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Understanding the signaling cascades that govern adipocyte metabolism and differentiation is necessary for the development of therapies for obesity. Toll-like receptors (TLRs) are key mediators in adipogenesis, but their specific role is not completely understood. In this study, siRNA knockdown of Tlr2 in 3T3-L1 cells allowed them to differentiate more efficiently into adipocytes, whereas the opposite was observed for the knockdown of Tlr4. At the same time, we show that TLR2 knock-out mice spontaneously developed mature-onset obesity and insulin resistance. Besides a higher incidence of hyperplasia and hypertrophy in white adipose tissue (WAT), we found a significantly increased number of adipocyte precursor cells in TLR2?/? mice compared to TLR4?/? mice. Interestingly, genetic inactivation of Tlr4 in TLR2?/? mice reverted their increased adiposity, insulin resistance, and restored normal levels of adipocyte precursor cells. These findings provide evidence that TLR2 and TLR4 play opposing roles in WAT homeostasis and point to the existence of cross-regulation among TLR2 and TLR4 during adipocyte differentiation both in vitro and in vivo.

BackgroundObesity is produced by the enlargement of the adipose tissue. Functioning as an endocrine organ, it releases and receives information through a complex network of cytokines, hormones, and substrates contributing to a low-chronic inflammation environment. Diet and healthy habits play key roles in the prevention of obesity and its related pathologies. In this regard, there is a need to switch to healthier and more appetizing diets, such as the Mediterranean one. ObjectiveTo compare the mid-and long-term effects of two Mediterranean diet (MedDiet) interventions, one energy-reduced plus physical activity promotion versus a non-restrictive diet, on peripheral satiety-related hormones, weight loss, glucose/lipid metabolism, and pro-inflammatory markers in subjects with obesity/overweight and metabolic syndrome. Materials and methodsA randomized, lifestyle intervention was conducted in 23 Spanish centers, with a large cohort of patients presenting metabolic syndrome. Our study is a subproject set in IMIM (Hospital del Mar Research Institute). Participants were men and women, aged 55-75 and 60-75, respectively, who at baseline met at least three metabolic syndrome components. Subjects were assigned to two intervention groups: (1) an intensive lifestyle intervention with an energy-reduced MedDiet and physical activity promotion (intervention group) with the aim of weight loss; and (2) a normocaloric MedDiet (control). We quantified in a subsample of 300 volunteers from Hospital del Mar Research Institute (Barcelona), following analytes at baseline, 6 months, and 1 year: glucose, HbA1c, triglycerides, total cholesterol, high-density lipoprotein cholesterol, LDL cholesterol, C-peptide, ghrelin, GLP-1, glucagon, insulin, leptin, PAI-1, resistin, and visfatin. Anthropometr

Scope Consumption of meat has been associated with a higher risk of type 2 diabetes (T2D), but if plasma metabolite profiles associated with these foods reflect this relationship is unknown. The objective is to identify a metabolite signature of consumption of total meat (TM), red meat (RM), processed red meat (PRM), and fish and examine if they are associated with T2D risk. Methods and results The discovery population includes 1833 participants from the PREDIMED trial. The internal validation sample includes 1522 participants with available 1-year follow-up metabolomic data. Associations between metabolites and TM, RM, PRM, and fish are evaluated with elastic net regression. Associations between the profiles and incident T2D are estimated using Cox regressions. The profiles included 72 metabolites for TM, 69 for RM, 74 for PRM, and 66 for fish. After adjusting for T2D risk factors, only profiles of TM (Hazard Ratio (HR): 1.25, 95% CI: 1.06-1.49), RM (HR: 1.27, 95% CI: 1.07-1.52), and PRM (HR: 1.27, 95% CI: 1.07-1.51) are associated with T2D. Conclusions The consumption of TM, its subtypes, and fish is associated with different metabolites, some of which have been previously associated with T2D. Scores based on the identified metabolites for TM, RM, and PRM show a significant association with T2D risk.

