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1.
Front Genet ; 14: 1195213, 2023.
Article in English | MEDLINE | ID: mdl-37424726

ABSTRACT

Background: Nasal polyps (NP) are benign inflammatory growths of nasal and paranasal sinus mucosa that can substantially impair patients' quality of life by various symptoms such as nasal obstruction, insomnia, and anosmia. NP often relapse even after surgical treatment, and the curative therapy would be challenging without understanding the underlying mechanisms. Genome wide association studies (GWASs) on NP have been conducted; however, few genes that are causally associated with NP have been identified. Methods: We aimed to prioritize NP associated genes for functional follow-up studies using the summary data-based Mendelian Randomization (SMR) and Bayesian colocalization (COLOC) methods to integrate the summary-level data of the GWAS on NP and the expression quantitative trait locus (eQTL) study in blood. We utilized the GWAS data including 5,554 NP cases and 258,553 controls with 34 genome-wide significant loci from the FinnGen consortium (data freeze 8) and the eQTL data from 31,684 participants of predominantly European ancestry from the eQTLGen consortium. Results: The SMR analysis identified several genes including TNFRSF18, CTSK, and IRF1 that were associated with NP due to not linkage but pleiotropy or causality. The COLOC analysis strongly suggested that these genes and the trait of NP were affected by shared causal variants, and thus were colocalized. An enrichment analysis by Metascape suggested that these genes might be involved in the biological process of cellular response to cytokine stimulus. Conclusion: We could prioritize several NP associated genes including TNFRSF18, CTSK, and IRF1 for follow-up functional studies in future to elucidate the underlying disease mechanisms.

2.
Article in English | MEDLINE | ID: mdl-36399588

ABSTRACT

Forearm amputees can use body-powered hooks and myoelectric hands for their daily activities. The body-powered hooks are suitable for delicate manipulation. However, their appearance is not always preferred by amputees, and a harness to pull a control cable is not easy to wear. Although the myoelectric hands have a natural appearance similar to the human hand and can be intuitively controlled by a myoelectric control system, they are not easy to try out and are heavy. This paper reports on the Finch, a prosthetic arm with three opposing fingers controlled by a muscle bulge. The aim of developing the Finch is to realize a lightweight prosthetic arm that is easy to wear and use. Three opposing fingers are controlled according to the degree of muscle bulge measured with a muscle bulge sensor on the user's forearm caused by muscle contraction. A supporter socket, consisting of a resin socket frame and a fabric supporter, allows easy fitting. A simple design using a linear actuator and 3D-printed parts achieved light weight (330 g) and low cost. Six functional tests and user tests using Southampton Hand Assessment Procedure showed that the Finch had a practical function that could be used in daily activities.


Subject(s)
Amputees , Artificial Limbs , Finches , Humans , Animals , Arm , Prosthesis Design , Fingers , Muscles
3.
Front Endocrinol (Lausanne) ; 13: 1014882, 2022.
Article in English | MEDLINE | ID: mdl-36568068

ABSTRACT

Background: Observational studies suggested that type 2 diabetes mellitus (T2DM) was associated with an increased risk of coronavirus disease 2019 (COVID-19). However, Mendelian randomization (MR) studies in the European population failed to find causal associations, partly because T2DM was pleiotropically associated with body mass index (BMI). We aimed to estimate the causal effects of T2DM on COVID-19 outcomes in the East Asian (EAS) population using a two-sample MR approach. Methods: We obtained summary statistics from a genome-wide association study (GWAS) that included 433,540 EAS participants as the exposure dataset for T2DM risk and from COVID-19 Host Genetics Initiative GWAS meta-analyses (round 7) of EAS ancestry as the outcome dataset for COVID-19 susceptibility (4,459 cases and 36,121 controls), hospitalization (2,882 cases and 31,200 controls), and severity (794 cases and 4,862 controls). As the main MR analysis, we performed the inverse variance weighted (IVW) method. Moreover, we conducted a series of sensitivity analyses, including IVW multivariable MR using summary statistics for BMI from a GWAS with 158,284 Japanese individuals as a covariate. Results: The IVW method showed that the risk of T2DM significantly increased the risk of COVID-19 susceptibility (odds ratio [OR] per log (OR) increase in T2DM, 1.11; 95% confidence interval [CI], 1.02-1.20; P = 0.014) and hospitalization (OR, 1.15; 95% CI, 1.04-1.26; P = 0.005), although the risk of severity was only suggestive. Moreover, IVW multivariable MR analysis indicated that the causal effects of T2DM on COVID-19 outcomes were independent of the effect of BMI. Conclusions: Our MR study indicated for the first time that genetically predicted T2DM is a risk factor for SARS-CoV-2 infection and hospitalized COVID-19 independent of obesity in the EAS population.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Humans , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/genetics , East Asian People , Genome-Wide Association Study , COVID-19/epidemiology , COVID-19/genetics , SARS-CoV-2
4.
PLoS One ; 16(12): e0261020, 2021.
Article in English | MEDLINE | ID: mdl-34898631

