PcrA helicase dismantles RecA filaments by reeling in DNA in uniform steps.

Translocation of helicase-like proteins on nucleic acids underlies key cellular functions. However, it is still unclear how translocation can drive removal of DNA-bound proteins, and basic properties like the elementary step size remain controversial. Using single-molecule fluorescence analysis on a prototypical superfamily 1 helicase, Bacillus stearothermophilus PcrA, we discovered that PcrA preferentially translocates on the DNA lagging strand instead of unwinding the template duplex. PcrA anchors itself to the template duplex using the 2B subdomain and reels in the lagging strand, extruding a single-stranded loop. Static disorder limited previous ensemble studies of a PcrA stepping mechanism. Here, highly repetitive looping revealed that PcrA translocates in uniform steps of 1 nt. This reeling-in activity requires the open conformation of PcrA and can rapidly dismantle a preformed RecA filament even at low PcrA concentrations, suggesting a mode of action for eliminating potentially deleterious recombination intermediates.

Therapeutic effectiveness of probiotics for atopic dermatitis: A systematic review and meta-analysis of randomized controlled trials with subgroup analysis.

BACKGROUND: The effect of probiotics in the treatment of atopic dermatitis (AD) is inconclusive, partially due to the heterogeneities of AD. OBJECTIVE: The aim of the present study was to investigate the efficacy of probiotics in the treatment of AD with a subgroup analysis according to country, severity of AD, duration of supplementation, and probiotic strain. METHODS: Original articles reporting the therapeutic efficacy of probiotics for AD were identified by searching PubMed, Cochrane Library databases, and Embase from inception to September 30, 2022. RESULTS: This meta-analysis included 1,382 patients with AD from 25 randomized controlled trials. Probiotic supplementation was effective for the treatment of AD, reflected in a significant decrease in the SCORing Atopic Dermatitis (SCORAD) index (SMD, -4.0; 95%CI, -7.3 to -0.7). The subgroup analysis showed a significant therapeutic effect for AD among patients with mild or moderate AD (SMD, -1.4; 95%CIs -2.2 to -0.7), in those supplemented for more than three months (SMD, -5.1; 95%CIs -9.7 to -0.4), and in those supplemented with a probiotic that contained Lactobacillus spp. strains combined with or without other strains (SMD, -4.4; 95%CIs -8.0 to -0.8). In addition, the therapeutic effects of probiotics showed differences according to country and geographic region. CONCLUSIONS: Probiotics can be beneficial for the treatment of AD, and their therapeutic effect may be individually tailored to improve it based on the severity of AD, strain of probiotics, duration of supplementation, and geographic region.

Effects of mechanical washing and drying on the removal of pet allergens.

Background: In Korea, the number of households with indoor pets is rapidly increasing in parallel with changes in cultural lifestyles. The sensitization rate of pet allergens is also increasing in Korea. Objective: We evaluated the effectiveness of washing machines to remove dog and cat hair and their allergens. In addition, this study aimed to investigate whether only a mechanical dryer without mechanical washing could be used for pet allergen removal. Method: We brushed cats and dogs, and thereafter collected their hair and used a residential vacuum cleaner to obtain dust and other particulate matter from a household. The contents of the vacuum bag were sifted through a 300-µm sieve filter. Some of the contents were placed in phosphate-buffered saline solution with 0.5% Tween 20 to make a liquid extract. Hair, dust, and liquid extract-contaminated fabric samples after mechanical washing or after drying without mechanical washing were analyzed for pet allergens (Fel d l [cat], Can f 1 [dog]) by using a two-site enzyme-linked immunosorbent assay. We assessed the remaining allergens in the contaminated fabrics after mechanical drying and washing. Results: The mean Fel d l and mean Can f 1 removal ratios after mechanical washing with detergent were > 99.99% for the dust, hair, and liquid extract. The removal ratios after mechanical washing without a detergent were lower for both Fel d 1 and Can f 1, for hair, dust, and their respective liquid extracts (p < 0.05). Mechanical drying was just as effective as mechanical washing with detergent for removing Can f 1 but was less effective for Fel d 1 (p < 0.05). Conclusion: Mechanical washing with detergent is important to remove pet allergens from contaminated fabrics. If washing is difficult, then using just a dryer without washing can be an alternative method to remove allergens from contaminated bedding or clothing.