In June 2020, we published a review focused on assessing the influence of various air pollutants on the transmission of SARS-CoV-2, and the severity of COVID-19 in patients infected by the coronavirus. The results of most of those reviewed studies suggested that chronic exposure to certain air pollutants might lead to more severe and lethal forms of COVID-19, as well as delays/complications in the recovery of the patients. Since then, a notable number of studies on this topic have been published, including also various reviews. Given the importance of this issue, we have updated the information published since our previous review. Taking together the previous results and those of most investigations now reviewed, we have concluded that there is a significant association between chronic exposure to various outdoor air pollutants: PM2.5, PM10, O3, NO2, SO2 and CO, and the incidence/risk of COVID-19 cases, as well as the severity/mortality of the disease. Unfortunately, studies on the potential influence of other important air pollutants such as VOCs, dioxins and furans, or metals, are not available in the scientific literature. In relation to the influence of outdoor air pollutants on the transmission of SARS-CoV-2, although the scientific evidence is much more limited, some studies point to PM2.5 and PM10 as potential airborne transmitters of the virus. Anyhow, it is clear that environmental air pollution plays an important negative role in COVID-19, increasing its incidence and mortality.

BackgroundCoronavirus-19 (COVID-19) disease is driven by an unchecked immune response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus which alters host mitochondrial-associated mechanisms. Compromised mitochondrial health results in abnormal reprogramming of glucose metabolism, which can disrupt extracellular signalling. We hypothesized that examining mitochondrial energy-related signalling metabolites implicated in host immune response to SARS-CoV-2 infection would provide potential biomarkers for predicting the risk of severe COVID-19 illness. MethodsWe used a semi-targeted serum metabolomics approach in 273 patients with different severity grades of COVID-19 recruited at the acute phase of the infection to determine the relative abundance of tricarboxylic acid (Krebs) cycle-related metabolites with known extracellular signaling properties (pyruvate, lactate, succinate and alpha-ketoglutarate). Abundance levels of energy-related metabolites were evaluated in a validation cohort (n=398) using quantitative fluorimetric assays. ResultsIncreased levels of four energy-related metabolites (pyruvate, lactate, a-ketoglutarate and succinate) were found in critically ill COVID-19 patients using semi-targeted and targeted approaches (p<0.05). The combined strategy proposed herein enabled us to establish that circulating pyruvate levels (p<0.001) together with body mass index (p=0.025), C-reactive protein (p=0.039), D-Dimer (p<0.001) and creatinine (p=0.043) levels, are independent predictors of critical COVID-19. Furthermore, classification and regression tree (CART) analysis provided a cut-off value of pyruvate in serum (24.54 mu M; p<0.001) as an early criterion to accurately classify patients with critical outcomes. ConclusionOur findings support the

Anti-TNF biologics have been shown to markedly improve the quality of life for patients with Crohn's disease (CD), yet one-third of patients fail to benefit from this treatment. Patients with CD develop a characteristic wrapping of visceral adipose tissue (VAT) in the inflamed intestinal area, termed creeping fat, and it is known that adipose tissue expansion influences the efficacy of anti-TNF drugs. We questioned whether anti-TNF therapies impact the creeping fat in CD, which might affect the outcome of the disease. Adipose tissue biopsies were obtained from a cohort of 14 patients with CD that received anti-TNF drugs and from 29 non-anti-TNF-treated patients (control group) matched by sex, age, and body mass index undergoing surgical interventions for symptomatic complications. We found that anti-TNF therapies restored adipose tissue morphology and suppressed immune cell infiltration in the creeping fat. Additionally, anti-TNF treatments appeared to markedly improve the pro-inflammatory phenotype of adipose-tissue macrophages and adipose-tissue-derived stem cells. Our study provides evidence that anti-TNF medications influence immune cells and progenitor cells in the creeping of patients with CD, suppressing inflammation. We propose that perilesional VAT should be considered when administering anti-TNF therapy in patients with CD.

