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Several bat species act as asymptomatic reservoirs for many viruses that are highly pathogenic in other mammals. Here, we have characterized the functional diversification of the protein kinase R (PKR), a major antiviral innate defense system. Our data indicate that PKR has evolved under positive selection and has undergone repeated genomic duplications in bats in contrast to all studied mammals that have a single copy of the gene. Functional testing of the relationship between PKR and poxvirus antagonists revealed how an evolutionary conflict with ancient pathogenic poxviruses has shaped a specific bat host-virus interface. We determined that duplicated PKRs of the Myotis species have undergone genetic diversification, allowing them to collectively escape from and enhance the control of DNA and RNA viruses. These findings suggest that viral-driven adaptations in PKR contribute to modern virus-bat interactions and may account for bat-specific immunity.

Two trials were carried out to assess the effects of different ratios of standardized ileal digestible isoleucine:lysine (SID Ile:Lys) on the growth performance of broiler chickens fed low-protein diets. A total of 1,320 male chickens were distributed in each trial into 6 treatments, with 10 replicates with 22 birds each. A control diet was formulated that satisfied the nutritional requirements of the broilers, and a low-protein diet was formulated with reduced protein content, meeting broiler nutritional requirements, except for the SID Ile levels. Five SID Ile:Lys ratios (56%, 61%, 66%, 71%, and 76%) were obtained by adding l-isoleucine to the low-protein diet. The body weight (BW), body weight gain (BWG), average daily feed intake (ADFI), and feed conversion ratio (FCR) were evaluated from day 1 to day 21 in trial 1, and from day 22 to day 44 in trial 2. ANOVA was performed on the data, and the treatments were compared to the control group using Dunnett's test (P ≤ 0.05). Regression analyses were performed for modeling the variables assessed and the ratios of SID Ile:Lys. There was no significant difference between the treatments on ADFI of birds (P0.05). The BW, BWG, and FCR showed a quadratic effect as the SID Ile:Lys ratio increased in low-protein diets in trials 1 and 2 (P ≤ 0.05). In conclusion, the recommended ratio of SID Ile:Lys in low-protein diets for growth performance is around 66% for broiler chickens from 1 to 21 d old and is around 65% for broiler chickens from 22 to 44 d old.

Quantitative high throughput screening (qHTS) assays are used to assess toxicity for many chemicals in a short period by collectively analyzing them at several concentrations. Data are routinely analyzed using nonlinear regression models; however, we propose a new method to analyze qHTS data using a nonlinear mixed effects model. qHTS data are generated by repeating the same experiment several times for each chemical; therefor, they can be viewed as if they are repeated measures data and hence analyzed using a nonlinear mixed effects model which accounts for both intra- and inter-individual variabilities. Furthermore, we apply a one-step approach incorporating robust estimation methods to estimate fixed effect parameters and the variance-covariance structure since outliers or influential observations are not uncommon in qHTS data. The toxicity of chemicals from a qHTS assay is classified based on the significance of a parameter related to the efficacy of the chemicals using the proposed method. We evaluate the performance of the proposed method in terms of power and false discovery rate using simulation studies comparing with one existing method. The proposed method is illustrated using a dataset obtained from the National Toxicology Program.

