Expression of monocyte chemokine receptors in diabetes after non-surgical periodontal treatment: A pilot study.

The aim of this study was to evaluate the effect of non-surgical periodontal treatment in the expression of chemokine receptors, in individuals with Periodontitis, associated or not with Diabetes. Pilot study, which included patients (n = 45) with Periodontitis, associated (n = 25) or not (n = 20) with Diabetes, submitted to the non-surgical periodontal treatment for one month. The expression of chemokine receptors CCR2, CCR5, and CX3CR1 at the mRNA level was evaluated in the peripheral mononuclear cells, as well as the expression of these receptors at the protein level was verified in monocyte subtypes (classical, intermediate, and non-classical monocytes). There was higher expression of CCR2 and CCR5 receptors at the initial visit in the group with Diabetes, with no differences for CX3CR1 (p = 0.002; p = 0.018, and p = 0.896, respectively), without differences after treatment. There was higher expression of CCR2 and CCR5 proteins in the group with Diabetes at the initial visit for classical, intermediate, and nonclassical monocytes, with no differences for CX3CR1 (CCR2: p = 0.004; p = 0.026; p = 0.024; CCR5: 0.045; p = 0.045; p = 0.013; CX3CR1: p = 0.424; p = 0.944; p = 0.392, respectively), without differences after the end of treatment. Concerning each group separately, there were reductions in the expression of CCR2 as well as CCR5 in classical, intermediate, and nonclassical monocytes, and reduction of CX3CR1 in classical monocytes after treatment in the group with Diabetes (p = 0.003; p = 0.006; p = 0.039; p = 0.007; p = 0.006; p = 0.004; p = 0.019, respectively), without differences in the group without Diabetes. The expression of the chemokine receptors CCR2 and CCR5, in patients with Periodontitis associated with Diabetes, is favorably modified after the end of the non-surgical periodontal treatment.

Evaluation of Extra-Prostatic Extension on Deep Learning-Reconstructed High-Resolution Thin-Slice T2-Weighted Images in Patients with Prostate Cancer.

The aim of this study was to compare diagnostic performance for extra-prostatic extension (EPE) and image quality among three image datasets: conventional T2-weighted images (T2WIconv, slice thickness, 3 mm) and high-resolution thin-slice T2WI (T2WIHR, 2 mm), with and without deep learning reconstruction (DLR) in patients with prostatic cancer (PCa). A total of 88 consecutive patients (28 EPE-positive and 60 negative) diagnosed with PCa via radical prostatectomy who had undergone 3T-MRI were included. Two independent reviewers performed a crossover review in three sessions, in which each reviewer recorded five-point confidence scores for the presence of EPE and image quality using a five-point Likert scale. Pathologic topographic maps served as the reference standard. For both reviewers, T2WIconv showed better diagnostic performance than T2WIHR with and without DLR (AUCs, in order, for reviewer 1, 0.883, 0.806, and 0.772, p = 0.0006; for reviewer 2, 0.803, 0.762, and 0.745, p = 0.022). The image quality was also the best in T2WIconv, followed by T2WIHR with DLR and T2WIHR without DLR for both reviewers (median, in order, 3, 4, and 5, p < 0.0001). In conclusion, T2WIconv was optimal in regard to image quality and diagnostic performance for the evaluation of EPE in patients with PCa.

Divergent Bimetallic Mechanisms in Copper(II)-Mediated C-C, N-N, and O-O Oxidative Coupling Reactions.

