Carrier frequency and incidence of aromatic L-amino acid decarboxylase deficiency: a gnomAD-based study.

BACKGROUND: Aromatic L-amino acid decarboxylase (AADC) deficiency is an autosomal recessive neurotransmitter metabolism disorder and is clinically characterized by infancy hypotonia, ophthalmic crisis, and developmental delay. With the emergence of gene therapy for AADC deficiency, accurate prediction of AADC deficiency is required. This study aimed to analyze the carrier frequency and expected incidence of AADC deficiency using exome data from the Genome Aggregation Database (gnomAD). METHODS: We analyzed 125,748 exomes from gnomAD, including 9197 East Asian exomes, for the DDC gene. All identified variants were classified according to the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines. RESULTS: The worldwide carrier frequency of AADC deficiency was 0.17%; the highest frequency was observed in East Asians at 0.78%, and the lowest was in Latinos at 0.07%. The estimated incidence of AADC deficiency was 1 in 1,374,129 worldwide and 1 in 65,266 in East Asians. CONCLUSION: The results demonstrated that East Asians have a higher carrier frequency of AADC deficiency than other ethnic groups. The variant spectrum of DDC genes in East Asian populations differed greatly from those of other ethnic groups. Our data will serve as a reference for further investigation of AADC deficiency. IMPACT: This study analyzed exome data from the Genome Aggregation Database (gnomAD) to estimate the carrier frequency and expected incidence of aromatic L-amino acid decarboxylase (AADC) deficiency. The article provides updated carrier frequency and incidence estimates for AADC deficiency, particularly in East Asian populations, and emphasizes the significant differences in the variant spectrum of DDC genes in this population compared to other ethnic groups. The study provides important information for accurate prediction and early diagnosis of AADC deficiency, particularly in high-risk populations, and may aid in the development of more effective targeted screening programs and gene therapies for this disorder.

The Diagnostic Yield and Difficulties of Utilizing Soft-clipped Read Clusters Encountered in Clinical Exome Sequencing.

BACKGROUND: Despite the wide use of next generation sequencing, there are still many difficulties in detecting structural variants. A split read is one of the clues of structural variants and is represented as a soft-clipped read in the raw sequencing data. Considering that most of the breakpoints of structural variants reside in non-coding regions, split read information has not been routinely used in exome sequencing or targeted panel sequencing. Recently, SCRAMble, a software capable of detecting mobile element insertion (MEI) and deletion based on soft-clipped read clusters (SCRCs), was shown to provide an additional diagnostic yield of 0.03 - 0.25%. SCRAMble is the only software that can be used for exome sequencing or targeted panel sequencing to detect structural variants based on SCRC information. The aim of present study was to establish a working procedure of utilizing SCRC information using SCRAMble in clinical exome sequencing and to assess its diagnostic yield. METHODS: Raw sequencing data of clinical exome sequencing were retrospectively analyzed using SCRAMble to search MEIs and deletions. SCRAMble software was installed according to the manufacturer's instructions and default parameters except for one, mei-score, which was adjusted for sensitivity, were used. RefSeq gene annotation was performed for both MEI and deletion calls using ANNOVAR. Blacklist-based filtering was used to reduce candidate MEI/deletion calls. Clinical relevance was manually evaluated for the remaining variant calls. RESULTS: One diagnostic MEI, which is a founder variant in East Asia, was detected in two cases (2/266, 0.75%). In addition, two diagnostic deletions, which had been previously detected in depth-of-coverage (DOC)-based copy number variant (CNV) callers, were detected (2/266, 0.75%). Base-level breakpoints that could not be derived by the DOC-based callers were identified for these two deletions using SCRAMble. Most SCRCs were repetitive among cases and blacklist-based filtering reduced candidate MEI/deletion calls by 49.5 - 94.5%, leaving a considerable number of variant calls to be manually validated. CONCLUSIONS: SCRC screening in exome or targeted panel sequencing may provide additional diagnostic yield either by pathogenic MEI detection or reassurance of deletions identified by DOC-based CNV callers. Development of an efficient filtering algorithm is warranted.