ABSTRACT

Chronic kidney disease (CKD) and atrial fibrillation are both major burdens on the health care system worldwide. Several observational studies have reported clinical associations between CKD and atrial fibrillation; however, causal relationships between these conditions remain to be elucidated due to possible bias by confounders and reverse causations. Here, we conducted bidirectional two-sample Mendelian randomization analyses using publicly available summary statistics of genome-wide association studies (the CKDGen consortium and the UK Biobank) to investigate causal associations between CKD and atrial fibrillation/flutter in the European population. Our study suggested a causal effect of the risk of atrial fibrillation/flutter on the decrease in serum creatinine-based estimated glomerular filtration rate (eGFR) and revealed a causal effect of the risk of atrial fibrillation/flutter on the risk of CKD (odds ratio, 9.39 per doubling odds ratio of atrial fibrillation/flutter; 95% coefficient interval, 2.39-37.0; P = 0.001), while the causal effect of the decrease in eGFR on the risk of atrial fibrillation/flutter was unlikely. However, careful interpretation and further studies are warranted, as the underlying mechanisms remain unknown. Further, our sample size was relatively small and selection bias was possible.


Subject(s)
Atrial Fibrillation/complications , Atrial Flutter/etiology , Renal Insufficiency, Chronic/etiology , Atrial Fibrillation/genetics , Genome-Wide Association Study , Glomerular Filtration Rate , Humans , Mendelian Randomization Analysis , Polymorphism, Single Nucleotide , Renal Insufficiency, Chronic/genetics , Risk Assessment
5.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 4670-4673, 2021 11.
Article in English | MEDLINE | ID: mdl-34892255

ABSTRACT

Table tennis is a popular sport for forearm amputees. However, forearm amputees with limited pronation and supination movements cannot switch the racket angle properly for forehand and backhand drives. This paper reports a table tennis prosthetic hand controlled based on distance measurement using a ToF Sensor. The developed hand can switch the racket angle between forehand drive and backhand drive based on the distance between the wrist and the trunk or upper arm measured by the ToF sensor attached to an electric wrist. The participant with forearm amputation could play table tennis with the developed hand in the test play. The racket angle was switched to the appropriate angle for the forehand drive and the backhand drive, and the participant could return a ball 6.3 times in 10 seconds. The satisfaction of the participant with the prosthetic hand was good.


Subject(s)
Tennis , Biomechanical Phenomena , Hand , Humans , Upper Extremity , Wrist Joint
6.
BMC Med Genomics ; 14(1): 269, 2021 11 13.
Article in English | MEDLINE | ID: mdl-34774031

