Patterns of microbial colonization and succession in Guadua weberbaueri internodes

Honors (Bachelor's)MicrobiologyUniversity of Michiganhttps://deepblue.lib.umich.edu/bitstream/2027.42/147362/1/soahluw.pd

Varenicline versus placebo for waterpipe smoking cessation : a double-blind randomized controlled trial

Background and Aims: Waterpipe tobacco smoking is a growing public health concern. There is limited research using pharmacotherapy and no research using varenicline (established treatment for smoking cessation) in waterpipe smokers. We tested the efficacy of varenicline in achieving abstinence from all tobacco use among waterpipe smokers. Design: Two-arm, parallel group, placebo-controlled, double-blind, multi-centre (n = 4), individually randomized trial with follow-up to 25 weeks. Settings: District general hospitals and catchment communities within four districts of Punjab, Pakistan. Participants: Adult daily waterpipe smokers (n = 510; 253 in varenicline and 257 in placebo arms), who were interested in quitting, were recruited and analysed between March and November 2016. Of these, 220 (87%) in the varenicline and 239 (93%) in the placebo arms completed all follow-ups. Participants were on average aged 49 [standard deviation (SD) = 15.2] years, daily smokers and smoked for the last 27 (SD = 15.9) years. More than half (261, 51.2%) also smoked cigarettes. Intervention and comparator: All trial participants received two structured sessions of behavioural support (of 30 and 10 minutes) one at the time of registration and the other 1 week later. Participants were randomized to varenicline (active arm) and placebo (control arm) stratified on district, sex and concomitant cigarette smoking. Varenicline and placebo were dispensed as identical unlabelled tablets for 12 weeks: 0.5 mg for 1 week (once on days 1–3, twice on days 4–7) and 1 mg for the subsequent 11 weeks (twice daily). Measurements: The trial participants were followed-up for a period of 25 weeks post-randomization. The primary outcome was 7-day repeated point prevalence abstinence from all forms of tobacco, self-reported at each of weeks 5, 12 and 25, verified by carbon-monoxide cut-off < 10 parts per million. Findings: No evidence of statistically significant difference in repeated point prevalence abstinence between the varenicline (12 of 253; 4.7%) and placebo (11 of 257; 4.3%) arms (relative risk = 1.11, 95% confidence interval = 0.50–2.47, P = 0.80) was observed (Bayes factor = 0.048). Adverse events reported in 27 participants were 34 (15 in varenicline and 19 in placebo); none was serious. Conclusions: Varenicline was not more effective than placebo in aiding cessation of tobacco use in long-term daily waterpipe smokers

From cacti to carnivores: Improved phylotranscriptomic sampling and hierarchical homology inference provide further insight into the evolution of Caryophyllales

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143660/1/ajb21069.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143660/2/ajb21069_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143660/3/ajb21069-sup-0002-AppendixS2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143660/4/ajb21069-sup-0005-AppendixS5.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143660/5/ajb21069-sup-0001-AppendixS1.pd

Brabykinin B1 Receptor Antagonism Is Beneficial in Renal Ischemia-Reperfusion Injury

Previously we have demonstrated that bradykinin B1 receptor deficient mice (B1KO) were protected against renal ischemia and reperfusion injury (IRI). Here, we aimed to analyze the effect of B1 antagonism on renal IRI and to study whether B1R knockout or antagonism could modulate the renal expression of pro and anti-inflammatory molecules. To this end, mice were subjected to 45 minutes ischemia and reperfused at 4, 24, 48 and 120 hours. Wild-type mice were treated intra-peritoneally with antagonists of either B1 (R-954, 200 µg/kg) or B2 receptor (HOE140, 200 µg/kg) 30 minutes prior to ischemia. Blood samples were collected to ascertain serum creatinine level, and kidneys were harvested for gene transcript analyses by real-time PCR. Herein, B1R antagonism (R-954) was able to decrease serum creatinine levels, whereas B2R antagonism had no effect. The protection seen under B1R deletion or antagonism was associated with an increased expression of GATA-3, IL-4 and IL-10 and a decreased T-bet and IL-1β transcription. Moreover, treatment with R-954 resulted in lower MCP-1, and higher HO-1 expression. Our results demonstrated that bradykinin B1R antagonism is beneficial in renal IRI

Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P \u3c 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P &lt; 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.</p

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

A double-blind, placebo-controlled, randomized trial of varenicline in hookah tobacco smokers in Pakistan

Background Hookah tobacco smoking has increased worldwide yet there is little evidence for the efficacy of pharmacological therapies to achieve abstinence among hookah smokers. Our objective was to assess the efficacy of varenicline when added to behavioural support for hookah tobacco cessation. Methods In 2016, we conducted a double-blind, placebo controlled, randomized trial in Pakistan enrolling 510 daily hookah users who were willing to quit. All participants received behavioural support and either varenicline or placebo at randomisation. The primary outcome was 25 weeks continuous abstinence biochemically verified by a carbon monoxide level of < 10 ppm. Results Among the 510 trial participants, 429 (84%) were male and 81 (16%) female; 249 (49%) smoked only hookah and 261 (51%) smoked both hookah and cigarettes. 21 participants withdrew from treatment mainly due to adverse events. We recently completed the last follow-up (25 weeks) on May 23 rd , 2017 with a 93% (475/510) retention rate. The data will remain blinded for treatment allocation until the primary analysis is complete. [Trial Flow Chart] Conclusions We will report our primary outcome results at the '17th World conference on Tobacco or Health' in Cape Town for the first ever trial of varenicline among hookah smokers. The findings of this pharmacotherapy trial will have major implications for knowledge translation, practice and policy regarding hookah tobacco use

Dependence and withdrawal symptoms among waterpipe tobacco smokers enrolled in a double-blind, placebo-controlled, randomised trial

Background The prevalence of waterpipe tobacco smoking has been steadily increasing worldwide. Whereas cigarette smoking dependence and withdrawal scales have been developed and used extensively, this is not the case for waterpipe smoking. Our objective was to explore correlates of the Mood and Physical Symptoms Scale (MPSS), a withdrawal scale, and smoking dependency using the Lebanon Waterpipe Dependency Scale (LWDS-11) among waterpipe smokers in South-East Asia. Methods MPSS and LWDS-11 were translated for use in a sample of Pakistani adults taking part in a double-blind, placebo-controlled randomised trial evaluating the efficacy of varenicline for abstinence among waterpipe smokers. Participants included adults using waterpipe on a daily basis who were willing to quit. A total of 510 participants were randomised. The scales were administered at baseline and at week 25, the last follow-up that was just completed on May 23, 2017. Results Among the 510 trial participants, 249 (49%) participants used only waterpipe for tobacco smoking whereas the other 261 (51%) used cigarettes as well. At baseline and week 25, respectively, the MPSS was completed by 501 (98.2%) and 475 (93%), whereas the LWDS-11 was completed by 505 (99%) and 475 (93%). Conclusions Complete findings will be reported at 'The 17th World conference on Tobacco or Health' in Cape Town for the first application of LWDS-11 and MPSS Scale among waterpipe tobacco smokers in Pakistan. The application of these scales in Pakistan will inform whether they can be used in practice to assess the extent of dependency and withdrawal symptoms in South-East Asia