Osteoarthritis improvement effect of Chrysanthemum zawadskii var. latilobum extract in relation to genotype.

Objectives: To determine whether SNPs of osteoarthritis (OA)-related genes predict the effect of Chrysanthemum zawadskii var. latilobum (CZ) extract in OA patients with OA. Subjects/methods: To analyze correlations between CZ extract effects in humans and their genotypes, 121 Korean patients with OA were recruited. Patients ingested 600 mg/day of the CZ extract GCWB106 (one tablet daily), including 250-mg CZ, or placebo (one tablet daily) for 12 weeks. Twenty SNPs were genotyped in 11 genes associated with OA pathogenesis, including tumor necrosis factor-alpha (TNF-α) and matrix metalloproteinases (MMPs), and 9 genes involved in OA-related dietary intervention. The Visual Analogue Scale (VAS) and Korean Western Ontario and McMaster Universities (K-WOMAC) were measured as indicators of GCWB106 effect. Statistical comparisons were performed using Kruskal-Wallis tests to identify associations between these scales and genotyped loci in patients with OA. Results: Three SNPs (PPARG rs3856806, MMP13 rs2252070, and ZIP2 rs2234632) were significantly associated with the degree of change in VAS pain score. Homozygous CC genotype carriers of rs3856806, G allele carriers (GA or GG) of rs2252070, and T allele carriers (GT or TT) of rs2234632 showed lower VAS score (i.e., less severe symptoms) in the GCWB106 group (n=53) than the placebo group (n=57) (p=0.026, p=0.009, and p=0.025, respectively). Gene-gene interaction effects on GCWB106-mediated pain relief were then examined, and it was found that the addition of each genotype resulted in a greater decrease in VAS pain score in the GCWB106 group (p=0.0024) but not the placebo group (p=0.7734). Conclusions: These novel predictive markers for the pain-relieving effects of GCWB106 may be used in the personalized treatment of patients with OA.

Polymerizations with Elemental Sulfur: From Petroleum Refining to Polymeric Materials.

The production of elemental sulfur from petroleum refining has created a technological opportunity to increase the valorization of elemental sulfur by the synthesis of high-performance sulfur-based plastics with improved optical, electrochemical, and mechanical properties aimed at applications in thermal imaging, energy storage, self-healable materials, and separation science. In this Perspective, we discuss efforts in the past decade that have revived this area of organosulfur and polymer chemistry to afford a new class of high-sulfur-content polymers prepared from the polymerization of liquid sulfur with unsaturated monomers, termed inverse vulcanization.

Sulfenyl Chlorides: An Alternative Monomer Feedstock from Elemental Sulfur for Polymer Synthesis.

A polymerization methodology is reported using sulfur monochloride (S2Cl2) as an alternative feedstock for polymeric materials. S2Cl2 is an inexpensive petrochemical derived from elemental sulfur (S8) but has numerous advantages as a reactive monomer for polymerization vs S8. This new process, termed sulfenyl chloride inverse vulcanization, exploits the high reactivity and miscibility of S2Cl2 with a broad range of allylic monomers to prepare soluble, high molar-mass linear polymers, segmented block copolymers, and crosslinked thermosets with greater synthetic precision than achieved using classical inverse vulcanization. This step-growth addition polymerization also allows for preparation of a new class of thiol-free, inexpensive, highly optically transparent thermosets (α = 0.045 cm-1 at 1310 nm), which exhibit among the best optical transparency and low birefringence relative to commodity optical polymers, while possessing a higher refractive index (n > 1.6) in the visible and near-infrared spectra. The fabrication of large-sized optical components is also demonstrated.

A Clinical Decision Support System for Sleep Staging Tasks With Explanations From Artificial Intelligence: User-Centered Design and Evaluation Study.

