The first report of single nucleotide polymorphisms in the open reading frame of the prion-like protein gene in rabbits.

Background: Natural cases of prion disease have not been reported in rabbits, and prior attempts to identify a prion conversion agent have been unsuccessful. However, recent applications of prion seed amplifying experimental techniques have sparked renewed interest in the potential susceptibility of rabbits to prion disease infections. Among several factors related to prion disease, polymorphisms within the prion-like protein gene (PRND), a member of the prion protein family, have been reported as significantly associated with disease susceptibility in various species. Therefore, our study aimed to investigate polymorphisms in the PRND gene of rabbits and analyze their genetic characteristics. Methods: Genomic DNA was extracted from 207 rabbit samples to investigate leporine PRND polymorphisms. Subsequently, amplicon sequencing targeting the coding region of the leporine PRND gene was conducted. Additionally, linkage disequilibrium (LD) analysis was employed to assess the connection within and between loci. The impact of non-synonymous single nucleotide polymorphisms (SNPs) on the Doppel protein was evaluated using PolyPhen-2. Results: We found nine novel SNPs in the leporine PRND gene: c.18A > G, c.76G > C, c.128C > T, c.146C > T, c.315A > G, c.488G > A, c.525G > C, c.544G > A, and c.579A > G. Notably, seven of these PRND SNPs, excluding c.525G > C and c.579A > G, exhibited strong LD values exceeding 0.3. In addition, LD analysis confirmed a robust link between PRNP SNP c.234C > T and PRND SNPs at c.525G > C and c.579A > G. Furthermore, according to PolyPhen-2 and SIFT analyses, the four non-synonymous SNPs were predicted to have deleterious effects on the function or structure of the Doppel protein. However, PANTHER and Missense3D did not indicate such effects. Conclusion: In this paper, we have identified novel SNPs in the rabbit PRND gene and predicted their potential detrimental effects on protein function or structure through four non-synonymous SNPs. Additionally, we observed a genetic linkage between SNPs in the PRND and PRNP genes. These findings may provide insights into understanding the characteristics of rabbits as partially resistant species. To the best of our knowledge, this study is the first to genetically characterize PRND SNPs in rabbits.

Determining the vertebra for pedicle subtraction osteotomy in surgical correction for ankylosing spondylitis with thoracolumbar kyphosis.

OBJECTIVE: This study aimed to provide a method for determining the apical vertebra for pedicle subtraction osteotomy (PSO) in corrective surgery for patients with ankylosing spondylitis (AS) with thoracolumbar kyphosis (TLK). METHODS: The medical records of AS patients with TLK who underwent PSO between May 2009 and August 2022 were retrospectively reviewed, and 235 patients were included in the study. Using the proposed method, choosing the vertebra based on Kim's apex (KA), which is defined as the farthest vertebra from a line drawn from the center of the T10 vertebral body to the midpoint of the S1 upper endplate, the authors analyzed 229 patients with apices at T12, L1, or L2 (excluding L3 because of the small sample size, n = 6). They divided all patients into two groups. Group A (n = 144) underwent PSO at the KA vertebra, while group B (n = 85) underwent PSO at a different level. Demographic and radiological data, including sagittal spinopelvic parameters of the entire spine, were collected. An additional analysis was performed on patients with the same KA vertebra. RESULTS: The vertebra distributions of patients based on KA were T12 (28 [12.2%]), L1 (119 [52.0%]), and L2 (82 [35.8%]). The corrections of sagittal vertical axis (SVA; 101.0 ± 48.5 mm vs 82.0 ± 53.8 mm, p = 0.010), global kyphosis (GK; 31.6° ± 10.0° vs 26.4° ± 10.5°, p = 0.005), and TLK (29.4° ± 10.2° vs 24.2° ± 12.9°, p = 0.012) in group A were significantly greater than those in group B, and there was no difference in the corrections of thoracic kyphosis (TK), lumbar lordosis, and pelvic incidence between the two groups. On further analysis, group A showed greater correction in TK (26.2° ± 13.7° vs 0.1° ± 8.1°, p = 0.013) for patients with T12 as the KA; greater improvements in SVA (101.5 ± 44.2 mm vs 73.4 ± 48.7 mm, p = 0.020), GK (30.6° ± 11.0° vs 25.0° ± 10.4°, p = 0.046), and TLK (32.6° ± 7.8° vs 26.7° ± 9.9°, p = 0.012) for those with L1 as the KA; and significant correction in TLK (30.0° ± 6.3° vs 4.3° ± 19.5°, p = 0.008) for patients with L2 as the KA, compared with group B. CONCLUSIONS: PSO at the apical vertebra provides a greater degree of correction of sagittal imbalance. The proposed method, selecting the vertebra based on KA, is easily reproducible for determining the apex level in AS patients with TLK.

