To examine the associations of physical fitness (i.e. cardiorespiratory fitness, muscular strength, and speed/agility) with psychological distress and psychological well-being in overweight/obese ...pre-adolescent children.
110 overweight/obese children (10.0±1.1years old, 61 boys) from the ActiveBrains project (http://profith.ugr.es/activebrains) participated in this cross-sectional study.
Physical fitness was evaluated by the ALPHA battery test. Cardiorespiratory fitness was additionally evaluated by a maximal incremental treadmill. Stress was assessed by the Children’s Daily Stress Inventory, anxiety by the State-Trait Anxiety Inventory, depression by the Children Depression Inventory, positive affect and negative affect by the Positive and Negative Affect Scale for Children, happiness by the Subjective Happiness Scale, optimism by the Life Orientation Test, and self-esteem by the Rosenberg Self-Esteem questionnaire. Linear regression adjusted for sex and peak height velocity was used to examine associations.
Absolute upper-body muscular strength was negatively associated with stress and negative affect (β=−0.246, p=0.047; β=−0.329, p=0.010, respectively). Furthermore, absolute lower-body muscular strength was negatively associated with negative affect (β=−0.301, p=0.029). Cardiorespiratory fitness, expressed by the last completed lap, and relative upper-body muscular strength were positively associated with optimism (β=0.220, p=0.042; β=0.240, p=0.017, respectively). Finally, absolute upper-body muscular strength was positively associated with self-esteem (β=0.362, p=0.003) independently of sex and weight status (p for interactions >0.3), and absolute lower-body muscular strength was also positively associated with self-esteem (β=0.352, p=0.008).
Muscular strength was associated with psychological distress (i.e. stress and negative affect) and psychological well-being (i.e. optimism and self-esteem) as well as cardiorespiratory fitness was associated with optimism. Therefore, increased levels of physical fitness, specifically muscular strength, could have significant benefits for overweight/obese children psychological health.
Fusion oncogenes (FOs) are common in many cancer types and are powerful drivers of tumor development. Because their expression is exclusive to cancer cells and their elimination induces cell ...apoptosis in FO-driven cancers, FOs are attractive therapeutic targets. However, specifically targeting the resulting chimeric products is challenging. Based on CRISPR/Cas9 technology, here we devise a simple, efficient and non-patient-specific gene-editing strategy through targeting of two introns of the genes involved in the rearrangement, allowing for robust disruption of the FO specifically in cancer cells. As a proof-of-concept of its potential, we demonstrate the efficacy of intron-based targeting of transcription factors or tyrosine kinase FOs in reducing tumor burden/mortality in in vivo models. The FO targeting approach presented here might open new horizons for the selective elimination of cancer cells.
Depression is a major health problem worldwide. Most prescribed anti-depressants, the selective serotonin reuptake inhibitors (SSRI) show limited efficacy and delayed onset of action, partly due to ...the activation of somatodendritic 5-HT(1A)-autoreceptors by the excess extracellular serotonin (5-HT) produced by SSRI in the raphe nuclei. Likewise, 5-HT(1A) receptor (5-HT(1A)R) gene polymorphisms leading to high 5-HT(1A)-autoreceptor expression increase depression susceptibility and decrease treatment response. In this study, we report on a new treatment strategy based on the administration of small-interfering RNA (siRNA) to acutely suppress 5-HT(1A)-autoreceptor-mediated negative feedback mechanisms. We developed a conjugated siRNA (C-1A-siRNA) by covalently binding siRNA targeting 5-HT(1A) receptor mRNA with the SSRI sertraline in order to concentrate it in serotonin axons, rich in serotonin transporter (SERT) sites. The intracerebroventricular (i.c.v.) infusion of C-1A-siRNA to mice resulted in its selective accumulation in serotonin neurons. This evoked marked anti-depressant-like effects in the forced swim and tail suspension tests, but did not affect anxiety-like behaviors in the elevated plus-maze. In parallel, C-1A-siRNA administration markedly decreased 5-HT(1A)-autoreceptor expression and suppressed 8-OH-DPAT-induced hypothermia (a pre-synaptic 5-HT(1A)R effect in mice) without affecting post-synaptic 5-HT(1A)R expression in hippocampus and prefrontal cortex. Moreover, i.c.v. C-1A-siRNA infusion augmented the increase in extracellular serotonin evoked by fluoxetine in prefrontal cortex to the level seen in 5-HT(1A)R knockout mice. Interestingly, intranasal C-1A-siRNA administration produced the same effects, thus opening the way to the therapeutic use of C-1A-siRNA. Hence, C-1A-siRNA represents a new approach to treat mood disorders as monotherapy or in combination with SSRI.
Objective Previous trials have shown little benefit for preventing preterm birth in twin pregnancies using 90–200 mg of daily vaginal natural progesterone. Higher doses have not been tested. Our aim ...was to determine the efficacy and safety of two different daily doses of vaginal natural progesterone (200 and 400 mg), compared with placebo, for preventing preterm birth in unselected twin pregnancies.
Design Randomised controlled double‐blind multicentre trial (1:1:1).