El objetivo de este artículo es resumir de manera objetiva el informe del Comité Científico Europeo que acaba de actualizar el algoritmo en el que se basa el logotipo nutricional Nutri-Score. Se revisa la metodología utilizada, las prioridades establecidas y sus justificaciones, y los diferentes escenarios probados, las modificaciones propuestas y su impacto en los diferentes grupos de alimentos afectados.

Background: Excess circulating endocannabinoids (eCBs) and imbalanced N-acylethanolamines (NAEs) related eCBs abundance could influence dietary weight loss success. We aimed to examine sex differences in the impact of a 3-years Mediterranean diet (MedDiet) intervention on circulating eCBs, NAEs and their precursor fatty acids, and to analyze the interplay between changes in eCBs or NAEs ratios, insulin resistance and the achievement of clinically meaningful weight reductions. Methods: Prospective cohort study in a subsample of N = 105 participants (54.3% women; 65.6 ± 4.6 years) with overweight or obesity and metabolic syndrome that underwent a 3-years MedDiet intervention (PREDIMED-Plus study). Plasma eCBs and NAEs, including 2-arachidonoylglycerol (2-AG), anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), fatty acids, diet, glycemic homeostasis (including the assessment of insulin resistance-HOMA-IR), and cardiovascular risk markers were monitored (at 0-6-12-36 months). Results: Mediterranean diet adherence increased in both sexes and remained high during the 3 years of follow-up. Reductions in body weight, glycemic and cardiovascular parameters were larger in men than in women. Women presented higher concentrations of NAEs than men throughout the study. In both sexes, AEA and other NAEs (including OEA, and PEA) decreased after 6 months (for AEA: −4.9%), whereas the ratio OEA/AEA increased after 1 year (+5.8%). Changes in 2-AG (−3.9%) and the ratio OEA/PEA (+8.2%) persisted over the 3 years of follow-up. In women, 6-months changes in AEA (OR = 0.65) and the ratio OEA/AEA (OR = 3.28) were associated with the achievement of 8% weight reductions and correlated with HOMA-IR changes (r = 0.29 and r = −0.34). In men, OEA/PEA changes were associated

Background & aims: Maternal ultra-processed food (UPF) consumption during pregnancy may adversely affect child development. Pregnancy sugar-sweetened beverage consumption (as a part of UPF) has been associated with child cognitive dysfunction in the general population, but the role of total UPF con-sumption during pregnancy in later child neuropsychological development has not been studied. We aimed to analyse the association between maternal pregnancy UPF consumption and child neurodevelopment.Methods: This study involved 2377 pairs of pregnant women and their offspring from a Spanish birth cohort (recruitment period: 2004e20 08, INMA project). Dietary intake was estimated using a 101-item food frequency questionnaire in the third trimester of pregnancy. The NOVA classification was used to identify UPFs, and their consumption was calculated as the daily percentage of total food consumption and categorized into tertiles. Child neuropsychological development was assessed with the Bayley Scales of Infant and Toddler Development (1-year-old, n = 1929) and the McCarthy Scales of Children's Abilities (4-5 years-old, n = 1679). Potential associations were analysed using multivariate linear regression models adjusted for a range of family and child characteristics.Results: UPF consumption among pregnant women represented an average of 17% of the total diet, with sugar-sweetened beverages being the most commonly consumed type of UPF (40%). Children born to mothers in the highest tertile of UPF consumption (28.9% or more of the total diet) vs the lowest tertile (7.2% or less), showed a lower score (B =-2.29 [95% Confidence Interval (CI),-4.13;-0.46]) in the Verbal Scale of the McCarthy Scales (p-for-trend = 0.02). No associations were observed with the McCarthy Scales assessing

