Explore the vast range of titles available.

Ethanol toxicity in the yeast Saccharomyces cerevisiae limits titer and productivity in the industrial production of transportation bioethanol. We show that strengthening the opposing potassium and proton electrochemical membrane gradients is a mechanism that enhances general resistance to multiple alcohols. The elevation of extracellular potassium and pH physically bolsters these gradients, increasing tolerance to higher alcohols and ethanol fermentation in commercial and laboratory strains (including a xylose-fermenting strain) under industrial-like conditions. Production per cell remains largely unchanged, with improvements deriving from heightened population viability. Likewise, up-regulation of the potassium and proton pumps in the laboratory strain enhances performance to levels exceeding those of industrial strains. Although genetically complex, alcohol tolerance can thus be dominated by a single cellular process, one controlled by a major physicochemical component but amenable to biological augmentation.

Microbial contamination is an obstacle to widespread production of advanced biofuels and chemicals. Current practices such as process sterilization or antibiotic dosage carry excess costs or encourage the development of antibiotic resistance. We engineered Escherichia coli to assimilate melamine, a xenobiotic compound containing nitrogen. After adaptive laboratory evolution to improve pathway efficiency, the engineered strain rapidly outcompeted a control strain when melamine was supplied as the nitrogen source. We additionally engineered the yeasts Saccharomyces cerevisiae and Yarrowia lipolytica to assimilate nitrogen from cyanamide and phosphorus from potassium phosphite, and they outcompeted contaminating strains in several low-cost feedstocks. Supplying essential growth nutrients through xenobiotic or ecologically rare chemicals provides microbial competitive advantage with minimal external risks, given that engineered biocatalysts only have improved fitness within the customized fermentation environment.

Background Diarrhoea kills 500,000 children every year despite availability of cheap and effective treatment. In addition, a large number are inappropriately treated with antibiotics, which do not benefit the patient but can contribute to the development of antibiotic resistance. We investigated whether the prevalence of antibiotic use among children under the age of five with diarrhoea in Uganda changed following a national intervention to increase the use of oral rehydration salts (ORS), and whether any socioeconomic characteristics were associated with antibiotic use. Methods A cross-sectional survey was conducted among caregivers of children under the age of five and among private health care providers and drug sellers in Uganda in 2014. This was compared to a similar survey among private health care providers, and the national demographic and health survey in Uganda in 2016. Logistic regression was used to find associations between antibiotic use and socioeconomic characteristics, and chi-square test and independent sample t-test were used to find significant differences between groups. Results The prevalence of antibiotic use among children under the age of five with diarrhoea in Uganda decreased from 30.5% in 2014 to 20.0% ( p  < 0.001) in 2016. No associations between socioeconomic characteristics and the use of antibiotics were significant in both 2014 and 2016. Conclusions The use of antibiotics in children with diarrhoeal disease decreased significantly in Uganda between 2014 and 2016. However, the extent of the contribution of the ORS scale-up programme to this decrease cannot be determined from this study.

By testing variants of the budding yeast phosphate response ( PHO ) genes, it is shown that the affinity of DNA binding sites that are accessible to a transcription factor determines the threshold for promoter activation, and that the binding sites within nucleosomal regions serve to influence the maximal expression of a gene once the nucleosomes are remodelled. Thus nucleosomes can decouple a promoter's threshold of activation from its dynamic range. Chromatin influences gene expression by restricting access of DNA binding proteins to their cognate sites in the genome 1 , 2 , 3 . Large-scale characterization of nucleosome positioning in Saccharomyces cerevisiae has revealed a stereotyped promoter organization in which a nucleosome-free region (NFR) is present within several hundred base pairs upstream of the translation start site 4 , 5 . Many transcription factors bind within NFRs and nucleate chromatin remodelling events which then expose other cis -regulatory elements 6 , 7 , 8 , 9 . However, it is not clear how transcription-factor binding and chromatin influence quantitative attributes of gene expression. Here we show that nucleosomes function largely to decouple the threshold of induction from dynamic range. With a series of variants of one promoter, we establish that the affinity of exposed binding sites is a primary determinant of the level of physiological stimulus necessary for substantial gene activation, and sites located within nucleosomal regions serve to scale expression once chromatin is remodelled. Furthermore, we find that the S. cerevisiae phosphate response ( PHO ) pathway exploits these promoter designs to tailor gene expression to different environmental phosphate levels. Our results suggest that the interplay of chromatin and binding-site affinity provides a mechanism for fine-tuning responses to the same cellular state. Moreover, these findings may be a starting point for more detailed models of eukaryotic transcriptional control.

