Pain assessment in children undergoing venipuncture: the Wong–Baker faces scale versus skin conductance fluctuations

The aim of this study was to evaluate the efficacy of the subjective Wong–Baker faces pain rating scale (WBFS) and of the objective skin conductance fluctuation (SCF) test in assessing pain in children undergoing venipuncture. One-hundred and fifty children (aged 5–16 years) entered the study. All underwent venipuncture at the antecubital fossa to collect blood specimens for routine testing in the same environmental conditions. After venipuncture, the children indicated their pain intensity using the WBFS, whereas the number of SCFs was recorded before, during and after venipuncture. So, pain level was measured in each child with WBFS and SCF. We found that the level of WBFS-assessed pain was lower in all children, particularly those above 8 years of age, than SCF-assessed pain (p < 0.0001). Moreover, the number of SCFs was significantly higher during venipuncture than before or after venipuncture (p < 0.0001). At multivariate regression analysis, age and previous experience of venipuncture influenced the WBFS (β = −1.81, p < 0.001, and β = −0.86, p < 0.001, respectively) but not SCFs. In conclusion, although both procedures can be useful for research and clinical practice, our findings show that WBFS was affected by age and previous venipuncture, whereas SCF produced uniform data. If verified in other studies, our results should be taken into account when using these tools to evaluate pain in children

Whole-Genome Sequencing of Pharmacogenetic Drug Response in Racially Diverse Children with Asthma

RATIONALE: Albuterol, a bronchodilator medication, is the first-line therapy for asthma worldwide. There are significant racial/ethnic differences in albuterol drug response. OBJECTIVES: To identify genetic variants important for bronchodilator drug response (BDR) in racially diverse children. METHODS: We performed the first whole-genome sequencing pharmacogenetics study from 1,441 children with asthma from the tails of the BDR distribution to identify genetic association with BDR. MEASUREMENTS AND MAIN RESULTS: We identified population-specific and shared genetic variants associated with BDR, including genome-wide significant (P \u3c 3.53 × 10 CONCLUSIONS: The lack of minority data, despite a collaboration of eight universities and 13 individual laboratories, highlights the urgent need for a dedicated national effort to prioritize diversity in research. Our study expands the understanding of pharmacogenetic analyses in racially/ethnically diverse populations and advances the foundation for precision medicine in at-risk and understudied minority populations

Whole-genome sequencing of pharmacogenetic drug response in racially diverse children with asthma

RATIONALE: Albuterol, a bronchodilator medication, is the first-line therapy for asthma worldwide. There are significant racial/ethnic differences in albuterol drug response. OBJECTIVES: To identify genetic variants important for bronchodilator drug response (BDR) in racially diverse children. METHODS: We performed the first whole-genome sequencing pharmacogenetics study from 1,441 children with asthma from the tails of the BDR distribution to identify genetic association with BDR. MEASUREMENTS AND MAIN RESULTS: We identified population-specific and shared genetic variants associated with BDR, including genome-wide significant (P \u3c 3.53 × 10-7) and suggestive (P \u3c 7.06 × 10-6) loci near genes previously associated with lung capacity (DNAH5), immunity (NFKB1 and PLCB1), and β-adrenergic signaling (ADAMTS3 and COX18). Functional analyses of the BDR-associated SNP in NFKB1 revealed potential regulatory function in bronchial smooth muscle cells. The SNP is also an expression quantitative trait locus for a neighboring gene, SLC39A8. The lack of other asthma study populations with BDR and whole-genome sequencing data on minority children makes it impossible to perform replication of our rare variant associations. Minority underrepresentation also poses significant challenges to identify age-matched and population-matched cohorts of sufficient sample size for replication of our common variant findings. CONCLUSIONS: The lack of minority data, despite a collaboration of eight universities and 13 individual laboratories, highlights the urgent need for a dedicated national effort to prioritize diversity in research. Our study expands the understanding of pharmacogenetic analyses in racially/ethnically diverse populations and advances the foundation for precision medicine in at-risk and understudied minority populations

Integrating Gene Expression with Summary Association Statistics to Identify Genes Associated with 30 Complex Traits

Although genome-wide association studies (GWASs) have identified thousands of risk loci for many complex traits and diseases, the causal variants and genes at these loci remain largely unknown. Here, we introduce a method for estimating the local genetic correlation between gene expression and a complex trait and utilize it to estimate the genetic correlation due to predicted expression between pairs of traits. We integrated gene expression measurements from 45 expression panels with summary GWAS data to perform 30 multi-tissue transcriptome-wide association studies (TWASs). We identified 1,196 genes whose expression is associated with these traits; of these, 168&nbsp;reside more than 0.5 Mb away from any previously reported GWAS significant variant. We then used our approach to find 43 pairs of traits with significant genetic correlation at the level of predicted expression; of these, eight were not found through genetic correlation at the SNP level. Finally, we used bi-directional regression to find evidence that BMI causally influences triglyceride levels and that triglyceride levels causally influence low-density lipoprotein. Together, our results provide insight into the role of gene expression in the susceptibility of complex traits and diseases

Native American Ancestry and Air Pollution Interact to Impact Bronchodilator Response in Puerto Rican Children with Asthma.