ABSTRACT

BACKGROUND: As the number of COVID-19 deaths continues to rise worldwide, the identification of risk factors for the disease is an urgent issue, and it remains controversial whether atherogenic lipid-related traits including serum apolipoprotein B, low-density lipoprotein (LDL)-cholesterol, and triglyceride levels, are risk factors. The aim of this study was to estimate causal effects of lipid-related traits on COVID-19 risk in the European population using a two-sample Mendelian randomization (MR) approach. METHODS: We used summary statistics from a genome-wide association study (GWAS) that included 441,016 participants from the UK Biobank as the exposure dataset of lipid-related traits and from COVID-19 Host Genetics Initiative GWAS meta-analyses of European ancestry as the outcome dataset for COVID-19 susceptibility (32,494 cases and 1,316,207 controls), hospitalization (8316 cases and 1,549,095 controls), and severity (4792 cases and 1,054,664 controls). We performed two-sample MR analyses using the inverse variance weighted (IVW) method. As sensitivity analyses, the MR-Egger regression, weighted median, and weighted mode methods were conducted as were leave-one-out sensitivity analysis, the MR-PRESSO global test, PhenoScanner searches, and IVW multivariable MR analyses. A P value below 0.0055 with Bonferroni correction was considered statistically significant. RESULTS: This MR study suggested that serum apolipoprotein B or LDL-cholesterol levels were not significantly associated with COVID-19 risk. On the other hand, we inferred that higher serum triglyceride levels were suggestively associated with higher risks of COVID-19 susceptibility (odds ratio [OR] per standard deviation increase in lifelong triglyceride levels, 1.065; 95% confidence interval [CI], 1.001-1.13; P = 0.045) and hospitalization (OR, 1.174; 95% CI, 1.04-1.33; P = 0.012), and were significantly associated with COVID-19 severity (OR, 1.274; 95% CI, 1.08-1.50; P = 0.004). Sensitivity and bidirectional MR analyses suggested that horizontal pleiotropy and reverse causation were unlikely. CONCLUSIONS: Our MR study indicates a causal effect of higher serum triglyceride levels on a greater risk of COVID-19 severity in the European population using the latest and largest GWAS datasets to date. However, as the underlying mechanisms remain unclear and our study might be still biased due to possible horizontal pleiotropy, further studies are warranted to validate our findings and investigate underlying mechanisms.


Subject(s)
Apolipoprotein B-100 , COVID-19 , Cholesterol, LDL , Genetic Predisposition to Disease , Quantitative Trait, Heritable , SARS-CoV-2/metabolism , Triglycerides , Apolipoprotein B-100/blood , Apolipoprotein B-100/genetics , COVID-19/blood , COVID-19/genetics , Cholesterol, LDL/blood , Cholesterol, LDL/genetics , Female , Genome-Wide Association Study , Humans , Male , Mendelian Randomization Analysis , Risk Factors , Severity of Illness Index , Triglycerides/blood , Triglycerides/genetics
7.
Front Public Health ; 9: 673451, 2021.
Article in English | MEDLINE | ID: mdl-34150709

ABSTRACT

Observational studies have reported that the severity of COVID-19 depends not only on physical conditions but also on socioeconomic status, including educational level. Because educational attainment (EA), which measures the number of years of schooling, is moderately heritable, we investigated the causal association of EA on the risk of COVID-19 severity using the Mendelian randomization (MR) approach. A two-sample MR analysis was performed using publicly available summary-level data sets of genome-wide association studies (GWASs). A total of 235 single-nucleotide polymorphisms (SNPs) were extracted as instrumental variables for the exposure of EA from the Social Science Genetic Association Consortium GWAS summary data of 766,345 participants of European ancestry. The effect of each SNP on the outcome of COVID-19 severity risk was obtained from the GWAS summary data of 1,059,456 participants of European ancestry gathered from the COVID-19 Host Genetics Initiative. Using inverse variance weighted method, our MR study shows that EA was significantly associated with a lower risk of COVID-19 severity (odds ratio per one standard deviation increase in years of schooling, 0.540; 95% confidence interval, 0.376-0.777, P = 0.0009). A series of sensitivity analyses showed little evidence of bias. In conclusion, we show for the first time using a two-sample MR approach the associations between higher EA and the lower risk of COVID-19 severity in the European population. However, the genetic or epidemiological mechanisms underlying the association between EA and the risk of COVID-19 severity remain unknown, and further studies are warranted to validate the MR findings and investigate underlying mechanisms.