Copper-catalyzed aerobic oxidative coupling of diaryl imines provides a route for conversion of ammonia to hydrazine. The present study uses experimental and density functional theory computational methods to investigate the mechanism of N-N bond formation, and the data support a mechanism involving bimolecular coupling of Cu-coordinated iminyl radicals. Computational analysis is extended to CuII-mediated C-C, N-N, and O-O coupling reactions involved in the formation of cyanogen (NC-CN) from HCN, 1,3-butadiyne from ethyne (i.e., Glaser coupling), hydrazine from ammonia, and hydrogen peroxide from water. The results reveal two different mechanistic pathways. Heteroatom ligands with an uncoordinated lone pair (iminyl, NH2, OH) undergo charge transfer to CuII, generating ligand-centered radicals that undergo facile bimolecular radical-radical coupling. Ligands lacking a lone pair (CN and CCH) form bridged binuclear diamond-core structures that undergo C-C coupling. This mechanistic bifurcation is rationalized by analysis of spin densities in key intermediates and transition states, as well as multiconfigurational calculations. Radical-radical coupling is especially favorable for N-N coupling owing to energetically favorable charge transfer in the intermediate and thermodynamically favorable product formation.

Modulation of monocyte subtypes in diabetes after non-surgical periodontal treatment.

OBJECTIVES: The current study aims to evaluate the effect of non-surgical periodontal treatment on the modulation of monocyte phenotype, in the presence or absence of diabetes. MATERIALS AND METHODS: The identification, quantification, and phenotypic characterization of monocyte subtypes (classical, intermediate, and non-classical) were performed by flow cytometry, at baseline and 1 month after the end of non-surgical periodontal treatment, in patients with periodontitis, associated or not with diabetes. RESULTS: There was an increase in non-classical monocytes after treatment and a reduction in intermediate monocytes, without differences for the classical subtype, regardless of the diabetes status. Furthermore, there was a reduction in intermediate monocytes and an increase in non-classical and classical monocytes after treatment in the diabetes group, while no significant differences were observed for classical, intermediate, and non-classical monocytes in the group without diabetes. Comparisons between the two groups showed significant differences for classical, intermediate, and non-classical monocytes at baseline; these differences were not found one month after treatment. CONCLUSIONS: Non-surgical periodontal treatment leads to modulation of monocytes to a less inflammatory phenotype, especially in individuals with diabetes. CLINICAL RELEVANCE: A better understanding of the role of these biomarkers in the periodontitis contex may constitute a new strategic target for a better treatment of patiens with diabetes associated to periodontitis. CLINICAL TRIAL REGISTRATION: Brazilian Registry of Clinical Trials-RBR-35szwc. Jhefferson Miranda Alves and Danielle Borges Germano contributed equality to this study and should be considered first authors.

Ubiquitin-proteasome system as a target for anticancer treatment-an update.

As the ubiquitin-proteasome system (UPS) regulates almost every biological process, the dysregulation or aberrant expression of the UPS components causes many pathological disorders, including cancers. To find a novel target for anticancer therapy, the UPS has been an active area of research since the FDA's first approval of a proteasome inhibitor bortezomib in 2003 for treating multiple myeloma (MM). Here, we summarize newly described UPS components, including E3 ubiquitin ligases, deubiquitinases (DUBs), and immunoproteasome, whose malfunction leads to tumorigenesis and whose inhibitors have been investigated in clinical trials as anticancer therapy since 2020. We explain the mechanism and effects of several inhibitors in depth to better comprehend the advantages of targeting UPS components for cancer treatment. In addition, we describe attempts to overcome resistance and limited efficacy of some launched proteasome inhibitors, as well as an emerging PROTAC-based tool targeting UPS components for anticancer therapy.

Comparison of the Efficacy of Diluted Polyethylene Glycol and Low-Density (0.1% w/v) Barium Sulfate Suspension for CT Enterography.

