Rescue medication use as a patient-reported outcome in COPD: a systematic review and regression analysis.

BACKGROUND: Reducing rescue medication use is a guideline-defined goal of asthma treatment, however, little is known about the validity of rescue medicine use as a marker of symptoms in chronic obstructive pulmonary disease (COPD). To improve patient outcomes, greater insight is needed into the relationship between rescue medication use and alternative COPD outcomes. METHODS: A systematic search of electronic databases (Embase®, MEDLINE® and Cochrane CENTRAL) was conducted from database start to 26 May, 2015. Studies of bronchodilator therapy with a duration of ≥24 weeks were included if they reported either mean change from baseline (CFB) in rescue medication use in puffs/day or % rescue-free days (%RFD), and at least one other COPD endpoint. Correlation and meta-regression analyses were undertaken to test the association between rescue medication use and other COPD outcomes using weighted means (weights proportional to the sample size of the treatment group) and unweighted means (equal weight for each treatment group). Each association was assessed at 6 months and study end. RESULTS: Forty-six studies involving 46,531 patients provided mean data from 145 treatment groups for evaluation. Changes in both measures of rescue medication use were correlated with changes in trough forced expiratory volume in one second ([FEV1]; Pearson correlation coefficients |r| ≥ 0.63; p < 0.0001) and with St George's Respiratory Questionnaire (SGRQ) score (|r| ≥ 0.70; p < 0.0001) at study end. Change in rescue medication use in puffs/day during the study correlated with annualized rates of moderate/severe exacerbations at 6 months and study end (both r = 0.66; p ≤ 0.0028). CFB in puffs/day was not well correlated with Transition Dyspnoea Index (TDI), but %RFD did correlate with TDI score at 6 months and study end (both r = 0.69; p < 0.0001). The values for CFB in puffs/day corresponding to the proposed minimal clinically important differences for trough FEV1 and SGRQ score were -1.3 and -0.6 puffs/day, respectively. A -1.0 puffs/day CFB in rescue use corresponded to a change of 0.26 events/patient-year in moderate/severe exacerbations. CONCLUSION: This analysis provides clear evidence of associations at a patient group level between rescue medication use and other clinically important COPD outcomes

Identifying Potential Candidate SNP's and Genes Linked to Handedness for Future Study

The goal was to identify genes for future study that might be linked to handedness for potential candidate gene study. We were able to find 3 major genes through statistically analyzing SNP data within a Genome-wide association Statistical Analysis tool, PLINK. 27 SNPs were chosen based on P-values of below .001, further analysis was done to these 27 SNPs to figure out their gene locus. Using NCBI we found 21 SNPs were within a gene locus. A total of 16 genes were found from the 21 SNPs that were located within a gene locus. Three extra genes were examined since they were located in a gene of interest CTNNA2. The genes found were further screened for high expression in subcortical regions and that have been implicated in neural function or brain development. Out of the 17 genes determined, IRAK2, NRG1, and CTNNA2 adhered to the criteria for screening.Removed permission form from PDF and replaced file June 202

COVID-19 in Latin America: Novel transmission dynamics for a global pandemic?

The COVID-19 virus expanded from China into Western Asia, Europe, and North America, impacting many of the world’s wealthiest countries. Brazil reported Latin America’s first case in late February 2020, and in less than a month, over 7,000 COVID-19 cases have been confirmed among nearly every country and territory in Latin America and the Caribbean (LAC). The LAC outbreak appears to be about two weeks behind the United States and Canada and about three to four weeks behind Western Europe. Thus, the global COVID-19 pandemic is entering a new phase, not only expanding beyond primarily temperate Northern Hemisphere countries into the tropics but also spreading to a geopolitical region marked by significantly worse poverty, water access and sanitation, and distrust in public governance (Fig 1). We believe that these aspects of the Latin American context are likely to substantially affect the transmission dynamics and scope of the COVID-19 outbreak in LAC, with potential implications for the trajectory of the global pandemic.The COVID-19 virus expanded from China into Western Asia, Europe, and North America, impacting many of the world’s wealthiest countries. Brazil reported Latin America’s first case in late February 2020, and in less than a month, over 7,000 COVID-19 cases have been confirmed among nearly every country and territory in Latin America and the Caribbean (LAC). The LAC outbreak appears to be about two weeks behind the United States and Canada and about three to four weeks behind Western Europe. Thus, the global COVID-19 pandemic is entering a new phase, not only expanding beyond primarily temperate Northern Hemisphere countries into the tropics but also spreading to a geopolitical region marked by significantly worse poverty, water access and sanitation, and distrust in public governance (Fig 1). We believe that these aspects of the Latin American context are likely to substantially affect the transmission dynamics and scope of the COVID-19 outbreak in LAC, with potential implications for the trajectory of the global pandemic