The oil sands industry generates large volumes of oil sands process water (OSPW). There is an urgent need for OSPW treatment to reduce process water inventories and to support current reclamation approaches. This study discusses how efficient ozone (O3)-based combined advanced oxidation processes (AOPs), including hydrogen peroxide (H2O2) and UV-C, are at achieving mineralization while reducing the toxicity arising from such organic components as naphthenic acids (NAs) in OSPW. The results showed that the dissolved organic carbon (DOC) removals of 45%, 84%, 84% and 98%, obtained after 90-min treatments with O3, O3/H2O2, UVC/O3 and UVC/O3/H2O2, respectively, at a production rate of 6 g/L·h O3 were considerably higher than at lower O3 production rates. The acute toxicity on Vibrio fischeri was significantly reduced by all the treatments, which explains the high percentages of NA removal (up to 99% as confirmed by UPLC-QTOF-HRMS.) Mineralization (expressed as DOC removal) was highest with UVC/O3/H2O2 at ca. 2 mg C/L in the treated effluent, which means that it could be used as cooling/boiling process water in bitumen upgrading units. However, considering the energy demand of the treatments tested, the treatment using O3/H2O2 was found to be the most realistic for large-scale applications.

Grape seed derived procyanidins (GSPE) have been shown to effectively prevent intestinal disarrangements induced by a cafeteria diet in young rats. However, little is known about the effects of procyanidins and cafeteria diet on enterohormone secretion in aged rats, as the ageing processes modify these effects. To study these effects in aged rats, we subjected 21-month-old and young 2-month-old female rats to two sub-chronic preventive GSPE treatments. After three months of cafeteria diet administration, we analysed the basal and stimulated secretion and mRNA expression of CCK, PYY and GLP-1, caecal SCFA and intestinal sizes. We found that the effects of a cafeteria diet on the basal duodenal CCK secretion are age dependent. GLP-1 in the ileum was not modified regardless of the rat's age, and GSPE preventive effects differed in the two age groups. GSPE pre-treatment reduced GLP-1, PYY and ChgA in mRNA in aged ileum tissue, while the cafeteria diet increased these in aged colon. The GSPE treatments only modified low-abundance SCFAs. The cafeteria diet in aged rats increases the caecum size differently from that in young rats and GSPE pre-treatment prevents this increase. Therefore, ageing modifies nutrient sensing, and the cafeteria diet acts mainly on the duodenum and colon, while procyanidins have a larger effect on the ileum.

Objective: Tryptophan can be catabolised to various metabolites through host kynurenine and microbial indole pathways. We aimed to examine relationships of host and microbial tryptophan metabolites with incident type 2 diabetes (T2D), host genetics, diet and gut microbiota. Method: We analysed associations between circulating levels of 11 tryptophan metabolites and incident T2D in 9180 participants of diverse racial/ethnic backgrounds from five cohorts. We examined host genome-wide variants, dietary intake and gut microbiome associated with these metabolites. Results: Tryptophan, four kynurenine-pathway metabolites (kynurenine, kynurenate, xanthurenate and quinolinate) and indolelactate were positively associated with T2D risk, while indolepropionate was inversely associated with T2D risk. We identified multiple host genetic variants, dietary factors, gut bacteria and their potential interplay associated with these T2D-relaetd metabolites. Intakes of fibre-rich foods, but not protein/tryptophan-rich foods, were the dietary factors most strongly associated with tryptophan metabolites. The fibre-indolepropionate association was partially explained by indolepropionate-associated gut bacteria, mostly fibre-using Firmicutes. We identified a novel association between a host functional LCT variant (determining lactase persistence) and serum indolepropionate, which might be related to a host gene-diet interaction on gut Bifidobacterium, a probiotic bacterium significantly associated with indolepropionate independent of other fibre-related bacteria. Higher milk intake was associated with higher levels of gut Bifidobacterium and serum indolepropionate only among genetically lactase non-persistent individuals. Conclusion: Higher milk intake among lactase non-persistent individuals