Introduction: Elevated perceived stress is associated with adverse outcomes following myocardial infarction (MI) and accounts in part for poorer recovery in women compared with men. The goal of this multicenter randomized controlled trial was to assess efficacy of a telephone-based stress management program on perceived stress, depressive symptoms, anxiety and quality of life (QOL) among women with MI. Methods: Women with elevated stress levels (Perceived Stress Scale [PSS-4]≥6) at least 2 months after MI were enrolled from 12 hospitals in the U.S. and Canada participating in the NYU Women’s Heart Attack Research Program (HARP). Participants were randomized in 12 cohorts to stress management (mindfulness-based cognitive therapy adapted for telephone; MBCT-T) or enhanced usual care (EUC; heart disease education) and followed for 6 months. Both programs were delivered by phone in 8 weekly sessions (group and individual, respectively). Linear mixed effects models were used to test between-group differences in PSS-10 scores (primary outcome), depressive symptoms (PHQ-9), anxiety (Hospital Anxiety and Depression Scale) and QOL (Seattle Angina Questionnaire, PROMIS-Global) at 6 months. Results: The sample included 130 women with elevated stress at ≥2 months from MI (age 59.8±12.8 years, 33.8% racial/ethnic minorities, 26.2% with MI with non-obstructive coronary arteries [MINOCA]). Mean baseline PSS-10 scores were similar (18.2±5.2 MBCT-T vs. 18.3±5.6 EUC). The median number of sessions completed was 7 (IQR 3,8) for MBCT-T and 8 (IQR 6,8) for EUC. The 6-month retention rates were 82.1% (MBCT-T) and 82.5% (EUC). Perceived stress and anxiety declined in the EUC arm (p Conclusions: Stress management did not improve perceived stress or secondary outcomes more than enhanced usual care. Identifying predictors of treatment response will inform future studies of psychosocial interventions for women with MI.

Data visualization design often requires creativity, and research is needed to understand its nature and means for promoting it. The current visualization literature on creativity is not well developed, especially with respect to the experiences of professional data visualization designers. We conducted semi-structured interviews with 15 data visualization practitioners, focusing on a specific aspect of creativity known as design fixation. Fixation occurs when designers adhere blindly or prematurely to a set of ideas that limit creative outcomes. We present practitioners' experiences and perspectives from their own design practice, specifically focusing on their views of (i) the nature of fixation, (ii) factors encouraging fixation, and (iii) factors discouraging fixation. We identify opportunities for future research related to chart recommendations, inspiration, and perspective shifts in data visualization design., IEEE 2021 Visualization Conference (VIS), short papers

BACKGROUND: Korean American immigrants (KAIs) face diverse sociocultural stressors in the acculturation process. While stress is known to cause short sleep, little is known about how acculturative stress affects sleep differently for KAI men and women. The purpose of this cross-sectional study was to examine gender differences in the association between diverse domains of acculturative stress and sleep duration among KAIs. METHODS: Middle-aged KAIs were recruited in community settings and online. KAIs completed validated measures of acculturative stress (homesickness, social isolation, employment barriers, discrimination, civic disengagement, and family problems) and sleep duration. Multiple linear regression analysis was performed and stratified by gender. RESULTS: 343 KAIs participated (mean age = 41±10 years, 47% female, 11% short sleepers [

The Go Red for Women movement was initiated by the American Heart Association (AHA) in the early 2000s to raise awareness concerning cardiovascular disease (CVD) risk in women. In 2016, the AHA funded 5 research centers across the United States to advance our knowledge of the risks and presentation of CVD that are specific to women. This report highlights the findings of the centers, showing how insufficient sleep, sedentariness, and pregnancy‐related complications may increase CVD risk in women, as well as presentation and factors associated with myocardial infarction with nonobstructive coronary arteries and heart failure with preserved ejection fraction in women. These projects were augmented by collaborative ancillary studies assessing the relationships between various lifestyle behaviors, including nightly fasting duration, mindfulness, and behavioral and anthropometric risk factors and CVD risk, as well as metabolomic profiling of heart failure with preserved ejection fraction in women. The Go Red for Women Strategically Focused Research Network enhanced the evidence base related to heart disease in women, promoting awareness of the female‐specific factors that influence CVD.