Subject(s)
COVID-19 , Mendelian Randomization Analysis , Genome-Wide Association Study , Humans , Polymorphism, Single Nucleotide , SARS-CoV-2
8.
Medicine (Baltimore) ; 99(50): e22418, 2020 Dec 11.
Article in English | MEDLINE | ID: mdl-33327224

ABSTRACT

Hypertension (HT) has recently been defined as a systolic blood pressure (BP) of ≥130 mm Hg and/or a diastolic BP of ≥80 mm Hg. It is important to further understand the pathophysiology of essential HT as its proportion is larger among most of the diagnosed HT cases. The apelin and apelin receptor (APLNR) are known to play roles in regulating BP, but the putative associations of single nucleotide polymorphisms in the APLNR gene with the risk of development of essential HT have not yet been fully investigated. Herein, we conducted a meta-analysis to investigate the relationship between single nucleotide polymorphisms in the APLNR gene and the risk of essential HT.We conducted a search in the PubMed and Web of Science databases for eligible studies. The pooled odds ratios (ORs) with their 95% confidence intervals (CI) were calculated using random-effects models when heterogeneity was expected across the studies. Otherwise, fixed-effect models were used.Regarding the SNP rs7119375, 5 studies were analyzed, which included a total of 3567 essential HT patients and 3256 healthy controls. Four of the 5 studies were from China and 1 was from Mexico. The meta-analysis showed the existence of a significant association between the AA genotype of rs7119375 and the risk of developing essential HT in the Chinese population, as determined using additive and recessive models (OR, 2.11; 95% CI, 1.12-3.96; I = 86% for AA vs GG. OR, 1.53; 95% CI, 1.21-1.94; I = 28% for AA vs AG. OR, 1.88; 95% CI, 1.13-3.12; I = 79% for AA vs AG + GG).Our study showed, for the first time, the existence of an association between rs7119375 and the risk of development of essential HT in the Chinese population, although the sample size was small and there was considerable population heterogeneity. The apelin/APLNR system could be a novel therapeutic target for the treatment of essential HT, and more studies are warranted to further investigate the association.


Subject(s)
Apelin Receptors/genetics , Essential Hypertension/genetics , Polymorphism, Single Nucleotide/genetics , Asian People/genetics , Case-Control Studies , China/epidemiology , Essential Hypertension/diagnosis , Essential Hypertension/physiopathology , Female , Genotype , Humans , Male , Mexico/epidemiology , Risk Factors
9.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 4947-4950, 2020 07.
Article in English | MEDLINE | ID: mdl-33019097

ABSTRACT

Electric prosthetic hands have problems of heavyweight, unsuitability for working near water, and driving noise. Although body-powered prosthetic hands solve these problems, they have operability and wearability problems related to a cable control system. In this paper, we report a prosthetic gripper with three opposing fingers driven by a hydraulic actuator without electrical components. The three fingers are controlled simultaneously by pushing the lever of an operating interface mounted on the user's upper arm on the affected side. The hydraulic actuator enables users to open the fingers with a force of 16.6 N. The operating interface can be worn without a harness. The total weight is 316 g. Grasping tests of abstract and daily objects in which two amputees participated demonstrated that two amputees were able to grasp various objects. Quietness was also confirmed by them.


Subject(s)
Amputees , Fingers , Hand , Hand Strength , Humans , Prosthesis Design
10.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 4963-4966, 2020 07.
Article in English | MEDLINE | ID: mdl-33019101

ABSTRACT

Prosthetic hands are developed to replace lost hands. However, it has been hard to ensure the same level grasping and manipulating objects as human hands and the cosmetic appearance is also important. In a previous work, Rehand II: an electric and cosmetic prosthetic hand was developed. Its function is limited to simple object grasping, but it has the cosmetic appearance and is relatively light. This paper aimed to improve Rehand II by introducing tactile sense. Tactile sense is available to detect physical contact, recognize physical attributes of objects such as their softness and texture, and ensure delicate operation while handling the objects. Additionally, tactile sense is relevant to build the body recognition. We focused on vibrotactile sense from the aspects of a wide receptive field, contribution to contact detection and various frequency information involved. A simple electric and cosmetic prosthetic hand with vibrotactile sense was developed by improving Rehand II with polyvinylidene difluoride film sensors for detecting skin-propagated vibrations and soft vibrators for the feedback. The sensors were embedded at the thumb, index finger, and back of the hand of the prosthetic hand. First, recognition tests involving tapped part were conducted. Then, recognition and realistic rating tests involving operations were conducted. Results showed high recognition of tapped parts and operations and the good realistic.


