A mathematical model for the interpretation of nuclear bomb test derived 14C incorporation in biological systems

International audienceHuman tissues continually replace dying cells with newborn cells. However, the rate of renewal varies by orders of magnitudes between blood cells, which are renewed every day and neurons, for which renewal is non-existent or limited to specific regions of the brain. Between those extreme are many tissues that turnover on a time scale of years, although no direct measurements have been done. We present here a mathematical method to estimate cell turnover in slowly renewing biological systems. Age distribution of DNA can be estimated from the integration of radiocarbon derived from nuclear bomb-testing during the cold war (1955–1963). For slowly renewing tissues, this method provides a better estimate of the average age of the tissue than direct estimates from the bomb-curve. Moreover, death, birth and turnover rates can be estimated. We highlight this method with data from human fat cells

Effectiveness of diet and physical activity interventions amongst adults attending colorectal and breast cancer screening: a systematic review and meta-analysis

Purpose: To estimate the effectiveness of tailored physical activity and dietary interventions amongst adults attending colorectal and breast cancer screening. Methods: Five literature databases were systematically searched to identify randomised controlled trials (RCTs) of tailored physical activity and/or dietary interventions with follow-up support initiated through colorectal and breast cancer screening programmes. Outcomes included markers of body fatness, physical activity, and dietary intake. Mean differences (MDs) or standardised mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using random effects models. Results: Five RCTs met the inclusion criteria encompassing a total of 722 participants. Diet and physical activity interventions led to statistically significant reductions in body mass (MD − 1.6 kg, 95% CI − 2.7 to − 0.39 kg; I2 = 81%; low quality evidence), body mass index (MD − 0.78 kg/m2, 95% CI − 1.1 to − 0.50 kg/m2; I2 = 21%; moderate quality evidence), and waist circumference (MD − 2.9 cm, 95% CI − 3.8 to − 1.91; I2 = 0%; moderate quality evidence), accompanied by an increase in physical activity (SMD 0.31, 95% CI 0.13 to 0.50; I2 = 0%; low quality evidence) and fruit and vegetable intake (SMD 0.33, 95% CI 0.01 to 0.64; I2 = 51%; low quality evidence). Conclusion: There is low quality evidence that lifestyle interventions involving follow-up support lead to modest weight loss and increased physical activity and fruit and vegetable intake. Due to the modest intervention effects, low quality of evidence and small number of studies, further rigorously designed RCTs with long-term follow-up of modifiable risk factors and embedded cost–benefit analyses are warranted (PROSPERO ref: CRD42020179960)

Adipocyte Turnover: Relevance to Human Adipose Tissue Morphology

International audienceOBJECTIVE: Adipose tissue may contain few large adipocytes (hypertrophy) or many small adipocytes (hyperplasia). We investigated factors of putative importance for adipose tissue morphology. RESEARCH DESIGN AND METHODS: Subcutaneous adipocyte size and total fat mass were compared in 764 subjects with BMI 18-60 kg/m(2). A morphology value was defined as the difference between the measured adipocyte volume and the expected volume given by a curved-line fit for a given body fat mass and was related to insulin values. In 35 subjects, in vivo adipocyte turnover was measured by exploiting incorporation of atmospheric (14)C into DNA. RESULTS: Occurrence of hyperplasia (negative morphology value) or hypertrophy (positive morphology value) was independent of sex and body weight but correlated with fasting plasma insulin levels and insulin sensitivity, independent of adipocyte volume (beta-coefficient = 0.3, P < 0.0001). Total adipocyte number and morphology were negatively related (r = -0.66); i.e., the total adipocyte number was greatest in pronounced hyperplasia and smallest in pronounced hypertrophy. The absolute number of new adipocytes generated each year was 70% lower (P < 0.001) in hypertrophy than in hyperplasia, and individual values for adipocyte generation and morphology were strongly related (r = 0.7, P < 0.001). The relative death rate (approximately 10% per year) or mean age of adipocytes (approximately 10 years) was not correlated with morphology. CONCLUSIONS: Adipose tissue morphology correlates with insulin measures and is linked to the total adipocyte number independently of sex and body fat level. Low generation rates of adipocytes associate with adipose tissue hypertrophy, whereas high generation rates associate with adipose hyperplasia

Methods and measures for investigating microscale motility

Motility is an essential factor for an organism's survival and diversification. With the advent of novel single-cell technologies, analytical frameworks and theoretical methods, we can begin to probe the complex lives of microscopic motile organisms and answer the intertwining biological and physical questions of how these diverse lifeforms navigate their surroundings. Herein, we give an overview of different experimental, analytical, and mathematical methods used to study a suite of microscale motility mechanisms across different scales encompassing molecular-, individual- to population-level. We identify transferable techniques, pressing challenges, and future directions in the field. This review can serve as a starting point for researchers who are interested in exploring and quantifying the movements of organisms in the microscale world.Comment: 24 pages, 2 figure