The production and consumption of ultra-processed foods (UPF) has increased considerably during the last years worldwide. Collective evidence shows the association between UPF consumption and adverse health outcomes, including inflammatory gastro-intestinal disorders and obesity. The gut microbiota has been suggested as potential mediator of the effects of UPF consumption on metabolism and health. However, few studies have been conducted in order to elucidate these aspects. Therefore, the aim of the present study was to assess the cross-sectional associations between UPF consumption and gut microbiota in a population of senior subjects (n = 645) within the frame of the PREDIMED-Plus trial. Eligible participants were men and women (aged 55-75 years), without documented history of cardiovascular disease at enrollment, with overweight/obesity (body mass index <= 27 and <40 kg/m(2)) and metabolic syndrome. Using the information of food frequency questionnaires, the consumption of UPF, expressed as a percentage of total dietary energy intake in kcal/day, was calculated considering those food items classified in group 4 of NOVA system. Population was categorized according to tertiles of UPF consumption. Taxonomic fecal microbiota information, along with blood biochemical parameters, anthropometric measurements and clinical data were obtained. Bioinformatics analysis was performed to study the association between fecal microbiota composition and UPF consumption. We observed that subjects allocated in the highest tertile of UPF consumption (21.4 +/- 5.0 % kcal/day) presented lower adherence to MedDiet (p < 0.001) and higher total energy intake (p < 0.001). The taxonomic analysis of the fecal microbiota revealed a significant (Benjamini-Hochberg adjusted p < 0.2) positive associ

Bisphenol A (BPA) is a widely known endocrine disruptor (ED) found in many children's products such as toys, feeding utensils, and teething rings. Recent epidemiology association studies have shown postnatal BPA exposure resulted in developing various diseases such as diabetes, obesity, and neurodegeneration, etc., later in their lives. However, little is known about its sex-specific metabolism and consequently internal exposure. The aim of this study was to develop a sex-specific pediatric physiologically based pharmacokinetic model (PBPK) for BPA to compare their toxicokinetic differences. First, the published adult PBPK model was re-validated, and then this model was extended by interpolation to incorporate pediatric sex specific physiological and biochemical parameters. We used both the classical body weight and ontogeny-based scaling approach to interpolate the metabolic process. Then, the pharmacokinetic attributes of the models using the two-scaling approach mentioned above were compared with adult model. Further, a sex-specific PBPK model with an ontogeny scaling approach was preferred to evaluate the pharmacokinetic differences. Moreover, this model was used to reconstruct the BPA exposure from two cohorts (Helix and PBAT Cohort) from 7 EU countries. The half-life of BPA was found to be almost the same in boys and girls at the same exposure levels. Our model estimated BPA children's exposure to be about 1500 times higher than the tolerable daily intake (TDI) recently set by European Food Safety Authority (EFSA) i.e., 0.04 ng/kg BW/day. The model demonstrated feasibility of extending the adult PBPK to sex-specific pediatric, thus investigate a gender-specific health risk assessment.

Iron participates as an essential cofactor in the biosynthesis of critical cellular components, including DNA, proteins and lipids. The ergosterol biosynthetic pathway, which is an important target of antifungal treatments, depends on iron in four enzymatic steps. Our results in the model yeast Saccharomyces cerevisiae show that the expression of ergosterol biosynthesis (ERG) genes is tightly modulated by iron availability probably through the iron-dependent variation of sterol and heme levels. Whereas the transcription factors Upc2 and Ecm22 are responsible for the activation of ERG genes upon iron deficiency, the heme-dependent factor Hap1 triggers their Tup1-mediated transcriptional repression. The combined regulation by both activating and repressing regulatory factors allows for the fine-tuning of ERG transcript levels along the progress of iron deficiency, avoiding the accumulation of toxic sterol intermediates and enabling efficient adaptation to rapidly changing conditions. The lack of these regulatory factors leads to changes in the yeast sterol profile upon iron-deficient conditions. Both environmental iron availability and specific regulatory factors should be considered in ergosterol antifungal treatments.