Purpose: To compare small bowel distension and side effects between a diluted polyethylene glycol (PEG) solution and a low-density (0.1% w/v) barium sulfate suspension (LDBSS) for CT enterography (CTE) preparation. Materials and Methods: Total 173 consecutive patients who underwent CTE were enrolled in this study. The LDBSS (1 L) was used in 50 patients, and the diluted iso-osmotic PEG solution (1 L) was used in 123 patients. Two blinded radiologists independently scored jejunal and ileal distensions on a 5-point scale. To compare side effects between the two groups, the patients reported whether they had immediate complications after the administration of the oral contrast media. Results: For ileal and jejunal distension, the diluted PEG solution showed no difference from the LDBSS for either reader (ileum: reader 1, median, 4; 4, interquartile range, 3-4; 3-4, p = 0.997; reader 2, median, 4; 4, interquartile range, 3.3-4.0; 3-4, p = 0.064; jejunum: reader 1, median, 2; 2, interquartile range, 2-3; 2-3, p = 0.560; reader 2, median, 3; 2, interquartile range, 2-3; 2-3, p = 0.192). None of the patients complained of immediate complications following administration of either of the oral contrast media. Conclusion: The diluted PEG solution showed comparable bowel distension compared to LDBSS and no immediate side effects; thus, it can be a useful alternative.

Splenic epidermoid cyst in a dog.

Splenic epithelial cysts are rare in humans and have not been reported in animals, to our knowledge. During a routine medical examination of a 12-y-old castrated male Maltese dog, a splenic mass was found and subsequently removed via splenectomy. Histologically, a well-defined multilocular cyst in the spleen was lined mostly by simple cuboidal, multifocally by stratified cuboidal, or occasionally by stratified squamous epithelium. Immunohistochemically, the lining cells were positive for cytokeratin and negative for vimentin, CD31, and Wilms tumor protein 1. The case was diagnosed as a primary splenic epidermoid cyst.

Accuracy of guided dental implant surgery using a fully digital workflow: A case series.

STATEMENT OF PROBLEM: Computer-guided implant surgery facilitated by intraoral scanning may enhance the efficiency of the digital workflow. However, it is necessary to assess technique accuracy to evaluate the accuracy of implant placement. PURPOSE: The purpose of this clinical study was to evaluate the accuracy of a virtual computer-aided design and computer-aided manufacturing (CAD-CAM) static guided surgery technique associated with intraoral scanning in partially edentulous participants by analyzing the overlap among preoperative and postoperative cone beam computed tomography (CBCT) scans, virtual planning, and the guided surgery performed. MATERIAL AND METHODS: Eleven partially edentulous participants underwent CBCT and intraoral scanning (TRIOS3). Data were integrated into a software program (ImplantViewer 3.5) for the virtual planning of implants and 3-dimensional (3D) printing of the prototype CAD-CAM surgical guide. A total of 18 implants were placed using the CAD-CAM static computer-aided implant surgery technique (Strong SW). After 15 days, postoperative CBCT scans were made and 4 variables (angular, coronal, apical, and vertical deviation) were measured to compare the virtually planned implants and the implants placed by analyzing the overlap between preoperative and postoperative of the virtual planning and guided surgery performed using the ImplantViewer 3.5 and Rhino 6 software programs. RESULTS: Deviations were found in all parameters analyzed. The mean angular deviation was 2.68 ±1.62 degrees; mean coronal deviation, 0.82 ±0.44 mm; mean apical deviation, 1.14 ±0.44 mm; and mean vertical deviation, 0.62 ±0.44 mm. CONCLUSIONS: The implants placed using the CAD-CAM static guided surgery technique associated with intraoral scanning in partially edentulous participants exhibited angular and linear deviations when compared with virtual planning implants. However, these deviations were not clinically significant.

Maxillary Reconstruction with Xenogeneic Bone Graft, Platelet-Rich Fibrin, and Titanium Mesh for Rehabilitation with Implants: A 5-year Follow-Up Study.

Aim: Alveolar deficiency is considered one of the main limitations for placement of osseointegrated implants, as well as for their long-term success, especially in the anterior region of the maxilla. Objective: To report a clinical case of reconstruction of atrophic maxilla with deproteinized bovine bone associated with platelet-rich fibrin (PRF) and titanium mesh and to assess the linear and volumetric bone gains and rehabilitation with implants in a 5-year follow-up. Case: Patient with bone deficiency in the anterior maxilla region underwent bone reconstruction with deproteinized bovine bone associated with PRF and titanium mesh. After six months, the necessary bone height and volume were obtained for placement of implants, and the bone contour was restored in the anterior region, providing functional and aesthetic improvement. The amount of linear and volumetric bone gains was compared to baseline computed tomography scans. Three implants were placed in the grafted region, and a bone tissue sample was obtained at the time of their placement. Histological analysis showed neo-formed bone tissue in contact with the remaining particles of the biomaterial. After six months, the implants were activated, and the prosthesis was placed on the implants, which were monitored for five years. Conclusion: Implants can be placed predictably in regions with vertical and horizontal bone augmentations by using xenogeneic bone grafts associated with titanium mesh and PRF.

