Effectiveness of contact tracing and quarantine on reducing COVID-19 transmission: a retrospective cohort study.

OBJECTIVES: Contact tracing and quarantine are common measures used in the management of infectious disease outbreaks. However, few studies have measured their impact on the control of the COVID-19 pandemic. This study aimed to assess the effectiveness of those measures on reducing transmission of severe acute respiratory syndrome coronavirus 2 in a community setting. STUDY DESIGN: The study design is a retrospective cohort study. METHODS: A retrospective cohort study of COVID-19 cases notified in Eastern Porto from March 1st to April 30th, 2020 was performed. Intervention and control cohorts were defined based on whether cases were subjected to contact tracing and quarantine measures before the laboratory confirmation of disease. The number of secondary cases per index case and the proportion of cases with subsequent secondary cases were the primary outcomes. Secondary outcomes included the time from symptom onset to specimen collection and the number of close contacts. The analysis was stratified according to whether national lockdown measures had already been implemented. RESULTS: The intervention and control cohorts comprised 98 and 453 cases, respectively. No differences were observed concerning primary outcomes. The intervention group had a shorter time between symptom onset and specimen collection (median: 3 days, interquartile range [IQR]: 1-6, vs. median: 5 days, IQR: 2-7, P-value = 0.004) and fewer close contacts (median: 0, IQR: 0-2, vs. median: 2, IQR: 1-4, P-value<0.001). The stratified analysis returned similar results. CONCLUSION: Local public health measures were effective in reducing the time between symptom onset and laboratory diagnosis and the number of close contacts per case. No effect was apparent on secondary case figures, suggesting that further measures may be required.

Accuracy of a combined heart rate and motion sensor for assessing energy expenditure in free-living adults during a double-blind crossover caffeine trial using doubly labeled water as the reference method.

BACKGROUND/OBJECTIVES: A combined heart rate (HR) and motion sensor (Actiheart) has been proposed as an accurate method for assessing total energy expenditure (TEE) and physical activity energy expenditure (PAEE). However, the extent to which factors such as caffeine may affect the accuracy by which the estimated HR-related PAEE contribution will affect TEE and PAEE estimates is unknown. Therefore, we examined the validity of Actiheart in estimating TEE and PAEE in free-living adults under a caffeine trial compared with doubly labeled water (DLW) as reference criterion. SUBJECTS/METHODS: Using a double-blind crossover trial (Clinicaltrials.gov ID: #NCT01477294) with two conditions (4-day each with a 3-day-washout period), randomly ordered as caffeine (5 mg/kg per day) and placebo (malt-dextrine) intake, TEE was measured by DLW in 17 physically active men (20-38 years) who were non-caffeine users. In each condition, resting energy expenditure (REE) was assessed by indirect calorimetry and PAEE was calculated as (TEE-(REE+0.1 TEE)). Simultaneously, PAEE and TEE were estimated by Actiheart using an individual calibration (ACC+HRstep). RESULTS: Under caffeine, ACC+HRstep explained 76 and 64% of TEE and PAEE from DLW, respectively; corresponding results for the placebo condition were 82 and 66%. No mean bias was found between ACC+HRstep and DLW for TEE (caffeine:-468 kJ per day; placebo:-407 kJ per day), although PAEE was slightly underestimated (caffeine:-856 kJ per day; placebo:-1147 kJ per day). Similar limits of agreement were observed in both conditions ranging from -2066 to 3002 and from -3488 to 1776 kJ per day for TEE and PAEE, respectively. CONCLUSIONS: Regardless of caffeine intake, the combined HR and motion sensor is valid for estimating free-living energy expenditure in a group of healthy men but is less accurate for an individual assessment.

Age-related gene-specific changes of A-to-I mRNA editing in the human brain.

A-to-I editing is an adenosine-to-inosine modification of mRNA particularly widespread in the human brain, where it affects thousands of genes. A growing body of evidence suggests that A-to-I RNA editing is necessary for normal development and maintenance in mammals and that its deficiencies contribute to a number of pathological states. In this study, we examined whether mRNA editing levels of two mRNA species, CYFIP2 and GABRA3, change with aging. CYFIP2 has been implicated in synaptic maintenance, while GABRA3 is a GABA receptor subunit, a part of the major inhibitory neurotransmitter system in the CNS. The levels of mRNA editing were assessed in cortex samples of 20 subjects 22-102 years old. The data show an age-dependent statistically significant decrease in editing in CYFIP2. GABRA3 editing remained much more stable with age, implying that age-related decline of RNA editing is gene-specific. This is the first report of age-dependent decline in A-to-I editing. Further examination of these and other vulnerable genes may reveal specific RNA editing mechanisms that contribute to the aging phenotype.

Systems biology and longevity: an emerging approach to identify innovative anti-aging targets and strategies.