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°.

Anterior Column Realignment Through Open Pre-posterior Release-Anterior-Posterior Fusion Versus Hybrid Minimally Invasive-Anterior-Posterior Fusion for Dynamic Sagittal Imbalance of the Spine.

STUDY DESIGN: Retrospective comparative study. OBJECTIVES: To investigate the clinical and radiological outcomes after anterior column realignment (ACR) through pre-posterior release-anterior-posterior surgery (PAP) and minimally invasive surgery -lateral lumbar interbody fusion (MIS-LLIF) using hybrid anterior-posterior surgery (AP). METHODS: A total of 91 patients who underwent ACR with long fusions from T10 vertebra to the sacropelvis with a follow-up period of at least 2 years after corrective surgery for adult spinal deformity were included and divided into two groups by surgical method: AP and PAP. AP was performed in 26 and PAP in 65 patients. Clinical outcomes and radiological parameters were investigated and compared. A further comparison was conducted after propensity score matching between the groups. RESULTS: The more increase of LL and decrease of PI-LL mismatch were observed in the PAP group than in the AP group postoperatively. After propensity score matching, total operation time and intraoperative bleeding were greater, and intensive care unit care and rod fracture were more frequent in the PAP group than in the AP group with statistical significance. Reoperation rate was higher in PAP (29.2%) than in AP (16.7%) without statistical significance. CONCLUSIONS: PAP provides a more powerful correction for severe sagittal malalignment than AP procedures. AP results in less intraoperative bleeding, operation time, and postoperative complications. Therefore, this study does not suggest that one treatment is superior to the other. LEVEL OF EVIDENCE: III.

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.

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.

Reoperation depending on time period following pedicle subtraction osteotomy for thoracolumbar kyphosis in patients with ankylosing spondylitis.

OBJECTIVE: The aim of this study was to investigate time-dependent rates and indications of unplanned reoperation and to evaluate the most common indication depending on the time interval after pedicle subtraction osteotomy (PSO) for correction of thoracolumbar kyphosis in patients with ankylosing spondylitis (AS). METHODS: A total of 321 consecutive patients with AS (284 men; mean age 43.8 years) with thoracolumbar kyphosis who underwent PSO were included. Patients who underwent reoperation after the index surgery were divided according to the duration of the follow-up period. RESULTS: A total of 51 patients (15.9%) underwent unplanned reoperations. The reoperation groups had greater preoperative and postoperative C7 sagittal vertical axis (SVA), and less lordotic postoperative osteotomy angle (-4.3° ± 18.6° vs -15.0° ± 13.7°, p < 0.001). The perioperative change in SVA was not significantly different between groups (-10.0 ± 7.1 cm vs -10.0 ± 5.1 cm, p = 0.970), while that in the osteotomy angle was significantly different (-22.4° ± 21.3° vs -30.0° ± 11.5°, p = 0.014). Most reoperations (45.1%; 23/51) were performed within 2 weeks of the initial operation. Within 2 weeks, the most common cause of reoperation was neurological deficit in 10 patients, with a cumulative reoperation rate of 3.2%. After 3 years, the most common complications were mechanical complications in 8 patients, accounting for 15.7% (8/51) of patients. Overall, the most common indications for reoperation were mechanical complications (17 patients; 5.3%), followed by neurological deficits (12 patients; 3.7%). CONCLUSIONS: PSO may be the most effective surgical procedure for the correction of thoracolumbar kyphosis in patients with AS. However, 51 patients (15.9%) required an unplanned reoperation.

Prion infection modulates hematopoietic stem/progenitor cell fate through cell-autonomous and non-autonomous mechanisms.

