Characteristics and standards of severe sagittal imbalance in adult patients with spinal deformities: a retrospective analysis.

OBJECTIVE: To analyze the characteristics of "severe" dynamic sagittal imbalance (DSI) in patients with adult spinal deformity (ASD) and establish criteria for them. METHODS: We retrospectively analyzed 102 patients with ASD presenting four cardinal signs of lumbar degenerative kyphosis. All patients underwent deformity corrective surgery and were divided into three groups according to the diagnostic criteria based on the Oswestry disability index and dynamic features (△Timewalk: time until C7 sagittal vertical axis [C7SVA] reaches ≥ 20 cm after the start of walking) of sagittal imbalance. The paravertebral back muscles were analyzed and compared using T2-weighted axial imaging. We performed a statistically time-dependent spinopelvic sagittal parameter analysis of full standing lateral lumbar radiographs. Lumbar flexibility was analyzed using dynamic lateral lumbar radiography. RESULTS: The patients were classified into the mild (△Timewalk ≥ 180 s, 35 patients), moderate (180 s > △Timewalk ≥ 30 s, 38 patients), and severe (△Timewalk < 30 s, 29 patients) groups. The back muscles in the severe group exhibited a significantly higher signal intensity (533.4 ± 237.5, p < 0.05) and larger area of fat infiltration (35.2 ± 5.4, p < 0.05) than those in the mild (223.8 ± 67.6/22.9 ± 11.9) and moderate groups (294.4 ± 214.7/21.6 ± 10.6). The analysis of lumbar flexibility revealed significantly lower values in the severe group (5.8° ± 2.5°, p < 0.05) than in the mild and moderate groups (14.2° ± 12.4° and 11.4° ± 8.7°, respectively). The severe group had significantly lower lumbar lordosis (LL, 25.1° ± 22.7°, p < 0.05) and Pelvic incidence-LL mismatch (PI-LL, 81.5° ± 26.6°, p < 0.001) than those of the mild (8.2° ± 16.3°/58.7° ± 18.8°) and moderate (14.3° ± 28.6°/66.8° ± 13.4°) groups. On receiver operating characteristic curve analysis, PI-LL was statistically significant, with an area under the curve of 0.810 (95% confidence interval) when the baseline was set at 75.3°. The severe group had more postoperative complications than the other groups. CONCLUSIONS: Our results suggest the following criteria for severe DSI: C7SVA > 20 cm within 30 s of walking or standing, a rigid lumbar curve < 10° on dynamic lateral radiographs, and a PI-LL mismatch > 75.3°.

Coronal vertical fracture of vertebral body following minimally invasive lateral lumbar interbody fusion: risk factor analysis in consecutive case series.

BACKGROUND: To investigate the incidence and risk factors of coronal vertical vertebral body fracture (CV-VBF) during lateral lumbar interbody fusion (LLIF) for degenerative lumbar disease. METHODS: Clinical data, including age, sex, body mass index, and bone mineral density, were reviewed. Radiological assessments, such as facet joint arthrosis, intervertebral disc motion, index disc height, and cage profiles, were conducted. Posterior instrumentation was performed using either a single or staged procedure after LLIF. Demographic and surgical data were compared between patients with and without VBF. RESULTS: Out of 273 patients (552 levels), 7 (2.6%) experienced CV-VBF. Among the 552 levels, VBF occured in 7 levels (1.3%). All VBF cases developed intraoperatively during LLIF, with no instances caused by cage subsidence during the follow-up period. Sagittal motion in segments adjacent to VBF was smaller than in others (4.6° ± 2.6° versus 6.5° ± 3.9°, P = 0.031). The average grade of facet arthrosis was 2.5 ± 0.7, indicating severe facet arthrosis. All fractures developed due to oblique placement of a trial or cage into the index disc space, leading to a nutcracker effect. These factors were not related to bone quality. CONCLUSIONS: CV-VBF after LLIF occurred in 2.6% of patients, accounting for 1.3% of all LLIF levels. A potential risk factor for VBF involves the nutcracker-impinging effect due to the oblique placement of a cage. Thorough preoperative evaluations and surgical procedures are needed to avoid VBF when considering LLIF in patients with less mobile spine.