Increased sensitization rates to tree pollens in allergic children and adolescents and a change in the pollen season in the metropolitan area of Seoul, Korea.

INTRODUCTION: Children with allergies are at greater risk of becoming sensitized to allergenic pollens in response to environmental changes. This study investigated the relationship between changes in pollination associated with meteorologic changes and the sensitization rates of children to tree pollen allergens in the metropolitan area of Seoul, Korea. METHODS: The study population consisted of 8,295 children who visited the pediatric allergy clinics at Hanyang University Seoul and Guri Hospital for allergy symptoms between January 1, 1998, and December 31, 2019. Pollen was collected at the two hospitals during the study using a Burkard 7-day sampler. Meteorologic data were obtained from the National Weather Service. RESULTS: Among the major tree pollens, the largest increase in allergic sensitization was to oak, hazel, and alder pollens (0.28% annually). The pollen-sensitization rates increased annually within younger age groups. The duration of the pollen season was 98 days in 1998 and 140 days in 2019. Positive correlations were determined between the duration of the pollen season and the rates of sensitization to tree pollens, as well as between the pollen-sensitization rates and increasing temperature. CONCLUSIONS: This study demonstrated the correlation between weather changes and the resulting changes in the pollen season with sensitization rates to allergenic pollens in children living in the Seoul metropolitan area. An annual increase in sensitization rates in younger children was determined. This pattern is expected to continue due to continuing climate change.

Annual and seasonal patterns in etiologies of pediatric community-acquired pneumonia due to respiratory viruses and Mycoplasma pneumoniae requiring hospitalization in South Korea.

BACKGROUND: Community-acquired pneumonia (CAP) is one of the leading worldwide causes of childhood morbidity and mortality. Its disease burden varies by age and etiology and is time dependent. We aimed to investigate the annual and seasonal patterns in etiologies of pediatric CAP requiring hospitalization. METHODS: We conducted a retrospective study in 30,994 children (aged 0-18 years) with CAP between 2010 and 2015 at 23 nationwide hospitals in South Korea. Mycoplasma pneumoniae (MP) pneumonia was clinically classified as macrolide-sensitive MP, macrolide-less effective MP (MLEP), and macrolide-refractory MP (MRMP) based on fever duration after initiation of macrolide treatment, regardless of the results of in vitro macrolide sensitivity tests. RESULTS: MP and respiratory syncytial virus (RSV) were the two most commonly identified pathogens of CAP. With the two epidemics of MP pneumonia (2011 and 2015), the rates of clinical MLEP and MRMP pneumonia showed increasing trends of 36.4% of the total MP pneumonia. In children < 2 years of age, RSV (34.0%) was the most common cause of CAP, followed by MP (9.4%); however, MP was the most common cause of CAP in children aged 2-18 years of age (45.3%). Systemic corticosteroid was most commonly administered for MP pneumonia. The rate of hospitalization in intensive care units was the highest for RSV pneumonia, and ventilator care was most commonly needed in cases of adenovirus pneumonia. CONCLUSIONS: The present study provides fundamental data to establish public health policies to decrease the disease burden due to CAP and improve pediatric health.

Compound heterozygous mutations of SH3TC2 in Charcot-Marie-Tooth disease type 4C patients.

Charcot-Marie-Tooth disease type 4C (CMT4C) is an autosomal recessive neuropathy caused by SH3TC2 mutations, characterized by spine deformities and cranial nerve involvement. This study identified four CMT4C families with compound heterozygous SH3TC2 mutations from 504 Korean demyelinating or intermediate CMT patients. The frequency of the CMT4C was calculated as 0.79% in demyelinating and intermediate patients (n = 504), but it was calculated as 2.02% in patients without PMP22 duplication (n = 198). The CMT4C frequency was similar to patients in Japan, but it was relatively low compared to those patients in other populations. The symptom was less severe and slowly progressed compared to the other AR-CMT. A patient harboring an intermediate neuropathy showed cranial nerve involvement but did not have scoliosis. This study will be helpful in making molecular diagnoses of demyelinating or intermediate CMT due to SH3TC2 mutations.

Serum Periostin Level Has Limited Usefulness as a Biomarker for Allergic Disease in 7-Year-Old Children.

