Corynebacterium glutamicum CrtR and its orthologs in actinobacteria: conserved function and application as genetically encoded biosensor for detection of geranylgeranyl pyrophosphate

Henke NA, Austermeier S, Grothaus IL, et al. Corynebacterium glutamicum CrtR and its orthologs in actinobacteria: conserved function and application as genetically encoded biosensor for detection of geranylgeranyl pyrophosphate. International Journal of Molecular Sciences. 2020;21(15): 5482.Carotenoid biosynthesis in Corynebacteriumglutamicum is controlled by the MarR-type regulator CrtR, which represses transcription of the promoter of the crt operon (PcrtE) and of its own gene (PcrtR). Geranylgeranyl pyrophosphate (GGPP), and to a lesser extent other isoprenoid pyrophosphates, interfere with the binding of CrtR to its target DNA in vitro, suggesting they act as inducers of carotenoid biosynthesis. CrtR homologs are encoded in the genomes of many other actinobacteria. In order to determine if and to what extent the function of CrtR, as a metabolite-dependent transcriptional repressor of carotenoid biosynthesis genes responding to GGPP, is conserved among actinobacteria, five CrtR orthologs were characterized in more detail. EMSA assays showed that the CrtR orthologs from Corynebacteriumcallunae, Acidipropionibacteriumjensenii, Paenarthrobacternicotinovorans, Micrococcusluteus and Pseudarthrobacterchlorophenolicus bound to the intergenic region between their own gene and the divergently oriented gene, and that GGPP inhibited these interactions. In turn, the CrtR protein from C. glutamicum bound to DNA regions upstream of the orthologous crtR genes that contained a 15 bp DNA sequence motif conserved between the tested bacteria. Moreover, the CrtR orthologs functioned in C. glutamicum in vivo at least partially, as they complemented the defects in the pigmentation and expression of a PcrtE_gfpuv transcriptional fusion that were observed in a crtR deletion mutant to varying degrees. Subsequently, the utility of the PcrtE_gfpuv transcriptional fusion and chromosomally encoded CrtR from C. glutamicum as genetically encoded biosensor for GGPP was studied. Combined FACS and LC-MS analysis demonstrated a correlation between the sensor fluorescent signal and the intracellular GGPP concentration, and allowed us to monitor intracellular GGPP concentrations during growth and differentiate between strains engineered to accumulate GGPP at different concentrations

The use of YouTube for the self-management of arthritis and joint pain: a patient and public involvement study

This is an accepted manuscript of an article published by OUP in Rheumatology on 12/04/2019, available online: https://doi.org/10.1093/rheumatology/kez110.052 The accepted version of the publication may differ from the final published version

Magnetic resonance imaging of diverticular disease and its association with adipose tissue compartments and constitutional risk factors in subjects from a western general population

Purpose To determine the association of asymptomatic diverticular disease as assessed by magnetic resonance imaging (MRI) with adipose tissue compartments, hepatic steatosis and constitutional risk factors within a cohort drawn from a Western general population. Materials and Methods Asymptomatic subjects enrolled in a prospective case-control study underwent a 3 Tesla MRI scan, including an isotropic VIBE-Dixon sequence of the entire trunk. The presence and extent of diverticular disease were categorized according to the number of diverticula in each colonic segment in a blinded fashion. The amount of visceral, subcutaneous, and total adipose tissue (VAT, SAT, and TAT) was quantified by MRI. Additionally, the degree of hepatic steatosis, indicated as hepatic proton density fat fraction (hepatic PDFF) was determined using a multi-echo T1w sequence. Constitutional cardiometabolic risk factors were obtained and univariate and multivariate associations were calculated. Results A total of 371 subjects were included in the analysis (58.2% male, 56.2±9.2 years). Based on MRI, 154 participants (41.5%) had diverticular disease with 62 cases (17%) being advanced diverticular disease. Subjects with advanced diverticular disease had a significantly higher body mass index (BMI) (BMI: 29.9±5.1 vs. 27.5±4.6, p<0.001; respectively). Furthermore, all adipose tissue compartments were increased in subjects with advanced diverticular disease (e.g. VAT: 6.0±2.8 vs. 4.2±2.6 and SAT: 9.2±3.6 vs. 7.8±3.6, all p<0.001, respectively). Similarly, subjects with advanced diverticular disease had significantly higher hepatic PDFF (4.9 [2.7, 11.4] vs. 6.1 [5.5, 14.6], p=0.002). Conclusion Advanced diverticular disease is associated with an increased volume of adipose tissue compartments and BMI, which may suggest a metabolic role in disease development. Key Points: Diverticular disease is associated with constitutional risk factors such as BMI. Excess of adipose tissue compartments and hepatic steatosis are associated with the prevalence of diverticular disease. Our results suggest a shared pathological pathway of cardiometabolic alterations and the prevalence of diverticular disease. MRI is feasible for the assessment of adipose tissue compartments, hepatic steatosis, and diverticular disease and allows identification of patients who are at risk but in an asymptomatic disease state. Citation Format Storz C, Rospleszcz S, Askani E etal. Magnetic Resonance Imaging of Diverticular Disease and its Association with Adipose Tissue Compartments and Constitutional Risk Factors in Subjects from a Western General Population. Fortschr Röntgenstr 2020; DOI: 10.1055/a-1212-5669

Assessing Communities of Practice in health policy : A conceptual framework as a first step towards empirical research

Peer reviewe

Views on and experiences of electronic cigarettes: a qualitative study of women who are pregnant or have recently given birth.

