Morphological bases of phytoplankton energy management and physiological responses unveiled by 3D subcellular imaging

Eukaryotic phytoplankton have a small global biomass but play major roles in primary production and climate. Despite improved understanding of phytoplankton diversity and evolution, we largely ignore the cellular bases of their environmental plasticity. By comparative 3D morphometric analysis across seven distant phytoplankton taxa, we observe constant volume occupancy by the main organelles and preserved volumetric ratios between plastids and mitochondria. We hypothesise that phytoplankton subcellular topology is modulated by energy-management constraints. Consistent with this, shifting the diatom Phaeodactylum from low to high light enhances photosynthesis and respiration, increases cell-volume occupancy by mitochondria and the plastid CO2-fixing pyrenoid, and boosts plastid mitochondria contacts. Changes in organelle architectures and interactions also accompany Nannochloropsis acclimation to different trophic lifestyles, along with respiratory and photosynthetic responses. By revealing evolutionarily-conserved topologies of energy-managing organelles, and their role in phytoplankton acclimation, this work deciphers phytoplankton responses at subcellular scales

Implementation strategies for knowledge products in primary healthcare: A systematic review of systematic reviews

BACKGROUND: The underuse or overuse of knowledge products leads to waste in healthcare, and primary care is no exception. OBJECTIVE: We aimed to characterize which knowledge products are frequently implemented, the implementation strategies used in primary care, and the implementation outcomes that are measured. METHODS: We performed a systematic review of systematic reviews (SR) using the Cochrane systematic approach to include eligible SR. The inclusion criteria were: any primary care contexts; healthcare professionals and patients; any EPOC implementation strategies of specified knowledge products; any comparator; and any implementation outcomes based on the Proctor framework. We searched the Medline, EMBASE, CINAHL, Ovid PsycINFO, Web of Science, and Cochrane Library databases from their inception to October 2019, without any restriction. We searched the references of the included SR. Pairs of reviewers independently performed selection, data extraction and methodological quality assessment with AMSTAR 2. Data extraction was informed by EPOC taxonomy for implementation strategies and the Proctor framework for implementation outcomes. We performed a descriptive analysis and summarized the results using a narrative synthesis. RESULTS: Of the 11,101 records identified, 81 SR were included. Forty-seven SR involved healthcare professionals alone. Fifteen SR were of high or moderate methodological quality. Most of them addressed one type of knowledge product (56/81), common clinical practice guidelines (26/56) or management, and behavioural or pharmacological health interventions (24/56). Mixed strategies were used for implementation (67/81), predominantly educational-based (meetings in 60/81, materials distribution in 59/81, and academic detailing in 45/81), reminder (53/81) and audit and feedback (40/81) strategies. Education meetings (P=.13) and academic detailing (P=.11) seem to be more used when the population is composed of Healthcare professionals alone. The improvement of the adoption of knowledge products was the most commonly measured outcome (72/81). The evidence level was reported in 10/81 SR on 62 outcomes (including 48 improvement of adoption), of which 16 outcomes were of moderate or high level. CONCLUSIONS: Clinical practice guidelines and management, behavioural or pharmacological health interventions are the most commonly implemented knowledge products through the mixed use of educational, reminders and audit and feedback strategies. There is need for a strong methodology for the SR of RCTs to explore their effectiveness and the whole cascade of implementation outcomes. CLINICALTRIAL: Not applicable

Multidrug-resistant tuberculosis control in Rwanda overcomes a successful clone that causes most disease over a quarter century