Introduction: Physical activity (PA), sedentary behavior (SB) and sleep form the finite 24-hour day; changes to one behavior result in changes to the others. Little is known about how shifting the balance of time spent in these behaviors affects cardiovascular (CV) risk factors. The purpose of this study is to model the effects of changes in PA, SB and sleep on body mass index (BMI), waist circumference (WC) and blood pressure (BP) in Asian American women, who have elevated CV risk. Methods: Normotensive middle-aged Asian American women completed 7 days of hip and wrist actigraphy monitoring (Actigraph, GT3X and GT9X) to assess 24-hour activity. Total sleep time was identified using the Cole-Kripke algorithm with sleep diaries, and moderate-to-vigorous PA (MVPA), light PA and SB were classified by Freedson’s cut-points from wake time. Isotemporal substitution models were used to test effects of replacing 30 mins of each behavior with the others on BMI, WC and BP adjusting for age, education and comorbidity. Results: Data from 75 women were included (age=61.4±8.0, 57% college educated, median comorbidities=1[IQR=0-2]). On average, their days were composed of 0.5 hrs MVPA, 6.2 hrs light PA, 10 hrs SB and 5.3 hrs sleep (2.1 hrs non-wear time). In partition models, where all behaviors were entered simultaneously, more MVPA and sleep were associated with lower BMI and WC. In isotemporal substitution models that held total wear time constant (Table 1), replacing 30 mins SB with an equal amount of MVPA or sleep decreased BMI by 1.7 and 0.6 and WC by 4.1 and 1.2 cm. Replacing 30 mins light PA with MVPA or sleep decreased BMI by 1.9 and 0.9 and WC by 4.5 and 1.6 cm. None of the modeled behavior changes affected BP. Conclusion: These findings suggest that substituting 30 mins of SB or light PA with MVPA or sleep could significantly reduce Asian American women’s BMI and WC. Future studies should test the impact of behavioral interventions that promote these changes on CV risk in Asian American women.

Vaccinia virus (VACV) was instrumental in eradicating variola virus (VARV), the causative agent of smallpox, from nature. Since its first use as a vaccine, VACV has been developed as a vector for therapeutic vaccines and as an oncolytic virus. These applications take advantage of VACV's easily manipulated genome and broad host range as an outstanding platform to generate recombinant viruses with a variety of therapeutic applications. Several methods have been developed to generate recombinant VACV, including marker selection methods and transient dominant selection. Here, we present a refinement of a host range selection method coupled with visual identification of recombinant viruses. Our method takes advantage of selective pressure generated by the host antiviral protein kinase R (PKR) coupled with a fluorescent fusion gene expressing mCherry-tagged E3L, one of two VACV PKR antagonists. The cassette, including the gene of interest and the mCherry-E3L fusion is flanked by sequences derived from the VACV genome. Between the gene of interest and mCherry-E3L is a smaller region that is identical to the first ~150 nucleotides of the 3' arm, to promote homologous recombination and loss of the mCherry-E3L gene after selection. We demonstrate that this method permits efficient, seamless generation of rVACV in a variety of cell types without requiring drug selection or extensive screening for mutant viruses.

Introduction: Despite the importance of physical activity (PA) for cardiovascular health, there is a scarcity of data on objectively measured PA in women with myocardial infarction (MI). We aim to describe 24-hour PA patterns and examine their variation by demographic and psychological factors in women with MI. Methods: Participants were enrolled in an ongoing multicenter trial of stress management in women with a history of MI. Participants completed self-reported psychological measures and 7-days of wrist-actigraphy monitoring (GT3X, Actigraph) at baseline (≥2 months post-MI). PA volumes were defined as the average vector magnitude (VM) counts per minute (cpm), a metric incorporating movement across all three axes of the accelerometer. This approach minimizes loss of information related to use of cut-points and describes accumulated 24-hour PA volumes. Hourly VM cpm were plotted to visualize 24-hour PA patterns and compared by age groups, race, elevated depressive symptoms (Patient Health Questionnaire-9 ≥5), and high stress levels (top quartile of Perceived Stress Scale-10). Due to the skewness, VM cpm were log-transformed and linear regression analysis was conducted to identify correlates of overall 24-hour PA. Results: Analyses included 85 participants (age = 59.9 ± 13.0, 20% African American, 16% participating in cardiac rehabilitation, 70% elevated depressive symptoms, 25% high stress). Patterns of PA across 24 hours differed by age, race, stress and depressive symptoms (Figure 1). For example, African American women with MI had peak PA later in the day than non-African American women, and less PA overall. Women with high (vs. low) stress had less PA overall and a less pronounced evening drop in PA, which may affect sleep. Those with elevated (vs. low) depressive symptoms showed lower PA levels, especially during the late afternoon and evening. After adjusting for age, race and cardiac rehabilitation, overall 24-hour PA volumes (log of average VM cpm) were significantly lower with higher stress (b = -0.26, p = 0.02) and elevated depressive symptoms (b = -0.22, p = 0.04). Conclusion: These findings may be considered to identify women with MI who may benefit from interventions to increase PA, which could reduce risk of recurrent CVD. Our data on timing of PA may be helpful in the tailored design of such programs.