ObjectiveAsthma is the most common chronic disease in children. Short-acting bronchodilator medications are the most commonly prescribed asthma treatment worldwide, regardless of disease severity. Puerto Rican children display the highest asthma morbidity and mortality of any US population. Alarmingly, Puerto Rican children with asthma display poor bronchodilator drug response (BDR). Reduced BDR may explain, in part, the increased asthma morbidity and mortality observed in Puerto Rican children with asthma. Gene-environment interactions may explain a portion of the heritability of BDR. We aimed to identify gene-environment interactions associated with BDR in Puerto Rican children with asthma.SettingGenetic, environmental, and psycho-social data from the Genes-environments and Admixture in Latino Americans (GALA II) case-control study.ParticipantsOur discovery dataset consisted of 658 Puerto Rican children with asthma; our replication dataset consisted of 514 Mexican American children with asthma.Main outcome measuresWe assessed the association of pairwise interaction models with BDR using ViSEN (Visualization of Statistical Epistasis Networks).ResultsWe identified a non-linear interaction between Native American genetic ancestry and air pollution significantly associated with BDR in Puerto Rican children with asthma. This interaction was robust to adjustment for age and sex but was not significantly associated with BDR in our replication population.ConclusionsDecreased Native American ancestry coupled with increased air pollution exposure was associated with increased BDR in Puerto Rican children with asthma. Our study acknowledges BDR's phenotypic complexity, and emphasizes the importance of integrating social, environmental, and biological data to further our understanding of complex disease

Integrative genomic analysis in African American children with asthma finds three novel loci associated with lung function.

Bronchodilator (BD) drugs are commonly prescribed for treatment and management of obstructive lung function present with diseases such as asthma. Administration of BD medication can partially or fully restore lung function as measured by pulmonary function tests. The genetics of baseline lung function measures taken before BD medication have been extensively studied, and the genetics of the BD response itself have received some attention. However, few studies have focused on the genetics of post-BD lung function. To address this gap, we analyzed lung function phenotypes in 1103 subjects from the Study of African Americans, Asthma, Genes, and Environment, a pediatric asthma case-control cohort, using an integrative genomic analysis approach that combined genotype, locus-specific genetic ancestry, and functional annotation information. We integrated genome-wide association study (GWAS) results with an admixture mapping scan of three pulmonary function tests (forced expiratory volume in 1 s [FEV1 ], forced vital capacity [FVC], and FEV1 /FVC) taken before and after albuterol BD administration on the same subjects, yielding six traits. We identified 18 GWAS loci, and five additional loci from admixture mapping, spanning several known and novel lung function candidate genes. Most loci identified via admixture mapping exhibited wide variation in minor allele frequency across genotyped global populations. Functional fine-mapping revealed an enrichment of epigenetic annotations from peripheral blood mononuclear cells, fetal lung tissue, and lung fibroblasts. Our results point to three novel potential genetic drivers of pre- and post-BD lung function: ADAMTS1, RAD54B, and EGLN3

Dysregulated invertebrate tropomyosin–dectin-1 interaction confers susceptibility to allergic diseases

The key factors underlying the development of allergic diseases-the propensity for a minority of individuals to develop dysfunctional responses to harmless environmental molecules-remain undefined. We report a pathway of immune counter-regulation that suppresses the development of aeroallergy and shrimp-induced anaphylaxis. In mice, signaling through epithelially expressed dectin-1 suppresses the development of type 2 immune responses through inhibition of interleukin-33 (IL-33) secretion and the subsequent recruitment of IL-13-producing innate lymphoid cells. Although this homeostatic pathway is functional in respiratory epithelial cells from healthy humans, it is dramatically impaired in epithelial cells from asthmatic and chronic rhinosinusitis patients, resulting in elevated IL-33 production. Moreover, we identify an association between a single-nucleotide polymorphism (SNP) in the dectin-1 gene loci and reduced pulmonary function in two cohorts of asthmatics. This intronic SNP is a predicted eQTL (expression quantitative trait locus) that is associated with reduced dectin-1 expression in human tissue. We identify invertebrate tropomyosin, a ubiquitous arthropod-derived molecule, as an immunobiologically relevant dectin-1 ligand that normally serves to restrain IL-33 release and dampen type 2 immunity in healthy individuals. However, invertebrate tropomyosin presented in the context of impaired dectin-1 function, as observed in allergic individuals, leads to unrestrained IL-33 secretion and skewing of immune responses toward type 2 immunity. Collectively, we uncover a previously unrecognized mechanism of protection against allergy to a conserved recognition element omnipresent in our environment