BACKGROUND: Previous studies have used serum periostin levels as a biomarker of Th2-driven inflammatory responses. However, no population-based study has yet examined the association of serum periostin levels with the allergic status of children. OBJECTIVES: The aim of this study was to determine the usefulness of periostin as a biomarker for allergy in a group of 7-year-old Korean children. METHOD: This prospective cross-sectional study examined 451 children (aged 7 years to 7 years and 11 months) from the general pediatric population who attended 6 different schools between June and July 2016. A total of 249 children, all of whom completed the questionnaire and skin prick test and provided blood samples, were included in the final analysis. RESULTS: The geometric mean serum periostin level was 107.6 ng/mL (95% CI 104.5-110.7). After adjustment for confounding, serum periostin levels were significantly associated with sensitization to poly-allergens (adjusted odds ratio, aOR 1.032, 95% CI 1.006-1.059, p = 0.016) and pollen (aOR 1.020, 95% CI 1.002-1.039, p = 0.026). Serum periostin levels were also associated with eosinophil levels (adjusted ß = 0.023, SE = 0.009, p = 0.010), but were unrelated to body mass index, sex, obesity, or presence of an allergic disease. CONCLUSIONS: Our results suggest thatserum periostin level may have limited usefulness as a biomarker of allergic disease in children.

Efficacy of glucocorticoids for the treatment of macrolide refractory mycoplasma pneumonia in children: meta-analysis of randomized controlled trials.

BACKGROUND: Mycoplasma pneumoniae is one of the most common pathogens causing community acquired pneumonia in children. Although the rate of macrolide-refractory Mycoplasma pneumoniae (MRMP) has increased, systemic glucocorticoids as a treatment option has not been validated yet. The purpose of this study was to assess the efficacy of glucocorticoids add-on in the treatment of MRMP in children through systematic review and meta-analysis. METHODS: Data sources A systematic literature search was conducted using ten electronic bibliographic databases including English, Korean, Chinese and Japanese languages, up to March 8, 2018. Study selection The study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist and selected randomized control trials which compared the efficacy of glucocorticoids add-on to macrolide in the treatment of MRMP in children. Data extraction Two independent reviewers extracted: primary outcomes as hospital days, fever duration, and change in C-reactive protein (CRP) and main analysis was performed through meta-analysis with random effects model. RESULTS: Twenty-four unique randomized controlled trials met the inclusion criteria. The mean length of hospital stay in glucocorticoids treatment group was significantly shorter than that in conventional macrolide-treatment group (Weighted mean difference (WMD) = - 4.03 days). The mean length of fever duration was significantly shorter in the glucocorticoid treatment group in comparison with the conventional treatment group (WMD = -3.32 days). Level of CRP after treatment was significantly lower in the glucocorticoid treatment group than that in the conventional treatment group (WMD = -16.03). Sensitivity analysis and subgroup analysis showed no significant improvement in heterogeneity. As limitations of the study, most of the studies included were from a single country and we were unable to control for heterogeneity across interventions, lack of standardized measures, and different time points of assessments across studies. CONCLUSIONS: Glucocorticoid add-on treatment for MRMP can significantly shorten the duration of fever and hospital stay and decrease the level of CRP. These results should be confirmed by adequately powered studies in the future.

Impulse oscillometry and spirometry exhibit different features of lung function in bronchodilation.

OBJECTIVE: Bronchodilator responses (BDRs) from impulse oscillometry (IOS) are not interchangeable with those from spirometry. We aimed to identify the characteristics of children with small airway hyperresponsiveness and to determine whether BDR from IOS provides an important supplement to BDR from spirometry. METHODS: The records of 592 children with asthma or suspected asthma who underwent spirometric and oscillometric BDRs were retrospectively reviewed. Oscillometric BDR was defined as positive when relative or absolute changes of Rrs5 or Xrs5 were beyond two standard deviations and spirometric BDR as positive when absolute change of forced expiratory volume in one second (FEV1) was ≥12%. Subjects were classified as positive for spirometric BDR only, positive for oscillometric BDR only, positive for both BDRs, or negative for both BDRs. RESULTS: The results indicated that 101 (17.6%) subjects were positive for spirometric BDR only, 49 (8.5%) positive for oscillometric BDR only, 48 (8.3%) positive for both BDRs, and 377 (65.6%) negative for both BDRs. The agreement between spirometric and oscillometric BDRs was poor. Baseline FEV1, Rrs5, and Xrs5 values strongly influenced the BDRs. Subjects positive for oscillometric BDR only were found to be younger than those positive for spirometric BDR only (P < 0.001). Subjects positive for both BDRs were more likely to have asthma, atopic dermatitis, wheezing apart from cold, or decreased baseline lung function relative to those positive in either test (P < 0.001). CONCLUSIONS: There was a low concordance between spirometric and oscillometric BDRs. Use of IOS to detect small airway hyperresponsiveness may add more information about a clinical profile of subjects with asthma.

