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Research shows that the arts hold a particular potential for promoting health, well-being and social inclusion for vulnerable people. However, the use and consumption of the arts tend to be socially skewed in favour of people with high cultural, social and economic capital. While extensive research has been conducted on how to create equal access to arts activities for vulnerable groups, little research has investigated how to ensure meaningful engagement with the arts by this group. Shared Reading (SR) has had considerable success in engaging vulnerable groups in collective literary practices, and research suggests that this may partly be due to the unique forms of social and literary engagement that the concept fosters. These forms of engagement, we suggest, lay the foundation for a sense of equality among participants that may promote social connectedness and well-being. On this basis, the present study aims to investigate whether and how a sense of equality may play a role in SR practices. The study found that SR promotes a sense of equality by creating a space where social interaction and relatedness does not hinge on social roles, but rather on lived experiences-and vulnerabilities inherent to these-conveyed through literary texts and shared among participants. However, to promote a sense of equality in SR, meaningful engagement for all participants must be ensured, making facilitation an essential element of SR practices and an important focus in arts interventions in general. We conclude that SR, and arts interventions more generally, may be a promising way to promote a sense of equality, but further research is needed on the specific qualities of and potential contexts for the promotion of a sense of equality.
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STUDY QUESTION: Is cervical intraepithelial neoplasia (CIN) associated with reduced fecundability, defined as the probability of conceiving per menstrual cycle? SUMMARY ANSWER: Overall, we observed no meaningful association between CIN and fecundability, regardless of surgical status, although a recent diagnosis of moderate or severe CIN might be associated with slightly reduced fecundability for 2 years after diagnosis. WHAT IS KNOWN ALREADY: About 15% of couples experience infertility. Few studies have examined the influence of CIN on fertility, and the results have been inconsistent. No study has investigated the association between fecundability and pathologist-reported CIN diagnoses, particularly with respect to the recency of the specific CIN diagnoses. STUDY DESIGN, SIZE, DURATION: This prospective cohort study included 9586 women trying to conceive. The women were enrolled from 1 June 2007 to 3 February 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women were invited to complete a baseline questionnaire and bimonthly follow-up questionnaires for up to 12 months or until pregnancy occurred. Data on cervical cytologies and biopsies were retrieved from The National Pathology Registry (DNPR), which holds records of all cervical specimens examined in Denmark. Women were categorized based on their most severe diagnosis of CIN: no lesion, other cervical changes, mild CIN (CIN1), or moderate/severe CIN (CIN2+) with or without surgery. To investigate the association between CIN and fecundability, we computed fecundability ratios (FR) and 95% confidence intervals (CI) using a proportional probabilities regression model. We adjusted for age at study entry, partner age, body mass index, smoking status, timing of intercourse, parity, education, number of sexual partners, and household income. MAIN RESULTS AND THE ROLE OF CHANCE: Compared with no lesion, the adjusted FRs (95% CI) for the association between CIN and fecundability were: other cervical lesions, 0.97 (0.91-1.04); CIN1, 1.04 (0.96-1.13); CIN2+ no surgery, 1.00 (0.82-1.22); and CIN2+ with surgery 0.99 (0.89-1.10). The FRs (95% CI) for a recent diagnosis (<2 years) of CIN were 0.98 (0.86-1.11) for other cervical lesions; 1.13 (0.99-1.29) for CIN1; 0.89 (0.62-1.26) for CIN2+ no surgery and 0.91 (0.75-1.10) for CIN2+ with surgery compared with the no lesion group. LIMITATIONS, REASONS FOR CAUTION: In the analyses, we adjusted for several covariates related to the women. However, we had little information on the male partners which could lead to unmeasured confounding as fecundability is a couple-based measure of fertility. Furthermore, a CIN diagnosis may not be constant as it may regress or progress spontaneously; therefore, it is possible that we have misclassified some women, especially women categorized as having normal cells or CIN1. WIDER IMPLICATIONS OF THE FINDINGS: Our results contribute important knowledge to women who are concerned about their future fertility after receiving a CIN diagnosis. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by The Danish Cancer Society (R167-A11036-17-S2). The overall cohorts were funded by the National Institute of Child Health and Human Development (R01-HD086742 and R03-HD094117). The authors report no competing interests. TRIAL REGISTRATION NUMBER: N/A.