An Unusual Presentation of Extensive Ductal Carcinoma in Situ Accompanying Invasive Ductal Carcinoma on MRI: A Case Report.

The incidence of ductal carcinoma in situ has increased with the rise in screening mammography; currently, ductal carcinoma in situ constitutes 20%-25% of all breast cancers, and up to half of them may become invasive. Its early detection is critical in improving the cure rate. Moreover, MRI has higher sensitivity for its detection than mammography. Herein, we report an unusual case of ductal carcinoma in situ presenting as a continuous, serpentine, linear enhancement with regional distribution on MRI.

Comparison of Computed Diffusion-Weighted Imaging b2000 and Acquired Diffusion-Weighted Imaging b2000 for Detection of Prostate Cancer.

Purpose: To compare the sensitivity of tumor detection and inter-observer agreement between acquired diffusion-weighted imaging (aDWI) b2000 and computed DWI (cDWI) b2000 in patients with prostate cancer (PCa). Materials and Methods: Eighty-eight patients diagnosed with PCa by radical prostatectomy and having undergone pre-operative 3 Tesla-MRI, including DWI (b, 0, 100, 1000, 2000 s/mm2), were included in the study. cDWI b2000 was obtained from aDWI b0, b100, and b1000. Two independent reviewers performed a review of the aDWI b2000 and cDWI b2000 images in random order at 4-week intervals. A region of interest was drawn for the largest tumor on each dataset, and a Prostate Imaging-Reporting and Data System (PI-RADS) score based on PI-RADS v2.1 was recorded. Histologic topographic maps served as the reference standard. Results: The study population's Gleason scores were 6 (n = 16), 7 (n = 53), 8 (n = 9), and 9 (n = 10). According to the reviewers, the sensitivities of cDWI b2000 and aDWI b2000 showed no significant differences (for reviewer 1, both 94% [83/88]; for reviewer 2, both 90% [79/88]; p = 1.000, respectively). The kappa values of cDWI b2000 and aDWI b2000 for the PI-RADS score were 0.422 (95% confidence interval [CI], 0.240-0.603) and 0.495 (95% CI, 0.308-0.683), respectively. Conclusion: cDWI b2000 showed comparable sensitivity with aDWI b2000, in addition to sustained moderate inter-observer agreement, in the detection of PCa.

Gene-environment interaction in type 2 diabetes in Korean cohorts: Interaction of a type 2 diabetes polygenic risk score with triglyceride and cholesterol on fasting glucose levels.

Type 2 diabetes (T2D) is caused by genetic and environmental factors as well as gene-environment interactions. However, these interactions have not been systematically investigated. We analyzed these interactions for T2D and fasting glucose levels in three Korean cohorts, HEXA, KARE, and CAVAS, using the baseline data with a multiple regression model. Two polygenic risk scores for T2D (PRST2D ) and fasting glucose (PRSFG ) were calculated using 488 and 82 single nucleotide polymorphisms (SNP) for T2D and fasting glucose, respectively, which were extracted from large-scaled genome-wide association studies with multiethnic data. Both lifestyle risk factors and T2D-related biochemical measurements were assessed. The effect of interactions between PRST2D -triglyceride (TG) and PRST2D -total cholesterol (TC) on fasting glucose levels was observed as follows: ß ± SE = 0.0005 ± 0.0001, p = 1.06 × 10-19 in HEXA, ß ± SE = 0.0008 ± 0.0001, p = 2.08 × 10-8 in KARE for TG; ß ± SE = 0.0006 ± 0.0001, p = 2.00 × 10-6 in HEXA, ß ± SE = 0.0020 ± 0.0004, p = 2.11 × 10-6 in KARE, ß ± SE = 0.0007 ± 0.0004, p = 0.045 in CAVAS for TC. PRST2D -based classification of the participants into four groups showed that the fasting glucose levels in groups with higher PRST2D were more adversely affected by both the TG and TC. In conclusion, blood TG and TC levels may affect the fasting glucose level through interaction with T2D genetic factors, suggesting the importance of consideration of gene-environment interaction in the preventive medicine of T2D.