Double-stranded RNA-activated protein kinase R (PKR) is an important and rapidly evolving antiviral kinase. Most poxviruses contain two distinct PKR inhibitors, called E3 and K3 in vaccinia virus (VACV), the prototypic orthopoxvirus. E3 prevents PKR homodimerization by binding double-stranded RNA, while K3 acts as a pseudosubstrate inhibitor by binding directly to activated PKR and thereby inhibiting interaction with its substrate eIF2α. In our study here, we analyzed E3 and K3 orthologs from the phylogenetically distinct capripoxviruses (CaPVs), which include lumpy skin disease virus, sheeppox virus, and goatpox virus. Whereas the sheeppox virus E3 ortholog did not substantially inhibit PKR, all three CaPV K3 orthologs showed species-specific inhibition of PKR, with strong inhibition of sheep, goat, and human PKR but only weak inhibition of cow and mouse PKR. In contrast, VACV K3 strongly inhibited cow and mouse PKR but not sheep, goat, or human PKR. Infection of cell lines from the respective species with engineered VACV strains that contained different K3 orthologs showed a good correlation of PKR inhibition with virus replication and eIF2α phosphorylation. Our results show that K3 orthologs can have dramatically different effects on PKR of different species and indicate that effective PKR inhibition by K3 orthologs is crucial for virus replication.

Awareness during general anesthesia occurs in approximately 0.1-0.2% of cases; nevertheless, particular attention is required because it can lead to critical complications including insomnia, depression, anxiety, and post-traumatic stress disorder. To prevent these complications, bispec -tral index (BIS) and end-tidal anesthetic gas (ETAG) concentration monitoring are commonly used to examine patient consciousness during surgery. In the present case, an 80-year-old man was scheduled for total gastrectomy. Anesthesia was maintained using desflurane 4.0-5.0% vol, oxygen, and nitrous oxide. The authors simultaneously monitored BIS, which was maintained between 37 and 43, and ETAG, which was maintained between 0.9 and 1.2 minimum alveolar concentration (MAC). After the operation, however, the authors were surprised to learn that the patient complained of awareness during anesthesia. Although BIS and ETAG concentration monitoring are useful in preventing awareness during anesthesia, they cannot be completely trusted. Even though BIS was maintained at approximately 40 and ETAG at 0.7-1.3 MAC, awareness during anesthesia occurred.

The antiviral protein kinase R (PKR) is an important host restriction factor, which poxviruses must overcome to productively infect host cells. To inhibit PKR, many poxviruses encode a pseudosubstrate mimic of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2), designated K3 in vaccinia virus. Although the interaction between PKR and eIF2α is highly conserved, some K3 orthologs from host-restricted poxviruses were previously shown to inhibit PKR in a species-specific manner. To better define this host range function, we compared the sensitivity of PKR from 17 mammals to inhibition by K3 orthologs from closely related orthopoxviruses, a genus with a generally broader host range. The K3 orthologs showed species-specific inhibition of PKR and exhibited three distinct inhibition profiles. In some cases, PKR from closely related species showed dramatic differences in their sensitivity to K3 orthologs. Vaccinia virus expressing the camelpox virus K3 ortholog replicated more than three orders of magnitude better in human and sheep cells than a virus expressing vaccinia virus K3, but both viruses replicated comparably well in cow cells. Strikingly, in site-directed mutagenesis experiments between the variola virus and camelpox virus K3 orthologs, we found that different amino acid combinations were necessary to mediate improved or diminished inhibition of PKR derived from different host species. Because there is likely a limited number of possible variations in PKR that affect K3-interactions but still maintain PKR/eIF2α interactions, it is possible that by chance PKR from some potential new hosts may be susceptible to K3-mediated inhibition from a virus it has never previously encountered. We conclude that neither the sensitivity of host proteins to virus inhibition nor the effectiveness of viral immune antagonists can be inferred from their phylogenetic relatedness but must be experimentally determined., Author summary Most virus families are composed of large numbers of virus species. However, in general, only a few prototypic viruses are experimentally studied in-depth, and it is often assumed that the obtained results are representative of other viruses in the same family. In order to test this assumption, we compared the sensitivity of the antiviral protein kinase PKR from various mammals to inhibition by multiple orthologs of K3, a PKR inhibitor expressed by several closely related orthopoxviruses. We found strong differences in PKR inhibition by the K3 orthologs, demonstrating that sensitivity to a specific inhibitor was not indicative of broad sensitivity to orthologs of these inhibitors from closely related viruses. We also show that PKR from even closely related species displayed markedly different sensitivities to these poxvirus inhibitors. Furthermore, we identified amino acid residues in these K3 orthologs that are critical for enhanced or decreased PKR inhibition and found that distinct amino acid combinations affected PKRs from various species differently. Our study shows that even closely related inhibitors of an antiviral protein can vary dramatically in their inhibitory potential, and cautions that results from host-virus interaction studies of a prototypic virus genus member cannot necessarily be extrapolated to other viruses in the same genus without experimental verification.