Human aging and longevity are complex and multi-factorial traits that result from a combination of environmental, genetic, epigenetic and stochastic factors, each contributing to the overall phenotype. The multi-factorial process of aging acts at different levels of complexity, from molecule to cell, from organ to organ systems and finally to organism, giving rise to the dynamic "aging mosaic". At present, an increasing amount of experimental data on genetics, genomics, proteomics and other -omics are available thanks to new high-throughput technologies but a comprehensive model for the study of human aging and longevity is still lacking. Systems biology represents a strategy to integrate and quantify the existing knowledge from different sources into predictive models, to be later tested and then implemented with new experimental data for validation and refinement in a recursive process. The ultimate goal is to compact the new acquired knowledge into a single picture, ideally able to characterize the phenotype at systemic/organism level. In this review we will briefly discuss the aging phenotype in a systems biology perspective, showing four specific examples at different levels of complexity, from a systemic process (inflammation) to a cascade-process pathways (coagulation) and from cellular organelle (proteasome) to single gene-network (PON-1), which could also represent targets for anti-aging strategies.

A database of vertebrate longevity records and their relation to other life-history traits.

Longevity is a major characteristic of animals that has long fascinated scientists. In this work, we present a comprehensive database of animal longevity records and related life-history traits entitled AnAge, which we compiled and manually curated from an extensive literature. AnAge started as a collection of longevity records, but has since been expanded to include quantitative data for numerous other life-history traits, including body masses at different developmental stages, reproductive data such as age at sexual maturity and measurements of reproductive output, and physiological traits related to metabolism. AnAge features over 4000 vertebrate species and is a central resource for applying the comparative method to studies of longevity and life-history evolution across the tree of life. Moreover, by providing a reference value for longevity and other life-history traits, AnAge can prove valuable to a broad range of biologists working in evolutionary biology, ecology, zoology, physiology and conservation biology. AnAge is freely available online (http://genomics.senescence.info/species/).

Growth kinetics rather than stress accelerate telomere shortening in cultures of human diploid fibroblasts in oxidative stress-induced premature senescence.

WI-38 human diploid fibroblasts underwent accelerated telomere shortening (490 bp/stress) and growth arrest after exposure to four subcytotoxic 100 microM tert-butylhydroperoxide (t-BHP) stresses, with a stress at every two population doublings (PD). After subcytotoxic 160 microM H2O2 stress or five repeated 30 microM t-BHP stresses along the same PD, respectively a 322 +/- 55 and 380 +/- 129 bp telomere shortening was observed only during the first PD after stress. The percentage of cells resuming proliferation after stress suggests this telomere shortening is due to the number of cell divisions accomplished to reach confluence during the first PD after stress.

Subcytotoxic H2O2 stress triggers a release of transforming growth factor-beta 1, which induces biomarkers of cellular senescence of human diploid fibroblasts.

Stress-induced premature senescence (SIPS) is induced 3 days after exposure of human diploid fibroblasts to subcytotoxic oxidative stress with H(2)O(2), with appearance of several biomarkers of replicative senescence. In this work, we show that transforming growth factor-beta1 (TGF-beta1) regulates the induction of several of these biomarkers in SIPS: cellular morphology, senescence-associated beta-galactosidase activity, increase in the steady-state level of fibronectin, apolipoprotein J, osteonectin, and SM22 mRNA. Indeed, the neutralization of TGF-beta1 or its receptor (TGF-beta RII) using specific antibodies decreases sharply the percentage of cells positive for the senescent-associated beta-galactosidase activity and displaying a senescent morphology. In the presence of each of these antibodies, the steady-state level of fibronectin, osteonectin, apolipoprotein J, and SM22 mRNA is no more increased at 72 h after stress. Results obtained on fibroblasts retrovirally transfected with the human papillomavirus E7 cDNA suggest that retinoblastoma protein (Rb) regulates the expression of TGF-beta1 in stressful conditions, leading to SIPS and overexpression of these four genes.

Stress-induced premature senescence as alternative toxicological method for testing the long-term effects of molecules under development in the industry.

No alternative in vitro method exists for detecting the potential long-term genotoxic effects of molecules at subcytotoxic concentrations, in terms of days and weeks after exposure(s) to the molecule tested. A theoretical model of cellular senescence led to the concept that subcytotoxic stresses under any molecules at subcytotoxic doses, such as molecules under development in the pharmaceutical, cosmetics and food industry, might lead human fibroblasts into a state closely related to in vitro senescence. This concept was then experimentally confirmed in vitro: many biomarkers of replicative senescence of human fibroblasts were found 72 h after their exposure to various kinds of stressors used at non-cytotoxic concentrations. This phenomenon has been termed stress-induced premature senescence (SIPS). Moreover, proteomics studies have revealed that, besides their effects on the appearance of the biomarkers of senescence, sublethal stresses under a variety of stressors also lead to long-term specific changes in the expression level of proteins which are stress-specific. These changes have been coined the molecular scars of stress. The proteins corresponding to these molecular scars may be identified using the latest developments in mass spectrometry. This model of stress-induced premature senescence may be applied to the toxicological sciences when testing for the potential irreversible long-term effects of molecules on the cell fate.