Studies of PrPC-derived prion disease generally focus on neurodegeneration. However, little is known regarding the modulation of hematopoietic stem progenitor cells (HSPCs) that express PrPC in prion infection. Among bone marrow (BM) hematopoietic cells, hematopoietic stem cells (HSCs) strongly express PrPC. A bioassay revealed the presence of misfolded prion protein (PrPSc) in BM cells derived from prion-infected mice; these BM cells demonstrated reproducible prion infectivity. At 5 months after infection with ME7, mice exhibited a significant decrease in the number of HSPCs. This decrease was mainly driven by increased apoptotic cell death, rather than cell cycle progression and senescence, in PrPC-positive but not PrPC-negative HSPC populations through a cell-autonomous mechanism. Notably, both PrPC-positive and PrPC-negative HSCs underwent cellular senescence, as indicated by high levels of senescence-associated factors and deficits in repopulation and self-renewal capacities at 7 months after infection. Senescence of HSCs occurred in the ME7-impaired BM microenvironment with aging phenotypes through non-cell autonomous mechanisms. These data provide novel evidence that prion infection differentially modulates HSC fate through both cell-autonomous and non-autonomous mechanisms.

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.

First report of structural characteristics and polymorphisms of the prion protein gene in raccoon dogs: The possibility of prion disease-resistance.

Prion diseases are fatal degenerative encephalopathies caused by misfolded prion protein (PrPSc) converted from normal prion protein (PrPC). Previous studies have reported that genetic polymorphisms of the prion protein gene (PRNP) play a critical role in susceptibility to prion diseases. In addition, prion disease-resistant animals showed unique structural features of prion protein (PrP) related to species-specific amino acids. However, investigations of genetic polymorphisms of the PRNP gene and structural characteristics of PrP have not been performed in raccoon dogs thus far. We investigated genetic polymorphisms of PRNP in 87 raccoon dogs using amplicon sequencing and analyzed the genotype, allele, haplotype frequencies, and linkage disequilibrium (LD) using Haploview version 4.2. In addition, we performed phylogenetic analysis and multiple sequence alignment (MSA) using MEGA X version 10.1.8 and Clustal X version 2.1, respectively. We estimated the impact of raccoon dog and Canidae family-specific amino acids using PolyPhen-2, PROVEAN, and AMYCO. Furthermore, we analyzed the effect of raccoon dog and Canidae family-specific amino acids using the AlphaFold2 and Swiss-PdbViewer programs. We found 4 novel single nucleotide polymorphisms (SNPs) of the raccoon dog PRNP gene. In addition, the raccoon dog PrP showed 99.61% identity and the closest genetic distance to dog PrP. Among the substitutions of Canidae-specific amino acids with interspecific amino acids, D163N showed increased amyloidogenic propensity, and R181H showed alterations of hydrogen bonds. Furthermore, electrostatic potentials were changed according to the substitutions of D163N and R181H. By comparing PrP between raccoon dogs and raccoons, R168K and K224R were found to be related to changes in hydrogen bonds, and K224R altered the electrostatic potential of raccoon dog PrP. In the present study, we first reported 4 novel synonymous SNPs of the raccoon dog PRNP gene. We also identified that the PrP of raccoon dog has high homology (99.61%) with PrP of dog, which is a prion-resistant animal. In addition, raccoon dog PrP-specific amino acids are related to low amyloid propensity and inherent characteristics of 3D structure of raccoon dog PrP compared to the PrP of prion-susceptible species.

Cephalomedullary Nailing versus Dynamic Hip Screw Fixation in Basicervical Femoral Neck Fracture: A Systematic Review and Meta-Analysis.