Background: Community–acquired pneumonia (CAP) is one of the leading worldwide causes of childhood morbidity and mortality and its disease burden is affected by age and etiologies with time-dependent changes. 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 (0-18 years old) with CAP between 2010 and 2015 at 23 nationwide hospitals in Korea. Mycoplasma pneumoniae (MP) pneumonia was clinically classified into 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 36.36% of the total MP pneumonia. In children less than 2 years of age, RSV (34.01%) was the most common cause of CAP, followed by MP (9.44%), whereas MP was the most common cause of CAP in children 2-18 years of age. Systemic corticosteroid was most commonly administered in MP pneumonia. The rate of hospitalization in intensive care unit was highest for RSV pneumonia, and ventilator care was most commonly needed in cases of adenovirus pneumonia. Conclusions: The present study provides fundamental data for establishment of public health policies to decrease disease burden due to CAP as well as for improvement of pediatric health.

Background Previous cross‐sectional studies have shown conflicting results regarding the effects of television viewing and occupational sitting on cardiovascular disease ( CVD ) risk factors. The purpose of this study was to compare the association of both television viewing and occupational sitting with CVD events and all‐cause mortality in blacks. Methods and Results Participants included 3592 individuals enrolled in the Jackson Heart Study, a community‐based study of blacks residing in Jackson, Mississippi. Television viewing (4 h/day) and occupational sitting (never/seldom, sometimes, often/always) were self‐reported. Over a median follow‐up of 8.4 years, there were 129 CVD events and 205 deaths. The highest category of television viewing (>4 h/day) was associated with a greater risk for a composite CVD events/all‐cause mortality end point compared with the lowest category (CI , 1.13–1.97). In contrast, the highest category of occupational sitting (often/always) was not associated with risk for a composite CVD events/all‐cause mortality end point compared with the lowest category (never/seldom; hazard ratio, 0.90; 95% CI , 0.69–1.18). Moderate‐to‐vigorous physical activity moderated the association of television viewing with CVD events/all‐cause mortality such that television viewing was not associated with greater risk among those with high moderate‐to‐vigorous physical activity levels. Conclusions Television viewing was associated with greater risk of CVD events and all‐cause mortality, while occupational sitting had no association with these outcomes. These findings suggest that minimizing television viewing may be more effective for reducing CVD and mortality risk in blacks compared with reducing occupational sedentary behavior.