Background We introduce BPG, a framework for generating publication-quality, highly-customizable plots in the R statistical environment. Results This open-source package includes multiple methods of displaying high-dimensional datasets and facilitates generation of complex multi-panel figures, making it suitable for complex datasets. A web-based interactive tool allows online figure customization, from which R code can be downloaded for integration with computational pipelines. Conclusion BPG provides a new approach for linking interactive and scripted data visualization and is available at http://labs.oicr.on.ca/boutros-lab/software/bpg or via CRAN at https://cran.r-project.org/web/packages/BoutrosLab.plotting.general

Background An estimated 50% of suspected malaria cases in sub-Saharan Africa first seek care in the private sector, especially in private medicine retail outlets. Quality of care in these outlets is generally unknown but considered poor with many patients not receiving a confirmatory diagnosis or the recommended first-line artemisinin-based combination therapy (ACT). In 2010, a subsidy pilot scheme, the Affordable Medicines Facility malaria, was introduced to crowd out the use of monotherapies in favour of WHO-pre-qualified artemisinin-based combinations (WHO-PQ-ACTs) in the private health sector. The scheme improved the availability, market share, and cost of WHO-PQ-ACTs in countries like Nigeria and Uganda, but in 2018, the subsidies were halted in Nigeria and significantly reduced in Uganda. This paper presents findings from six retail audit surveys conducted from 2014 to 2021 in Nigeria and Uganda to assess whether the impact of subsidies on the price, availability, and market share of artemisinin-based combinations has been sustained after the subsidies were reduced or discontinued. Methods Six independent retail audits were conducted in private medicine retail outlets, including pharmacies, drug shops, and clinics in Nigeria (2016, 2018, 2021), and Uganda (2014, 2019, 2020) to assess the availability, price, and market share of anti-malarials, including WHO-PQ-ACTs and non-WHO-PQ-ACTs, and malaria rapid diagnostic tests (RDTs). Results Between 2016 and 2021, there was a 57% decrease in WHO-PQ-ACT availability in Nigeria and a 9% decrease in Uganda. During the same period, non-WHO-PQ-ACT availability increased in Nigeria by 41% and by 34% in Uganda. The price of WHO-PQ-ACTs increased by 42% in Nigeria to $0.68 and increased in Uganda by 24% to $0.95. The price of non-WHO-PQ-ACTs decreased in Nigeria by 26% to $1.08 and decreased in Uganda by 64% to $1.23. There was a 76% decrease in the market share of WHO-PQ-ACTs in Nigeria and a 17% decrease in Uganda. Malaria RDT availability remained low throughout. Conclusion With the reduction or termination of subsidies for WHO-PQ-ACTs in Uganda and Nigeria, retail prices have increased, and retail prices of non-WHO-PQ-ACTs decreased, likely contributing to a shift of higher availability and increased use of non-WHO-PQ-ACTs.