BACKGROUND: Despite the unprecedented performance of deep learning algorithms in clinical domains, full reviews of algorithmic predictions by human experts remain mandatory. Under these circumstances, artificial intelligence (AI) models are primarily designed as clinical decision support systems (CDSSs). However, from the perspective of clinical practitioners, the lack of clinical interpretability and user-centered interfaces hinders the adoption of these AI systems in practice. OBJECTIVE: This study aims to develop an AI-based CDSS for assisting polysomnographic technicians in reviewing AI-predicted sleep staging results. This study proposed and evaluated a CDSS that provides clinically sound explanations for AI predictions in a user-centered manner. METHODS: Our study is based on a user-centered design framework for developing explanations in a CDSS that identifies why explanations are needed, what information should be contained in explanations, and how explanations can be provided in the CDSS. We conducted user interviews, user observation sessions, and an iterative design process to identify three key aspects for designing explanations in the CDSS. After constructing the CDSS, the tool was evaluated to investigate how the CDSS explanations helped technicians. We measured the accuracy of sleep staging and interrater reliability with macro-F1 and Cohen κ scores to assess quantitative improvements after our tool was adopted. We assessed qualitative improvements through participant interviews that established how participants perceived and used the tool. RESULTS: The user study revealed that technicians desire explanations that are relevant to key electroencephalogram (EEG) patterns for sleep staging when assessing the correctness of AI predictions. Here, technicians wanted explanations that could be used to evaluate whether the AI models properly locate and use these patterns during prediction. On the basis of this, information that is closely related to sleep EEG patterns was formulated for the AI models. In the iterative design phase, we developed a different visualization strategy for each pattern based on how technicians interpreted the EEG recordings with these patterns during their workflows. Our evaluation study on 9 polysomnographic technicians quantitatively and qualitatively investigated the helpfulness of the tool. For technicians with <5 years of work experience, their quantitative sleep staging performance improved significantly from 56.75 to 60.59 with a P value of .05. Qualitatively, participants reported that the information provided effectively supported them, and they could develop notable adoption strategies for the tool. CONCLUSIONS: Our findings indicate that formulating clinical explanations for automated predictions using the information in the AI with a user-centered design process is an effective strategy for developing a CDSS for sleep staging.

Cancer subtype classification and modeling by pathway attention and propagation.

MOTIVATION: Biological pathway is an important curated knowledge of biological processes. Thus, cancer subtype classification based on pathways will be very useful to understand differences in biological mechanisms among cancer subtypes. However, pathways include only a fraction of the entire gene set, only one-third of human genes in KEGG, and pathways are fragmented. For this reason, there are few computational methods to use pathways for cancer subtype classification. RESULTS: We present an explainable deep-learning model with attention mechanism and network propagation for cancer subtype classification. Each pathway is modeled by a graph convolutional network. Then, a multi-attention-based ensemble model combines several hundreds of pathways in an explainable manner. Lastly, network propagation on pathway-gene network explains why gene expression profiles in subtypes are different. In experiments with five TCGA cancer datasets, our method achieved very good classification accuracies and, additionally, identified subtype-specific pathways and biological functions. AVAILABILITY AND IMPLEMENTATION: The source code is available at http://biohealth.snu.ac.kr/software/GCN_MAE. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Segmented Polyurethanes and Thermoplastic Elastomers from Elemental Sulfur with Enhanced Thermomechanical Properties and Flame Retardancy.

The production of elemental sulfur from petroleum refining has created a technological opportunity to increase the valorization of elemental sulfur by the creation of high-performance sulfur based plastics with improved thermomechanical properties, elasticity and flame retardancy. We report on a synthetic polymerization methodology to prepare the first example of sulfur based segmented multi-block polyurethanes (SPUs) and thermoplastic elastomers that incorporate an appreciable amount of sulfur into the final target material. This approach applied both the inverse vulcanization of S8 with olefinic alcohols and dynamic covalent polymerizations with dienes to prepare sulfur polyols and terpolyols that were used in polymerizations with aromatic diisocyanates and short chain diols. Using these methods, a new class of high molecular weight, soluble block copolymer polyurethanes were prepared as confirmed by Size Exclusion Chromatography, NMR spectroscopy, thermal analysis, and microscopic imaging. These sulfur-based polyurethanes were readily solution processed into large area free standing films where both the tensile strength and elasticity of these materials were controlled by variation of the sulfur polyol composition. SPUs with both high tensile strength (13-24 MPa) and ductility (348 % strain at break) were prepared, along with SPU thermoplastic elastomers (578 % strain at break) which are comparable values to classical thermoplastic polyurethanes (TPUs). The incorporation of sulfur into these polyurethanes enhanced flame retardancy in comparison to classical TPUs, which points to the opportunity to impart new properties to polymeric materials as a consequence of using elemental sulfur.