Hepatitis C virus (HCV) is the major causative agent of chronic liver diseases, including liver cirrhosis and hepatocellular carcinoma. The recent development of highly effective direct-acting antivirals (DAAs) has revolutionized the treatment of HCV patients. However, these DAAs are exorbitantly expensive for the majority of HCV patients worldwide. Moreover, these drugs still show genotypic difference in cure rate and have some resistant-associated variants. Tylophorine, a natural compound derived from Tylophora indica plants, is known to have anti-inflammatory and anti-cancerous growth activities. In the present study, we showed that two tylophorine intermediates, 5-Oxo-1-[(2,3,6,7-tetramethoxy-9-phenanthrenyl) methyl]-L-proline (O859585) and 2,3,6,7-tetramethoxy-9-phenanthrenecarboxylic acid (T298875), displayed anti-HCV activity with an EC50 of 38.25 µM for T298875 and 29.11~35.3 µM for O859585 in various HCV genotypes. We demonstrated that O859585 efficiently blocked HCV attachment by neutralizing free viral particles without affecting other stages of the HCV life cycle and interferon stimulation. O859585 interrupted binding between HCV E2 and CD81. Of note, co-treatment of O859585 with either interferon alpha (IFNα) or sofosbuvir exerted either an additive or synergistic antiviral activity in HCV-infected cells with no measurable effect on cell viability. Most importantly, O859585 in combination with IFNα and sofosbuvir exhibited synergistic effects on anti-HCV activity in primary human hepatocytes. Collectively, these data suggest that O859585 may be a novel antiviral agent for HCV therapy.

Background. The quantification of asthma medication reduction and its relation to an aggravation of asthma during pregnancy at an individual level are unclear.Methods. We conducted a nationwide retrospective cohort study of asthmatic pregnant women in South Korea. All of the asthma medications were ranked from 1 to 4 according to the guideline-based stepwise approach. We assessed the daily sums of the ranks of the asthma medications and their association with exacerbations during three phases based on the individual’s delivery date: before, during, and after pregnancy.Results. The study cohort included 115,169 asthmatic pregnant women who gave birth between 2011 and 2013. The subjects were clustered into four groups according to the daily rank sums of their asthma medication. Asthma medications were rapidly reduced at the beginning of the pregnancy and then slowly increased after delivery. Exacerbations were more frequent in the group with higher rank-sum values than in the group with lower values. Overall exacerbations were reduced during pregnancy compared to before or after delivery.Conclusions. Asthmatic pregnant women tended to reduce their asthma medication use during pregnancy. This led to a greater number of exacerbations in a small part of the study population.

Double-stranded RNA-activated protein kinase R (PKR) is an important and rapidly evolving antiviral kinase. Most poxviruses contain two distinct PKR inhibitors, called E3 and K3 in vaccinia virus (VACV), the prototypic orthopoxvirus. E3 prevents PKR homodimerization by binding double-stranded RNA, while K3 acts as a pseudosubstrate inhibitor by binding directly to activated PKR and thereby inhibiting interaction with its substrate eIF2α. In our study here, we analyzed E3 and K3 orthologs from the phylogenetically distinct capripoxviruses (CaPVs), which include lumpy skin disease virus, sheeppox virus, and goatpox virus. Whereas the sheeppox virus E3 ortholog did not substantially inhibit PKR, all three CaPV K3 orthologs showed species-specific inhibition of PKR, with strong inhibition of sheep, goat, and human PKR but only weak inhibition of cow and mouse PKR. In contrast, VACV K3 strongly inhibited cow and mouse PKR but not sheep, goat, or human PKR. Infection of cell lines from the respective species with engineered VACV strains that contained different K3 orthologs showed a good correlation of PKR inhibition with virus replication and eIF2α phosphorylation. Our results show that K3 orthologs can have dramatically different effects on PKR of different species and indicate that effective PKR inhibition by K3 orthologs is crucial for virus replication.

