The First Genetic Characterization of the SPRN Gene in Pekin Ducks (Anas platyrhynchos domesticus).

Prion diseases are fatal neurodegenerative disorders characterized by an accumulation of misfolded prion protein (PrPSc) in brain tissues. The shadow of prion protein (Sho) encoded by the shadow of prion protein gene (SPRN) is involved in prion disease progress. The interaction between Sho and PrP accelerates the PrPSc conversion rate while the SPRN gene polymorphisms have been associated with prion disease susceptibility in several species. Until now, the SPRN gene has not been investigated in ducks. We identified the duck SPRN gene sequence and investigated the genetic polymorphisms of 184 Pekin ducks. We compared the duck SPRN nucleotide sequence and the duck Sho protein amino acid sequence with those of several other species. Finally, we predicted the duck Sho protein structure and the effects of non-synonymous single nucleotide polymorphisms (SNPs) using computational programs. We were the first to report the Pekin duck SPRN gene sequence. The duck Sho protein sequence showed 100% identity compared with the chicken Sho protein sequence. We found 27 novel SNPs in the duck SPRN gene. Four amino acid substitutions were predicted to affect the hydrogen bond distribution in the duck Sho protein structure. Although MutPred2 and SNPs&GO predicted that all non-synonymous polymorphisms were neutral or benign, SIFT predicted that four variants, A22T, G49D, A68T, and M105I, were deleterious. To the best of our knowledge, this is the first report about the genetic and structural characteristics of the duck SPRN gene.

Microstructural Evolution, Hardness and Wear Resistance of WC-Co-Ni Composite Coatings Fabricated by Laser Cladding.

This study investigated how process parameters of laser cladding affect the microstructure and mechanical properties of WC-12Co composite coating for use as a protective layer of continuous caster rolls. WC-Co powders, WC-Ni powders, and Ni-Cr alloy powder with various wear resistance characteristics were evaluated in order to determine their applicability for use as cladding materials for continuous caster roll coating. The cladding process was conducted with various parameters, including laser powers, cladding speeds, and powder feeding rates, then the phases, microstructure, and micro-hardness of the cladding layer were analyzed in each specimen. Results indicate that, to increase the hardness of the cladding layer in WC-Co composite coating, the dilution of the cladding layer by dissolution of Fe from the substrate should be minimized, and the formation of the Fe-Co alloy phase should be prevented. The mechanical properties and wear resistance of each powder with the same process parameters were compared and analyzed. The microstructure and mechanical properties of the laser cladding layer depend not only on the process parameters, but also on the powder characteristics, such as WC particle size and the type of binder material. Additionally, depending on the degree of thermal decomposition of WC particles and evolution of W distribution within the cladding layer, the hardness of each powder can differ significantly, and the wear mechanism can change.

Novel polymorphisms and genetic studies of the shadow of prion protein gene (SPRN) in pheasants.

Background: Prion diseases in mammals are caused by the structural conversion of the natural prion protein (PrPC) to a pathogenic isoform, the "scrapie form of prion protein (PrPSc)." Several studies reported that the shadow of prion protein (Sho), encoded by the shadow of prion protein gene (SPRN), is involved in prion disease development by accelerating the conformational conversion of PrPC to PrPSc. Until now, genetic polymorphisms of the SPRN gene and the protein structure of Sho related to fragility to prion disease have not been investigated in pheasants, which are a species of poultry. Methods: Here, we identified the SPRN gene sequence by polymerase chain reaction (PCR) and compared the SPRN gene and Sho protein sequences among various prion disease-susceptible and -resistant species to identify the distinctive genetic features of pheasant Sho using Clustal Omega. In addition, we investigated genetic polymorphisms of the SPRN gene in pheasants and analyzed genotype, allele, and haplotype frequencies, as well as linkage disequilibrium among the genetic polymorphisms. Furthermore, we used in silico programs, namely Mutpred2, MUpro and AMYCO, to investigate the effect of non-synonymous single nucleotide polymorphisms (SNPs). Finally, the predicted secondary and tertiary structures of Sho proteins from various species were analyzed by Alphafold2. Results: In the present study, we reported pheasant SPRN gene sequences for the first time and identified a total of 14 novel SNPs, including 7 non-synonymous and 4 synonymous SNPs. In addition, the pheasant Sho protein sequence showed 100% identity with the chicken Sho protein sequence. Furthermore, amino acid substitutions were predicted to affect the hydrogen bond distribution in the 3D structure of the pheasant Sho protein. Conclusion: To the best of our knowledge, this is the first report of the genetic and structural features of the pheasant SPRN gene.

