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The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Background: Axial myopathy is a rare neuromuscular disorder of variable etiology characterised by preferential involvement of the paraspinal muscles. We reviewed clinical features of patients with axial myopathies and the diagnostic yield of myositis-associated antibodies and targeted next generation sequencing panels. Methods: We performed a retrospective review of patients presenting with axial myopathy at the Montreal Neurological Hospital from 2011-2018. Data collection included clinical presentation, disease course, results of electromyography, imaging, laboratory and genetic testing, and histopathology on muscle biopsy. Results: Twenty-five patients were identified. Initial manifestation of axial weakness was head drop (15), camptocormia (8), and rigid spine (2). Autoimmune myositis was diagnosed in 9 patients, seropositive in 7 out of 7 tested for myositis-associated antibodies. Genetic testing was consistent with oculopharyngeal muscular dystrophy in one patient and RYR-1 (ryanodine receptor 1) related core myopathy in another. Local radiotherapy or spine surgery preceded the onset of axial weakness in 1 and 6 patients, respectively. Muscle biopsies were available in 17 patients and revealed myopathic changes (16), inflammatory changes (6), and myopathy with vacuoles (3). Conclusions: Recent advancements in genetic and antibody testing, combined with paraspinal muscle biopsy, allow for more precise classification and identification of potentially treatable axial myopathies.
During the summer of 2016, the Hawaii Department of Health responded to the second-largest domestic foodborne hepatitis A virus (HAV) outbreak in the post-vaccine era. The epidemiological investigation included case finding and investigation, sequencing of RNA positive clinical specimens, product trace-back and virologic testing and sequencing of HAV RNA from the product. Additionally, an online survey open to all Hawaii residents was conducted to estimate baseline commercial food consumption. We identified 292 confirmed HAV cases, of whom 11 (4%) were possible secondary cases. Seventy-four (25%) were hospitalised and there were two deaths. Among all cases, 94% reported eating at Oahu or Kauai Island branches of Restaurant Chain A, with 86% of those cases reporting raw scallop consumption. In contrast, a food consumption survey conducted during the outbreak indicated 25% of Oahu residents patronised Restaurant Chain A in the 7 weeks before the survey. Product trace-back revealed a single distributor that supplied scallops imported from the Philippines to Restaurant Chain A. Recovery, amplification and sequence comparison of HAV recovered from scallops revealed viral sequences matching those from case-patients. Removal of product from implicated restaurants and vaccination of those potentially exposed led to the cessation of the outbreak. This outbreak further highlights the need for improved imported food safety.
The asymptotic phase θ of an initial point x in the stable manifold of a limit cycle (LC) identifies the phase of the point on the LC to which the flow φt(x) converges as t → ∞. The infinitesimal phase response curve (iPRC) quantifies the change in timing due to a small perturbation of a LC trajectory. For a stable LC in a smooth dynamical system, the iPRC is the gradient ∇x(θ) of the phase function, which can be obtained via the adjoint of the variational equation. For systems with discontinuous dynamics, the standard approach to obtaining the iPRC fails. We derive a formula for the iPRCs of LCs occurring in piecewise smooth (Filippov) dynamical systems of arbitrary dimension, subject to a transverse flow condition. Discontinuous jumps in the iPRC can occur at the boundaries separating subdomains, and are captured by a linear matching condition. The matching matrix, M, can be derived from the saltation matrix arising in the associated variational problem. For the special case of linear dynamics away from switching boundaries, we obtain an explicit expression for the iPRC. We present examples from cell biology (Glass networks) and neuroscience (central pattern generator models). We apply the iPRCs obtained to study synchronization and phase-locking in piecewise smooth LC systems in which synchronization arises solely due to the crossing of switching manifolds.
