Role of the \u3ci\u3eEscherichia coli\u3c/i\u3e FadR Regulator in Stasis Survival and Growth Phase-Dependent Expression of the \u3ci\u3euspA, fad\u3c/i\u3e, and \u3ci\u3efab\u3c/i\u3e Genes

The increased expression of the uspA gene of Escherichia coli is an essential part of the cell’s response to growth arrest. We demonstrate that stationary-phase activation of the uspA promoter is in part dependent on growth phase-dependent inactivation or repression of the FadR regulator. Transcription of uspA is derepressed during exponential growth in fadR null mutants or by including the fatty acid oleate in the growth medium of FadR1 cells. The results of DNA footprinting analysis show that FadR binds downstream of the uspA promoter in the noncoding region. Thus, uspA is a member of the fadR regulon. All the fad-lacZ fusions examined (fadBA, fadL, and fadD) are increasingly expressed in stationary phase with kinetics similar to that of the increased expression of uspA. In contrast, b-galactosidase levels decrease during stationary phase in a fabA-lacZ lysogen, consistent with the role of FadR as an activator of fabA. The growth phase-dependent increased and decreased transcription of fad genes and fabA, respectively, is dependent on the status of the fadR gene. Cells carrying a mutation in the FadR gene (fadRS219N) that makes it nonderepressible exhibit a weak stationary-phase induction of uspA and fad genes. In addition, cells carrying fadRS219N survive long-term stasis poorly, indicating that FadR-dependent alterations in fatty acid metabolism are an integral and important part of the adaptation to stationary phase

Role of the \u3ci\u3eEscherichia coli\u3c/i\u3e FadR Regulator in Stasis Survival and Growth Phase-Dependent Expression of the \u3ci\u3euspA, fad\u3c/i\u3e, and \u3ci\u3efab\u3c/i\u3e Genes

The increased expression of the uspA gene of Escherichia coli is an essential part of the cell’s response to growth arrest. We demonstrate that stationary-phase activation of the uspA promoter is in part dependent on growth phase-dependent inactivation or repression of the FadR regulator. Transcription of uspA is derepressed during exponential growth in fadR null mutants or by including the fatty acid oleate in the growth medium of FadR1 cells. The results of DNA footprinting analysis show that FadR binds downstream of the uspA promoter in the noncoding region. Thus, uspA is a member of the fadR regulon. All the fad-lacZ fusions examined (fadBA, fadL, and fadD) are increasingly expressed in stationary phase with kinetics similar to that of the increased expression of uspA. In contrast, b-galactosidase levels decrease during stationary phase in a fabA-lacZ lysogen, consistent with the role of FadR as an activator of fabA. The growth phase-dependent increased and decreased transcription of fad genes and fabA, respectively, is dependent on the status of the fadR gene. Cells carrying a mutation in the FadR gene (fadRS219N) that makes it nonderepressible exhibit a weak stationary-phase induction of uspA and fad genes. In addition, cells carrying fadRS219N survive long-term stasis poorly, indicating that FadR-dependent alterations in fatty acid metabolism are an integral and important part of the adaptation to stationary phase

Impact of antibiotic treatment duration on outcomes in older men with suspected urinary tract infection: retrospective cohort study

Purpose Clinical guidelines recommend at least 7 days of antibiotic treatment for older men with urinary tract infection (UTI). There may be potential benefits for patients, health services, and antimicrobial stewardship if shorter antibiotic treatment resulted in similar outcomes. We aimed to determine if treatment duration could be reduced by estimating risk of adverse outcomes according to different prescription durations. Methods This retrospective cohort study included men aged greater than or equal to 65 years old with a suspected UTI. We compared outcomes in men prescribed 3, 5, 7, and 8 to 14 days of antibiotic treatment in a multivariable logistic regression analysis and 3 versus 7 days in a propensity‐score matched analysis. Our outcomes were reconsultation and represcription (proxy for treatment failure), hospitalisation for UTI, sepsis, or acute kidney injury (AKI), and death. Results Of 360 640 men aged greater than or equal to 65 years, 33 745 (9.4%) had a UTI. Compared with 7 days, men prescribed 3‐day treatment had greater odds of reconsultation and represcription (adjusted OR 1.48; 95% CI, 1.25‐1.74) but lower odds of AKI hospitalisation (adjusted OR 0.66; 95% CI, 0.45‐0.97). We estimated that treating 150 older men with 3 days instead of 7 days of antibiotics could result in four extra reconsultation and represcriptions and one less AKI hospitalisation. We estimated annual prescription cost savings at around £2.2 million. Conclusions Antibiotic treatment for older men with suspected UTI could be reduced to 3 days, albeit with a small increase in risk of treatment failure. A definitive randomised trial is urgently needed