Subject(s)
Artificial Limbs , Feedback, Sensory , Hand , Hand Strength , Humans , Touch
11.
Sci Rep ; 10(1): 13119, 2020 08 04.
Article in English | MEDLINE | ID: mdl-32753608

ABSTRACT

Although many studies investigated the associations between single-nucleotide polymorphisms (SNPs) in the M-type phospholipase A2 receptor-1 (PLA2R1) gene and susceptibility to idiopathic membranous nephropathy (IMN), some showed inconsistent results. Here, we conducted a meta-analysis examining the associations between PLA2R1 SNPs and IMN susceptibility after systematic searches in the PubMed and Web of Science databases. Our meta-analysis for rs4664308 A>G including 2,542 IMN patients and 4,396 controls in seven studies showed a significant association between the G allele and a lower risk of IMN, as determined using an allelic model (odds ratio, 0.45; 95% confidence interval [0.41-0.50]), an additive model (for GG vs. AA: 0.26; [0.21-0.33]; for AG vs. AA: 0.40; [0.36-0.45]), a dominant model (0.37; [0.34-0.42]) and a recessive model (0.38; [0.31-0.48]). Our meta-analysis also suggested associations between rs3828323, rs35771982, rs3749117 and rs3749119 and IMN susceptibility although high heterogeneities and/or publication biases were observed. We did not study in our meta-analysis, but other studies indicated that high-risk genotype combinations of rs2187668 in the human leucocyte antigen-DQ a-chain 1 gene and rs4664308 in the PLA2R1 gene had even stronger associations and could affect the formation of anti-PLA2R1 antibodies, suggesting these SNPs could be novel therapeutic targets.


Subject(s)
Genetic Predisposition to Disease/genetics , Glomerulonephritis, Membranous/genetics , Polymorphism, Single Nucleotide , Receptors, Phospholipase A2/genetics , Humans
12.
Elife ; 92020 05 05.
Article in English | MEDLINE | ID: mdl-32369019

ABSTRACT

While regulation of gene-enhancer interaction is intensively studied, its application remains limited. Here, we reconstituted arrays of CTCF-binding sites and devised a synthetic topological insulator with tetO for chromatin-engineering (STITCH). By coupling STITCH with tetR linked to the KRAB domain to induce heterochromatin and disable the insulation, we developed a drug-inducible system to control gene activation by enhancers. In human induced pluripotent stem cells, STITCH inserted between MYC and the enhancer down-regulated MYC. Progressive mutagenesis of STITCH led to a preferential escalation of the gene-enhancer interaction, corroborating the strong insulation ability of STITCH. STITCH also altered epigenetic states around MYC. Time-course analysis by drug induction uncovered deposition and removal of H3K27me3 repressive marks follows and reflects, but does not precede and determine, the expression change. Finally, STITCH inserted near NEUROG2 impaired the gene activation in differentiating neural progenitor cells. Thus, STITCH should be broadly useful for functional genetic studies.


Subject(s)
Chromatin/drug effects , Enhancer Elements, Genetic/genetics , Gene Expression Regulation/drug effects , Genes/genetics , CCCTC-Binding Factor/drug effects , CCCTC-Binding Factor/genetics , CCCTC-Binding Factor/metabolism , Chromatin/metabolism , Epigenesis, Genetic/drug effects , Epigenesis, Genetic/genetics , Genetic Engineering/methods , Humans , Induced Pluripotent Stem Cells/drug effects , Induced Pluripotent Stem Cells/metabolism , Proto-Oncogene Proteins c-myc/genetics , Proto-Oncogene Proteins c-myc/metabolism , Transcriptional Activation/drug effects , Transcriptional Activation/genetics , Transcriptome
13.
Annu Int Conf IEEE Eng Med Biol Soc ; 2019: 6661-6664, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31947369

ABSTRACT

Five-fingered electric prosthetic hands have been commercialized to assist the activities of forearm amputees in their daily life. Since the five-fingered electric prosthetic hands use a complicated mechanism and several actuators, the total weight is 1 kg or more. Although some hands are covered with a dedicated silicon glove, the appearance of them is not realistic compared to a general cosmetic hand. In this paper, we report a wire-driven five-fingered electric prosthetic hand utilizing elasticity of a cosmetic glove termed as Rehand II. The five fingers are flexed by pulling wires with a single servo motor and are extended by the elasticity of the cosmetic glove. In addition, a fitting mechanism in the hand allows the hand to fit the shape of various objects. With this approach, we developed an electric prosthetic hand with a simple grasping function that solves appearance and weight problems in conventional hands. The total weight of the developed hand was 562 g. The results of evaluation tests via Southampton Hand Assessment Procedure (SHAP) and grasping test of daily necessities in which a forearm amputee participated demonstrated that the developed prosthesis exhibited function to manipulate various objects used in daily activities.