Towards personalised anti-microbial and immune approaches to infections in acute care. Can real-time genomic-informed diagnosis of pathogens, and immune-focused therapies improve outcomes for patients? An observational, experimental study protocol

Introduction: Infection causes a vast burden of disease, with significant mortality, morbidity and costs to health-care systems. However, identifying the pathogen causative infection can be challenging, resulting in high use of broad-spectrum antibiotics, much of which may be inappropriate. Novel metagenomic methods have potential to rapidly identify pathogens, however their clinical utility for many infections is currently unclear. Outcome from infection is also impacted by the effectiveness of immune responses, which can be impaired by age, co-morbidity and the infection itself. The aims of this study are twofold: 1. To compare diversity of organisms identified and time-to-result using metagenomic methods versus traditional culture -based techniques, to explore the potential clinical role of metagenomic approaches to pathogen identification in a range of infections.2. To characterise the ex vivo function of immune cells from patients with acute infection, exploring host and pathogen-specific factors which may affect immune function and overall outcomes. Methods: This is a prospective observational study of patients with acute infection. Patients with symptoms suggestive of an acute infection will be recruited, and blood and bodily fluid relevant to the site of infection collected (for example, sputum and naso-oropharyngeal swabs for respiratory tract infections, or urine for a suspected urinary tract infection). Metagenomic analysis of samples will be compared to traditional microbiology, alongside the antimicrobials received. Blood and respiratory samples such as bronchoalveolar lavage will be used to isolate immune cells and interrogate immune cell function. Where possible, similar samples will be collected from matched participants without a suspected infection to determine the impact of infection on both microbiome and immune cell function.</p

Charge separation and triplet exciton formation pathways in small molecule solar cells as studied by time-resolved EPR spectroscopy

Funding: EPSRC EP/G03673X/1 (SAJT), Royal Society Wolfson research merit award (IDWS).Organic solar cells are a promising renewable energy technology, offering the advantages of mechanical flexibility and solution processability. An understanding of the electronic excited states and charge separation pathways in these systems is crucial if efficiencies are to be further improved. Here we use light induced electron paramagnetic resonance (LEPR) spectroscopy and density functional theory calculations (DFT) to study the electronic excited states, charge transfer (CT) dynamics and triplet exciton formation pathways in blends of the small molecule donors (DTS(FBTTh2)2, DTS(F2BTTh2)2, DTS(PTTh2)2, DTG(FBTTh2)2 and DTG(F2BTTh2)2) with the fullerene derivative PC61BM. Using high frequency EPR the g-tensor of the positive polaron on the donor molecules was determined. The experimental results are compared with DFT calculations which reveal that the spin density of the polaron is distributed over a dimer or trimer. Time-resolved EPR (TR-EPR) spectra attributed to singlet CT states were identified and the polarization patterns revealed similar charge separation dynamics in the four fluorobenzothiadiazole donors, while charge separation in the DTS(PTTh2)2 blend is slower. Using TR-EPR we also investigated the triplet exciton formation pathways in the blend. The polarization patterns reveal that the excitons originate from both intersystem crossing (ISC) and back electron transfer (BET) processes. The DTS(PTTh2)2 blend was found to contain substantially more triplet excitons formed by BET than the fluorobenzothiadiazole blends. The higher BET triplet exciton population in the DTS(PTTh2)2 blend is in accordance with the slower charge separation dynamics observed in this blend.PostprintPostprintPeer reviewe

Post-exercise rehydration: Comparing the efficacy of three commercial oral rehydration solutions

IntroductionThis study compared the efficacy of three commercial oral rehydration solutions (ORS) for restoring fluid and electrolyte balance, after exercise-induced dehydration.MethodHealthy, active participants (N = 20; ♀ = 3; age ∼27 y, V˙O2peak ∼52 ml/kg/min) completed three randomised, counterbalanced trials whereby intermittent exercise in the heat (∼36°C, ∼50% humidity) induced ∼2.5% dehydration. Subsequently, participants rehydrated (125% fluid loss in four equal aliquots at 0, 1, 2, 3 h) with a glucose-based (G-ORS), sugar-free (Z-ORS) or amino acid-based sugar-free (AA-ORS) ORS of varying electrolyte composition. Urine output was measured hourly and capillary blood samples collected pre-exercise, 0, 2 and 5 h post-exercise. Sodium, potassium, and chloride concentrations in urine, sweat, and blood were determined.ResultsNet fluid balance peaked at 4 h and was greater in AA-ORS (141 ± 155 ml) and G-ORS (101 ± 195 ml) than Z-ORS (−47 ± 208 ml; P ≤ 0.010). Only AA-ORS achieved positive sodium and chloride balance post-exercise, which were greater for AA-ORS than G-ORS and Z-ORS (P ≤ 0.006), as well as for G-ORS than Z-ORS (P ≤ 0.007) from 1 to 5 h.Conclusionwhen provided in a volume equivalent to 125% of exercise-induced fluid loss, AA-ORS produced comparable/superior fluid balance and superior sodium/chloride balance responses to popular glucose-based and sugar-free ORS