E. coli metabolic protein aldehydealcohol dehydrogenase-E binds to the ribosome: a unique moonlighting action revealed

It is becoming increasingly evident that a high degree of regulation is involved in the protein synthesis machinery entailing more interacting regulatory factors. A multitude of proteins have been identified recently which show regulatory function upon binding to the ribosome. Here, we identify tight association of a metabolic protein aldehyde-alcohol dehydrogenase E (AdhE) with the E. coli 70S ribosome isolated from cell extract under low salt wash conditions. Cryo-EM reconstruction of the ribosome sample allows us to localize its position on the head of the small subunit, near the mRNA entrance. Our study demonstrates substantial RNA unwinding activity of AdhE which can account for the ability of ribosome to translate through downstream of at least certain mRNA helices. Thus far, in E. coli, no ribosome-associated factor has been identified that shows downstream mRNA helicase activity. Additionally, the cryo-EM map reveals interaction of another extracellular protein, outer membrane protein C (OmpC), with the ribosome at the peripheral solvent side of the 50S subunit. Our result also provides important insight into plausible functional role of OmpC upon ribosome binding. Visualization of the ribosome purified directly from the cell lysate unveils for the first time interactions of additional regulatory proteins with the ribosom

Genome Sequences of Chikungunya Virus Isolates from Bolivia

We generated nine coding-complete chikungunya virus genome sequences from blood samples collected during the early 2015 outbreak in Bolivia. Relative to other publicly available chikungunya sequences, the Bolivian samples represent a monophyletic group, suggesting that a single lineage was widely circulating in the country between February and May 2015.We generated nine coding-complete chikungunya virus genome sequences from blood samples collected during the early 2015 outbreak in Bolivia. Relative to other publicly available chikungunya sequences, the Bolivian samples represent a monophyletic group, suggesting that a single lineage was widely circulating in the country between February and May 2015

Seed-based IntaRNA prediction combined with GFP-reporter system identifies mRNA targets of the small RNA Yfr1

Motivation: Prochlorococcus possesses the smallest genome of all sequenced photoautotrophs. Although the number of regulatory proteins in the genome is very small, the relative number of small regulatory RNAs is comparable with that of other bacteria. The compact genome size of Prochlorococcus offers an ideal system to search for targets of small RNAs (sRNAs) and to refine existing target prediction algorithms

TPO antibody in euthyroid pregnant women and cognitive ability in the offspring: a focused review

Purpose A link between maternal thyroid dysfunction during pregnancy and the risk of cognitive and behavioral problems in the offspring has previously been established; however, the potential effects of maternal thyroid autoimmunity on neurodevelopment in the absence of maternal hypothyroidism are less clear. The present review aims to highlight the gaps in knowledge in this regard and provide a thorough assessment of relevant literature. Method Related keywords searched in MEDLINE, Web of Science, and Scopus till January 2021. Results There is some evidence that neuropsychological and intellectual developments of offspring are adversely affected by maternal thyroid autoimmunity, although the results of available studies are not concordant. The tools and measurements that have been applied in different studies to assess neurodevelopment or IQ vary widely and the children born to mothers with thyroid autoimmunity have been assessed at different chronological stages of life. Such variations may explain some of the differences across studies. In addition, the definition of thyroid autoimmunity has been based on TPOAb cut points provided by manufacturers in most cases, but it is preferable to define these values based on age, trimester, and method-specific reference ranges. Conclusion Well-designed studies are needed to assess verbal and non-verbal neurocognition of offspring born to mothers with autoimmune thyroid disease before or during pregnancy

In vitro experimental system for analysis of transcription–translation coupling

Transcription and translation are coupled in bacteria, meaning that translation takes place co-transcriptionally. During transcription–translation, both machineries mutually affect each others’ functions, which is important for regulation of gene expression. Analysis of interactions between RNA polymerase (RNAP) and the ribosome, however, are limited due to the lack of an in vitro experimental system. Here, we report the development of an in vitro transcription coupled to translation system assembled from purified components. The system allows controlled stepwise transcription and simultaneous stepwise translation of the nascent RNA, and permits investigation of the interactions of RNAP with the ribosome, as well as the effects of translation on transcription and transcription on translation. As an example of usage of this experimental system, we uncover complex effects of transcription–translation coupling on pausing of transcription