Risk of adverse outcomes following urinary tract infection in older people with renal impairment : Retrospective cohort study using linked health record data

Funding: This report is independent research arising from a National Institute of Health Research (NIHR) Doctoral Research Fellowship awarded to HA, and supported by Health and Care Research Wales (HCRW) (grant number DRF-2014-07-010). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Data Availability: Data analysed for this study were obtained under institutional license from the Clinical Practice Research Datalink, https://www.cprd.com/intro.asp. Data are not available for sharing but can be applied for through the CPRD. Relevant information to allow acquisition of a replicable data set is available in the paper and its Supporting Information files.Peer reviewedPublisher PD

Adverse childhood experiences during childhood and academic attainment at age 7 and 11 years: an electronic birth cohort study

Objectives Adverse childhood experiences (ACEs) have a negative impact on childhood health, but their impact on education outcomes is less well known. We investigated whether or not ACEs were associated with reduced educational attainment at age 7 and 11 years. Study design The study design used in the study is a population-based electronic cohort study. Methods We analysed data from a total population electronic child cohort in Wales, UK. ACEs (exposures) were living with an adult household member with any of (i) serious mental illness, (ii) common mental disorder (CMD), (iii) an alcohol problem; (iv) child victimisation, (v) death of a household member and (vi) low family income. We used multilevel logistic regression to model exposure to these ACEs and not attaining the expected level at statutory education assessments, Key Stage (KS) 1 and KS2 separately, adjusted for known confounders including perinatal, socio-economic and school factors. Results There were 107,479 and 43,648 children included in the analysis, with follow-up to 6–7 years (KS1) and 10–11 years (KS2), respectively. An increased risk of not attaining the expected level at KS1 was associated with living with adult household members with CMD (adjusted odds ratio [aOR]: 1.13 [95% confidence interval [CI]: 1.09–1.17]) or an alcohol problem (adjusted odds ratio [aOR]: 1.16 [95% confidence interval [CI]: 1.10–1.22]), childhood victimisation (adjusted odds ratio [aOR]: 1.58 [95% confidence interval [CI]: 1.37–1.82]), death of a household member (adjusted odds ratio [aOR]: 1.14 [95% confidence interval [CI]: 1.04–1.25]) and low family income (adjusted odds ratio [aOR]: 1.92 [95% confidence interval [CI]: 1.84–2.01]). Similar results were observed for KS2. Children with multiple adversities had substantially increased odds of not attaining the expected level at each educational assessment. Conclusion The educational potential of many children may not be achieved due to exposure to adversity in childhood. Affected children who come in to contact with services should have relevant information shared between health and care services, and schools to initiate and facilitate a coordinated approach towards providing additional support and help for them to fulfil their educational potential, and subsequent economic and social participation

Incidence and antibiotic prescribing for clinically diagnosed urinary tract infection in older adults in UK primary care, 2004-2014

Funding: This report is independent research arising from a National Institute of Health Research (NIHR) Doctoral Research Fellowship awarded to Haroon Ahmed, and supported by Health and Care Research Wales (HCRW) (Grant number: DRF-2014-07-010). The views expressed in this publication are those of the authors and not necessarily those of the NIHR, NHS Wales, HCRW or the Welsh Government. Hywel Jones is supported by The Farr Institute @ CIPHER, a Medical Research Council led multi-funder initiative for e-health research, MRC Grant Number: MR/K006525/1. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of this manuscript.Peer reviewedPublisher PD

The outstanding scientist, R.A. Fisher:His views on eugenics and race

R.A. Fisher was one of the greatest scientists of the 20th century (Fig. 1). He was a man of extraordinary ability and originality whose scientific contributions ranged over a very wide area of science, from biology through statistics to ideas on continental drift, and whose work has had a huge positive impact on human welfare. Not surprisingly, some of his large volume of work is not widely used or accepted at the current time, but his scientific brilliance has never been challenged. He was from an early age a supporter of certain eugenic ideas, and it is for this reason that he has been accused of being a racist and an advocate of forced sterilisation (Evans 2020). His promotion of eugenics has recently caused various organisations to remove his name from awards and dedications of buildings (Tarran 2020; Rothamsted Research 2020; Society for the Study of Evolution 2020; Gonville and Caius College 2020). A primary aim of this paper is to conduct a careful analysis of his own writings in these areas. Our purpose is neither to defend nor attack Fisher’s work in eugenics and views on race, but to present a careful account of their substance and nature.Publisher PDFPeer reviewe