Small airway bronchodilator response to different doses of salbutamol in 7-year-old children.

The Global Initiative for Asthma (GINA) guidelines do not specify a bronchodilator range for bronchodilator response (BDR) testing and simply recommend a salbutamol dose of 200 to 400 µg. We determined the oscillometric BDR results of children given low-dose (2 puffs, 200 µg) and standard-dose (4 puffs, 400 µg) salbutamol to compare the small airway responses of healthy controls (defined using criteria based on the guidelines developed at the American Thoracic Society) and exclusion subjects (defined as any child that did not meet the inclusion criteria for healthy controls). The oscillometric reactance of small airways is significantly associated with the dose of salbutamol used for BDR testing in exclusion children. We suggest use of the standard-dose of salbutamol for oscillometric BDR testing.

Prevalence and Clinical Characteristics of Local Allergic Rhinitis in Children Sensitized to House Dust Mites.

OBJECTIVE: The prevalence of local allergic rhinitis (LAR) in nonatopic children remains unknown. This study aimed to determine the prevalence, clinical characteristics, and severity of LAR in children in comparison to classical allergic rhinitis (AR) and nonallergic rhinitis (NAR). STUDY DESIGN: A total of 145 children (aged 1-18 years) were enrolled and classified into 3 groups (AR, NAR, and LAR) based on a skin prick test (SPT) and a nasal provocation test (NPT) with house dust mite, i.e., Dermatophagoides pteronyssinus. NPT positivity was defined as a symptom score ≥2 standard deviations (SDs) above the healthy control score. RESULTS: Eighty-one children had AR (55.9%), and 64 (44.1%) had symptoms of rhinitis with negative SPT; 59 NAR (40.7%) and 5 LAR (3.4%) children were identified. The κ score for agreement between the SPT and the NPT results was 0.778 (95% CI 0.726-0.830, p < 0.001). A significant correlation was observed between wheal diameter and maximum nasal symptom score provoked by D.pteronyssinus (rho = 0.589, p < 0.001). Nasal severity according to the ARIA guideline did not show any differences in the 3 groups (p = 0.693). The AR group was older than the LAR and NAR groups (AR > LAR > NAR, p = 0.003). CONCLUSIONS: Despite the evidence to support the existence of LAR in pediatric populations, we found that its prevalence was relatively low, possibly due to the high rate of agreement between SPT and NPT. Further investigations are needed to identify immunological as well as clinical implications of LAR.

An association of periostin levels with the severity and chronicity of atopic dermatitis in children.

BACKGROUND: Serum periostin might be a biomarker in the pathogenesis of T helper 2-type allergic diseases. The aim of this study was to investigate the relationship between serum periostin levels and the severity and chronicity of atopic dermatitis (AD) in children. METHODS: This population-based study examined 4076 children aged 4 to 13 years between June 2015 and July 2015. Of the 4076 children, 196-137 with a history of AD in the AD group and 59 without allergic diseases history in the healthy control (HC) group-were included for the final analysis. RESULTS: Serum periostin levels were higher in the AD group than in the HC group (P<.001) and were found to be positively associated with SCORAD score (Spearman's rho [r]=.24, P=.001). Children with AD-onset time <2 years had significantly higher periostin levels (P=.030) compared to those with AD-onset time ≥2 years. The total eosinophil (P=.189) and IgE levels (P=.140) were comparable between children with AD-onset time <2 years and those with AD-onset time ≥2 years. After adjustment for age, gender, and parental allergic history, serum periostin level (OR: 1.03, 95% CI: 1.00-1.06, P=.046) contributed to the development of AD in children with AD-onset time <2 years. CONCLUSION: Serum periostin level may play a role in the severity and chronicity of AD in children.