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Fertilidad , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/epidemiología , Adulto , Estudios Prospectivos , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Dinamarca/epidemiología , Embarazo , Adulto JovenRESUMEN
Traumatic brain injury (TBI) stands as a prominent global cause of disability, with motor deficits being a common consequence. Despite its widespread impact, the precise pathological mechanisms underlying motor deficits after TBI remain elusive. In this study, hindlimb postural asymmetry (HL-PA) development in rats subjected to focal TBI was investigated to explore the potential roles of collagen IV and laminin within the extracellular matrix (ECM) of selected hindlimb muscles in the emergence of motor deficits following TBI. A focal TBI was induced by ablating the left sensorimotor cortex in rats and motor deficits were assessed by measuring HL-PA. The expression of laminin and collagen IV in eight selected muscles on each side of the hindlimbs from both TBI- and sham-operated rats were studied using immunohistochemistry and semi-quantitatively analyzed. The results indicated that the TBI rats exhibited HL-PA, characterized by flexion of the contralateral (right) hindlimb. In the sham-operated rats, the immunoreactive components of laminin and collagen IV were evenly and smoothly distributed along the border of the muscle fibers in all the investigated muscles. In contrast, in the TBI rats, the pattern was broken into aggregated, granule-like, immunoreactive components. Such a labeling pattern was detected in all the investigated muscles both from the contra- and ipsilateral sides of the TBI rats. However, in TBI rats, most of the muscles from the contralateral hindlimb showed a significantly increased expression of these two proteins in comparison with those from the ipsilateral hindlimb. In comparison to sham-operated rats, there was a significant increase in laminin and collagen IV expression in various contralateral hindlimb muscles in the TBI rats. These findings suggest potential implications of laminin and collagen IV in the development of motor deficits following a focal TBI.
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Since 2020, our lab has received blood samples from traffic cases involving suspicion of driving under the influence of nitrous oxide (N2O). While N2O analysis by gas chromatography (GC) has been around for decades, quantitative results in blood from drivers have been only scarcely reported. We present a three-year (2020-2022) retrospective study of N2O from traffic cases in Eastern Denmark with suspected involvement of N2O intake. Whole blood samples from traffic cases were analysed for N2O using headspace-GC-MS. Freshly made calibration curves and additions of xenon gas as an internal standard were used for calculation of N2O concentrations. Positive samples have been defined as having concentrations greater than 0.1 mL N2O/L blood. Over a three-year period, we have tested 62 traffic case blood samples for the presence of N2O. Despite the technical challenges associated with the analysis of N2O, we have found N2O in 52 of the samples. Calculated concentrations were in the range 0.1-48 mL N2O/L blood, which are similar to the few cases previously found in the literature.
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Conducir bajo la Influencia , Óxido Nitroso , Óxido Nitroso/análisis , Estudios Retrospectivos , Cromatografía de Gases y Espectrometría de Masas , Cromatografía de GasesRESUMEN
OBJECTIVES: To examine associations between socioeconomic factors and (1) adherence to methicillin-resistant Staphylococcus aureus (MRSA) posttreatment follow-up swab sampling after 1 and 6 months and (2) successful decolonization treatment. DESIGN: Cohort study with 2 years of follow-up. Data on patients diagnosed with MRSA were extracted from a regional MRSA database and national registries. We used a cluster-based logistic regression model to estimate the adjusted odds ratios (aOR) and 95% confidence interval (CI) for associations between socioeconomic factors and decolonization treatment. SETTING: Danish primary health care. RESULTS: The rate of adherence to posttreatment follow-up swab sampling among 2,536 cases 1 month after decolonization treatment was 66% (95% CI, 64%-68%), and it decreased to 30% (95% CI, 28%-32%) after 6 months. Living in intermediate municipalities (76-159 inhabitants/km2) or having retired were associated with completed posttreatment follow-up swabs 1 month after decolonization treatment: aOR, 1.40 (95% CI, 1.2-1.74) and aOR, 2.67 (95% CI, 1.16-6.13), respectively. The rate of successful decolonization treatment 2 years after initiating treatment was 36% (95% CI, 34%-38%). Factors associated with successful decolonization treatment included individuals with higher education (aOR, 1.62; 95% CI, 1.22-2.15), early retirees (aOR, 1.63; 95% CI, 1.12-2.38), those living in intermediate municipalities (ie, 160-900+ inhabitants/km2; aOR, 1.35; 95% CI, 1.08-1.68), and those living in predominantly urban municipalities (ie, 160-900+ inhabitants/km2; aOR, 2.04; 95% CI, 1.5-2.76). CONCLUSIONS: Disparities in the effect of decolonization treatment and adherence to MRSA follow-up sampling among MRSA-positive individuals appear to be largely explained by the level of education, area of residence, and employment status.