Analysis of the Interaction between Polygenic Risk Score and Calorie Intake in Obesity in the Korean Population.

INTRODUCTION: Obesity results from an imbalance in the intake and expenditure of calories that leads to lifestyle-related diseases. Although genome-wide association studies (GWAS) have revealed many obesity-related genetic factors, the interactions of these factors and calorie intake remain unknown. This study aimed to investigate interactions between calorie intake and the polygenic risk score (PRS) of BMI. METHODS: Three cohorts, i.e., from the Korea Association REsource (KARE; n = 8,736), CArdioVAscular Disease Association Study (CAVAS; n = 9,334), and Health EXAminee (HEXA; n = 28,445), were used for this study. BMI-related genetic loci were selected from previous GWAS. Two scores, PRS, and association (a)PRS, were used; the former was determined from 193 single-nucleotide polymorphisms (SNPs) from 5 GWAS datasets, and the latter from 62 SNPs (potentially associated) from 3 Korean cohorts (meta-analysis, p < 0.01). RESULTS: PRS and aPRS were significantly associated with BMI in all 3 cohorts but did not exhibit a significant interaction with total calorie intake. Similar results were obtained for obesity. PRS and aPRS were significantly associated with obesity but did not show a significant interaction with total calorie intake. We further analyzed the interaction with protein, fat, and carbohydrate intake. The results were similar to those for total calorie intake, with PRS and aPRS found to not be associated with the interaction of any of the 3 nutrition components for either BMI or obesity. DISCUSSION: The interaction of BMI PRS with calorie intake was investigated in 3 independent Korean cohorts (total n = 35,094) and no interactions were found between PRS and calorie intake for obesity.

Identification of metabolic markers predictive of prediabetes in a Korean population.

Prediabetes (PD) is a high-risk state of developing type 2 diabetes, and cardiovascular and metabolic diseases. Metabolomics-based biomarker studies can provide advanced opportunities for prediction of PD over the conventional methods. Here, we aimed to identify metabolic markers and verify their abilities to predict PD, as compared to the performance of the traditional clinical risk factor (CRF) and previously reported metabolites in other population-based studies. Targeted metabolites quantification was performed in 1723 participants in the Korea Association REsource (KARE) cohort, from which 500 normal individuals were followed up for 6 years. We selected 12 significant metabolic markers, including five amino acids, four glycerophospholipids, two sphingolipids, and one acylcarnitine, at baseline, resulting in a predicted incidence of PD with an area under the curve (AUC) of 0.71 during follow-up. The performance of these metabolic markers compared to that of fasting glucose was significantly higher in obese patients (body mass index: BMI ≥ 25 kg/m2, 0.79 vs. 0.58, P < 0.001). The combination with metabolic markers, CRF, and fasting glucose yielded the best prediction performance (AUC = 0.86). Our results revealed that metabolic markers were not only associated with the risk of PD, but also improved the prediction performance in combination with conventional approaches.

Sex differences in adolescent mental health profiles in South Korea.