Consumption of grape seed proanthocyanidin extract (GSPE) has beneficial effects on the functionality of white adipose tissue (WAT). However, although WAT metabolism shows a clear diurnal rhythm, whether GSPE consumption could affect WAT rhythmicity in a time-dependent manner has not been studied. Ninety-six male Fischer rats were fed standard (STD, two groups) or cafeteria (CAF, four groups) diet for 9 weeks (n = 16 each group). From week 6 on, CAF diet animals were supplemented with vehicle or 25 mg GSPE/kg of body weight either at the beginning of the light/rest phase (ZT0) or at the beginning of the dark/active phase (ZT12). The two STD groups were also supplemented with vehicle at ZT0 or ZT12. In week 9, animals were sacrificed at 6 h intervals (n = 4) to analyze the diurnal rhythms of subcutaneous WAT metabolites by nuclear magnetic resonance spectrometry. A total of 45 metabolites were detected, 19 of which presented diurnal rhythms in the STD groups. Although most metabolites became arrhythmic under CAF diet, GSPE consumption at ZT12, but not at ZT0, restored the rhythmicity of 12 metabolites including compounds involved in alanine, aspartate, and glutamate metabolism. These results demonstrate that timed GSPE supplementation may restore, at least partially, the functional dynamics of WAT when it is consumed at the beginning of the active phase. This study opens an innovative strategy for time-dependent polyphenol treatment in obesity and metabolic diseases.

Background: Tobacco consumption during pregnancy is one of the most modifiable causes of morbidity and mortality for both pregnant smokers and their foetus. Even though pregnant smokers are conscious about the negative effects of tobacco consumption, they also had barriers for smoking cessation and most of them continue smoking, being a major public health problem. The aim of this study is to determine the effectiveness of an application (App) for mobile devices, designed with a gamification strategy, in order to help pregnant smokers to quit smoking during pregnancy and in the long term.Methods: This study is a multicentre randomized community intervention trial. It will recruit pregnant smokers (200 participants/group), aged more than 18 years, with sporadically or daily smoking habit in the last 30 days and who follow-up their pregnancy in the Sexual and Reproductive Health Care Services of the Camp de Tarragona and Central Catalonia Primary Care Departments. All the participants will have the usual clinical practice intervention for smoking cessation, whereas the intervention group will also have access to the App. The outcome measure will be prolonged abstinence at 12 months after the intervention, as confirmed by expired-carbon monoxide and urinary cotinine tests. Results will be analysed based on intention to treat. Prolonged abstinence rates will be compared, and the determining factors will be evaluated using multivariate statistical analysis.Discussion: The results of this study will offer evidence about the effectiveness of an intervention using a mobile App in smoking cessation for pregnant smokers, to decrease comorbidity associated with long-term smoking. If this technology is proven effective, it could be readily incorporated into primary care interventio

Background: Anticipating and avoiding preventable intrahospital cardiac arrest and clinical deterioration are important priorities for international healthcare systems and institutions. One of the internationally followed strategies to improve this matter is the introduction of the Rapid Response Systems (RRS). Although there is vast evidence from the international community, the evidence reported in a Spanish context is scarce. Methods: A nationwide cross-sectional research consisting of a voluntary 31-question online survey was performed. The Spanish Society of Intensive, Critical and Coronary Care Medicine (SEMICYUC) supported the research. Results: We received 62 fully completed surveys distributed within 13 of the 17 regions and two autonomous cities of Spain. Thirty-two of the participants had an established Rapid Response Team (RRT). Common frequency on measuring vital signs was at least once per shift but other frequencies were contemplated (48.4%), usually based on professional criteria (69.4%), as only 12 (19.4%) centers used Early Warning Scores (EWS) or automated alarms on abnormal parameters. In the sample, doctors, nurses (55%), and other healthcare professionals (39%) could activate the RRT via telephone, but only 11.3% of the sample enacted this at early signs of deterioration. The responders on the RRT are the Intensive Care Unit (ICU), doctors, and nurses, who are available 24/7 most of the time. Concerning the education and training of general ward staff and RRT members, this varies from basic to advanced and specific-specialized level, simulating a growing educational methodology among participants. A great number of participants have emergency resuscitation equipment (drugs, airway adjuncts, and defibrillators) in their general wards. In terms of qu