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Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Humanos , Infecciones Estafilocócicas/tratamiento farmacológico , Estudios de Cohortes , Portador Sano , Factores Socioeconómicos , Antibacterianos/uso terapéuticoRESUMEN
The indole scaffold is a recurring structure in multiple bioactive heterocycles and natural products. Substituted indoles like the amino acid tryptophan serve as a precursor for a wide range of natural products with pharmaceutical or agrochemical applications. Inspired by the versatility of these compounds, medicinal chemists have for decades exploited indole as a core structure in the drug discovery process. With the aim of tuning the properties of lead drug candidates, regioselective halogenation of the indole scaffold is a common strategy. However, chemical halogenation is generally expensive, has a poor atom economy, lacks regioselectivity, and generates hazardous waste streams. As an alternative, in this work we engineer the industrial workhorse Saccharomyces cerevisiae for the de novo production of halogenated tryptophan and tryptamine derivatives. Functional expression of bacterial tryptophan halogenases together with a partner flavin reductase and a tryptophan decarboxylase resulted in the production of halogenated tryptophan and tryptamine with chlorine or bromine. Furthermore, by combining tryptophan halogenases, production of di-halogenated molecules was also achieved. Overall, this works paves the road for the production of new-to-nature halogenated natural products in yeast.
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Productos Biológicos , Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Triptófano/metabolismo , Triptaminas/metabolismoRESUMEN
Retirement may bring about significant changes for those who retire. Studies have shown that men find it harder than women to adapt to retirement, putting them at greater risk of identity and meaning loss, which may reduce subjective well-being and increase the risk of depression. While men may experience retirement as a challenging life event that triggers processes of meaning-making motivated by an appropriation of meaning to a new life situation, their experiences of meaning in retirement are yet to be investigated. The aim of this study was to explore Danish men's reflections on meaning in life in the transition to retirement. Forty in-depth interviews were carried out with newly retired men between fall 2019 and fall 2020. Interviews were recorded, transcribed, coded, and analyzed using an abductive approach informed by an ongoing interaction between empirical insights and psychological and philosophical perspectives on meaning in life. Six themes central to men's meaning-making in the transition to retirement were identified: family ties, social connectedness, structure of everyday life, contribution, engagement, and time. On this basis, it is suggested that reestablishing a sense of belonging and engagement are central to meaningfulness in the transition to retirement. Having a web of relations, a sense of being part of a social entity, and engaging oneself in something that provides intersubjective value may replace senses of meaning found previously in work life. A better understanding of meaning in men's transitions to retirement may provide a valuable knowledge base for efforts seeking to strengthen men's transition to retirement.
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Hombres , Jubilación , Masculino , Humanos , Femenino , DinamarcaRESUMEN
BACKGROUND: Formula-fed infants are at increased risk of infections. Due to the cross-talk between the mucosal systems of the gastrointestinal and respiratory tracts, adding synbiotics (prebiotics and probiotics) to infant formula may prevent infections even at distant sites. Infants that were born full term and weaned from breast milk were randomized to prebiotic formula (fructo- and galactooligosaccharides) or the same prebiotic formula with Lactobacillus paracasei ssp. paracasei F19 (synbiotics) from 1 to 6 months of age. The objective was to examine the synbiotic effects on gut microbiota development. RESULTS: Fecal samples collected at ages 1, 4, 6, and 12 months were analyzed using 16S rRNA gene sequencing and a combination of untargeted gas chromatography-mass spectrometry/liquid chromatography-mass spectrometry. These analyses revealed that the synbiotic group had a lower abundance of Klebsiella, a higher abundance of Bifidobacterium breve compared to the prebiotic group, and increases in the anti-microbial metabolite d-3-phenyllactic acid. We also analyzed the fecal metagenome and antibiotic resistome in the 11 infants that had been diagnosed with lower respiratory tract infection (cases) and 11 matched controls using deep metagenomic sequencing. Cases with lower respiratory tract infection had a higher abundance of Klebsiella species and antimicrobial resistance genes related to Klebsiella pneumoniae, compared to controls. The results obtained using 16S rRNA gene amplicon and metagenomic sequencing were confirmed in silico by successful recovery of the metagenome-assembled genomes of the bacteria of interest. CONCLUSIONS: This study demonstrates the additional benefit of feeding specific synbiotics to formula-fed infants over prebiotics only. Synbiotic feeding led to the underrepresentation of Klebsiella, enrichment of bifidobacteria, and increases in microbial degradation metabolites implicated in immune signaling and in the gut-lung and gut-skin axes. Our findings support future clinical evaluation of synbiotic formula in the prevention of infections and associated antibiotic treatment as a primary outcome when breastfeeding is not feasible. TRIAL REGISTRATION: ClinicalTrials.gov NCT01625273 . Retrospectively registered on 21 June 2012.