Identification of a novel risk factor for chronic wasting disease (CWD) in elk: S100G single nucleotide polymorphism (SNP) of the prion protein gene (PRNP).

Prion diseases are fatal and malignant infectious encephalopathies induced by the pathogenic form of prion protein (PrPSc) originating from benign prion protein (PrPC). A previous study reported that the M132L single nucleotide polymorphism (SNP) of the prion protein gene (PRNP) is associated with susceptibility to chronic wasting disease (CWD) in elk. However, a recent meta-analysis integrated previous studies that did not find an association between the M132L SNP and susceptibility to CWD. Thus, there is controversy about the effect of M132L SNP on susceptibility to CWD. In the present study, we investigated novel risk factors for CWD in elk. We investigated genetic polymorphisms of the PRNP gene by amplicon sequencing and compared genotype, allele, and haplotype frequencies between CWD-positive and CWD-negative elk. In addition, we performed a linkage disequilibrium (LD) analysis by the Haploview version 4.2 program. Furthermore, we evaluated the 3D structure and electrostatic potential of elk prion protein (PrP) according to the S100G SNP using AlphaFold and the Swiss-PdbViewer 4.1 program. Finally, we analyzed the free energy change of elk PrP according to the S100G SNP using I-mutant 3.0 and CUPSAT. We identified 23 novel SNP of the elk PRNP gene in 248 elk. We found a strong association between PRNP SNP and susceptibility to CWD in elk. Among those SNP, S100G is the only non-synonymous SNP. We identified that S100G is predicted to change the electrostatic potential and free energy of elk PrP. To the best of our knowledge, this was the first report of a novel risk factor, the S100G SNP, for CWD.

Discovery of dioxo-benzo[b]thiophene derivatives as potent YAP-TEAD interaction inhibitors for treating breast cancer.

Disruption of protein-protein interaction between transcriptional enhancer factor (TEA)-domain (TEAD; a transcription factor) and its co-activator Yes-associated protein (YAP)/ transcriptional co-activator with PDZ-binding motif (TAZ) is a potential therapeutic strategy against various types of solid tumors. Based on hit compound 8 and 9a, hydrazone derivatives with dioxo-benzo[d]isothiazole (9b-n) and oxime ester (10a-s) or amide derivatives (11a-r) with dioxo-benzo[b]thiophene were designed and synthesized as novel TEAD-YAP interaction inhibitors. Amide derivative 11q exhibited a higher potency in inhibiting TEAD-YAP reporter expression activity (IC50 = 12.7 µM), endogenous target gene (e.g., CTGF and CYR61) expression, breast cancer cell growth (GI50 = 3.2 µM), and anchorage-independent growth in soft agar. Molecular docking analysis suggested that the newly synthesized compounds bound to interface 2 of TEAD had lower docking scores compared to the compounds that bind to interface 3; moreover, they were predicted to overlap with YAP. Therefore, we identified 11q as an attractive therapeutic agent for treating solid tumors overexpressing YAP/TAZ.

Elevated E200K Somatic Mutation of the Prion Protein Gene (PRNP) in the Brain Tissues of Patients with Sporadic Creutzfeldt-Jakob Disease (CJD).

Sporadic Creutzfeldt-Jakob disease (CJD) is a major human prion disease worldwide. CJD is a fatal neurodegenerative disease caused by an abnormal prion protein (PrPSc). To date, the exact etiology of sporadic CJD has not been fully elucidated. We investigated the E200K and V203I somatic mutations of the prion protein gene (PRNP) in sporadic CJD patients and matched healthy controls using pyrosequencing. In addition, we estimated the impact of somatic mutations on the human prion protein (PrP) using PolyPhen-2, PANTHER and PROVEAN. Furthermore, we evaluated the 3D structure and electrostatic potential of the human PrP according to somatic mutations using DeepView. The rates of PRNP K200 somatic mutation were significantly increased in the frontal cortex and hippocampus of sporadic CJD patients compared to the matched controls. In addition, the electrostatic potential of the human PrP was significantly changed by the K200 somatic mutation of the PRNP gene. To the best of our knowledge, this is the first report on an association of the PRNP K200 somatic mutation with sporadic CJD.