Background Electronic cigarettes (ECs) are increasingly used for reducing or stopping smoking, with some studies showing positive outcomes. However, little is known about views on ECs during pregnancy or postpartum and previous studies have nearly all been conducted in the US and have methodological limitations, such as not distinguishing between smokers and ex/non-smokers. A greater understanding of this topic will help to inform both clinicians and EC interventions. We elicited views and experiences of ECs among UK pregnant or recently pregnant women. Methods We conducted semi-structured telephone interviews, using topic guides, with pregnant or recently pregnant women, who were current or recent ex-smokers. To ensure broad views of ECs were obtained, recruitment was from several geographical locations and via various avenues of recruitment. This included stop smoking services, antenatal and health visitor clinics, a pregnancy website and an informal network. Participants were 15 pregnant and 15 postpartum women, including nine current EC users, 11 ex-users, and 10 never-users. Five women who were interviewed in pregnancy were later interviewed in postpartum to explore if their views had changed. Audio data was transcribed verbatim and framework analysis was applied. Results Five main themes emerged: motivations for use (e.g., for stopping or reducing smoking), social stigma (e.g., avoiding use in public, preferring ‘discrete’ NRT), using the EC (e.g., mostly used at home); consumer aspects (e.g., limited advice available), and harm perceptions (e.g., viewed as less harmful than smoking; concerns about safety and addiction). Conclusions ECs were viewed positively by some pregnant and postpartum women and seen as less harmful than smoking and useful as aids for reducing and stopping smoking. However, due to perceived social stigma, some women feel uncomfortable using ECs in public, especially during pregnancy, and had concerns about safety and nicotine dependence. Health professionals and designers of EC interventions need to provide women with up-to-date and consistent information and advice about safety and dependence, as well as considering the influence of social stigma

Health care utilisation under the 30-Baht Scheme among the urban poor in Mitrapap slum, Khon Kaen, Thailand: a cross-sectional study

Background: In 2001, the Government of Thailand introduced a universal coverage scheme with the aim of ensuring equitable health care access for even the poorest citizens. For a flat user fee of 30 Baht per consultation, or for free for those falling into exemption categories, every scheme participant may access registered health services. The exemption categories include children under 12 years of age, senior citizens aged 60 years and over, the very poor, and volunteer health workers. The functioning of these exemption mechanisms and the effect of the scheme on health service utilisation among the poor is controversial. Methods: This cross-sectional study investigated the prevalence of 30-Baht Scheme registration and subsequent self-reported health service utilisation among an urban poor population in the Teparuk community within the Mitrapap slum in Khon Kaen city, northeastern Thailand. Furthermore, the effectiveness of the exemption mechanisms in reaching the very poor and the elderly was examined. Factors for users' choice of health facilities were identified. Results: Overall, the proportion of the Teparuk community enrolled with the 30-Baht Scheme was high at 86%, with over one quarter of these exempted from paying the consultation fee. User fee exemption was significantly more frequent among households with an above-poverty-line income (64.7%) compared to those below the poverty line (35.3%), χ2 (df) = 5.251 (1); p-value = 0.018. In addition, one third of respondents over 60 years of age were found to be still paying user fees. Self-reported use of registered medical facilities in case of illness was stated to be predominantly due to the service being available through the scheme, with service quality not a chief consideration. Overall consumer satisfaction was high, especially among those not required to pay the 30 Baht user fee. Conclusion: Whilst the 30-Baht Scheme seems to cover most of the poor population of Mitrapap slum in Khon Kaen, the user fee exemption mechanism only works partially with regard to reaching the poorest and exempting senior citizens. Service utilisation and satisfaction are highest amongst those who are fee-exempt. Service quality was not an important factor influencing choice of health facility. Ways should be sought to improve the effectiveness of the current exemption mechanisms.Sophie Coronini-Cronberg, Wongsa Laohasiriwong and Christian A Gerick

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Machine learning uncovers the most robust self-report predictors of relationship quality across 43 longitudinal couples studies

Given the powerful implications of relationship quality for health and well-being, a central mission of relationship science is explaining why some romantic relationships thrive more than others. This large-scale project used machine learning (i.e., Random Forests) to 1) quantify the extent to which relationship quality is predictable and 2) identify which constructs reliably predict relationship quality. Across 43 dyadic longitudinal datasets from 29 laboratories, the top relationship-specific predictors of relationship quality were perceived-partner commitment, appreciation, sexual satisfaction, perceived-partner satisfaction, and conflict. The top individual-difference predictors were life satisfaction, negative affect, depression, attachment avoidance, and attachment anxiety. Overall, relationship-specific variables predicted up to 45% of variance at baseline, and up to 18% of variance at the end of each study. Individual differences also performed well (21% and 12%, respectively). Actor-reported variables (i.e., own relationship-specific and individual-difference variables) predicted two to four times more variance than partner-reported variables (i.e., the partner’s ratings on those variables). Importantly, individual differences and partner reports had no predictive effects beyond actor-reported relationship-specific variables alone. These findings imply that the sum of all individual differences and partner experiences exert their influence on relationship quality via a person’s own relationship-specific experiences, and effects due to moderation by individual differences and moderation by partner-reports may be quite small. Finally, relationship-quality change (i.e., increases or decreases in relationship quality over the course of a study) was largely unpredictable from any combination of self-report variables. This collective effort should guide future models of relationships