A Randomized Controlled Trial Comparing Colonoscopic Enema With Additional Oral Preparation as a Salvage for Inadequate Bowel Cleansing Before Colonoscopy.

GOALS: The goal of this study was to evaluate the noninferiority of colonoscopic enema to additional oral preparation in salvage bowel cleansing for inadequate preparation for a morning colonoscopy. BACKGROUND: Colonoscopic enema, administering additional cathartics into the right colon through the colonoscope accessory channel, is suggested to rescue poor bowel preparation for a colonoscopy but lacking comparative study. STUDY: In this prospective, randomized, actively-controlled, parallel group, noninferiority trial, consecutive outpatients and health checkup recipients aged from 19 to 70 years with inappropriate bowel preparation during an elective colonoscopy were enrolled to receive either a colonoscopic enema of 1 L polyethylene glycol (PEG) (enema group) or additional oral intake of 2 L PEG (oral group). The primary endpoint was the proportion of adequate bowel preparation evaluated using the Boston Bowel Preparation Scale. RESULTS: Overall, 131 participants were randomized. Adequate bowel preparation was achieved in 53% (35/66) of the enema group, which was significantly inferior to the oral group (81.5%; 53/67) with a difference of -28.5% (95% confidence interval, -44.1, -12.9; P=0.001). The largest difference in the proportion of adequate bowel preparation was observed in the right colon (57.8% in the enema group vs. 86.9% in the oral group; P<0.001), followed by the transverse colon (85.9% vs. 98.4%; P=0.017) and the left colon (90.6% vs. 96.7%; P=0.274). CONCLUSIONS: The colonoscopic enema of 1 L PEG was inferior to the additional oral ingestion of 2 L PEG regarding efficacy as a salvage bowel preparation in adults with inadequate bowel cleansing for colonoscopy.

Infrared Fingerprint Engineering: A Molecular-Design Approach to Long-Wave Infrared Transparency with Polymeric Materials.

Optical technologies in the long-wave infrared (LWIR) spectrum (7-14 µm) offer important advantages for high-resolution thermal imaging in near or complete darkness. The use of polymeric transmissive materials for IR imaging offers numerous cost and processing advantages but suffers from inferior optical properties in the LWIR spectrum. A major challenge in the design of LWIR-transparent organic materials is that nearly all organic molecules absorb in this spectral window which lies within the so-called IR-fingerprint region. We report on a new molecular-design approach to prepare high refractive index polymers with enhanced LWIR transparency. Computational methods were used to accelerate the design of novel molecules and polymers. Using this approach, we have prepared chalcogenide hybrid inorganic/organic polymers (CHIPs) with enhanced LWIR transparency and thermomechanical properties via inverse vulcanization of elemental sulfur with new organic co-monomers.

Impact of clinically evident portal hypertension on clinical outcome of patients with hepatocellular carcinoma treated by transarterial chemoembolization.