Creutzfeldt-Jakob Disease Incidence, South Korea, 2001-2019.

We found increasing trends of Creutzfeldt-Jakob disease (CJD) cases and annual incidence in South Korea during 2001-2019. We noted relatively low (5.7%) distribution of familial CJD. An unusually high percentage (≈1%) of patients were in the 30-39 age group, which should prompt a preemptive CJD control system.

Catalyzing Storytelling in Communication Infrastructure Theory: A Study of Local Ethnic Media.

Communication infrastructure theory (CIT) suggests that an ethnic enclave's communication infrastructure (CI) shapes the community's unique social processes that give rise to social determinants of health. A well-integrated CI in ethnic enclaves that includes community-based organizations (CBOs), local ethnic media, and resident networks is positively associated with residents' health outcomes. Through storytelling, CBOs and other community actors obtain and disseminate information, develop a sense of belonging to the community, and participate in problem-solving activities, including health-related ones. Local ethnic media can play an important role in building a network of neighborhood storytellers by catalyzing storytelling about local resources and problems. We propose three main categories of "catalyzing storytelling" by local ethnic media: 1) CBO stories, 2) geo-ethnic stories, and 3) presentation of root causes and solutions for community problems. This study examines the content of Boston Chinatown's local ethnic news media outlet, Sampan, to assess the three categories of catalyzing stories. We analyzed a total of 340 news articles and one interview with the editor. The findings showed that Sampan tells stories in all three categories. Based on our findings, we further develop the concept of catalyzing as a communication process in CIT. This new concept in CIT has practical implications for public health communication as it demonstrates a process through which local ethnic media can foster community engagement and health. Health communicators should seek opportunities to work collaboratively with local ethnic media in ways that will serve to catalyze community.

Surgical sequence in anterior column realignment with posterior osteotomy is important for degree of adult spinal deformity correction: advantages and indications for posterior to anterior sequence.

BACKGROUND: We hypothesized that posterior osteotomy prior to ACR (Anterior column realignment) through P-A-P surgical sequence would permit a greater correction for deformity corrective surgery than the traditional A-P sequence without posterior osteotomy. This study aimed to determine the impact of the P-A-P sequence on the restoration of lumbar lordosis (LL) compared to the A-P sequence in deformity corrective surgery for adult spinal deformity (ASD) patients and to identify the characteristics of patients who require this sequence.  METHODS: Between 2017 and 2019, 260 ASD patients who had undergone combined corrective surgery were reviewed retrospectively. This study included 178 patients who underwent posterior osteotomy before the ACR (P-A group) and 82 patients who underwent the A-P sequence (A-P group). Sagittal spinopelvic parameters were determined from pre- and postoperative whole-spine radiographs and compared between the groups. To find better indications for the P-A-P sequence, we conducted additional analysis on postoperative outcomes of patients in the A-P group.  RESULTS: The P-A group showed a significantly higher change in LL (53.7° vs. 44.3°, p < 0.001), C7 sagittal vertical axis (C7 SVA: 197.4 mm vs. 146.1 mm, p = 0.021), segmental lordosis (SL) L2/3 (16.2° vs. 14.4°, p = 0.043), SL L3/4 (16.2° vs. 13.8°, p = 0.004), and SL L4/5 (15.1° vs. 11.3°, p = 0.001) compared to the A-P group. At the final follow-up, pelvic incidence (PI) minus LL mismatch (PI - LL mismatch) was significantly higher in the A-P group (13.4° vs. 2.9°, p < 0.001). Stepwise logistic regression analysis showed that age ≥ 75 years (odds ratio [OR] = 2.151; 95% confidence interval [CI], 1.414-3.272; p < 0.001), severe osteoporosis (OR = 2.824; 95% CI, 1.481-5.381; p = 0.002), rigid lumbar curve with dynamic changes in LL < 10° (OR = 5.150; 95% CI, 2.296-11.548; p < 0.001), and severe facet joint osteoarthritis (OR = 4.513; 95% CI, 1.958-10.402; p < 0.001) were independent risk factors for PI - LL mismatch ≥ 10° after A-P surgery. CONCLUSION: P-A-P sequence for deformity corrective surgery in ASD offers greater LL correction than the A-P sequence. Indications for the procedure include patients aged ≥ 75 years, severe osteoporosis, rigid lumbar curve with dynamic change in LL < 10°, or more than four facet joints of Pathria grade 3 in the lumbar region.