Background Pneumonia is the leading infectious cause of death in children worldwide, accounting for 15% of all deaths in children under the age of five. Hypoxemia is a major cause of death in patients suffering from pneumonia. There is strong evidence that using pulse oximetry and having reliable oxygen sources in health care facilities can reduce deaths due to pneumonia by one-third. Despite its importance, hypoxemia is frequently overlooked in resource-constrained settings. Aside from the limited availability of pulse oximetry, evidence showed that healthcare workers did not use it as frequently to generate evidence-based decisions on the need for oxygen therapy. As a result, the goal of this study was to assess the availability of medical oxygen devices, operating manuals, guidelines, healthcare workers’ knowledge, and skills in the practice of hypoxemia diagnosis and oxygen therapy in piloted health centers of Ethiopia. Methods A pre-post non-experimental study design was employed. An interviewer-administered questionnaire was used to collect primary data and review medical record charts. A chi-square test with a statistical significance level of P  < 0.05 was used as a cut-off point for claiming statistical significance. Results Eighty one percent of healthcare workers received oxygen therapy training, up from 6% at baseline. As a result of the interventions, knowledge of pulse oximetry use and oxygen therapy provision, skills such as oxygen saturation and practices of oxygen therapy have significantly improved among healthcare workers in the piloted Health Centers. In terms of availability of oxygen devices (e.g. cylinders, concentrators, and pulse oximeters) in the facilities, seven (58%) facilities did not have any at baseline, but due to the interventions, all facilities were equipped with the oxygen devices. Conclusions Given the prevalence of pneumonia and hypoxemia, a lack of access to oxygen delivery devices, as well as a lack of knowledge and skills among healthcare workers in the administration of oxygen therapy, may represent an important and reversible barrier to improving child survival. Therefore, scaling up clinician training, technical support, availability of oxygen devices, guidelines, manuals, strengthening maintenance schemes, and close monitoring of healthcare workers and health facilities is strongly advised.

Background Hypoxemia is a severe condition associated with high rates of mortality, particularly in low- and middle-income countries (LMICs) with poor access to oxygen therapy. Despite its clinical significance, there have been few studies to describe the burden of hypoxemia. Thus, the primary objective of this study is to systematically describe the prevalence of hypoxemia among pediatric and adult patients in low- and middle-income countries. Methods/design Standard systematic review methods will be used. Bibliographic databases (MEDLINE, EMBASE, CINAHL) will be searched from 1998 onwards. The search strategy aims to identify studies that have measured peripheral blood oxygen saturation (SpO 2 ) in children and adults presenting to health facilities in LMICs. Studies will be included if oxygen saturation measurements by pulse oximetry were measured. No studies will be excluded based on study design though patients recruited from intensive care units and post-operative care will be excluded. The primary outcome is the prevalence of hypoxemia on presentation to the healthcare facility. We define hypoxemia on the basis of SpO 2 measurements, and use a threshold of SpO 2 less than 90% at sea level though allow for a lower threshold for studies conducted at higher altitude and where justified. Standardized tools will be used to extract data on number of patients with SpO 2 measurements, number of patients with hypoxemia, patient population characteristics, and study characteristics. Quality of the included studies will be assessed using the “Checklist for Prevalence Studies” developed by the Joanna Briggs Institute. If there are enough studies to do so, we will conduct meta-analysis using a random effects model to estimate prevalence of hypoxemia and conduct subgroup analyses by age and disease groups. Discussion Hypoxemia is a critical condition and understanding the burden of hypoxemia may support decision-making in LMICs to deploy pulse oximeters and oxygen treatments more efficiently to address diseases and patient populations with the highest burden. Previous studies on hypoxemia prevalence have focused too narrowly on a few diseases or specific patient populations (e.g., pneumonia in children under five) whereas any effort to improve access to oxygen requires understanding of the potential demand for oxygen for all diseases and population groups. Governments, UN agencies, donors, and NGOs are investing strongly to improve oxygen systems in LMICs. Effective oxygen system planning requires estimation of oxygen need, informed by robust data on hypoxemia prevalence and admission patterns at all the levels of the health system. This study aims to fill that gap by providing comprehensive estimates of hypoxemia prevalence. Systematic review registration PROSPERO CRD42019136622 .