BACKGROUND AND AIM: The aim of this study is to determine the impact of clinically evident portal hypertension (CEPH) on prognosis of hepatocellular carcinoma (HCC) patients with Child-Pugh A cirrhosis who underwent transarterial chemoembolization (TACE). METHODS: A retrospective data analysis was performed for a total of 388 treatment-naïve HCC patients with Child-Pugh A cirrhosis who underwent TACE as first-line treatment from January 2000 to June 2014. Cumulative occurrence rate of complete response (CR), progression-free survival (PFS), and overall survival (OS) were compared between patients with CEPH and those without CEPH (esophageal/gastric varices or low platelet count [< 100 000 per mm3 ] associated with splenomegaly). RESULTS: Among 388 patients, 252 (64.9%) had CEPH, while 136 (35.1%) had no evidence of CEPH at the time of HCC diagnosis. Cumulative probability of the occurrence of CR was significantly lower in patients with CEPH than that in patients without CEPH (P < 0.001). Median PFS was significantly shorter in patients with CEPH than that in patients without CEPH (5 vs 31 months, P < 0.001). Five-year OS rate was significantly lower in patients with CEPH than that in patients without CEPH (41.5% vs 77.5%, P < 0.001). Multivariate analysis indicated that the presence of CEPH was the most powerful poor prognostic factor for the occurrence of CR (adjusted hazard ratio [aHR], 0.16; 95% confidence interval [CI], 0.09-0.28; P < 0.001), PFS (aHR, 5.01; 95% CI, 3.08-8.12; P < 0.001), and OS (aHR, 2.95; 95% CI, 1.66-5.23; P < 0.001). CONCLUSIONS: The presence of CEPH should be considered as a major negative prognostic factor for patients with HCC who will undergo TACE.

Carrier frequency of Wilson's disease in the Korean population: a DNA-based approach.

Wilson's disease (WD) is an autosomal recessive disorder caused by ATP7B gene mutation. The frequency of WD is about 1 in 30 000 worldwide. In the present study, we screened 14 835 dried blood spots (DBSs) from asymptomatic Korean neonates and retrospectively reviewed massively parallel sequencing of 1090 control individuals to estimate carrier frequency. TaqMan real-time PCR assays were conducted to detect six mutations that account for 58.3% of mutations in Korean WD patients: c.2333G>T (p.Arg778Leu), c.2621C>T (p.Ala874Val), c.3086C>T (p.Thr1029Ile), c.3247C>T (p.Leu1083Phe), c.3556G>A (p.Gly1186Ser) and c.3809A>G (p.Asn1270Ser). We also retrospectively reviewed data from 1090 individuals with various indications other than WD for whom whole-exome or panel sequencing data were available. Mutant allele frequency based on the six most common mutations was 0.0067 among the total of 14 835 DBSs screened. Given that these six mutations account for 58.3% of mutations in Korean WD patients, the corrected mutant allele frequency is 0.0115 (95% confidence interval (CI): 0.0103-0.0128). Corresponding incidence (q2) and carrier frequency (2pq) were estimated to be 1:7561 and 1:44, respectively. In retrospective data analysis of 1090 control individuals, allele frequency of pathogenic or likely pathogenic variants was 0.0096 (95% CI: 0.0063-0.0146). Corresponding carrier frequency was estimated to be 1:53. Estimated allele and carrier frequencies based on DNA screening were relatively higher than those reported previously based on clinical ascertainment.

Natural courses of branch duct intraductal papillary mucinous neoplasm.

PURPOSE: The study was done to elucidate the clinico-radiologic predictive factors for cancerous change detected by disease progression (PD) mainly defined by interval increase in cyst size and change of cyst morphology, for branch duct intraductal papillary mucinous neoplasm (BD-IPMN) patients with relatively long-term follow-up. METHODS: Retrospective analysis of medical records and imaging findings were performed on 107 patients with BD-IPMN enrolled from July 2005 to May 2013, in whom the communication between the cystic lesion and pancreatic duct was confirmed by either endoscopic ultrasonography (EUS), magnetic resonance cholangiopancreatography (MRCP), or endoscopic retrograde cholangiopancreatography (ERCP). RESULTS: During the mean ± SD follow-up period of 51.5 ± 24.5 months, PD was noticed in 43 (40.2%) of 107 BD-IPMN patients. Among these 107 patients, 21 (19.6%) displayed cancerous change. By univariate analyses, septated/multilocular cyst morphology, cyst size larger than 30 mm, cyst wall thickening, mural nodules, and the presence of symptoms were significant predictive factors for cancerous changes in BD-IPMN patients. A Cox forward stepwise linear regression model revealed that cyst wall thickening (OR 9.187, 95% CI 1.883~44.820, P < 0.01) and mural nodules (OR 6.224, 95% CI 1.311~29.549, P = 0.021) were significant and independent predictive factors for cancerous change in BD-IPMN patients. CONCLUSIONS: A significant proportion of patients with BD-IPMN showed PD and cancerous change during the long-term follow-up. Cyst wall thickening and mural nodules were significant and independent predictive factors of cancerous change in patients with BD-IPMN.