Design, Synthesis and Biological Evaluation of 1,3,5-Triazine Derivatives Targeting hA1 and hA3 Adenosine Receptor.

Adenosine mediates various physiological activities in the body. Adenosine receptors (ARs) are widely expressed in tumors and the tumor microenvironment (TME), and they induce tumor proliferation and suppress immune cell function. There are four types of human adenosine receptor (hARs): hA1, hA2A, hA2B, and hA3. Both hA1 and hA3 AR play an important role in tumor proliferation. We designed and synthesized novel 1,3,5-triazine derivatives through amination and Suzuki coupling, and evaluated them for binding affinities to each hAR subtype. Compounds 9a and 11b showed good binding affinity to both hA1 and hA3 AR, while 9c showed the highest binding affinity to hA1 AR. In this study, we discovered that 9c inhibits cell viability, leading to cell death in lung cancer cell lines. Flow cytometry analysis revealed that 9c caused an increase in intracellular reactive oxygen species (ROS) and a depolarization of the mitochondrial membrane potential. The binding mode of 1,3,5-triazine derivatives to hA1 and hA3 AR were predicted by a molecular docking study.

Development of a chicken interferon-induced transmembrane protein 3 (IFITM3)-specific monoclonal antibody using phage display.

Interferon-induced transmembrane protein 3 (IFITM3) has potent antiviral activity against several viruses. Recent studies have reported that the chicken IFITM3 gene also plays a pivotal role in blocking viral replication, but these studies are considerably limited due to being conducted at the RNA level only. Thus, the development of a chicken IFITM3 protein-specific antibody is needed to validate the function of IFITM3 at the protein level. Epitope prediction was performed with the immune epitope database analysis resource (IEDB-AR) program. The epitope was validated by four in silico programs, Jped4, Clustal Omega, TMpred and SOSUI. Chicken IFITM3 protein-specific monoclonal antibodies were screened by enzyme-linked immunosorbent assay through affinity between recombinant IFITM3 protein and phage-displayed candidate antibodies. Validation of the reactivity of the chicken IFITM3 protein-specific antibody to chicken tissues was carried out using western blotting. We developed a chicken IFITM3 protein-specific monoclonal antibody using phage display. The reactivity of the antibody with peripheral chicken tissues was confirmed using western blotting. To the best of our knowledge, this was the first development of a chicken IFITM3 protein-specific monoclonal antibody using phage display.

The First Evaluation of Proteinase K-Resistant Prion Protein (PrPSc) in Korean Appendix Specimens.

Background and Objectives: Prion diseases are fatal neurodegenerative disorders caused by the abnormal proteinase K-resistant prion protein (PrPSc). Since variant Creutzfeldt-Jakob disease (CJD) was first reported in the United Kingdom (UK) in 1996, the occurrence of variant CJD has been reported in over 10 countries. To date, variant CJD has not been reported in Korea. However, the E211K somatic mutation in the prion protein gene (PRNP), which is related to bovine spongiform encephalopathy (BSE), was reported in Korean Holstein cattle, and atypical BSE, which is supposed to be sporadic BSE, has been occurring in many countries, including Japan and the USA. These results suggest that BSE may occur naturally in Korea. Thus, we performed a preemptive PrPSc test in appendix specimens to diagnose variant CJD in a Korean population. Materials and Methods: In the present study, we investigated CJD-related mutations and polymorphisms of the PRNP gene and carried out an examination on PrPSc in appendix specimens of Korean patients after appendectomy. Results: In all Korean appendix specimens tested, PrPSc bands were not detected. Conclusion: To the best of our knowledge, this was the first evaluation of PrPSc in Korean appendix specimens.

Large-scale lipidomic profiling identifies novel potential biomarkers for prion diseases and highlights lipid raft-related pathways.