PURPOSE: Although many studies have reported the use of dynamic hip screws (DHS) and cephalomedullary nailing (CMN) for basicervical femoral neck fracture (BFNF), no clear treatment protocols have been recommended. The present study aimed to compare the surgical outcomes associated with DHS and CMN to determine the appropriate fixation method for BFNF. MATERIALS AND METHODS: We systematically searched MEDLINE, Embase, and the Cochrane Library for studies published up to January 9, 2021 that compared the treatment outcomes between CMN and DHS in BFNF. The primary outcomes of the present meta-analysis were fracture union time, postoperative cut-out rate, and reoperation rate. RESULTS: We included seven studies involving 353 cases of BFNF in our review. Of these, 206 patients were treated using CMN, and DHS were utilized in 147 patients. In a pooled analysis, the DHS group required a longer time to achieve fracture union compared to the CMN group [mean difference (MD): -0.41; 95% confidence interval (CI): -0.70, -0.12; p=0.006; I²=0%]. However, the cut-out and reoperation rates exhibited no statistically significant differences between the DHS and CMN groups [cut-out odds ratio (OR): 0.54; 95% CI: 0.10, 2.82; p=0.47; I²=24%, reoperation rate OR: 0.65; 95% CI: 0.15, 2.86; p=0.57; I²=19%, respectively]. CONCLUSION: Stable fixation using DHS and CMN does not show a significant clinical or radiographical difference in BFNF, and the implant can be selected based on the surgeon's preference.

Novel Polymorphisms and Genetic Characteristics of the Prion Protein Gene in Pheasants.

Transmissible spongiform encephalopathies (TSEs) also known as prion diseases, are fatal neurodegenerative diseases. Prion diseases are caused by abnormal prion protein (PrPSc) derived from normal prion protein (PrPC), which is encoded by the prion protein gene (PRNP). Prion diseases have been reported in several mammals. Notably, chickens, one species of bird, have not been reported to develop prion diseases and showed resistance to bovine spongiform encephalopathy (BSE) infection. However, genetic polymorphisms of the PRNP gene and protein structure of the prion protein (PrP) related to vulnerability to prion diseases have not been investigated in pheasants, another species of bird. We performed amplicon sequencing of the pheasant PRNP gene to identify genetic polymorphisms in 148 pheasants. We analyzed the genotype, allele and haplotype frequencies of the pheasant PRNP polymorphisms. In addition, we evaluated the effect of genetic polymorphisms of the pheasant PRNP gene on pheasant PrP by the AMYCO, PROVEAN, PolyPhen-2 and PANTHER softwares. Furthermore, we compared the amino acid sequences of tandem repeat domains and secondary and tertiary structures of prion proteins (PrPs) among several animals. Finally, we investigated the impact of non-synonymous single nucleotide polymorphisms (SNPs) on hydrogen bonds and tertiary structures of pheasant PrP by Swiss PDB viewer software. We identified 34 novel genetic polymorphisms of the pheasant PRNP gene including 8 non-synonymous SNPs and 6 insertion/deletion polymorphisms. Among the non-synonymous SNPs, the L23F, G33C and R177Q SNPs showed that they could have a deleterious effect on pheasant PrP. In addition, the R177Q SNP was predicted to show an increase in amyloid propensity and a reduction in hydrogen bonds of pheasant PrP. Among the insertion/deletion polymorphisms, c.163_180delAACCCGGGGTATCCCCAC showed that it could have a detrimental effect on pheasant PrP. Furthermore, secondary and tertiary structures of pheasant PrP were predicted to have structures similar to those of chicken PrP. To the best of our knowledge, this is the first study on genetic polymorphisms of the pheasant PRNP gene.

Spadework for Establishing Integrative Enhanced Recovery Program After Spine Surgery: Web-Based Survey Assessing Korean Medical Doctors' Perspectives.

Introduction: Efforts are necessary to promote postoperative patient management to reduce complications or side effects, particularly those adapted to spinal surgery. Considering compatible medical system in Korea, the study objective is to report the opinions of Korean medical doctors regarding integrative enhanced recovery after spine surgery. Methods: From December 2020 to January 2021, members of the Korean Medical Association were asked to complete an online questionnaire regarding an integrative enhanced recovery program after spine surgery. A total of 726 participants responded to the survey. Results: Approximately half of the respondents had more than 10 years of medical experience in the Korean health-care system, and 58.29% were affiliated with primary Korean medical clinics. The majority of respondents were not aware of the ERAS program (N = 412, 79.08%) but said that patient management would be advanced from the establishment of a postoperative medical program that reflected an integrated medical perspective (N = 505, 96.92%). Furthermore, Korean medical professionals believe that Korean medical interventions should play a major role in the pain management and digestive improvement sections of the upcoming postoperative program. Moreover, respondents claimed that Korean traditional medical modalities such as acupuncture, moxibustion, cupping, and herbal decoction should be included in the program. Discussion/Conclusion: Responses collected from the present study can be used as a spadework for future studies. A study on the development of a comprehensive postoperative program that reflects the perspectives of patients and conventional medical doctors is needed.