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Probióticos , Simbióticos , Femenino , Humanos , Lactante , ARN Ribosómico 16S/genética , Prebióticos , PulmónRESUMEN
Monoterpene indole alkaloids (MIAs) are a diverse family of complex plant secondary metabolites with many medicinal properties, including the essential anti-cancer therapeutics vinblastine and vincristine1. As MIAs are difficult to chemically synthesize, the world's supply chain for vinblastine relies on low-yielding extraction and purification of the precursors vindoline and catharanthine from the plant Catharanthus roseus, which is then followed by simple in vitro chemical coupling and reduction to form vinblastine at an industrial scale2,3. Here, we demonstrate the de novo microbial biosynthesis of vindoline and catharanthine using a highly engineered yeast, and in vitro chemical coupling to vinblastine. The study showcases a very long biosynthetic pathway refactored into a microbial cell factory, including 30 enzymatic steps beyond the yeast native metabolites geranyl pyrophosphate and tryptophan to catharanthine and vindoline. In total, 56 genetic edits were performed, including expression of 34 heterologous genes from plants, as well as deletions, knock-downs and overexpression of ten yeast genes to improve precursor supplies towards de novo production of catharanthine and vindoline, from which semisynthesis to vinblastine occurs. As the vinblastine pathway is one of the longest MIA biosynthetic pathways, this study positions yeast as a scalable platform to produce more than 3,000 natural MIAs and a virtually infinite number of new-to-nature analogues.
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Antineoplásicos , Reactores Biológicos , Vías Biosintéticas , Ingeniería Metabólica , Saccharomyces cerevisiae , Vinblastina , Alcaloides de la Vinca , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/provisión & distribución , Catharanthus/química , Genes Fúngicos , Genes de Plantas , Ingeniería Metabólica/métodos , Fosfatos de Poliisoprenilo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Triptófano , Vinblastina/biosíntesis , Vinblastina/química , Vinblastina/provisión & distribución , Alcaloides de la Vinca/biosíntesis , Alcaloides de la Vinca/química , Alcaloides de la Vinca/provisión & distribuciónRESUMEN
Abscisic acid (ABA) is a phytohormone with applications in agriculture and human health. ABA can be produced by Botrytis cinerea, a plant pathogenic filamentous fungus. However, the cultivation process is lengthy and strain improvement by genetic engineering is difficult. Therefore, we engineered the oleaginous yeast Yarrowia lipolytica as an alternative host for ABA production. First, we expressed five B. cinerea genes involved in ABA biosynthesis (BcABA1,BcABA2,BcABA3,BcABA4 and BcCPR1) in a Y. lipolytica chassis with optimized mevalonate flux. The strain produced 59.2 mg/L of ABA in small-scale cultivation. Next, we expressed an additional copy of each gene in the strain, but only expression of additional copy of BcABA1 gene increased the ABA titer to 168.5 mg/L. We then integrated additional copies of the mevalonate pathway and ABA biosynthesis encoding genes, and we expressed plant ABA transporters resulting in an improved strain producing 263.5 mg/L and 9.1 mg/g dry cell weight (DCW) ABA. Bioreactor cultivation resulted in a specific yield of 12.8 mg/g DCW ABA; however, surprisingly, the biomass level obtained in bioreactors was only 10.5 g DCW/L, with a lower ABA titer of 133.6 mg/L. While further optimization is needed, this study confirms Y. lipolytica as a potential alternative host for the ABA production.