Subject(s)
Amputees , Artificial Limbs , Fingers , Hand , Elasticity , Hand Strength , Humans , Prosthesis Design
14.
Annu Int Conf IEEE Eng Med Biol Soc ; 2019: 6665-6668, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31947370

ABSTRACT

Children with congenital forearm deficiency have difficulty in daily activities and body balance problem. Since most electric prostheses have been developed for adult amputees, it is necessary to develop a compact and lightweight electric prosthesis for children to manipulate various daily objects. In this paper, we report a compact and lightweight transradial electric prosthesis for children with forearm deficiency. Based on an electric prosthesis termed as Finch for adult amputees, we designed a smaller electric prosthesis by using a compact actuator and a control unit. We downsized the fingers of the Finch without impairing the workability. The total weight of the developed prosthesis was 274 g, which was about 100 g lighter than that of the conventional electric prosthesis for children. The result of upper limb function evaluation using developed prosthesis participated in a child with congenital forearm deficiency demonstrated that the effectiveness of the prosthesis to manipulate daily objects.


Subject(s)
Amputees , Artificial Limbs , Forearm , Child , Humans , Prosthesis Design , Upper Extremity
15.
Annu Int Conf IEEE Eng Med Biol Soc ; 2018: 1668-1671, 2018 Jul.
Article in English | MEDLINE | ID: mdl-30440715

ABSTRACT

Recently, many five-fingered prosthetic hands have been commercialized. However, most five-fingered prosthetic hands have heavyweight problems. In addition, their fingers with high rigidity are difficult to fit the object to be grasped. This paper reports a five-fingered prosthetic hand driven with curved pneumatic artificial muscles. By using the curved pneumatic artificial muscles as a skeleton and an actuator of the finger, flexible grasps and natural motions are achieved. Its weight of 255 g is less than one-third of the conventional fivefingered prosthetic hand. An evaluation using SHAP demonstrated that an amputee was able to operate various abstract objects.


Subject(s)
Artificial Limbs , Fingers , Hand , Prosthesis Design , Amputees , Humans , Musculoskeletal System
16.
Epigenetics Chromatin ; 11(1): 51, 2018 09 14.
Article in English | MEDLINE | ID: mdl-30213272

ABSTRACT

BACKGROUND: Contact domains of chromatin serve as a fundamental unit to regulate action of enhancers for target genes. Looping between a pair of CCCTC-binding factor (CTCF)-binding sites in convergent orientations underlies the formation of contact domains, while those in divergent orientations establish domain boundaries. However, every CTCF site is not necessarily engaged in loop or boundary structures, leaving functions of CTCF in varied genomic contexts still elusive. The locus containing Tfap2c and Bmp7 encompasses two contact domains separated by a region between the two genes, termed transition zone (TZ), characterized by two arrays of CTCF sites in divergent configuration. In this study, we created deletion and inversion alleles of these and other regions across the locus and investigated how they impinge on the conformation. RESULTS: Deletion of the whole two CTCF arrays with the CRISPR/Cas9 system resulted in impairment of blocking of chromatin contacts by the TZ, as assessed by the circular chromatin conformation capture assay (4C-seq). Deletion and inversion of either of the two arrays similarly, but less pronouncedly, led to reduction in the blocking activity. Thus, the divergent configuration provides the TZ with the strong boundary activity. Uniquely, we show the TZ harbors a 50-kb region within one of the two arrays that contacts broadly with the both flanking intervals, regardless of the presence or orientation of the other CTCF array. Further, we show the boundary CTCF array has little impact on intra-domain folding; instead, locally associating CTCF sites greatly affect it. CONCLUSIONS: Our results show that the TZ not only separates the two domains, but also bears a wide interval that shows isotropic behavior of chromatin folding, indicating a potentially complex nature of actual boundaries in the genome. We also show that CTCF-binding sites inside a domain greatly contribute to the intra-domain folding of chromatin. Thus, the study reveals diverse and context-dependent roles of CTCF in organizing chromatin conformation at different levels.