Four Times of Relapse of Plasmodium vivax Malaria Despite Primaquine Treatment in a Patient with Impaired Cytochrome P450 2D6 Function.

Plasmodium vivax exhibits dormant liver-stage parasites, called hypnozoites, which can cause relapse of malaria. The only drug currently used for eliminating hypnozoites is primaquine. The antimalarial properties of primaquine are dependent on the production of oxidized metabolites by the cytochrome P450 isoenzyme 2D6 (CYP2D6). Reduced primaquine metabolism may be related to P. vivax relapses. We describe a case of 4 episodes of recurrence of vivax malaria in a patient with decreased CYP2D6 function. The patient was 52-year-old male with body weight of 52 kg. He received total gastrectomy and splenectomy 7 months before the first episode and was under chemotherapy for the gastric cancer. The first episode occurred in March 2019 and each episode had intervals of 34, 41, and 97 days, respectively. At the first and second episodes, primaquine was administered as 15 mg for 14 days. The primaquine dose was increased with 30 mg for 14 days at the third and fourth episodes. Seven gene sequences of P. vivax were analyzed and revealed totally identical for all the 4 samples. The CYP2D6 genotype was analyzed and intermediate metabolizer phenotype with decreased function was identified.

First report of a strong association between genetic polymorphisms of the prion protein gene (PRNP) and susceptibility to chronic wasting disease in sika deer (Cervus nippon).

Prion diseases are incurable neurodegenerative disorders caused by proteinase K-resistant prion protein (PrPSc ) derived from normal prion protein (PrPC ) encoded by the prion protein gene (PRNP). Although the cervid PRNP gene plays a pivotal role in the pathological mechanism of chronic wasting disease (CWD), there is no existing association analysis between susceptibility to CWD and genetic polymorphisms of the PRNP gene in sika deer. We investigated genetic polymorphisms of the PRNP gene using amplicon sequencing in sika deer. In addition, to identify a genetic susceptibility factor, we compared the genotype, allele and haplotype frequencies of the PRNP gene between CWD-positive and CWD-negative sika deer. Furthermore, to assess the effect of the genetic polymorphisms on sika deer prion protein (PrP), we performed in silico analysis using PolyPhen-2, PROVEAN and AMYCO. Finally, we analysed the tertiary structure and electrostatic potential of sika deer PrP based on single nucleotide polymorphisms (SNPs) using the SWISS-MODEL and Swiss-PdbViewer programs. We found a total of 24 SNPs of the PRNP gene, including 22 novel SNPs (10 synonymous SNPs and 12 nonsynonymous SNPs), in sika deer. Among the nonsynonymous SNPs, we found a strong association of susceptibility to CWD with c.56G > A (Ser19Asn). In addition, we found that c.56G > A (Ser19Asn), c.296A > T (His99Leu) and c.560T > A (Val187Asp) were predicted to have damaging effects on sika deer PrP. Furthermore, we observed significant alterations in the electrostatic potential of sika deer PrP by genetic polymorphisms of the 187Asp allele. To the best of our knowledge, this was the first association study between genetic polymorphisms of the PRNP gene and susceptibility to CWD in sika deer.

Improvements in lower-extremity patient-reported outcomes after lumbar interbody fusion.