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Yarrowia , Ácido Abscísico/metabolismo , Reactores Biológicos , Humanos , Ingeniería Metabólica/métodos , Ácido Mevalónico/metabolismo , Yarrowia/genética , Yarrowia/metabolismoRESUMEN
Lipoprotein subfractions are biomarkers for the early diagnosis of cardiovascular diseases. The reference method, ultracentrifugation, for measuring lipoproteins is time-consuming, and there is a need to develop a rapid method for cohort screenings. This study presents partial least-squares regression models developed using 1H nuclear magnetic resonance (NMR) spectra and concentrations of lipoproteins as measured by ultracentrifugation on 316 healthy Danes. This study explores, for the first time, different regions of the 1H NMR spectrum representing signals of molecules in lipoprotein particles and different lipid species to develop parsimonious, reliable, and optimal prediction models. A total of 65 lipoprotein main and subfractions were predictable with high accuracy, Q2 of >0.6, using an optimal spectral region (1.4-0.6 ppm) containing methylene and methyl signals from lipids. The models were subsequently tested on an independent cohort of 290 healthy Swedes with predicted and reference values matching by up to 85-95%. In addition, an open software tool was developed to predict lipoproteins concentrations in human blood from standardized 1H NMR spectral recordings.
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Lipoproteínas LDL , Lipoproteínas , Humanos , Espectroscopía de Resonancia Magnética/métodos , Espectroscopía de Protones por Resonancia Magnética , SueciaRESUMEN
When assessing oil spills in marine environments, focus has often been on describing degradation and removal of hydrocarbons. However, more and more attention is now given to the formation of mineral oil transformation products, and their potential toxicity and persistency in the environment. The aim of this study was to investigate the formation of dissolved acidic degradation products from crude oil in sea water from the Persian Gulf in a lab-experiment. A super-complex mixture of acidic degradation products was formed in the water phase and compound groups of aliphatic acids, monocyclic aromatic acids-, and polycyclic aromatic acids were identified. More specifically, alkylated PAHs were biodegraded to a high number of aromatic, carboxylic acids by hydroxylation of the alkyl side chains. These degradation products are more bioavailable than their parent compounds, and may therefore constitute a new group of contaminants that should be considered in oil spill assessments.
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Contaminación por Petróleo , Petróleo , Hidrocarburos Policíclicos Aromáticos , Contaminantes Químicos del Agua , Petróleo/análisis , Contaminación por Petróleo/análisis , Hidrocarburos Policíclicos Aromáticos/análisis , Agua , Contaminantes Químicos del Agua/análisisRESUMEN
BACKGROUND: The impact of a pandemic on unplanned hospital attendance has not been extensively examined. The aim of this study is to report the nationwide consequences of the COVID-19 pandemic on unplanned hospital attendances in Denmark for 7 weeks after a 'shelter at home' order was issued. METHODS: We merged data from national registries (Civil Registration System and Patient Registry) to conduct a study of unplanned (excluding outpatient visits and elective surgery) hospital-based healthcare and mortality of all Danes. Using data for 7 weeks after the 'shelter at home' order, the incidence rate of unplanned hospital attendances per week in 2020 was compared with corresponding weeks in 2017-2019. The main outcome was hospital attendances per week as incidence rate ratios. Secondary outcomes were general population mortality and risk of death in-hospital, reported as weekly mortality rate ratios (MRRs). RESULTS: From 2 438 286 attendances in the study period, overall unplanned attendances decreased by up to 21%; attendances excluding COVID-19 were reduced by 31%; non-psychiatric by 31% and psychiatric by 30%. Out of the five most common diagnoses expected to remain stable, only schizophrenia and myocardial infarction remained stable, while chronic obstructive pulmonary disease exacerbation, hip fracture and urinary tract infection fell significantly. The nationwide general population MRR rose in six of the recorded weeks, while MRR excluding patients who were COVID-19 positive only increased in two. CONCLUSION: The COVID-19 pandemic and a governmental national 'shelter at home' order was associated with a marked reduction in unplanned hospital attendances with an increase in MRR for the general population in two of 7 weeks, despite exclusion of patients with COVID-19. The findings should be taken into consideration when planning for public information campaigns.