Ubiquitous polygenicity of human complex traits: genome-wide analysis of 49 traits in Koreans.

Recent studies in population of European ancestry have shown that 30% ~ 50% of heritability for human complex traits such as height and body mass index, and common diseases such as schizophrenia and rheumatoid arthritis, can be captured by common SNPs and that genetic variation attributed to chromosomes are in proportion to their length. Using genome-wide estimation and partitioning approaches, we analysed 49 human quantitative traits, many of which are relevant to human diseases, in 7,170 unrelated Korean individuals genotyped on 326,262 SNPs. For 43 of the 49 traits, we estimated a nominally significant (P<0.05) proportion of variance explained by all SNPs on the Affymetrix 5.0 genotyping array ([Formula: see text]). On average across 47 of the 49 traits for which the estimate of h(G)(2) is non-zero, common SNPs explain approximately one-third (range of 7.8% to 76.8%) of narrow sense heritability. The estimate of h(G)(2) is highly correlated with the proportion of SNPs with association P<0.031 (r(2) = 0.92). Longer genomic segments tend to explain more phenotypic variation, with a correlation of 0.78 between the estimate of variance explained by individual chromosomes and their physical length, and 1% of the genome explains approximately 1% of the genetic variance. Despite the fact that there are a few SNPs with large effects for some traits, these results suggest that polygenicity is ubiquitous for most human complex traits and that a substantial proportion of the "missing heritability" is captured by common SNPs.

A genome-wide scan for signatures of directional selection in domesticated pigs.

BACKGROUND: Animal domestication involved drastic phenotypic changes driven by strong artificial selection and also resulted in new populations of breeds, established by humans. This study aims to identify genes that show evidence of recent artificial selection during pig domestication. RESULTS: Whole-genome resequencing of 30 individual pigs from domesticated breeds, Landrace and Yorkshire, and 10 Asian wild boars at ~16-fold coverage was performed resulting in over 4.3 million SNPs for 19,990 genes. We constructed a comprehensive genome map of directional selection by detecting selective sweeps using an F ST-based approach that detects directional selection in lineages leading to the domesticated breeds and using a haplotype-based test that detects ongoing selective sweeps within the breeds. We show that candidate genes under selection are significantly enriched for loci implicated in quantitative traits important to pig reproduction and production. The candidate gene with the strongest signals of directional selection belongs to group III of the metabolomics glutamate receptors, known to affect brain functions associated with eating behavior, suggesting that loci under strong selection include loci involved in behaviorial traits in domesticated pigs including tameness. CONCLUSIONS: We show that a significant proportion of selection signatures coincide with loci that were previously inferred to affect phenotypic variation in pigs. We further identify functional enrichment related to behavior, such as signal transduction and neuronal activities, for those targets of selection during domestication in pigs.

Cetaceans evolution: insights from the genome sequences of common minke whales.

BACKGROUND: Whales have captivated the human imagination for millennia. These incredible cetaceans are the only mammals that have adapted to life in the open oceans and have been a source of human food, fuel and tools around the globe. The transition from land to water has led to various aquatic specializations related to hairless skin and ability to regulate their body temperature in cold water. RESULTS: We present four common minke whale (Balaenoptera acutorostrata) genomes with depth of ×13 ~ ×17 coverage and perform resequencing technology without a reference sequence. Our results indicated the time to the most recent common ancestors of common minke whales to be about 2.3574 (95% HPD, 1.1521 - 3.9212) million years ago. Further, we found that genes associated with epilation and tooth-development showed signatures of positive selection, supporting the morphological uniqueness of whales. CONCLUSIONS: This whole-genome sequencing offers a chance to better understand the evolutionary journey of one of the largest mammals on earth.