Subject(s)
Bone Morphogenetic Protein 7/genetics , Chromatin Assembly and Disassembly , Transcription Factor AP-2/genetics , Animals , Binding Sites , Bone Morphogenetic Protein 7/metabolism , CCCTC-Binding Factor/metabolism , Cell Line , Humans , Male , Mice , Protein Binding , Transcription Factor AP-2/metabolism
17.
Knee ; 25(6): 1027-1032, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30108012

ABSTRACT

BACKGROUND: Patients with discoid lateral meniscus (DLM) are prone to meniscal injuries related to its shape and abnormal mobility. The anatomical joint inclination of the proximal tibiofibular joint (PTFJ) can also affect joint movement in knee motion. However, an association between PTFJ morphology and DLM remains unclear. The purpose of this study was to investigate the morphology of the PTFJ on MRI and how this differs between patients with and without DLM. MATERIALS AND METHODS: Fifty-eight patients with DLM and 58 age-matched controls (normal meniscus) were included in this study. Slices from preoperative MRI sagittal images that clearly showed the PTFJ were used for measurements. The angle between the PTFJ and the perpendicular line of the fibula axis was measured as the inclination angle, and patients were classified as horizontal-type (<20°) or oblique-type (>20°). The inclination angle was also compared among patients with open and closed epiphysis in both groups to assess the effect of age. RESULTS: Patients in the horizontal-type PTFJ group frequently had DLM. Before epiphyseal closure, most patients had a horizontal-type PTFJ, with or without DLM. However, in older patients with a closed epiphysis, most with a normal meniscus had an oblique-type PTFJ, and those with DLM retained the horizontal-type joint. CONCLUSION: The horizontal-type PTFJ was significantly associated with DLM, and patients with DLM tended to retain a horizontal-type PTFJ after epiphyseal closure. In contrast, in patients with a normal meniscus, the PTFJ may change from a horizontal-type to an oblique-type PTFJ in line with bone maturity.


Subject(s)
Knee Joint/diagnostic imaging , Magnetic Resonance Imaging/methods , Menisci, Tibial/abnormalities , Adolescent , Adult , Child , Epiphyses/diagnostic imaging , Female , Humans , Knee Joint/anatomy & histology , Knee Joint/surgery , Male , Menisci, Tibial/diagnostic imaging , Menisci, Tibial/surgery , Middle Aged , Range of Motion, Articular , Retrospective Studies , Young Adult
18.
Foot Ankle Int ; 39(9): 1120-1127, 2018 09.
Article in English | MEDLINE | ID: mdl-29774751

ABSTRACT

BACKGROUND: Although chondral or osteochondral injuries are usually assessed by magnetic resonance imaging, its accuracy can be low, presumably related to the relatively thin cartilage layer and the close apposition of the cartilage of the talus and tibial plafond. We hypothesized that axial traction could provide a contrast between the articular cartilage and joint cavity, and it enabled the simultaneous evaluation of cartilage and subchondral bone. The purpose of this study was to assess the feasibility of using computed tomography (CT) imaging with axial traction for the diagnosis of articular cartilage injuries. METHODS: Chondral lesions in 18 ankles were evaluated by CT with axial traction using a tensioning device and ankle strap for enlargement of the joint space of the ankle. CT was done in 3-mm slices and programmed for gray scale, and then CT images were allocated colors to make it easier to evaluate the cartilage layer. The International Cartilage Repair Society (ICRS) grades on CT were compared with those on arthroscopic findings. RESULTS: The respective sensitivity and specificity of CT imaging with traction using ICRS grading were 74.4%, and 96.3%. The level of agreement of the ICRS grading between CT images and arthroscopic findings was moderate (kappa coefficient, 0.547). Adding axial traction to CT increased the delineation of the cartilage surface, including chondral thinning, chondral defect, and cartilage separation. CONCLUSIONS: CT with axial traction produced acceptable levels of sensitivity and specificity for the evaluation of articular cartilage injuries, in addition to the assessment of subchondral bone. LEVEL OF EVIDENCE: Level III, comparative case series.