Prion diseases are transmissible spongiform encephalopathies induced by the abnormally-folded prion protein (PrPSc), which is derived from the normal prion protein (PrPC). Previous studies have reported that lipid rafts play a pivotal role in the conversion of PrPC into PrPSc, and several therapeutic strategies targeting lipids have led to prolonged survival times in prion diseases. In addition, phosphatidylethanolamine, a glycerophospholipid member, accelerated prion disease progression. Although several studies have shown that prion diseases are significantly associated with lipids, lipidomic analyses of prion diseases have not been reported thus far. We intraperitoneally injected phosphate-buffered saline (PBS) or ME7 mouse prions into mice and sacrificed them at different time points (3 and 7 months) post-injection. To detect PrPSc in the mouse brain, we carried out western blotting analysis of the left hemisphere of the brain. To identify potential novel lipid biomarkers, we performed lipid extraction on the right hemisphere of the brain and liquid chromatography mass spectrometry (LC/MS) to analyze the lipidomic profiling between non-infected mice and prion-infected mice. Finally, we analyzed the altered lipid-related pathways by a lipid pathway enrichment analysis (LIPEA). We identified a total of 43 and 75 novel potential biomarkers at 3 and 7 months in prion-infected mice compared to non-infected mice, respectively. Among these novel potential biomarkers, approximately 75% of total lipids are glycerophospholipids. In addition, altered lipids between the non-infected and prion-infected mice were related to sphingolipid, glycerophospholipid and glycosylphosphatidylinositol (GPI)-anchor-related pathways. In the present study, we found novel potential biomarkers and therapeutic targets of prion disease. To the best of our knowledge, this study reports the first large-scale lipidomic profiling in prion diseases.

Communication Infrastructure in an Asian Immigrant Community.

The health benefits of having a supportive community and access to community resources are well documented and for many immigrant communities, community-based organizations (CBOs) play an important role by providing culturally competent services. The current study uses communication infrastructure theory (CIT) to examine the associations between connections to CBOs, civic engagement, and protective health behaviors within the context of Boston Chinatown's Chinese immigrant community. According to CIT, neighborhood communication resources encourage residents to engage in civic activities and health-related problem-solving behaviors. To assess these associations, data from a needs assessment survey (N = 360) were analyzed. Results showed that connections to CBOs had a positive association with total number of protective health behaviors. Civic engagement was not found to be associated with health behaviors. We also found no indirect effect of connections to CBOs on the protective health behaviors via civic engagement. These results carry important theoretical and practical implications.

Surgical correction for adult spinal deformity increases acetabular lateral coverage of femoral heads.

BACKGROUND: Studies explaining the relationship between hip and spine reported that spinal corrective surgery affected acetabular orientation and changes in pelvic tilt were capable of influencing radiographic measures of acetabular coverage. This study aimed to assess the change in coronal parameters for acetabular coverage as a result of adult spinal deformity (ASD) correction and to analyze the relationship between the postoperative changes in sagittal spinopelvic parameters and coronal acetabular coverage parameters. METHODS: Fifty-two consecutive patients who had undergone multilevel spinal surgical correction were enrolled and evaluated. Coronal acetabular coverage parameters included Tönnis angle (TA), lateral center edge angle (LCEA), and the angle of Sharp (SA). All radiographic parameters were evaluated at the preoperative and the postoperative 1 year. Paired t test was used to determine whether there were significant changes between the time points. Bivariate correlation and linear regression analysis were used to assess the relationship between the postoperative changes of spinal alignment and acetabular orientation. RESULTS: The surgical correction resulted in significant decrease of TA, increase of LCEA and SA, respectively (p < 0.001). The changes in pelvic tilt (PT) demonstrated weak correlation on TA (ß = 0.117, p < 0.001 for right; ß = 0.111, p < 0.001 for left). CONCLUSIONS: Although the surgical correction of ASD significantly changed PT resulting in increased acetabular lateral coverage parameters, the correlation between the changes of PT following sagittal correction of ASD and acetabular coverage parameters was low. TRIAL REGISTRATION: This study was retrospectively registered with approval by the institutional review board (IRB) of our institution (approval number: KHNMC-2020-10-010).

Use of iliac screw associated with more correction of lumbar lordosis than S2-alar-iliac screw for adult spinal deformity.