Accumulating evidence indicates that sex of adolescents is a major factor affecting mental health. This study aimed to compare mental health profiles and longitudinal effects of various factors on mental health between male and female adolescents using the Korean Children and Youth Panel Survey. Results showed that females were more depressed, aggressive, and likely to develop somatic symptoms than males, while males exhibited more attention deficits than females. Moreover, abusive parenting behavior was associated with a lower level of mental health in both male and female adolescents. In addition, we found significant differences in the effects of individual factors (subjective health status and smartphone addiction), family-related factors (living with both parents, working mother, and neglectful parenting behavior), and school-related factors (school adjustment and satisfaction with grades) on mental health between male and female adolescents. These findings indicate sex differences in adolescent mental health profiles in South Korea. Further studies are needed to develop comprehensive mental health strategies that consider personal, family, and school-related factors and sex differences.

O-GlcNAc stabilizes SMAD4 by inhibiting GSK-3ß-mediated proteasomal degradation.

O-linked ß-N-acetylglucosamine (O-GlcNAc) is a post-translational modification which occurs on the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins. It has been reported that the presence of this single sugar motif regulates various biological events by altering the fate of target proteins, such as their function, localization, and degradation. This study identified SMAD4 as a novel O-GlcNAc-modified protein. SMAD4 is a component of the SMAD transcriptional complex, a major regulator of the signaling pathway for the transforming growth factor-ß (TGF-ß). TGF-ß is a powerful promoter of cancer EMT and metastasis. This study showed that the amount of SMAD4 proteins changes according to cellular O-GlcNAc levels in human lung cancer cells. This observation was made based on the prolonged half-life of SMAD4 proteins. The mechanism behind this interaction was that O-GlcNAc impeded interactions between SMAD4 and GSK-3ß which promote proteasomal degradation of SMAD4. In addition, O-GlcNAc modification on SMAD4 Thr63 was responsible for stabilization. As a result, defects in O-GlcNAcylation on SMAD4 Thr63 attenuated the reporter activity of luciferase, the TGF-ß-responsive SMAD binding element (SBE). This study's findings imply that cellular O-GlcNAc may regulate the TGF-ß/SMAD signaling pathway by stabilizing SMAD4.

Dental implants in patients seropositive for HIV: A 12-year follow-up study.

BACKGROUND AND OVERVIEW: Patients seropositive HIV and AIDS represent a group of patients who experience longer longevity at the expense of effective therapies for infection control and related opportunistic diseases. However, the prolonged use of these drugs is often associated with adverse events, which theoretically may influence dental management and the long-term stability of dental implants. The objective of this study was to prospectively evaluate a group of HIV-positive people from a previous study who had received dental implants for 12 years after oral rehabilitation and functional loading. CASE DESCRIPTION: Nine patients with a total of 18 implants participated in this study. Viral load was undetectable in 8 patients, with 1 who had 48 copies/milliliter. The cluster of differentiation 4 T lymphocyte count ranged from 227 through 1,000 cells/cubic millimeter, mean (standard deviation [SD]) 564 (271.13) cells/mm3. Five of the 9 (55.5%) patients had visible plaque, and 5 (55.5%) had bleeding on probing with no implant mobility. Radiographs obtained at 6 months, 12 months, and 12 years of functional loading showed mean (SD) marginal bone losses of 0.32 (0.23) mm, 0.37 (0.23) mm, and 2.43 (1.48), respectively. CONCLUSION AND PRACTICAL IMPLICATIONS: These results suggest that dental implant treatment in HIV-positive patients achieved long-term survival, with a success rate comparable with that observed in healthy patients, indicating that implant rehabilitation is not a contraindication for HIV-positive patients.

Effects of Multicomponent Exercise on Cognitive Function in Elderly Korean Individuals.