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COVID-19 , Pandemias , Servicio de Urgencia en Hospital , Hospitales , Humanos , Incidencia , SARS-CoV-2RESUMEN
BACKGROUND AND PURPOSE: Tumour growth during radiotherapy may lead to geographical misses of the target volume. This study investigates the evolution of the tumour extent and evaluates the need for plan adaptation to ensure dose coverage of the target in glioblastoma patients. MATERIALS AND METHODS: The prospective study included 29 patients referred for 59.4 Gy in 33 fractions. Magnetic resonance imaging (MRI) was performed at the time of treatment planning, at fraction 10, 20, 30, and three weeks after the end of radiotherapy. The gross tumour volume (GTV) was defined as the T1w contrast-enhanced region plus the surgical cavity on each MRI set. The relative GTV volume and the maximum distance (Dmax) of the extent of the actual GTV outside the original GTV were measured. Based on the location of the actual GTV during radiotherapy and the original planned dose, a prospective clinical decision was made whether to adapt the treatment. RESULTS: Dose coverage of the GTV during radiotherapy was not compromised, and none of the radiotherapy plans was adapted. The median Dmax (range) was 5.7 (2.0-18.9) mm, 8.0 (2.0-27.4) mm, 8.0 (1.9-27.3) mm, and 8.9 (1.9-34.4) mm at fraction 10, 20, 30, and follow-up. The relative GTV volume and Dmax observed at fraction 10 were correlated with the values observed at follow-up (R = 0.74, p < 0.001 and R = 0.79, p < 0.001, respectively). CONCLUSION: Large variations in the GTV extent were observed, and changes often occurred early in the treatment. Plan adaptation for geographical misses was not performed in our cohort due to sufficient CTV margins.
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Glioblastoma , Radioterapia Conformacional , Glioblastoma/diagnóstico por imagen , Glioblastoma/radioterapia , Humanos , Imagen por Resonancia Magnética , Estudios Prospectivos , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Carga TumoralRESUMEN
The application of small amounts of natural plant growth hormones, such as gibberellins (GAs), can increase the productivity and quality of many vegetable and fruit crops. However, gibberellin growth hormones usage is limited by the high cost of their production, which is currently based on fermentation of a natural fungal producer Fusarium fujikuroi that produces a mix of several GAs. We explored the potential of the oleaginous yeast Yarrowia lipolytica to produce specific profiles of GAs. Firstly, the production of the GA-precursor ent-kaurenoic acid (KA) at 3.75 mg/L was achieved by expression of biosynthetic enzymes from the plant Arabidopsis thaliana and upregulation of the mevalonate (MVA) pathway. We then built a GA4-producing strain by extending the GA-biosynthetic pathway and upregulating the MVA-pathway further, resulting in 17.29 mg/L GA4. Additional expression of the F. fujikoroi GA-biosynthetic enzymes resulted in the production of GA7 (trace amounts) and GA3 (2.93 mg/L). Lastly, through protein engineering and the expression of additional KA-biosynthetic genes, we increased the GA3-production 4.4-fold resulting in 12.81 mg/L. The developed system presents a promising resource for the recombinant production of specific gibberellins, identifying bottlenecks in GA biosynthesis, and discovering new GA biosynthetic genes. CLASSIFICATION: Biological Sciences, Applied Biological Sciences.
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Fusarium , Giberelinas , Vías Biosintéticas , Reguladores del Crecimiento de las Plantas/genéticaRESUMEN
BACKGROUND AND AIMS: Body mass index (BMI) and waist circumference (WC) are commonly used markers of cardiometabolic risk. However, sagittal abdominal diameter (SAD) has been proposed as a possibly more sensitive marker of intra-abdominal obesity. We investigated differences in how SAD, WC, and BMI were correlated with cardiometabolic risk markers. METHODS AND RESULTS: This cross-sectional study investigated anthropometric and metabolic baseline measurements of individuals from six trials. Multiple linear regression and (partial) correlation coefficients were used to investigate associations between SAD, WC, and BMI and cardiometabolic risk markers, including components of the metabolic syndrome as well as insulin resistance, blood lipids, and lowgrade inflammation. In total 1516 mostly overweight or obese individuals were included in the study. SAD was significantly more correlated with TG than WC for all studies, and overall increase in correlation was 0.05 (95% CI (0.02; 0.08). SAD was significantly more correlated with the markers TG and DBP 0.11 (95% CI (0.08, 0.14)) and 0.04 (95% CI (0.006, 0.07), respectively compared to BMI across all or most studies. CONCLUSION: This study showed that no single anthropometric indicator was consistently more strongly correlated across all markers of cardiometabolic risk. However, SAD was significantly more strongly correlated with TG than WC and significantly more strongly correlated with DBP and TG than BMI.