Subject(s)
Ankle Injuries/diagnostic imaging , Ankle Joint/diagnostic imaging , Cartilage, Articular/injuries , Tomography, X-Ray Computed/methods , Traction , Adolescent , Adult , Aged , Cartilage, Articular/diagnostic imaging , Chronic Disease , Female , Humans , Male , Middle Aged , Sensitivity and Specificity , Talus/diagnostic imaging , Talus/pathology , Young Adult
19.
Foot Ankle Int ; 39(8): 908-915, 2018 08.
Article in English | MEDLINE | ID: mdl-29652193

ABSTRACT

BACKGROUND: In the evaluation of osteochondral lesions of the talar dome (OLT), bone marrow lesions (BML) are commonly observed in the subchondral bone on magnetic resonance imaging (MRI). However, the significance of BML, such as the histology of the overlying cartilage, is still unclear. The purpose of this study was to investigate the relationship between the BML and cartilage degeneration in OLT. METHODS: Thirty-three ankles with OLT were included in this study. All ankles underwent CT and MRI and had operative treatment. The ankles were divided into 2 groups, depending on the presence of bone sclerosis (ie, with or without) in the host bone just below the osteochondral fragment (nonsclerosis group and sclerosis group). The area of BML was compared between the 2 groups. Biopsies of the osteochondral fragment from 20 ankles were performed during surgery, and the correlation between the BML and cartilage degeneration was analyzed. The remaining 13 ankles had the CT and MRI compared with the arthroscopic findings. RESULTS: The mean area of BML in the nonsclerosis group was significantly larger than that in the sclerosis group. In the histologic analysis, there was a significant and moderate correlation between the Mankin score and the area of BML. The mean Mankin score in the nonsclerosis group was significantly lower than that in the sclerosis group. CONCLUSIONS: This study revealed that a large area of BML on MRI exhibited low degeneration of cartilage of the osteochondral fragment, while a small area of BML indicated sclerosis of the subchondral bone with severe degeneration of cartilage. The evaluation of BML may predict the cartilage condition of the osteochondral fragment. LEVEL OF EVIDENCE: Level III, comparative series.


Subject(s)
Bone Diseases/diagnostic imaging , Bone Marrow/pathology , Cartilage Diseases/diagnostic imaging , Magnetic Resonance Imaging , Talus/diagnostic imaging , Adolescent , Adult , Biopsy, Needle , Bone Diseases/pathology , Bone Marrow/diagnostic imaging , Cartilage Diseases/pathology , Cartilage, Articular/diagnostic imaging , Cartilage, Articular/pathology , Female , Humans , Male , Middle Aged , Talus/pathology , Tomography, X-Ray Computed , Young Adult
20.
Arthrosc Tech ; 7(2): e125-e129, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29552478

ABSTRACT

Ankle arthroscopy is a minimally invasive technique for ankle joint treatment. However, injury to the intermediate dorsal cutaneous nerve (IDCN) and the medial dorsal cutaneous nerve (MDCN) is a common complication during anterior portal placement. To prevent injuries, methods such as palpating the nerves topographically and marking the nerves by transilluminating the skin with an arthroscope have been proposed. Easier and more definitive methods of identifying the IDCN and MDCN should result in a reduction of complications. Recently, a vein imaging system was developed that projects images of subcutaneous vasculature directly onto the skin with the use of near-infrared (NIR) light. Because anatomic studies have shown that superficial veins accompany the IDCN and MDCN, protecting the subcutaneous veins could lower the risk of nerve injury. We introduce our technique for the creation of an ankle arthroscopic portal using an NIR imaging system, which displays the vein image on the skin, to prevent injury to the superficial veins and, consequently, reduce IDCN and MDCN injuries. This is the first technical report on the prevention of vein and nerve injuries using an NIR imaging system. Our technique for avoiding vein injury using a peripheral vein illumination device during anterior portal placement in ankle arthroscopy could lower the risk of complications.

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