METHODS: Through Seoul National Dental Hospital, 137 participants (46 LFT negatives, 91 LFT positives) were recruited. For salivary diagnostics, 150 µl of the unstimulated saliva was applied to LFT-POC kit. To make a diagnosis of periodontitis, stage II-IV in modified new international classification system was used. Covariates encompassing age, sex, smoking and obesity were evaluated through face-to-face interview. Enzyme-linked immunosorbent assay was used for quantification of salivary MMP-9. To develop a diagnostic algorithm, multivariable logistic regression analysis was used. Receiver operating characteristic curve was applied for evaluating diagnostic ability. RESULTS: Diagnostic ability of salivary MMP-9 LFT-POC test was 0.82 (sensitivity of 0.92, specificity of 0.72) in total participants. Diagnostic algorithm using POC test resulted in a response equation, that is algorithm score = -3.675 + 2.877*LFT + 0.034*age + 0.121*sex + 0.372*smoking + 0.192*obesity. Diagnostic ability of the algorithm was 0.88 (sensitivity of 0.92, specificity of 0.85) with cut-off score of 0.589. CONCLUSIONS: Salivary MMP-9 LFT-POC kit showed appropriate diagnostic ability for periodontitis and would be an efficient tool for screening of periodontitis.

Diagnostic and Prognostic ability of salivary MMP-9 and S100A8 for periodontitis.

OBJECTIVES: Salivary diagnostic using matrix metalloproteinase (MMP) and S100 for periodontitis is a promising issue. However, its prognostic effect is still unclear. This study aimed to evaluate the prognostic ability of salivary MMP-9 and S100A8 for periodontitis through non-surgical periodontitis treatment clinical trial. MATERIALS AND METHODS: Total 149 participants, 99 periodontitis and 50 healthy, were recruited. Among 99 non-surgical periodontitis treatment participants, 74 participants were revisited after three months. Periodontitis was classified as stage II-IV of new classification of periodontitis proposed at 2018. Enzyme-linked immunosorbent assay kit was used to quantify salivary MMP-9 and S100A8. Receiver operating characteristic curve was applied for diagnostic ability. Paired t test was applied for prognostic ability evaluating changes in salivary markers between pre- and post-treatment. RESULTS: Salivary MMP-9 and S100A8 were associated with periodontitis (p < .05). The screening ability of algorithm using salivary MMP-9 and S100A8 for periodontitis was 0.86 (p < .05). After treatment, reduction rate of salivary S100A8 and MMP-9 was 83.7% and 23.5%, respectively, (p < .05): only salivary S100A8 was superior compared to clinical parameters. CONCLUSION: Algorithm using salivary MMP-9 and S100A8 showed high diagnostic power for periodontitis. Both salivary S100A8 and MMP-9 showed prognostic ability for periodontitis, but S100A8 was better.

Comparison of Amyloid in Cerebrospinal Fluid, Brain Imaging, and Autopsy in a Case of Progressive Supranuclear Palsy.

Cerebrospinal fluid (CSF) amyloid-beta 1-42 (Aß1-42) and amyloid positron emission tomography (PET) are the 2 main Alzheimer disease amyloid biomarkers that have been validated in neuropathologically confirmed Alzheimer disease cases. Although many studies have shown concordance of amyloid positivity or negativity between CSF Aß1-42 and amyloid PET, several studies also reported discrepancies between these 2 Aß biomarkers. We conducted a comparison of CSF Aß1-42 level, amyloid PET, and autopsy findings in a case with progressive supranuclear palsy in which biomarker acquisition and postmortem pathologic examination were conducted almost at the same time. Our case with antemortem CSF Aß1-42 (+)/amyloid PET (-) who was pathologically confirmed with Aß pathology in the cerebral cortex may indicate CSF Aß1-42 is more sensitive for assessing in vivo Aß than amyloid PET.

Dysbiotic oral microbiota and infected salivary glands in Sjögren's syndrome.

Key events in the pathogenesis of SjÓ§gren syndrome (SS) include the change of salivary gland epithelial cells into antigen-presenting cell-like phenotypes and focal lymphocytic sialadenitis (FLS). However, what triggers these features in SS is unknown. Dysbiosis of the gut and oral microbiomes is a potential environmental factor in SS, but its connection to the etiopathogenesis of SS remains unclear. This study aimed to characterize the oral microbiota in SS and to investigate its potential role in the pathogenesis of SS. Oral bacterial communities were collected by whole mouthwash from control subjects (14 without oral dryness and 11 with dryness) and primary SS patients (8 without oral dryness and 17 with dryness) and were analyzed by pyrosequencing. The SS oral microbiota was characterized by an increased bacterial load and Shannon diversity. Through comparisons of control and SS in combined samples and then separately in non-dry and dry conditions, SS-associated taxa independent of dryness were identified. Three SS-associated species and 2 control species were selected and used to challenge human submandibular gland tumor (HSG) cells. Among the selected SS-associated bacterial species, Prevotella melaninogenica uniquely upregulated the expression of MHC molecules, CD80, and IFNλ in HSG cells. Concomitantly, P. melaninogenica efficiently invaded HSG cells. Sections of labial salivary gland (LSG) biopsies from 8 non-SS subjects and 15 SS patients were subjected to in situ hybridization using universal and P. melaninogenica-specific probes. Ductal cells and the areas of infiltration were heavily infected with bacteria in the LSGs with FLS. Collectively, dysbiotic oral microbiota may initiate the deregulation of SGECs and the IFN signature through bacterial invasion into ductal cells. These findings may provide new insights into the etiopathogenesis of SS.