Single-molecule packaging initiation in real time by a viral DNA packaging machine from bacteriophage T4.

Viral DNA packaging motors are among the most powerful molecular motors known. A variety of structural, biochemical, and single-molecule biophysical approaches have been used to understand their mechanochemistry. However, packaging initiation has been difficult to analyze because of its transient and highly dynamic nature. Here, we developed a single-molecule fluorescence assay that allowed visualization of packaging initiation and reinitiation in real time and quantification of motor assembly and initiation kinetics. We observed that a single bacteriophage T4 packaging machine can package multiple DNA molecules in bursts of activity separated by long pauses, suggesting that it switches between active and quiescent states. Multiple initiation pathways were discovered including, unexpectedly, direct DNA binding to the capsid portal followed by recruitment of motor subunits. Rapid succession of ATP hydrolysis was essential for efficient initiation. These observations have implications for the evolution of icosahedral viruses and regulation of virus assembly.

Serotonin promotes exploitation in complex environments by accelerating decision-making.

BACKGROUND: Fast responses can provide a competitive advantage when resources are inhomogeneously distributed. The nematode Caenorhabditis elegans was shown to modulate locomotion on a lawn of bacterial food in serotonin (5-HT)-dependent manners. However, potential roles for serotonergic signaling in responding to food discovery are poorly understood. RESULTS: We found that 5-HT signaling in C. elegans facilitates efficient exploitation in complex environments by mediating a rapid response upon encountering food. Genetic or cellular manipulations leading to deficient serotonergic signaling resulted in gradual responses and defective exploitation of a patchy foraging landscape. Physiological imaging revealed that the NSM serotonergic neurons responded acutely upon encounter with newly discovered food and were key to rapid responses. In contrast, the onset of responses of ADF serotonergic neurons preceded the physical encounter with the food. The serotonin-gated chloride channel MOD-1 and the ortholog of mammalian 5-HT1 metabotropic serotonin receptors SER-4 acted in synergy to accelerate decision-making. The relevance of responding rapidly was demonstrated in patchy environments, where the absence of 5-HT signaling was detrimental to exploitation. CONCLUSIONS: Our results implicate 5-HT in a novel form of decision-making, demonstrate its fitness consequences, suggest that NSM and ADF act in concert to modulate locomotion in complex environments, and identify the synergistic action of a channel and a metabotropic receptor in accelerating C. elegans decision-making.

Socioeconomic and sociodemographic factors related to allergic diseases in Korean adolescents based on the Seventh Korea Youth Risk Behavior Web-based Survey: a cross-sectional study.

BACKGROUND: Various international reports have shown that socioeconomic and sociodemographic variables are correlated with allergic diseases; however, little is known about how these variables affect Korean adolescents. This study was conducted to identify socioeconomic and sociodemographic risk factors for allergic diseases in Korean adolescents to provide information for preventing and managing such conditions. METHODS: Data from the 2011 Korea Youth Risk Behavior Web-based Survey (KYRBWS-VII) of 75,643 adolescents were used. An anonymously administered online survey was conducted to collect dependent variable information on perceived sexes, residence, family affluence (Family Affluence Scale; FAS), parental education levels, subjective academic achievement, obesity, drinking and smoking. The independent variables were asthma, allergic rhinitis and atopic dermatitis. Multivariate logistic regression was used to analyze the correlations between the dependent and independent variables. RESULTS: Low subjective academic achievement, obesity, drinking and smoking were risk factors for asthma. High FAS, parental bachelor's degree and high subjective academic achievement were risk factors for allergic rhinitis. Finally, high FAS, maternal bachelor's degree and high subjective academic achievement were risk factors for atopic dermatitis. CONCLUSION: We found that high socioeconomic status (SES) was a risk factor for allergic diseases in Korean adolescents. We propose that the greater access to medical services and immunization (e.g., hygiene hypothesis) afforded by high SES influenced the prevalence of allergic diseases. Thus, as the Korean economy develops further, the prevalence of allergic diseases is likely to increase. Controlling harmful behavioral risk factors, such as drinking and smoking, may help to prevent adolescent allergic diseases.