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.

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.

No Association between SARS-CoV-2 Infection and the Polymorphism of the Toll-like Receptor 7 (TLR7) Gene in Female Population.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a single-stranded RNA virus. Toll-like receptor 7 (TLR7) recognizes single-stranded RNA viruses. The TLR7 gene plays a critical role in the human innate and adaptive immune response to SARS-CoV-2 infections. Genetic factors probably affect SARS-CoV-2 infection susceptibility. In the current study, our aim was to search for genetic variations associated with COVID-19 patients in the TLR7 gene of a Korean population. We designed five gene-specific primers to cover the coding region of the human TLR7 gene. Using amplicon sequencing, we screened the genetic polymorphisms in the coding region of the TLR7 gene in COVID-19 patients and healthy controls. The genotype frequencies, allele frequencies, and Hardy-Weinberg equilibrium (HWE) were examined. We identified a low-frequency synonymous single nucleotide polymorphism (SNP) (rs864058) in the coding region of the TLR7 gene. There were no significant differences in the genotype or allele frequencies of the TLR7 rs864058 polymorphism between COVID-19 female patients and healthy controls (p = 1.0). In conclusion, TLR7 (rs864058) polymorphism is low frequency in Korean populations and is not associated with SARS-CoV-2 infection.

The first report of polymorphisms of the prion protein gene (PRNP) in Pekin ducks (Anas platyrhynchos domestica).

Background: Prion diseases have been extensively reported in various mammalian species and are caused by a pathogenic prion protein (PrPSc), which is a misfolded version of cellular prion protein (PrPC). Notably, no cases of prion disease have been reported in birds. Single nucleotide polymorphisms (SNPs) of the prion protein gene (PRNP) that encodes PrP have been associated with susceptibility to prion diseases in several species. However, no studies on PRNP polymorphisms in domestic ducks have been reported thus far. Method: To investigate PRNP polymorphisms in domestic ducks, we isolated genomic DNA from 214 Pekin duck samples and sequenced the coding region of the Pekin duck PRNP gene. We analyzed genotype, allele, and haplotype distributions and linkage disequilibrium (LD) among the SNPs of the Pekin duck PRNP gene. In addition, we evaluated the effects of the one non-synonymous SNP on the function and structure of PrP using the PROVEAN, PANTHER, SNPs & GO, SODA, and AMYCO in silico prediction programs. Results: We found five novel SNPs, c.441 T > C, c.495 T > C, c.582A > G, c.710C > T(P237L), and c.729C > T, in the ORF region of the PRNP gene in 214 Pekin duck samples. We observed strong LD between c.441 T > C and c.582A > G (0.479), and interestingly, the link between c.495 T > C and c.729C > T was in perfect LD, with an r2 value of 1.0. In addition, we identified the five major haplotype frequencies: TTACC, CTGCC, CTACC, CCGCT, and CTATC. Furthermore, we found that the non-synonymous SNP, c.710C > T (P237L), had no detrimental effects on the function or structure of Pekin duck PrP. However, the non-synonymous SNP had deleterious effects on the aggregation propensity and solubility of Pekin duck PrP compared with wildtype Pekin duck PrP. Conclusion: To the best of our knowledge, this study is the first report on the genetic characteristics of PRNP SNPs in Pekin ducks.

Ions-Silica Percolated Ionic Dielectric Elastomer Actuator for Soft Robots.