BACKGROUND AND PURPOSE: The aim of this study was to investigate the effects of multicomponent exercise on cognitive function, depression, and quality of life in elderly individuals. METHODS: This study prospectively recruited 605 participants, and constructed an exercise pyramid comprising even distributions of daily physical activities, aerobic exercise, muscle-strengthening exercise, flexibility exercise, balance exercise, and activities that subjects could perform while sitting down. The exercise program was divided into six stages according to the participant's level of frailty. The 12-week exercise program intervention was conducted once yearly. RESULTS: The exercise regimen was followed by 402 of the 605 enrolled participants, giving a dropout rate of 33.6%. The 27-month exercise program was completed by 60 participants. The scores for the Mini Mental State Examination for dementia screening (MMSE-DS), short form of the Geriatric Depression Scale, World Health Organization Quality of Life Assessment (WHOQOL-BREF), International Physical Activity Questionnaire (IPAQ), fear of falling, handgrip strength, and walking speed were improved after the exercise intervention. The analysis of frailty revealed that participants in the frail group showed greater improvements for the MMSE-DS, WHOQOL-BREF, IPAQ, fear of falling, handgrip strength, and walking speed. CONCLUSIONS: Individually customized, multicomponent exercise programs lead to improved levels of cognitive function, depression, and quality of life, especially among those who are more frail.

Are Genetic Variants Associated with the Location of Cerebral Arterial Lesions in Stroke Patients?

BACKGROUND: Genetic variants may play a role in determining the location of cerebral atherosclerosis. We aimed to investigate the association between RNF213, MMP2, and genetic polymorphisms linked to vascular tortuosity with the location of cerebral arterial atherosclerosis. METHODS: A prospective case-control study was conducted on patients with ischemic stroke and age- and sex-matched stroke-free controls. The stroke patients were categorized into those with intracranial artery atherosclerosis (ICAS), extracranial artery atherosclerosis (ECAS), and small vessel occlusion (SVO). Six single nucleotide polymorphisms (SNPs) including rs2118181 (FBN1), rs2179357 (SLC2A10), rs1036095 (TGFBR2), rs243865 (MMP2), rs1800470 (TGFB1), and rs112735431 (RNF213) were analyzed with the TaqMan Genotyping Assay, and the distribution of genotypes across groups was compared. RESULTS: None of the 6 SNPs were associated with stroke on comparing the 449 stroke patients (71 with ECAS, 169 with ICAS, and 209 with SVO) to the 447 controls. In the subgroup analysis, the adjusted odds ratios (aORs) for age and sex indicated a significant association between rs112735431 and ICAS in the allele comparison analysis and in the additive and dominant model analyses. rs112735431 was associated with anterior circulation involvement and increased burden of cerebral atherosclerosis. rs2179357 was significantly associated with ICAS in the recessive model analysis, and rs1800470 was significantly associated with ECAS in the recessive model analysis when compared to controls. CONCLUSION: rs112735431 was associated with ICAS and increased atherosclerosis burden in Korean stroke patients. Further studies are needed to elucidate the role of rs112735431 and to confirm the association of rs2179357 and rs1800470 with cerebral atherosclerosis.

O-GlcNAcylation on LATS2 disrupts the Hippo pathway by inhibiting its activity.

The Hippo pathway controls organ size and tissue homeostasis by regulating cell proliferation and apoptosis. The LATS-mediated negative feedback loop prevents excessive activation of the effectors YAP/TAZ, maintaining homeostasis of the Hippo pathway. YAP and TAZ are hyperactivated in various cancer cells which lead to tumor growth. Aberrantly increased O-GlcNAcylation has recently emerged as a cause of hyperactivation of YAP in cancer cells. However, the mechanism, which induces hyperactivation of TAZ and blocks LATS-mediated negative feedback, remains to be elucidated in cancer cells. This study found that in breast cancer cells, abnormally increased O-GlcNAcylation hyperactivates YAP/TAZ and inhibits LATS2, a direct negative regulator of YAP/TAZ. LATS2 is one of the newly identified O-GlcNAcylated components in the MST-LATS kinase cascade. Here, we found that O-GlcNAcylation at LATS2 Thr436 interrupted its interaction with the MOB1 adaptor protein, which connects MST to LATS2, leading to activation of YAP/TAZ by suppressing LATS2 kinase activity. LATS2 is a core component in the LATS-mediated negative feedback loop. Thus, this study suggests that LATS2 O-GlcNAcylation is deeply involved in tumor growth by playing a critical role in dysregulation of the Hippo pathway in cancer cells.