The life cycle of hepatitis C virus (HCV) is highly dependent on host cellular proteins for virus propagation. In order to identify the cellular factors involved in HCV propagation, we performed protein microarray assay using the HCV nonstructural 5A (NS5A) protein as a probe. Of ∼9,000 human cellular proteins immobilized in a microarray, approximately 90 cellular proteins were identified as NS5A interactors. Of these candidates, Pim1, a member of serine/threonine kinase family composed of three different isoforms (Pim1, Pim2, and Pim3), was selected for further study. Pim kinases share a consensus sequence which overlaps with kinase activity. Pim kinase activity has been implicated in tumorigenesis. In the present study, we verified the physical interaction between NS5A and Pim1 by both in vitro pulldown and coimmunoprecipitation assays. Pim1 interacted with NS5A through amino acid residues 141 to 180 of Pim1. We demonstrated that protein stability of Pim1 was increased by NS5A protein and this increase was mediated by protein interplay. Small interfering RNA (siRNA)-mediated knockdown or pharmacological inhibition of Pim kinase abrogated HCV propagation. By employing HCV pseudoparticle entry and single-cycle HCV infection assays, we further demonstrated that Pim kinase was involved in HCV entry at a postbinding step. These data suggest that Pim kinase may represent a new host factor for HCV entry. IMPORTANCE Pim1 is an oncogenic serine/threonine kinase. HCV NS5A protein physically interacts with Pim1 and contributes to Pim1 protein stability. Since Pim1 protein expression level is upregulated in many cancers, NS5A-mediated protein stability may be associated with HCV pathogenesis. Either gene silencing or chemical inhibition of Pim kinase abrogated HCV propagation in HCV-infected cells. We further showed that Pim kinase was specifically required at an early entry step of the HCV life cycle. Thus, we have identified Pim kinase not only as an HCV cell entry factor but also as a new anti-HCV therapeutic target.

Hepatitis C virus (HCV) is a major cause of chronic liver disease and is highly dependent on cellular proteins for virus propagation. To identify the cellular factors involved in HCV propagation, we recently performed protein microarray assays using the HCV nonstructural 5A (NS5A) protein as a probe. Of 90 cellular protein candidates, we selected the soluble resistance-related calcium-binding protein (sorcin) for further characterization. Sorcin is a calcium-binding protein and is highly expressed in certain cancer cells. We verified that NS5A interacted with sorcin through domain I of NS5A, and phosphorylation of the threonine residue 155 of sorcin played a crucial role in protein interaction. Small interfering RNA (siRNA)-mediated knockdown of sorcin impaired HCV propagation. Silencing of sorcin expression resulted in a decrease of HCV assembly without affecting HCV RNA and protein levels. We further demonstrated that polo-like kinase 1 (PLK1)-mediated phosphorylation of sorcin was increased by NS5A. We showed that both phosphorylation and calcium-binding activity of sorcin were required for HCV propagation. These data indicate that HCV modulates sorcin activity via NS5A protein for its own propagation. IMPORTANCE Sorcin is a calcium-binding protein and regulates intracellular calcium homeostasis. HCV NS5A interacts with sorcin, and phosphorylation of sorcin is required for protein interaction. Gene silencing of sorcin impaired HCV propagation at the assembly step of the HCV life cycle. Sorcin is phosphorylated by PLK1 via protein interaction. We showed that sorcin interacted with both NS5A and PLK1, and PLK1-mediated phosphorylation of sorcin was increased by NS5A. Moreover, calcium-binding activity of sorcin played a crucial role in HCV propagation. These data provide evidence that HCV regulates host calcium metabolism for virus propagation, and thus manipulation of sorcin activity may represent a novel therapeutic target for HCV.

CONTEXT: Reducing sedentary behaviors, or time spent sitting, is an important target for health promotion in children. Standing desks in schools may be a feasible, modifiable, and acceptable environmental strategy to this end. OBJECTIVE: To examine the impact of school-based standing desk interventions on sedentary behavior and physical activity, health-related outcomes, and academic and behavioral outcomes in school-aged children. DATA SOURCES: Ovid Embase, Medline, PsycINFO, Web of Science, Global Health, and CINAHL. STUDY SELECTION: Full-text peer-reviewed journal publications written in English; samples of school-aged youth (5–18 years of age); study designs including the same participants at baseline and follow-up; and use of a standing desk as a component of the intervention. DATA EXTRACTION: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Eight studies satisfied selection criteria and used quasi-experimental (n = 4), randomized controlled trial (n = 3), and pre–post, no control (n = 1) designs. When examined, time spent standing increased in all studies (effect sizes: 0.38–0.71), while sitting time decreased from a range of 59 to 64 minutes (effect sizes: 0.27–0.49). Some studies reported increased physical activity and energy expenditure and improved classroom behavior. LIMITATIONS: One-half of the studies had nonrandomized designs, and most were pilot or feasibility studies. CONCLUSIONS: This initial evidence supports integrating standing desks into the classroom environment; this strategy has the potential to reduce sitting time and increase standing time among elementary schoolchildren. Additional research is needed to determine the impact of standing desks on academic performance and precursors of chronic disease risk.