Внешнеэкономическое сотрудничество России и Казахстана: от истории к современности

Abstract: Предмет/тема. Россия и Казахстан являются странами, имеющими тесные партнерские политические и экономические отношения в разных форматах: ЕАЭС и Таможенного союза, а также ОДКБ и СНГ. У России и Казахстана имеется общий рынок, отсутствует таможенная граница, могут свободно перемещаться товары, услуги, рабочая сила, но, несмотря на эту внешнюю открытость, не решен ряд проблем, связанных с современной экономической и политической ситуацией. В статье проанализированы тенденции внешней торговли между двумя странами, освещены основные проблемы внешнеэкономического сотрудничества России и Казахстана. Актуальность темы исследования обусловлена тем, что в 2017-2018 гг. наблюдается несоответствие между экономическими и политическими линиями развития Российской Федерации и Республики Казахстан, что негативно влияет на внешне-экономические, политические и культурные связи России. Цели/задачи. Целями данной статьи является исследование исторических аспектов и современных реалий двусторонних отношений между Республикой Казахстан и Российской Федерацией; выявление факторов, оказывающих влияние на усиление экономического и политического неравенства между Россией и Республикой Казахстан, которое отрицательно сказывается на исторически дли-тельные отношения между странами, что, в свою очередь, отрицательно влияет как на внешнюю торговлю, так и на социокультурный обмен. Методология. Методической основой являются литературные источники по теме исследования, а также открытые аналитические материалы. Методами исследования являются общенаучные методы анализа и синтеза. Результаты. В настоящей статье авторы приходят к выводу, что решение ряда проблем, возникших в процессе внешнеэкономического сотрудничества России и Казахстана, кроется в формировании надгосударственного института агентов экономической дипломатии. Такой институт обеспечит согласованность интересов политических дипломатов и деловых кругов, а также может явиться основой для выработки рекомендаций в области координации важнейших направлений стратегического развития Российской Федерации и Республики Казахстан. Выводы/значимость. Проведенное исследование исторических и современных аспектов двусторонних отношений между Российской Федерацией и Республикой Казахстан позволило сделать следующие важные выводы. Во-первых, Россия и Казахстан, несмотря на негативные исторические аспекты совместного развития, смогли сформировать единое и относительно эффективное экономическое пространство, использующее преимущества сотрудничества, созданного в советское время. Во-вторых, Казахстан нуждается в большем развитии двусторонних экономических отношений (в том числе в рамках единого таможенного пространства) в большей степени, чем Россия, поскольку это зависит от внешней торговли с Российской Федерацией. В-третьих, Россия, находящаяся под внешне-политическим и внешнеэкономическим давлением со стороны европейских стран и США, нуждается в поддержке со стороны Республики Казахстан, а также стран, вступающих в Таможенный союз и Евразийский экономический союз. Применение. Полученные выводы и результаты исследования могут быть использованы при решении проблем, связанных с современной экономической и политической ситуацией в мире и в странах ЕАЭС в целом. Статья подготовлена в рамках государственного задания ИПР РАН, тема НИР «Социально-экономическое и научно-технологическое развитие на разных уровнях управления в отраслях, комплексах и сферах деятельности национального хозяйства России»

Genetic Determinants of Telomere Length in African American Youth.

Telomere length (TL) is associated with numerous disease states and is affected by genetic and environmental factors. However, TL has been mostly studied in adult populations of European or Asian ancestry. These studies have identified 34 TL-associated genetic variants recently used as genetic proxies for TL. The generalizability of these associations to pediatric populations and racially diverse populations, specifically of African ancestry, remains unclear. Furthermore, six novel variants associated with TL in a population of European children have been identified but not validated. We measured TL from whole blood samples of 492 healthy African American youth (children and adolescents between 8 and 20 years old) and performed the first genome-wide association study of TL in this population. We were unable to replicate neither the 34 reported genetic associations found in adults nor the six genetic associations found in European children. However, we discovered a novel genome-wide significant association between TL and rs1483898 on chromosome 14. Our results underscore the importance of examining genetic associations with TL in diverse pediatric populations such as African Americans