Soft robotics systems are currently under development using ionic electroactive polymers (i-EAP) as soft actuators for the human-machine interface. However, this endeavor has been impeded by the dilemma of reconciling the competing demands of force and strain in i-EAP actuators. Here, the authors present a novel design called "ions-silica percolated ionic dielectric elastomer (i-SPIDER)", which exhibits ionic liquid-confined silica microstructures that effectively resolve the chronic issue of conventional i-EAP actuators. The i-SPIDER actuator demonstrates remarkable electromechanical conversion capacity at low voltage, thanks to improved ion accumulation facilitated by interpreting electrode polarization at the electrolyte-electrode interface. This approach concurrently enhances both strain (by approximately 1.52%) and force (by roughly 1.06 mN) even at low Young's modulus (merely 5.9 MPa). Additionally, by demonstrating arachnid-inspired soft robots endowed with user-desired tasks through control of various form factors, the development of soft robots using the i-SPIDER that can concomitantly enhance strain and force holds promise as a compelling avenue for ushering in the next generation of miniaturized, low-powered soft robotics.

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.

First report of a novel polymorphism and genetic characteristics of the leporine prion protein (PRNP) gene.

Transmissible spongiform encephalopathies (TSEs) have been reported in a broad spectrum of hosts. The genetic polymorphisms and characteristics of the prion protein (PRNP) gene have a vital impact on the development of TSEs. Notably, natural TSE infection cases have never been reported in rabbits, and genetic variations of the leporine PRNP gene have not been investigated to date. To identify leporine PRNP gene polymorphism, we performed amplicon sequencing in 203 rabbits. We report a novel single nucleotide polymorphism on the leporine PRNP gene. In addition, we performed a comparative analysis of amino acid sequences of prion protein (PrP) across several hosts using ClustalW2. Furthermore, we evaluated the effect of changes of unique leporine PrP amino acids with those conserved among various species using Swiss-Pdb Viewer. Interestingly, we found seven unique leporine amino acids, and the change of unique leporine amino acids with those conserved among other species, including S175N, Q221K, Q221R, A226Y, A230G, and A230S, was predicted to reduce hydrogen bonds in leporine PrP.

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.

Self-recovering passive cooling utilizing endothermic reaction of NH4NO3/H2O driven by water sorption for photovoltaic cell.

Power efficiency of photovoltaic cell is significantly affected by the cell temperature. Here, a self-recovering passive cooling unit is developed. The water-saturated zeolite 13X is coated on the back side of photovoltaic cell, and ammonium nitrate is dispersed as a layer to form a thin film. When heat is supplied, water is desorbed from zeolite 13X (latent cooling), and dissolves ammonium nitrate to induce endothermic reaction cooling. It is a reversible process that recovers itself at night. The unit works on the basis that the water sorption performance of porous materials is inversely proportional to temperature, and the solubility of endothermic reaction pairs increases proportionally with temperature. The average temperature of photovoltaic cell can be reduced by 15.1 °C, and the cooling energy density reaches 2,876 kJ/kg with average cooling power of 403 W/m2. We show that highly efficient passive cooling comprising inexpensive materials for photovoltaic cell could be achieved.

Impact of different nutritional approaches on sarcopenia: a protocol for systematic review and network meta-analysis.

Although it is known that proper nutrition is effective in managing sarcopenia, the most powerful nutrients have not yet been determined. This study is designed to investigate the effects of various nutritional approaches on muscle mass, muscle strength, and sarcopenia prevention in systematic reviews. In study design, network and pairwise meta-analyses of randomized clinical trials were considered. Clinical studies regarding the nutritional effects associated with the physiological activity of skeletal muscle and management of sarcopenia will be covered. The main outcomes will cover the following five elements: anti-fatigue impact with skeletal muscle, muscle atrophy prevention, differentiation level with skeletal muscular cell, anti-inflammatory effect, and muscle injury prevention. Authors will conduct the study selection, extracting data process, and methodological quality investigation.Systematic review registrationOSF registry (ethical approval number: https://osf.io/ye4q7 ).

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.

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.

No association of prion protein gene (PRNP) polymorphisms with susceptibility to the pandemic 2009 swine flu.

Background: The pandemic 2009 swine flu is a highly infectious respiratory disorder caused by H1N1 influenza A viruses. A recent study reported that knockout of the prion protein gene (PRNP) induced susceptibility and lethality in influenza A virus-infected mice. Objective: Thus, we examined the association between genetic variations of the PRNP gene and susceptibility to pandemic 2009 swine flu. Results: We did not find an association between PRNP polymorphisms and susceptibility to pandemic 2009 swine flu. Conclusions: To the best of our knowledge, this was the first evaluation of the association between PRNP polymorphisms and vulnerability to pandemic 2009 swine flu.

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.