BACKGROUND: To date, there is a paucity of reports clarifying the change of spinopelvic parameters in patients with adult spinal deformity (ASD) who underwent long segment spinal fusion using iliac screw (IS) and S2-alar-iliac screw (S2AI) fixation. METHODS: A retrospective review of consecutive patients who underwent deformity correction surgery for ASD between 2013 and 2017 was performed. Patients were divided into two groups based on whether IS or S2AI fixation was performed. All radiographic parameters were measured preoperatively, immediately postoperatively, and the last follow-up. Demographics, intraoperative and clinical data were analyzed between the two groups. Additionally, the cohort was subdivided according to the postoperative change in pelvic incidence (PI): subgroup (C) was defined as change in PI ≥5° and subgroup (NC) with change < 5°. In subgroup analyses, the 2 different types of postoperative change of PI were directly compared. RESULTS: A total of 142 patients met inclusion criteria: 111 who received IS and 31 received S2AI fixation. The IS group (65.6 ± 26°, 39.8 ± 13.8°) showed a significantly higher change in lumbar lordosis (LL) and upper lumbar lordosis (ULL) than the S2AI group (54.4 ± 17.9°, 30.3 ± 9.9°) (p < 0.05). In subgroup (C), PI significantly increased from 53° preoperatively to 59° postoperatively at least 50% of IS cohort, with a mean change of 5.8° (p < 0.05). The clinical outcomes at the last follow-up were significantly better in IS group than in S2AI group in terms of VAS scores for back and leg. The occurrence of sacroiliac joint pain and pelvic screw fracture were significantly greater in S2AI group than in IS group (25.8% vs 9%, p < 0.05) and (16.1% vs 3.6%, p < 0.05). CONCLUSIONS: Compared with the S2AI technique, the IS technique usable larger cantilever force demonstrated more correction of lumbar lordosis, and possible increase in pelvic incidence. Further study is warranted to clarify the clinical impaction of these results.

How does long thoracolumbar realignment surgery of adult spinal kyphotic deformity affect lower extremity compensation? Using full body radiograph.

PURPOSE: By using full body radiograph, the aim of the current study was to elucidate the expected degree of lower extremity compensatory change after long thoracolumbar realignment surgery with adult spinal deformity patient who had normal or only mild osteoarthritis on lower extremities. METHODS: Two novel parameters were used for assessment of regional compensation of the lower extremity. The Pearson correlation test was used to assess the correlation of postoperative changes of lower extremity compensation with the other spinopelvic parameters. RESULTS: Overall, 113 spinal deformity patients (mean age was 54.5 years) were recruited and the average number of fused vertebrae was 13.3 ± 3.5. Except pelvic tilt (PT), postoperative sacrum-femur angle (SF) changes showed only moderate correlation with all angular spinopelvic parameters (r = 0.323-0.374; p < .001 to p = .001). Also C7 sagittal vertical axis showed no significant correlation with SF (p = .584-.621). However, postoperative changes of sagittal femur-tibia angle (SFT) reported strong correlation with all parameters evaluated (r = 0.455-0.586; p < .001 to p = .046). CONCLUSION: For adult spinal deformity patients who had normal or only mild osteoarthritis on the lower extremities underwent long thoracolumbar realignment surgery, the surgeon could expect improvement of compensatory change of the knee with correction of spinopelvic parameters. However, the degree of hip compensation improvement was relatively difficult to predict than that of the knee, except PT.

Phylogenetic and topological analyses of the bovine interferon-induced transmembrane protein (IFITM3).

Interferon-induced transmembrane protein 3 (IFITM3) plays a pivotal role in antiviral capacity in several species. However, to date, investigations of the IFITM3 protein in cattle have been rare. According to recent studies, interspecific differences in the IFITM3 protein result in several unique features of the IFITM3 protein relative to primates and birds. Thus, in the present study, we investigated the bovine IFITM3 protein based on nucleotide and amino acid sequences to find its distinct features. We found that the bovine IFITM3 gene showed a significantly different length and homology relative to other species, including primates, rodents and birds. Phylogenetic analyses indicated that the bovine IFITM3 gene and IFITM3 protein showed closer evolutionary distance with primates than with rodents. However, cattle showed an independent clade among primates, rodents and birds. Multiple sequence alignment of the IFITM3 protein indicated that the bovine IFITM3 protein contains 36 bovine-specific amino acids. Notably, the bovine IFITM3 protein was predicted to prefer inside-to-outside topology of intramembrane domain 1 (IMD1) and inside-to-outside topology of transmembrane domain 2 by TMpred and three membrane embedding domains according to the SOSUI system.