Setting The study was carried out in five university centres from Valencia, Murcia and Alicante (Spain).
Population Women with dichorionic diamniotic twin pregnancies.
Methods The women self‐inserted two vaginal pessaries daily, containing placebo (n = 96), 200 mg of natural progesterone (n = 97) or 400 mg of natural progesterone (n = 97), from 20 to 34 weeks of gestation or delivery. Randomisation was performed by an external centre. Data were analysed on an intention‐to‐treat basis.
Main outcome measure Preterm birth rate.
Results The baseline characteristics for placebo and progesterone groups were similar. Comparison of the three groups and analysis of progesterone‐treated versus untreated women showed similar pregnancy and neonatal outcomes. The proportion of preterm and very preterm births, low birthweight, perinatal mortality and neonatal morbidity showed no differences between the three groups. Similar results were also obtained when comparing the 200‐ versus 400‐mg progesterone groups. No serious adverse effects were encountered.
Conclusions Vaginal progesterone therapy was generally well tolerated, but failed to prevent preterm births in unselected dichorionic diamniotic twin pregnancies. The 400‐mg progesterone dose offered no advantages over the 200‐mg regimen.
► We grow Scenedesmus obliquus in urban wastewater in batch and continuous operation. ► Biomass in continuous operation can be predicted based on batch growth kinetics. ► Optimum operation residence ...times are based on specific growth rate from batch. ► Optimum hydraulic retention time depends on the objective of the culture.
A laboratory-scale flat panel photobioreactor was operated for the continuous growth of Scenedesmus obliquus and consequent removal of nutrients in wastewater. This study develops a simple model by which biomass values in continuous operation can be predicted from kinetic growth parameters obtained from a shorter batch experiment. Based on this study, biomass concentrations and productivities in continuous operation can be successfully predicted as a function of the specific hydraulic retention time (HRT) assumed. Considerable biomass production and nutrient uptake from wastewater were achieved in the experiment. Optimum operating conditions for the reactor depend on the particular objective: the maximization of biomass production and carbon dioxide biofixation involves a HRT of 2μ−1 (specific growth rate), whereas efficient nutrient removal involves a HRT as close as possible to μ−1 (as long as discharges comply fully with the parameters set); alternatively biomass intended for biodiesel or biogas production would involve a HRT>2μ−1.
Background
In twin pregnancies, the rates of adverse perinatal outcome and subsequent long‐term morbidity are substantial, and mainly result from preterm birth (PTB).
Objectives
To assess the ...effectiveness of progestogen treatment in the prevention of neonatal morbidity or PTB in twin pregnancies using individual participant data meta‐analysis (IPDMA).
Search strategy
We searched international scientific databases, trial registration websites, and references of identified articles.
Selection criteria
Randomised clinical trials (RCTs) of 17–hydroxyprogesterone caproate (17Pc) or vaginally administered natural progesterone, compared with placebo or no treatment.
Data collection and analysis
Investigators of identified RCTs were asked to share their IPD. The primary outcome was a composite of perinatal mortality and severe neonatal morbidity. Prespecified subgroup analyses were performed for chorionicity, cervical length, and prior spontaneous PTB.
Main results
Thirteen trials included 3768 women and their 7536 babies. Neither 17Pc nor vaginal progesterone reduced the incidence of adverse perinatal outcome (17Pc relative risk, RR 1.1; 95% confidence interval, 95% CI 0.97–1.4, vaginal progesterone RR 0.97; 95% CI 0.77–1.2). In a subgroup of women with a cervical length of ≤25 mm, vaginal progesterone reduced adverse perinatal outcome when cervical length was measured at randomisation (15/56 versus 22/60; RR 0.57; 95% CI 0.47–0.70) or before 24 weeks of gestation (14/52 versus 21/56; RR 0.56; 95% CI 0.42–0.75).
Author's conclusions
In unselected women with an uncomplicated twin gestation, treatment with progestogens (intramuscular 17Pc or vaginal natural progesterone) does not improve perinatal outcome. Vaginal progesterone may be effective in the reduction of adverse perinatal outcome in women with a cervical length of ≤25 mm; however, further research is warranted to confirm this finding.
The consumption of products with high nutritional value and antioxidant capacity has increased notably in recent years. Due to health problems such as triglycerides and cardiovascular problems, its ...use is becoming reduced. So that, chia (Salvia hispánica) and sachatomate (Cyphomandra betacea) have gained interest as an alternative to develop nutraceutical products, compared to conventional products. The objective of the study was to determine the effect of the partial substitution of mango (Mangifera indica) and ground chia (Salvia hispánica) on the antioxidant capacity in the elaboration of nectar based on Sachatomate. The physicochemical characteristics were determined where sample 11 complies with the established parameters: 13.4° Brix, pH 4.323, 0.354 of C6-H8-O7 and viscosity 3967.3 mPas, according to the NTP 203.110 standard. Regarding the antioxidant capacity, sample 12 was the most optimal, according to the DPPH method, it has been determined 104.3 micromoles Trolox equivalents; according to the ABTS method, it was determined with an antioxidant content of 187.4 micromoles Trolox equivalents. Regarding the proximal chemical evaluation, sample 12 was determined to be the most suitable with a moisture percentage of 87.45%, ash 0.32%, crude fiber 0.09%, fat 0.10%, protein 0.45% and carbohydrates 11.59%. Concluding that substituting sachatomate and ground chia significantly influences the antioxidant capacity, increasing to 104.3 and 187.4 micromoles Trolox equivalents, determined by both methods, indicates that nectar consumption can be used to improve the health of consumers.