Human bocaviruses (HBoVs) have been detected in human gastrointestinal infections worldwide. In 2005, HBoV was also discovered in infants and children with infections of the lower respiratory tract. Recently, several genotypes of this parvovirus, including HBoV genotype 2 (HBoV2), genotype 3 (HBoV3) and genotype 4 (HBoV4), were discovered and found to be closely related to HBoV. HBoV2 was first detected in stool samples from children in Pakistan, followed by detection in other countries. HBoV3 was detected in Australia and HBoV4 was identified in stool samples from Nigeria, Tunisia and the USA. Recently, HBoV infection has been on the rise throughout the world, particularly in countries neighbouring South Korea; however, there have been very few studies on Korean strains. In this study, we characterised the whole genome and determined the phylogenetic position of CUK-BC20, a new clinical HBoV strain isolated in South Korea. The CUK-BC20 genome of 5184 nucleotides (nt) contains three open-reading frames (ORFs). The genotype of CUK-BC20 is HBoV2, and 98.77% of its nt sequence is identical with those of other HBoVs, namely Rus-Nsc10-N386. Especially, the ORF3 amino acid sequences from positions 212–213 and 454 corresponding to a variable region (VR)1 and VR5, respectively, showed genotype-specific substitutions that distinguished the four HBoV genotypes. As the first whole-genome sequence analysis of HBoV in South Korea, this information will provide a valuable reference for the detection of recombination, tracking of epidemics and development of diagnosis methods for HBoV.
Outpatient parenteral antimicrobial therapy (OPAT) programmes facilitate hospital discharge, but patients remain at risk of complications and consequent healthcare utilisation (HCU). Here we elucidated the incidence of and risk factors associated with HCU in OPAT patients. This was a retrospective, single-centre, case–control study of adult patients discharged on OPAT. Cases (n = 63) and controls (n = 126) were patients that did or did not utilise the healthcare system within 60 days. Characteristics associated with HCU in bivariate analysis (P ≤ 0.2) were included in a multivariable logistic regression model. Variables were retained in the final model if they were independently (P < 0.05) associated with 60-day HCU. Among all study patients, the mean age was 55 ± 16, 65% were men, and wound infection (22%) and cellulitis (14%) were common diagnoses. The cumulative incidence of 60-day unplanned HCU was 27% with a disproportionately higher incidence in the first 30 days (21%). A statin at discharge (adjusted odds ratios (aOR) 0.23, 95% confidence intervals (CIs) 0.09–0.57), number of prior admissions in past 12 months (aOR 1.48, 95% CIs 1.05–2.10), and a sepsis diagnosis (aOR 4.62, 95% CIs 1.23–17.3) were independently associated with HCU. HCU was most commonly due to non-infection related complications (44%) and worsening primary infection (31%). There are multiple risk factors for HCU in OPAT patients, and formal OPAT clinics may help to risk stratify and target the highest risk groups.
This study evaluated the annual prevalence of anogenital warts (AGW) caused by human papillomavirus (HPV) and analysed the trend in annual per cent changes (APC) by using national claims data from the Health Insurance Review and Assessment of Korea, 2007–2015. We also estimated the socio-economic burden and co-morbidities of AGW. All analyses were performed based on data for primary A63.0, the specific diagnosis code for AGW. The socio-economic cost of AGW was calculated based on the direct medical cost, direct non-medical cost and indirect cost. The overall AGW prevalence and socio-economic burden has increased during the last 9 years. However, the prevalence of AGW differed significantly by sex. The female prevalence increased until 2012, and decreased thereafter (APC + 3·6%). It would fall after the introduction of routine HPV vaccination, principally for females, in Korea. The male prevalence increased continuously over time (APC + 11·6%), especially in those aged 20–49 years. Referring to the increasing AGW prevalence and its disease burden, active HPV infection control surveillance and prevention in males are worth consideration.
This study aimed to identify the effect of lateral neck dissection on voice change in thyroidectomised patients.
Medical records from 264 patients who underwent thyroidectomy with (n = 65) or without (n = 199) lateral neck dissection were reviewed. Clinical and voice evaluation data were compared between the two groups.
Patients who underwent surgery that included lateral neck dissection had lower fundamental frequencies and speaking fundamental frequencies. They also had a higher incidence of asymmetric mucosal wave and vocal fold oedema on videostroboscopy during the first month after surgery, with the incidence of vocal fold oedema remaining significantly higher at three months. Self-assessed voice quality scores were significantly higher in lateral neck dissection patients at both one and three months after surgery.
In thyroidectomised patients, lateral neck dissection lowers the vocal pitch in the initial period after surgery and induces vocal fold oedema that persists for several months. Although most objective parameters improved within a month, subjective symptoms lasted for longer.