Comparison of Diagnostic Performances Between Cerebrospinal Fluid Biomarkers and Amyloid PET in a Clinical Setting.

The diagnostic performances of cerebrospinal fluid (CSF) biomarkers and amyloid positron emission tomography (PET) were compared by examining the association and concordance or discordance between CSF Aß1-42 and amyloid PET, after determining our own cut-off values for CSF Alzheimer's disease (AD) biomarkers. Furthermore, we evaluated the ability of CSF biomarkers and amyloid PET to predict clinical progression. CSF Aß1-42, t-tau, and p-tau levels were analyzed in 203 individuals [27 normal controls, 38 mild cognitive impairment (MCI), 62 AD dementia, and 76 patients with other neurodegenerative diseases] consecutively recruited from two dementia clinics. We used both visual and standardized uptake value ratio (SUVR)-based amyloid PET assessments for analyses. The association of CSF biomarkers with amyloid PET SUVR, hippocampal atrophy, and cognitive function were investigated by linear regression analysis, and the risk of conversion from MCI to AD dementia was assessed using a Cox proportional hazards model. CSF p-tau/Aß1-42 and t-tau/Aß1-42 exhibited the best diagnostic accuracies among the CSF AD biomarkers examined. Correlations were observed between CSF biomarkers and global SUVR, hippocampal volume, and cognitive function. Overall concordance and discordance between CSF Aß1-42 and amyloid PET was 77% and 23%, respectively. Baseline positive CSF Aß1-42 for MCI demonstrated a 5.6-fold greater conversion risk than negative CSF Aß1-42 .  However, amyloid PET findings failed to exhibit significant prognostic value. Therefore, despite presence of a significant correlation between the CSF Aß1-42 level and SUVR of amyloid PET, and a relevant concordance between CSF Aß1-42 and amyloid PET, baseline CSF Aß1-42 better predicted AD conversion.

Associations of Anti-Aquaporin 5 Autoantibodies with Serologic and Histopathological Features of Sjögren's Syndrome.

Biomarkers to stratify the complex and heterogeneous phenotypes of Sjogren's syndrome (SS) are needed. We aimed to validate the prevalence of anti-aquaporin 5 (AQP5) IgG in a non-Korean cohort and to optimize the method to screen the anti-AQP5 IgG. The study cohort included 111 primary SS and 43 non-SS Sjögren's International Collaborative Clinical Alliance (SICCA) controls that were obtained from the Sjögren's International Collaborative Clinical Alliance registry, in addition to 35 systemic lupus erythematosus (SLE) and 35 rheumatoid arthritis (RA) phenotypes. Anti-AQP5 IgG was screened by cell-based immunofluorescence cytochemistry (CB-IFC) assay in the absence or presence of epitope peptides, as well as by ELISA using the epitope peptides as coated antigens. Anti-AQP5 IgG specific to an E1 epitope was best at discriminating between SS and non-SS, and the two different methods (CB-IFC and ELISA) presented comparable performance in diagnostic accuracy (0.690 vs. 0.707). Notably, the SLE and RA groups had substantially lower levels of anti-AQP5 IgG than the SS group. In addition, the presence of anti-AQP5_E1 IgG was associated with serologic and histopathological features of SS. In conclusion, a similar prevalence of anti-AQP5 IgG was confirmed in a non-Korean cohort. Screening anti-AQP5 autoantibodies may help to form subgroups of SS for targeted therapy.

Determination of Anti-aquaporin 5 Autoantibodies by Immunofluorescence Cytochemistry.

Cell-based assay by immunofluorescence cytochemistry (CBA-IFC) has been shown to be the most accurate method to detect anti-aquaporin (AQP) 4 autoantibodies. Detection of anti-AQP5 autoantibodies is delicate, which depends on the proper expression of AQP5 on the plasma membrane. Here, we describe methods to determine anti-AQP5 autoantibodies by CBA-IFC. Both anti-AQP5 IgG and IgA can be detected by this method.

Generalized Scheme for High Performing Photodetectors with a p-Type 2D Channel Layer and n-Type Nanoparticles.

A generalized scheme for the fabrication of high performance photodetectors consisting of a p-type channel material and n-type nanoparticles is proposed. The high performance of the proposed hybrid photodetector is achieved through enhanced photoabsorption and the photocurrent gain arising from its effective charge transfer mechanism. In this paper, the realization of this design is presented in a hybrid photodetector consisting of 2D p-type black phosphorus (BP) and n-type molybdenum disulfide nanoparticles (MoS2 NPs), and it is demonstrated that it exhibits enhanced photoresponsivity and detectivity compared to pristine BP photodetectors. It is found that the performance of hybrid photodetector depends on the density of NPs on BP layer and that the response time can be reduced with increasing density of MoS2 NPs. The rising and falling times of this photodetector are smaller than those of BP photodetectors without NPs. This proposed scheme is expected to work equally well for a photodetector with an n-type channel material and p-type nanoparticles.