Evaluation of proteinase K-resistant prion protein (PrPres) in Korean native black goats carrying a potential scrapie-susceptible haplotype of the prion protein gene (PRNP).

Prion disease is a fatal neurodegenerative disease with a broad host range in humans and animals. It is caused by proteinase K-resistant prion protein (PrPres). In previous studies, a heterogeneous infection in Cervidae and Caprinae was reported. Chronic wasting disease (CWD) has been frequently reported as the only prion disease in Korea that occurs in livestock. Thus, there is a possibility of transmission of CWD to Korean native black goats. However, PrPres has not been investigated thus far in Korean native black goats. We found strong linkage disequilibrium between c.126G>A and c.414T>C (r2 = 1) and between c.718C>T and c.126G>A (r2 = 0.638). In addition, the haplotype GTGTAAAC (representing codons 42, 102, 127, 138, 143, 146, 218 and 240) showed the highest frequency with 45.1%. Among 41 Korean native black goats, 20 animals (48.78%) were homozygous for the susceptible haplotypes (histidine at codon 143, asparagine at codon 146 and arginine at codon 154). Interestingly, we did not detect PrPres bands in any of the tested animals, including the 20 animals carrying potential scrapie susceptible haplotypes.

No Association between Single Nucleotide Polymorphisms (SNPs) of the Interferon-Induced Transmembrane Protein 3 (IFITM3) Gene and the Susceptibility of Alzheimer's Disease (AD).

Background and Objectives: Alzheimer's disease (AD) is the most common progressive neurodegenerative disorder, characterized by the accumulation of amyloid-beta (Aß) in the brain. A recent study reported that the interferon-induced transmembrane protein 3 (IFITM3) protein plays a pivotal role in Aß processing by the γ-secretase complex. Since several single nucleotide polymorphisms (SNPs) of the IFITM3 gene are related to the function and expression levels of the IFITM3 gene, the relationship between genetic polymorphisms in the IFITM3 gene and susceptibility to AD needs to be investigated. Materials and Methods: We investigated the genotype and allele frequencies of IFITM3 polymorphisms in 177 AD patients and 233 matched healthy controls by amplicon sequencing. In addition, we compared the genotype, allele and haplotype frequencies between AD patients and matched controls and performed an association analysis. Results: There were no significant differences in the genotype, allele or haplotype frequency distributions of the IFITM3 polymorphisms between AD patients and matched controls. Conclusions: To the best of our knowledge, this is the first case-control association study of the IFITM3 gene in AD.

Ethnic variation in risk genotypes based on single nucleotide polymorphisms (SNPs) of the interferon-inducible transmembrane 3 (IFITM3) gene, a susceptibility factor for pandemic 2009 H1N1 influenza A virus.

The interferon-inducible transmembrane 3 (IFITM3) protein is an effector of the host innate immune system that shows defensive activity against a wide range of viruses, including the influenza A virus. Previous studies have reported that three transcription-related regulatory single nucleotide polymorphisms (SNPs), rs12252, rs34481144, and rs6598045, showed potent associations with the severity of pandemic influenza A 2009 infection and susceptibility to this virus, respectively. However, the distribution of the risk genotypes of these three SNPs according to ethnic background has remained elusive. In this study, we compared the genotype and allele frequencies of the IFITM3 polymorphisms among several ethnic groups including American, African, European, South Asian, and East Asian using chi-square test. In addition, we analyzed the worldwide distribution of risk genotypes for pandemic influenza A 2009 virus infection. We found that the genotype and allele distributions of the rs12252, rs34481144, and rs6598045 SNPs were significantly different among several ethnic groups. In addition, the risk genotypes of the IFITM3 polymorphisms were also significantly different worldwide. To the best of our knowledge, this was the first simultaneous estimation of the risk genotypes of the IFITM3 gene with respect to pandemic influenza A 2009 virus infection.