Noroviruses (NoVs) are major causal agents of acute gastroenteritis in humans. NoV GII.4 is the predominant genotype globally. However, uncommon and minor types of NoVs are consistently detected and some have been shown to dominate over GII.4. Therefore, the prevalence of dominant and uncommon NoVs makes the identification of these viruses important for the prediction and prevention of pandemics. In this study, the full-genome sequence of a NoV (strain JW) detected in Korea was extensively characterized. The full-length genome was 7510 nucleotides long, and phylogenetic analysis based on the whole-genome sequences, including open reading frame (ORF)1, ORF2, and ORF3, indicated that it belonged to the GII.21 genotype. Strain JW showed maximum identity with strain YO284; however, comparison of the amino acid sequence of ORF2, which functions as an antigen, showed substitutions in several amino acids. GII.21 is not a prevalent epidemiological agent of acute gastroenteritis in humans, but it is consistently found in gastroenteritis patients from several countries. The present study provides the first full-genome sequence analysis of NoV GII.21 isolated from a patient in Korea. Our findings provide not only valuable genome information but also data for epidemiology studies, epidemic prevention, and vaccine development strategies.
Conchal cartilage is frequently used in rhinoplasty, but donor site morbidity data are seldom reported. This study aimed to investigate the complications of conchal cartilage harvesting in rhinoplasty.
A retrospective chart review of 372 patients who underwent conchal cartilage harvesting for rhinoplasty was conducted. Data regarding patient demographics, types of nasal deformities, graft usage and complications were analysed.
A total of 372 patients who underwent conchal cartilage harvesting for rhinoplasty were enrolled. The harvested conchal cartilage tissues were used in a variety of applications: tip graft, dorsal graft, septal reinforcement and correction of nostril asymmetry. Nine cases (2.4 per cent) with donor site morbidities were identified, including four cases (1.1 per cent) with keloids and five cases (1.3 per cent) with haematomas.
Conchal cartilage harvesting is a safe and useful technique for rhinoplasty, with a low complication rate. However, patients should be informed about the possibility of donor site morbidities such as keloids and haematomas.
This study aimed to examine the association between vitamin B6, folate and vitamin B12 biomarkers and plasma fatty acids in European adolescents. A subsample from the Healthy Lifestyle in Europe by Nutrition in Adolescence study with valid data on B-vitamins and fatty acid blood parameters, and all the other covariates used in the analyses such as BMI, Diet Quality Index, education of the mother and physical activity assessed by a questionnaire, was selected resulting in 674 cases (43 % males). B-vitamin biomarkers were measured by chromatography and immunoassay and fatty acids by enzymatic analyses. Linear mixed models elucidated the association between B-vitamins and fatty acid blood parameters (changes in fatty acid profiles according to change in 10 units of vitamin B biomarkers). DHA, EPA) and n-3 fatty acids showed positive associations with B-vitamin biomarkers, mainly with those corresponding to folate and vitamin B12. Contrarily, negative associations were found with n-6:n-3 ratio, trans-fatty acids and oleic:stearic ratio. With total homocysteine (tHcy), all the associations found with these parameters were opposite (for instance, an increase of 10 nmol/l in red blood cell folate or holotranscobalamin in females produces an increase of 15·85 µmol/l of EPA (P value <0·01), whereas an increase of 10 nmol/l of tHcy in males produces a decrease of 2·06 µmol/l of DHA (P value <0·05). Positive associations between B-vitamins and specific fatty acids might suggest underlying mechanisms between B-vitamins and CVD and it is worth the attention of public health policies.
Extended-spectrum β-lactamase (ESBL) production has been very rare in serotype K1 Klebsiella pneumoniae ST23 strains, which are well-known invasive community strains. Among 92 ESBL-producing strains identified in 218 isolates from nine Asian countries, serotype K1 K. pneumoniae strains were screened. Two ESBL-producing K. pneumoniae isolates from Singapore and Indonesia were determined to be serotype K1 and ST23. Their plasmids, which contain CTX-M-15 genes, are transferable rendering the effective transfer of ESBL resistance plasmids to other organisms.