Purpose: Croup is known to have epidemics in seasonal and biennial trends, and to be strongly associated with epidemics of para influenza virus. However, seasonal and annual epidemics of croup have not been clearly reported in Korea. This study aimed to ex amine the seasonal/annual patterns and etiologies of childhood croup in Korea during a consecutive 6-year period. Methods: Pediatric croup data were collected from 23 centers in Korea from 1 January 2010 to 31 December 2015. Electronic medi cal records, including multiplex reverse transcription polymerase chain reaction (RT-PCR) results, demographics and clinical informa tion were cross-sectionally reviewed and analyzed. Results: Overall, 2,598 childhood croup patients requiring hospitalization were identified during the study period. Among them, a total of 927 who underwent RT-PCR were included in the analysis. Males (61.5%) predominated, and most (63.0%) of them were younger than 2 years of age (median, 19 months; interquartile range, 11-31 months). Peak hospitalization occurred in 2010 and 2012 in even-numbered years, and parainfluenza virus (PIV, 39.7%) was the most common cause of childhood croup requiring hos pitalization, followed by respiratory syncytial virus (14.9%), human rhinovirus (12.5%), Mycoplasma pneumonaie (10.6%), and human coronavirus (7.3%). Conclusion: It is concluded that croup hospitalization has a biennial pattern in even-numbered years. PIV may be the most com mon cause of childhood croup; however, croup epidemics could be attributed to other viruses. (Allergy Asthma Respir Dis 2019;7:78-85)

Aim To identify factors that may serve as facilitators and barriers to self-management described by adults living with chronic illness by conducting a qualitative metasynthesis. Background Self-management is an individuals' active management of a chronic illness in collaboration with their family members and clinicians. Design Qualitative metasynthesis. Data sources We analysed studies (N = 53) published between January 2000–May 2013 that described factors affecting self-management in chronic illness as reported by adults aged over 18 years with chronic illness. Review methods Sandelowsi and Barroso approach to qualitative metasynthesis: literature search; quality appraisal; analysis and synthesis of findings. Results Collectively, article authors reported on sixteen chronic illnesses, most commonly diabetes (N = 28) and cardiovascular disease (N = 20). Participants included men and women (mean age = 57, range 18-94) from 20 countries representing diverse races and ethnicities. We identified five categories of factors affecting self-management: Personal/Lifestyle Characteristics; Health Status; Resources; Environmental Characteristics; and Health Care System. Factors may interact to affect self-management and may exist on a continuum of positive (facilitator) to negative (barrier). Conclusion Understanding factors that influence self-management may improve assessment of self-management among adults with chronic illness and may inform interventions tailored to meet individuals' needs and improve health outcomes.

Purpose: The purpose of this study was to develop a multi-disciplinary self-management intervention based on empowerment theory and to evaluate the effectiveness of the intervention for older adults with chronic illness. Methods: A randomized controlled trial design was used with 43 Korean older adults with chronic illness (Experimental group=22, Control group=21). The intervention consisted of two phases: (1) 8-week multi-disciplinary, team guided, group-based health education, exercise session, and individual empowerment counseling, (2) 16-week self-help group activities including weekly exercise and group discussion to maintain acquired self-management skills and problem-solving skills. Baseline, 8-week, and 24-week assessments measured health empowerment, exercise self-efficacy, physical activity, and physical function. Results: Health empowerment, physical activity, and physical function in the experimental group increased significantly compared to the control group over time. Exercise self-efficacy significantly increased in experimental group over time but there was no significant difference between the two groups. Conclusion: The self-management program based on empowerment theory improved health empowerment, physical activity, and physical function in older adults. The study finding suggests that a health empowerment strategy may be an effective approach for older adults with multiple chronic illnesses in terms of achieving a sense of control over their chronic illness and actively engaging self-management.