Bovine Genome-wide Association Study for Genetic Elements to Resist the Infection of Foot-and-mouth Disease in the Field.

Foot-and-mouth disease (FMD) is a highly contagious disease affecting cloven-hoofed animals and causes severe economic loss and devastating effect on international trade of animal or animal products. Since FMD outbreaks have recently occurred in some Asian countries, it is important to understand the relationship between diverse immunogenomic structures of host animals and the immunity to foot-and-mouth disease virus (FMDV). We performed genome wide association study based on high-density bovine single nucleotide polymorphism (SNP) chip for identifying FMD resistant loci in Holstein cattle. Among 624532 SNP after quality control, we found that 11 SNPs on 3 chromosomes (chr17, 22, and 15) were significantly associated with the trait at the p.adjust <0.05 after PERMORY test. Most significantly associated SNPs were located on chromosome 17, around the genes Myosin XVIIIB and Seizure related 6 homolog (mouse)-like, which were associated with lung cancer. Based on the known function of the genes nearby the significant SNPs, the FMD resistant animals might have ability to improve their innate immune response to FMDV infection.

Activation timing patterns of the abdominal and leg muscles during the sit-to-stand movement in individuals with chronic hemiparetic stroke.

[Purpose] The purpose of this study was to determine the activation timing patterns of abdominal and leg muscles during the sit-to-stand movement in individuals with chronic hemiparetic stroke. [Subjects] Twenty adults with chronic hemiparetic stroke participated in this study. [Methods] Subjects performed five sit-to-stand movements at a self-selected velocity without using their hands. Surface electromyography was used to measure the reaction time of the bilateral transverse abdominis/internal oblique, rectus femoris, and tibialis anterior muscles during the sit-to-stand movement. [Results] There were significant differences in the reaction time between the affected and unaffected sides of the abdominal and leg muscles. Muscles on the unaffected side had faster reaction time than those on the affected side. Activation of the transverse abdominis/internal oblique muscles was delayed relative to activation of the tibialis anterior muscle during the sit-to-stand movement. [Conclusion] Our findings provide information that may aid clinicians in the examination and management of paretic muscles for transfers in individuals with chronic hemiparetic stroke.

Genotype-environment interactions for quantitative traits in Korea Associated Resource (KARE) cohorts.

BACKGROUND: Due to the lack of statistical power and confounding effects of population structure in human population data, genotype-environment interaction studies have not yielded promising results and have provided only limited knowledge for exploring how genotype and environmental factors interact to in their influence onto risk. RESULTS: We analyzed 49 human quantitative traits in 7,170 unrelated Korean individuals on 326,262 autosomal single nucleotide polymorphisms (SNPs) collected from the KARE (Korean Association Resource) project, and we estimated the statistically significant proportion of variance that could be explained by genotype-area interactions in the supra-iliac skinfold thickness trait (hGE2 = 0.269 and P = 0.00032), which is related to abdominal obesity. Data suggested that the genotypes could have different effects on the phenotype (supra-iliac skinfold thickness) in different environmental settings (rural vs. urban areas). We then defined the genotype groups of individuals with similar genetic profiles based on the additive genetic relationships among individuals using SNPs. We observed the norms of reaction, and the differential phenotypic response of a genotype to a change in environmental exposure. Interestingly, we also found that the gene clusters responsible for cell-cell and cell-extracellular matrix interactions were enriched significantly for genotype-area interaction. CONCLUSIONS: This significant heritability estimate of genotype-environment interactions will lead to conceptual advances in our understanding of the mechanisms underlying genotype-environment interactions, and could be ultimately applied to personalized preventative treatments based on environmental exposures.