Percentile Distributions of Birth Weight according to Gestational Ages in Korea (2010-2012).

The Pediatric Growth Chart (2007) is used as a standard reference to evaluate weight and height percentiles of Korean children and adolescents. Although several previous studies provided a useful reference range of newborn birth weight (BW) by gestational age (GA), the BW reference analyzed by sex and plurality is not currently available. Therefore, we aimed to establish a national reference range of neonatal BW percentiles considering GA, sex, and plurality of newborns in Korea. The raw data of all newborns (470,171 in 2010, 471,265 in 2011, and 484,550 in 2012) were analyzed. Using the Korean Statistical Information Service data (2010-2012), smoothed percentile curves (3(rd)-97(th)) by GA were created using the lambda-mu-sigma method after exclusion and the data were distinguished by all live births, singleton births, and multiple births. In the entire cohort, male newborns were heavier than female newborns and singletons were heavier than twins. As GA increased, the difference in BW between singleton and multiples increased. Compared to the previous data published 10 years ago in Korea, the BW of newborns 22-23 gestational weeks old was increased, whereas that of others was smaller. Other countries' data were also compared and showed differences in BW of both singleton and multiple newborns. We expect this updated data to be utilized as a reference to improve clinical assessments of newborn growth.

Disability-Adjusted Life Years for Communicable Disease in the Korean Burden of Disease Study 2012.

Globally, the incidence of communicable diseases has decreased compared to non-communicable diseases. However, chronic communicable diseases such as HIV/AIDS and tuberculosis persist worldwide. Furthermore, emerging new infections such as H1N1 influenza pose a new threat to public health. However, most studies have focused on non-communicable diseases because of their increasing incidence, with fewer studies investigating communicable diseases. Therefore, we estimated the burden of communicable diseases in Korea using national representative 2012 data. To estimate the disability-adjusted life years (DALY), we used cause of death data from the Statistics Korea to estimate the years of life lost (YLL), applied the Korean garbage code algorithm, and used national claims data from the National Health Insurance Service (NHIS) to estimate years lived with disability (YLD). In 2012, the total DALYs of communicable disease were 445 per 100,000, with 129 YLLs per 100,000 and 316 YLDs per 100,000. The total DALYs in men were 468 per 100,000, greater than the 422 per 100,000 DALYs seen in women. The DALYs of lower respiratory infections were the highest value among communicable diseases at 143/100,000 DALYs followed by tuberculosis and upper respiratory infections. The 40-49 years old age group had the largest number of total DALYs. In contrast, the over 80 years old age group had the largest number of total DALYs per 100,000 followed by the 70-79 and 0-9 years old age groups. These results enable the prioritization of interventions related to communicable diseases and can be used for evidence-based public health policies.

Visualization of the nanospring dynamics of the IkappaBalpha ankyrin repeat domain in real time.

IκBα is a crucial regulator of NFκB transcription. NFκB-mediated gene activation is robust because levels of free IκBα are kept extremely low by rapid, ubiquitin-independent degradation of newly synthesized IκBα. IκBα has a weakly folded ankyrin repeat 5-6 (AR5-6) region that is critical in establishing its short intracellular half-life. The AR5-6 region of IκBα folds upon binding to NFκB. The NFκB-bound IκBα has a long half-life and requires ubiquitin-targeted degradation. We present single molecule FRET evidence that the native state of IκBα transiently populates an intrinsically disordered state characterized by a more extended structure and fluctuations on the millisecond time scale. Binding to NFκB or introduction of stabilizing mutations in AR 6 suppressed the fluctuations, whereas higher temperature or small amounts of urea increased them. The results reveal that intrinsically disordered protein regions transition between collapsed and extended conformations under native conditions.

The use of a self-expandable stent with a self-expandable stent graft in a Fontan baffle.

Intravascular or intracardiac stenosis occurs in various congenital heart diseases or after surgical repair. Although balloon angioplasty is the first option for relieving stenosis, frequently restenosis occurs because of elastic recoil or kingking component. The use of a self-expandable stent and covered stent in congenital heart disease has been reported for selected cases. In general, they have been performed for coarctation of the aorta or aortic aneurysm. We now report successful implantation of a self-expandable stent with a self-expandable covered stent graft in a case of lateral tunnel dehiscence with stenosis after a Fontan operation.