The fatty acid (FA) profile of wild Octopus vulgaris paralarvae of estimated age was individually analyzed for the very first time in order to establish a reference for comparison in rearing and ...nutritional studies. Age of each paralarvae was estimated by analysing daily increments on lateral hood surface of beaks. Wild paralarvae age ranged between 6 and 8days and their FA composition resembled that from hatchlings produced under culture conditions. However, when compared with the FA composition of up to 20days old cultured paralarvae described in the bibliography, some striking differences were found. Results showed higher levels of docosahexaenoic acid (22:6n−3, DHA), lower contents of 18:1n−9, 18:1n−7 and 18:2n−6 and negligible levels of 18:3n−3 in wild paralarvae, when collated to reared one. These results seem to indicate that preys/diets supplied to cultured paralarvae fail to resemble paralarval natural composition and as a result do not fulfil their FA requirement. The individual applied technique developed in this study will allow to refine the study of wild paralarvae along its development, as well as to compare wild and cultured paralarvae of similar age.
Artemia does not fulfil paralarval fatty acid requirements.
•For the very first time, the fatty acid profile of wild O. vulgaris paralarvae of estimated age was individually analyzed.•Beak reading is a more accurate tool than dorsal mantle length-based equations to estimate the age of wild individuals.•The fatty acid profile of wild paralarvae significantly differs to that observed in reared paralarvae.
Cardiac angiosarcoma (CAS) is a rare malignant tumour whose genetic basis is unknown. Here we show, by whole-exome sequencing of a TP53-negative Li-Fraumeni-like (LFL) family including CAS cases, ...that a missense variant (p.R117C) in POT1 (protection of telomeres 1) gene is responsible for CAS. The same gene alteration is found in two other LFL families with CAS, supporting the causal effect of the identified mutation. We extend the analysis to TP53-negative LFL families with no CAS and find the same mutation in a breast AS family. The mutation is recently found once in 121,324 studied alleles in ExAC server but it is not described in any other database or found in 1,520 Spanish controls. In silico structural analysis suggests how the mutation disrupts POT1 structure. Functional and in vitro studies demonstrate that carriers of the mutation show reduced telomere-bound POT1 levels, abnormally long telomeres and increased telomere fragility.
Abstract
Aims
Atherosclerotic plaque hypoxia is detrimental for macrophage function. Prolyl hydroxylases (PHDs) initiate cellular hypoxic responses, possibly influencing macrophage function in plaque ...hypoxia. Thus, we aimed to elucidate the role of myeloid PHDs in atherosclerosis.
Methods and results
Myeloid-specific PHD knockout (PHDko) mice were obtained via bone marrow transplantation (PHD1ko, PHD3ko) or conditional knockdown through lysozyme M-driven Cre recombinase (PHD2cko). Mice were fed high cholesterol diet for 6–12 weeks to induce atherosclerosis. Aortic root plaque size was significantly augmented 2.6-fold in PHD2cko, and 1.4-fold in PHD3ko compared to controls but was unchanged in PHD1ko mice. Macrophage apoptosis was promoted in PHD2cko and PHD3ko mice in vitro and in vivo, via the hypoxia-inducible factor (HIF) 1α/BNIP3 axis. Bulk and single-cell RNA data of PHD2cko bone marrow-derived macrophages (BMDMs) and plaque macrophages, respectively, showed enhanced HIF1α/BNIP3 signalling, which was validated in vitro by siRNA silencing. Human plaque BNIP3 mRNA was positively associated with plaque necrotic core size, suggesting similar pro-apoptotic effects in human. Furthermore, PHD2cko plaques displayed enhanced fibrosis, while macrophage collagen breakdown by matrix metalloproteinases, collagen production, and proliferation were unaltered. Instead, PHD2cko BMDMs enhanced fibroblast collagen secretion in a paracrine manner. In silico analysis of macrophage-fibroblast communication predicted SPP1 (osteopontin) signalling as regulator, which was corroborated by enhanced plaque SPP1 protein in vivo. Increased SPP1 mRNA expression upon PHD2cko was preferentially observed in foamy plaque macrophages expressing ‘triggering receptor expressed on myeloid cells-2’ (TREM2hi) evidenced by single-cell RNA, but not in neutrophils. This confirmed enhanced fibrotic signalling by PHD2cko macrophages to fibroblasts, in vitro as well as in vivo.
Conclusion
Myeloid PHD2cko and PHD3ko enhanced atherosclerotic plaque growth and macrophage apoptosis, while PHD2cko macrophages further activated collagen secretion by fibroblasts in vitro, likely via paracrine SPP1 signalling through TREM2hi macrophages.
Graphical Abstract
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