Summary background: Multidrug-resistant (MDR) tuberculosis (TB) poses an important challenge in TB management and control. Rifampicin resistance (RR) is a solid surrogate marker of MDR-TB. We investigated the RR-TB clustering rates, bacterial population dynamics to infer transmission dynamics, and the impact of changes to patient management on these dynamics over 27 years in Rwanda. Methods: We analysed whole genome sequences of a longitudinal collection of nationwide RR-TB isolates. The collection covered three important periods: before programmatic management of MDR-TB (PMDT; 1991–2005), the early PMDT phase (2006–2013), in which rifampicin drug-susceptibility testing (DST) was offered to retreatment patients only, and the consolidated phase (2014–2018), in which all bacteriologically confirmed TB patients had rifampicin DST done mostly via Xpert MTB/RIF assay. We constructed clusters based on a 5 SNP cut-off and resistance conferring SNPs. We used Bayesian modelling for dating and population size estimations, TransPhylo to estimate the number of secondary cases infected by each patient, and multivariable logistic regression to assess predictors of being infected by the dominant clone. Results: Of 308 baseline RR-TB isolates considered for transmission analysis, the clustering analysis grouped 259 (84.1%) isolates into 13 clusters. Within these clusters, a single dominant clone was discovered containing 213 isolates (82.2% of clustered and 69.1% of all RR-TB), which we named the “Rwanda Rifampicin-Resistant clone” (R3clone). R3clone isolates belonged to Ugandan sub-lineage 4.6.1.2 and its rifampicin and isoniazid resistance were conferred by the Ser450Leu mutation in rpoB and Ser315Thr in katG genes, respectively. All R3clone isolates had Pro481Thr, a putative compensatory mutation in the rpoC gene that likely restored its fitness. The R3clone was estimated to first arise in 1987 and its population size increased exponentially through the 1990s’, reaching maximum size (∼84%) in early 2000 s’, with a declining trend since 2014. Indeed, the highest proportion of R3clone (129/157; 82·2%, 95%CI: 75·3–87·8%) occurred between 2000 and 13, declining to 64·4% (95%CI: 55·1-73·0%) from 2014 onward. We showed that patients with R3clone detected after an unsuccessful category 2 treatment were more likely to generate secondary cases than patients with R3clone detected after an unsuccessful category 1 treatment regimen. Conclusions: RR-TB in Rwanda is largely transmitted. Xpert MTB/RIF assay as first diagnostic test avoids unnecessary rounds of rifampicin-based TB treatment, thus preventing ongoing transmission of the dominant R3clone. As PMDT was intensified and all TB patients accessed rifampicin-resistance testing, the nationwide R3clone burden declined. To our knowledge, our findings provide the first evidence supporting the impact of universal DST on the transmission of RR-TB

National tuberculosis prevalence surveys in Africa, 2008\u20132016: an overview of results and lessons learned

Objective and methods: Worldwide, tuberculosis (TB) is the leading cause of death from a single infectious agent. In many countries, national TB prevalence surveys are the only way to reliably measure the burden of TB disease and can also provide other evidence to inform national efforts to improve TB detection and treatment. Our objective was to synthesise the results and lessons learned from national surveys completed in Africa between 2008 and 2016, to complement a previous review for Asia. Results: Twelve surveys completed in Africa were identified: Ethiopia (2010\u20132011), Gambia (2011\u20132013), Ghana (2013), Kenya (2015\u20132016), Malawi (2013\u20132014), Nigeria (2012), Rwanda (2012), Sudan (2013\u20132014), Tanzania (2011\u20132012), Uganda (2014\u20132015), Zambia (2013\u20132014) and Zimbabwe (2014). The eligible population in all surveys was people aged 6515 years who met residency criteria. In total 588 105 individuals participated, equivalent to 82% (range 57\u201396%) of those eligible. The prevalence of bacteriologically confirmed pulmonary TB disease in those 6515 years varied from 119 (95% CI 79\u2013160) per 100 000 population in Rwanda and 638 (95% CI 502\u2013774) per 100 000 population in Zambia. The male:female ratio was 2.0 overall, ranging from 1.2 (Ethiopia) to 4.1 (Uganda). Prevalence per 100 000 population generally increased with age, but the absolute number of cases was usually highest among those aged 35\u201344 years. Of identified TB cases, 44% (95% CI 40\u201349) did not report TB symptoms during screening and were only identified as eligible for diagnostic testing due to an abnormal chest X-ray. The overall ratio of prevalence to case notifications was 2.5 (95% CI 1.8\u20133.2) and was consistently higher for men than women. Many participants who did report TB symptoms had not sought care; those that had were more likely to seek care in a public health facility. HIV prevalence was systematically lower among prevalent cases than officially notified TB patients with an overall ratio of 0.5 (95% CI 0.3\u20130.7). The two main study limitations were that none of the surveys included people <15 years, and 5 of 12 surveys did not have data on HIV status. Conclusions: National TB prevalence surveys implemented in Africa between 2010 and 2016 have contributed substantial new evidence about the burden of TB disease, its distribution by age and sex, and gaps in TB detection and treatment. Policies and practices to improve access to health services and reduce under-reporting of detected TB cases are needed, especially among men. All surveys provide a valuable baseline for future assessment of trends in TB disease burden