Background Nearly 90,000 under-five children die from diarrhoea annually in Nigeria. Over 90% of the deaths can be prevented with oral rehydration salt (ORS) and zinc treatment but coverage nationally was less than 34% for ORS and 3% for zinc with wide inequities. A program was implemented in eight states to address critical barriers to the optimal functioning of the health care market to deliver these treatments. In this study, we examine changes in the inequities of coverage of ORS and zinc over the intervention period. Methods Baseline and endline household surveys were used to measure ORS and zinc coverage and household assets. Principal component analysis was used to construct wealth quintiles. We used multi-level logistic regression models to estimate predictive coverage of ORS and zinc by wealth and urbanicity at each survey period. Simple measures of disparity and concentration indices and curves were used to evaluate changes in ORS and zinc coverage inequities. Results At baseline, 28% (95% CI: 22–35%) of children with diarrhoea from the poorest wealth quintile received ORS compared to 50% (95% CI: 52–58%) from the richest. This inequality reduced at endline as ORS coverage increased by 21%-points ( P  <  0.001) for the poorest and 17%-points ( P  <  0.001) for the richest. Zinc coverage increased significantly for both quintiles at endline from an equally low baseline coverage level. Consistent with the findings of the pairwise comparison of the poorest and the richest, the summary measure of disparity across all wealth quintiles showed a narrowing of inequities from baseline to endline. Concentration curves shifted towards equality for both treatments, concentration indices declined from 0.1012 to 0.0480 for ORS and from 0.2640 to 0.0567 for zinc. Disparities in ORS and zinc coverage between rural and urban at both time points was insignificant except that the use of zinc in the rural at endline was significantly higher at 38% (95%CI: 35–41%) compared to 29% (95%CI, 25–33%) in the urban. Conclusion The results show a pro-rural improvement in coverage and a reduction in coverage inequities across wealth quintiles from baseline to endline. This gives an indication that initiatives focused on shaping healthcare market systems may be effective in reducing health coverage gaps without detracting from equity as a health policy objective.

Background Oxygen therapy is a lifesaving treatment, however, in Ethiopia, oxygen is not readily available in many healthcare facilities. In 2015, the Federal Ministry of Health launched a national roadmap to increase access to oxygen. This study aims to evaluate whether availability of oxygen and its clinical practice in public hospitals of Ethiopia changed during the time the roadmap was being implemented. Methods Between December 2015 and December 2019, a multifaceted approach was undertaken to increase access to oxygen in public facilities in Ethiopia. The activities included formation of new policies, development of guidelines, procurement and maintenance of oxygen equipment, and training of healthcare workers. To evaluate whether access and use of oxygen changed during this period, facility-based surveys were conducted between December 2015 to December 2019. Primary data, including medical record reviews, were collected from 32 public hospitals bi-annually. A chi-square test that claimed P  < 0.05 used to assess the statistical significance differences. Results The study was conducted in 32 public hospitals of Ethiopia, where capacity building and technical support interventions implemented. Of these 32 facilities, 15 (46.9%) were general hospitals, 10 (31.2%) were referral hospitals, and 7 (21.9%) were primary hospitals. Functional availability of oxygen has shown a statistically significant increase from 62 to 100% in the pediatric in-patient departments of general and referral hospitals ( p -value < 0.001). Similarly, functional availability of pulse oximetry has shown a statistically significant increase from 45 to 96%. With regard to clinical practices, the blood oxygen saturation (SpO2) measurement at diagnosis increased from 10.2 to 75%, and SpO2 measurement at admission increased 20.5 to 83%. Conclusions Based on the intervention results, we conclude that multifaceted approaches targeting policy, healthcare workers’ capacity, increased device procurement, and device maintenance programs with on-site mentorship, can improve the availability of medical oxygen and pulse oximetry, as well as clinical practice of oxygen therapy in health facilities. Therefore, ensuring device availability along with regular technical support and close follow-up of healthcare workers and facilities are critical, and these interventions should be scaled further.