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Obesidad Abdominal/diagnóstico , Diámetro Abdominal Sagital , Circunferencia de la Cintura , Adulto , Factores de Riesgo Cardiometabólico , Ensayos Clínicos como Asunto , Estudios Transversales , Europa (Continente)/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad Abdominal/epidemiología , Obesidad Abdominal/fisiopatología , Valor Predictivo de las Pruebas , Pronóstico , Medición de RiesgoRESUMEN
Technological advances in high-resolution mass spectrometry (MS) vastly increased the number of samples that can be processed in a life science experiment, as well as volume and complexity of the generated data. To address the bottleneck of high-throughput data processing, we present SmartPeak (https://github.com/AutoFlowResearch/SmartPeak), an application that encapsulates advanced algorithms to enable fast, accurate, and automated processing of capillary electrophoresis-, gas chromatography-, and liquid chromatography (LC)-MS(/MS) data and high-pressure LC data for targeted and semitargeted metabolomics, lipidomics, and fluxomics experiments. The application allows for an approximate 100-fold reduction in the data processing time compared to manual processing while enhancing quality and reproducibility of the results.
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Procesamiento Automatizado de Datos/métodos , Metabolómica/métodos , Automatización , Cromatografía Liquida , Electroforesis Capilar , Espectrometría de Masas en Tándem , Factores de TiempoRESUMEN
Diet is an important component in weight management strategies, but heterogeneous responses to the same diet make it difficult to foresee individual weight-loss outcomes. Omics-based technologies now allow for analysis of multiple factors for weight loss prediction at the individual level. Here, we classify weight loss responders (N = 106) and non-responders (N = 97) of overweight non-diabetic middle-aged Danes to two earlier reported dietary trials over 8 weeks. Random forest models integrated gut microbiome, host genetics, urine metabolome, measures of physiology and anthropometrics measured prior to any dietary intervention to identify individual predisposing features of weight loss in combination with diet. The most predictive models for weight loss included features of diet, gut bacterial species and urine metabolites (ROC-AUC: 0.84-0.88) compared to a diet-only model (ROC-AUC: 0.62). A model ensemble integrating multi-omics identified 64% of the non-responders with 80% confidence. Such models will be useful to assist in selecting appropriate weight management strategies, as individual predisposition to diet response varies.
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Dietoterapia/métodos , Microbioma Gastrointestinal , Pérdida de Peso , Biomarcadores/sangre , Biomarcadores/orina , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Aprendizaje Automático , Masculino , Periodo Posprandial , Curva ROC , Ensayos Clínicos Controlados Aleatorios como Asunto , Reproducibilidad de los Resultados , Resultado del Tratamiento , Granos EnterosRESUMEN
Terpenoids are a diverse group of over 55,000 compounds with potential applications as advanced fuels, bulk and fine chemicals, pharmaceutical ingredients, agricultural chemicals, etc. To facilitate their bio-based production, there is a need for plug-and-play hosts, capable of high-level production of different terpenoids. Here we engineer Yarrowia lipolytica platform strains for the overproduction of mono-, sesqui-, di-, tri-, and tetraterpenoids. The monoterpene platform strain was evaluated by expressing Perilla frutescens limonene synthase, which resulted in limonene titer of 35.9 mg/L and was 100-fold higher than when the same enzyme was expressed in the strain without mevalonate pathway improvement. Expression of Callitropsis nootkatensis valencene synthase in the sesquiterpene platform strain resulted in 113.9 mg/L valencene, an 8.4-fold increase over the control strain. Platform strains for production of squalene, complex triterpenes, or diterpenes and carotenoids were also constructed and resulted in the production of 402.4 mg/L squalene, 22 mg/L 2,3-oxidosqualene, or 164 mg/L ß-carotene, respectively. The presented terpenoid platform strains can facilitate the evaluation of terpenoid biosynthetic pathways and are a convenient starting point for constructing efficient cell factories for the production of various terpenoids. The platform strains and exemplary terpenoid strains can be obtained from Euroscarf.