In the fields of engineering, nanoscience, and biomechanics, thin structural members, such as beams, plates, and shells, that are supported by an elastic medium are used in several applications. There is a possibility that these thin structures might buckle under severe loading conditions; higher-order, complicated elastic buckling modes can be found owing to the balance of rigidities between the thin members and elastic supports. In this study, we have shown a new and simple ‘power law’ relation between the critical buckling strain (or loads) and rigidity parameters in structural members supported by an elastic medium, which can be modelled as a Winkler foundation. The following structural members have been considered in this paper: i) a slender beam held by an outer elastic support under axial loading, ii) cylindrical shells supported by an inner elastic core under hydrostatic pressure (plane strain condition), and iii) complete spherical shells that are filled with an inner elastic medium.
Sparganosis is one of the top three tissue-dwelling heterologous helminthic diseases, along with cysticercosis and paragonimiasis, in Korea. Due to a lack of effective early diagnosis and treatment methods, this parasitic disease is regarded as a public health threat. This study evaluated reactivity, against sparganum extracts, of sera from inhabitants of Cheorwon-gun, Goseong-gun and Ongjin-gun in Korea. The sera from 836 subjects were subjected to enzyme-linked immunosorbent assay and immunoblot analysis. The sera from 18 (5.8%) and 15 (5.1%) inhabitants in Cheorwon-gun (n = 312) and Goseong-gun (n = 294), respectively, exhibited highly positive reactions to the sparganum antigen, whereas only two (0.9%) inhabitants in Ongjin-gun (n = 230) showed positivity. We sought antigenic proteins for serodiagnosis of positive sera by immunoproteomic approaches. Total sparganum lysates were separated by two-dimensional electrophoresis and then subjected to immunoblot analysis with mixed sparganosis-positive sera. We found seven antigenic spots and identified paramyosin as an antigenic protein by liquid chromatography–mass spectrometry. By two-dimensional (2D)-based mass analysis and immunoblotting against sparganosis-positive sera, paramyosin was identified as a candidate antigen for serodiagnosis of sparganosis.
We present recent observation results of Sgr A* at millimeter obtained with VLBI arrays in Korea and Japan.
7 mm monitoring of Sgr A* is part of our AGN large project. The results at 7 epochs during 2013-2014, including high resolution maps, flux density and two-dimensional size measurements are presented. The source shows no significant variation in flux and structure related to the G2 encounter in 2014. According to recent MHD simulations by kawashima et al., flux and magnetic field energy can be expected to increase several years after the encounter; We will keep our monitoring in order to test this prediction.
Astrometric observations of Sgr A* were performed in 2015 at 7 and 3.5 millimeter simultaneously. Source-frequency phase referencing was applied and a combined ”core-shift” of Sgr A* and a nearby calibrator was measured. Future observations and analysis are necessary to determine the core-shift in each source.
This research examined gender variations in depressive mood for high school students affected by emotional upset and how such depressive mood affect their sleep quality.
Research was conducted from September 2015 to October 2015. Both males and females were divided into normal group and depressive group by Zung Self-rating Depression Scale (ZSDS). Each group adopted the Pittsburgh Sleep Quality Index (PSQI) to measure sleep quality.
Analysis was made on a total of 155 students, which were 83 male students and 72 female. The average ZSDS for all high school students was 43.38 and the average PSQI was 5.39. The number of male students in the normal and depressive group who were diagnosed with sleep disorder were 2 (3.8%) and 9 (29.0%), respectively (P < 0.05). But the number of female students in the normal and depressive group who were diagnosed with sleep disorder were 11 (32.4%) and 33 (86.8%), respectively (P < 0.05). Both males and females shared a meaningful result over sleep latency, sleep disturbance, use of sleep medication, and daytime functional disturbance among 7 items of PSQI for sleep quality, and female students had a significantly meaningful result over sleep duration, habitual sleep effects (P < 0.05).
This research showed that sleep quality of all high school students was not too bad but it can be problematic for those with depressive mood. Especially, female students were diagnosed with sleep disorder more than male students.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
An acute gastroenteritis (AGE) outbreak was reported in May 2013 in Gyeonggi Province, South Korea. Eight students who had eaten breakfast on 21 May 2013 at a high-school restaurant exhibited AGE symptoms. Our case-control study showed that a strong association was observed between AGE symptoms and fermented oyster consumption. Virological studies also indicated that noroviruses (NoVs) were detected from both clinical samples and fermented oyster samples, and multiple different genotypes (genogroups GII.4, GII.11 and GII.14) of NoVs were present in both samples. The nucleotide sequence similarity between the strains found in the clinical samples and those in the fermented oysters was more than 99·5%. Therefore, to prevent further outbreaks, proper management of raw oysters is necessary and the food industry should be aware of the risk of viral gastroenteritis posed by fermented oysters contaminated with NoVs.