OBJECTIVE: Recently, new patient-reported outcome measures (PROMs) of the spine were designed to overcome the limitations of previous spinal PROMs and to consider the whole spine as a single kinetic functional unit. Owing to the significance of spine-hip-knee and global body balance, the spine and lower extremities cannot be considered separately. However, no reports have evaluated lower-extremity functional outcome using PROMs after lumbar spine surgery. The authors aimed to elucidate changes in hip and knee PROMs after lumbar interbody fusion and to evaluate the sagittal spinopelvic radiographic parameters that were most strongly correlated with lower-extremity PROMs. METHODS: In 2018, the authors consecutively evaluated patients who underwent lumbar interbody fusion surgery with at most three levels. Preoperative and 1-year postoperative clinical and radiographic data were assessed. Spinal functional outcomes were measured with the Oswestry Disability Index (ODI), visual analog scale (VAS) for pain, and Scoliosis Research Society-22r (SRS-22r) questionnaire. Lower-extremity functional outcomes were evaluated with the Harris Hip Score (HHS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Linear regression was used to evaluate the relationship between spinal and lower-extremity PROMs and spinopelvic radiographic parameters. RESULTS: The authors enrolled 67 patients, with a mean age of 66.4 years. The average number of surgical levels was 1.7. All assessed PROMs improved significantly after surgery (p < 0.001 for ODI, p < 0.001 for VAS, p = 0.017 for SRS-22r, p = 0.042 for HHS, and p = 0.033 for WOMAC). Spinopelvic parameters, including lumbar lordosis (LL), pelvic tilt (PT), C7 sagittal vertical axis, and sagittal radiographic parameters of hip and knee, significantly improved after surgery. On linear regression analysis, HHS and WOMAC correlated with LL and PT, respectively (ß = 0.554 and p = 0.043 for correlation of HHS with LL; ß = 1.573 and p = 0.021 for correlation of WOMAC with PT). CONCLUSIONS: The current study demonstrated that lumbar fusion surgery may induce postoperative improvements in lower-extremity functional and radiological outcomes. However, among radiographic parameters, changes in LL and PT were the most strongly associated with lower-extremity PROMs.

Morphological change of the posterior pole following the horizontal strabismus surgery with swept source optical coherence tomography.

Extraocular muscle movement during strabismus surgery causes changes in eyeball shape. Because extraocular muscle insertion is in front of the equator, it is thought that changes due to strabismus surgery mainly occur in the anterior segment. However, changes in the posterior segment of eye may also occur, which may also result in changes in refractive error after strabismus surgery. Using a 3-dimensional reconstruction technique (en face imaging) of the swept source optical coherence tomography, we determined and quantitatively measured the posterior polar change. The deepest interface between Bruch's membrane and the choroid could be identified as the deepest point of the eyeball (DPE), and the location of the DPE relative to the optic disc and the fovea was measured. After lateral rectus muscle recession, the DPE moved away from the fovea, but after medial rectus muscle recession, the DPE moved toward the fovea. The amount of DPE movement differed by age and preoperative refractive error. Our findings suggest that the positional shift of the rectus muscle in horizontal strabismus surgery causes a structural change in the posterior segment of the eye, and the postoperative refractive changes may be related to this shift.

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).

Regulatory Single Nucleotide Polymorphism of the Bovine IFITM3 Gene Induces Differential Transcriptional Capacities of Hanwoo and Holstein Cattle.

Interferon-induced transmembrane protein 3 (IFITM3), a crucial effector of the host's innate immune system, prohibits an extensive range of viruses. Previous studies have reported that single nucleotide polymorphisms (SNPs) of the IFITM3 gene are associated with the expression level and length of the IFITM3 protein and can impact susceptibility to infectious viruses and the severity of infection with these viruses. However, there have been no studies on polymorphisms of the bovine IFITM3 gene. In the present study, we finely mapped the bovine IFITM3 gene and annotated the identified polymorphisms. We investigated polymorphisms of the bovine IFITM3 gene in 108 Hanwoo and 113 Holstein cattle using direct sequencing and analyzed genotype, allele, and haplotype frequencies and linkage disequilibrium (LD) between the IFITM3 genes of the two cattle breeds. In addition, we analyzed transcription factor-binding sites and transcriptional capacity using PROMO and luciferase assays, respectively. Furthermore, we analyzed the effect of a nonsynonymous SNP of the IFITM3 gene using PolyPhen-2, PANTHER, and PROVEAN. We identified 23 polymorphisms in the bovine IFITM3 gene and found significantly different genotype, allele, and haplotype frequency distributions and LD scores between polymorphisms of the bovine IFITM3 gene in Hanwoo and Holstein cattle. In addition, the ability to bind the transcription factor Nkx2-1 and transcriptional capacities were significantly different depending on the c.-193T > C allele. Furthermore, nonsynonymous SNP (F121L) was predicted to be benign. To the best of our knowledge, this is the first genetic study of bovine IFITM3 polymorphisms.

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.