Obsessive–compulsive disorder (OCD) has been associated with abnormal cognitive and emotional functions and these dysfunctions may be dependent on the disruption of dynamic interactions within neuronal circuits associated with emotion regulation. Although several studies have shown the aberrant cognitive–affective processing in OCD patients, little is known about how to characterize effective connectivity of the disrupted neural interactions. In the present study, we applied effective connectivity analysis using dynamic causal modeling to explore the disturbed neural interactions in OCD patients.
A total of 20 patients and 21 matched healthy controls performed a delayed-response working memory task under emotional or non-emotional distraction while undergoing functional magnetic resonance imaging.
During the delay interval under negative emotional distraction, both groups showed similar patterns of activations in the amygdala. However, under negative emotional distraction, the dorsolateral prefrontal cortex (DLPFC) and the orbitofrontal cortex (OFC) exhibited significant differences between groups. Bayesian model averaging indicated that the connection from the DLPFC to the OFC was negatively modulated by negative emotional distraction in patients, when compared with healthy controls (p < 0.05, Bonferroni-corrected).
Exaggerated recruitment of the DLPFC may induce the reduction of top-down prefrontal control input over the OFC, leading to abnormal cortico-cortical interaction. This disrupted cortico-cortical interaction under negative emotional distraction may be responsible for dysfunctions of cognitive and emotional processing in OCD patients and may be a component of the pathophysiology associated with OCD.
Obsessive-compulsive disorder (OCD) is a chronic, relapsing mental illness. Selective serotonin reuptake inhibitors block serotonin transporters (SERTs) and are the mainstay of treatment for OCD. SERT abnormalities are reported in drug-free patients with OCD, but it is not known what happens to SERT levels during treatment. This is important as alterations in SERT levels in patients under treatment could underlie poor response, or relapse during or after treatment. The aim of the present study was first to validate a novel approach to measuring SERT levels in people taking treatment and then to investigate SERT binding potential (BP) using [11C]DASB PET in patients with OCD currently treated with escitalopram in comparison with healthy controls.
Twelve patients and age- and sex-matched healthy controls were enrolled. The patients and healthy controls underwent serial PET scans after administration of escitalopram and blood samples for drug concentrations were collected simultaneously with the scans. Drug-free BPs were obtained by using an inhibitory Emax model we developed previously.
The inhibitory Emax model was able to accurately predict drug-free SERT BP in people taking drug treatment. The drug-free BP in patients with OCD currently treated with escitalopram was significantly different from those in healthy volunteers [Cohen's d = 0.03 (caudate), 1.16 (putamen), 1.46 (thalamus), −5.67 (dorsal raphe nucleus)].
This result extends previous findings showing SERT abnormalities in drug-free patients with OCD by indicating that altered SERT availability is seen in OCD despite treatment. This could account for poor response and the high risk of relapse in OCD.
Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable psychiatric disorder. Additionally, environmental factors such as perinatal stress and early adversities contribute to the occurrence and severity of ADHD. Recently, DNA methylation has emerged as a mechanism that potentially mediates gene–environmental interaction effects in the aetiology and phenomenology of psychiatric disorders. Here, we investigated whether serotonin transporter gene (SLC6A4) methylation patterns were associated with clinical characteristics and regional cortical thickness in children with ADHD.
In 102 children with ADHD (age 6–15 years), the methylation status of the SLC6A4 promoter was measured. Brain magnetic resonance imaging was obtained and ADHD symptoms were evaluated.
A higher methylation status of the SLC6A4 promoter was significantly associated with worse clinical presentations (more hyperactive-impulsive symptoms and more commission errors). Additionally, a negative correlation was observed between SLC6A4 methylation levels and cortical thickness values in the right occipito-temproral regions.
Our results suggest that the SLC6A4 methylation status may be associated with certain symptoms of ADHD, such as behavioural disinhibition, and related brain changes. Future studies that use a larger sample size and a control group are required to corroborate these results.