Phenol-rich foods consumption such as virgin olive oil (VOO) has been shown to have beneficial effects on cardiovascular diseases. The broader biochemical impact of VOO and phenol-enriched OOs remains, however, unclear. A randomized, double-blind, cross-over, controlled trial was performed with thirty-three hypercholesterolemic individuals who ingested for 3-weeks (25 mL/day): (1) an OO enriched with its own olive oil phenolic compounds (PCs) (500 ppm; FOO); (2) an OO enriched with its own olive oil PCs (250 ppm) plus thyme PCs (250 ppm; FOOT); and (3) a VOO with low phenolic content (80 ppm). Serum lipid and glycemic profiles, serum H-1-NMR spectroscopy-based metabolomics, endothelial function, blood pressure, and cardiovascular risk were measured. We combined OPLS-DA with machine learning modelling to identify metabolites discrimination of the treatment groups. Both phenol-enriched OO interventions decreased the levels of glutamine, creatinine, creatine, dimethylamine, and histidine in comparison to VOO one. In addition, FOOT decreased the plasma levels of glycine and DMSO2 compared to VOO, while FOO decreased the circulating alanine concentrations but increased the plasma levels of acetone and 3-HB compared to VOO. Based on these findings, phenol-enriched OOs were shown to result in a favorable shift in the circulating metabolic phenotype, inducing a reduction in metabolites associated with cardiometabolic diseases.

Radiotherapy (RT) is part of the standard treatment of breast cancer (BC) because of its effects on relapse reduction and survival. However, response to treatment is highly variable, and some patients may develop disease progression (DP), a second primary cancer, or may succumb to the disease. Antioxidant systems and inflammatory processes are associated with the onset and development of BC and play a role in resistance to treatment. Here, we report our investigation into the clinical evolution of BC patients, and the impact of RT on the circulating levels of the antioxidant enzyme paraoxonase-1 (PON1), cytokines, and other standard biochemical and hematological variables. Gradient Boosting Machine (GBM) algorithm was used to identify predictive variables. This was a retrospective study in 237 patients with BC. Blood samples were obtained pre- and post-RT, with samples of healthy women used as control subjects. Results showed that 24 patients had DP eight years post-RT, and eight patients developed a second primary tumor. The algorithm identified interleukin-4 and total lymphocyte counts as the most relevant indices discriminating between BC patients and control subjects, while neutrophils, total leukocytes, eosinophils, very low-density lipoprotein cholesterol, and PON1 activity were potential predictors of fatal outcome.

Since the beginning of the COVID-19 pandemic and until September 2021, Spain suffered five waves of infection, the latter being related to the expansion of the Delta variant and with a high incidence. A vaccination campaign began in December 2020 and by the end of the fifth wave 77.3% of people had been fully vaccinated. Examining the changing dynamics of COVID-19 pandemic and its impact on outcomes among those hospitalized is essential. Our objective was to ascertain any differences in the characteristics and outcomes of hospitalized patients during that period compared to previous waves. We prospectively enrolled 200 consecutively admitted hospital patients from each wave and collected their clinical and demographic data from the medical records, including symptoms, comorbidities, deaths and whether they needed to be admitted to the Intensive Care Unit to receive assisted ventilation. We found that patients in the fifth wave were considerably younger than before, and the mortality rate fell from 22.5 to 2.0%. Admissions to the Intensive Care Unit decreased from 10 to 2%. Patients in the fifth wave had fewer comorbidities, and the age of the patients who died was higher than those who survived. Our results show a marked improvement in patient outcomes in the fifth wave, suggesting success of the vaccination campaign despite the explosion in cases due to the Delta variant.

The blood-brain barrier (BBB) is a structural and functional interface between the plasma and the human brain. Predictive BBB in-vitro models like immortalized human capillary microvascular endothelial cells (HCMEC/D3) can be used to explore the BBB disruption potential of daily exposed chemicals. The present study was focused on investigating the human BBB permeation potential of one organophosphate pesticide, chlorpyrifos (CPF), and two pyrethroids, permethrin (PMT) and cyfluthrin (CFT). HCMEC/D3 cells were exposed to the chemical and the time-dependent pass across BBB along with permeation coefficient (Papp) was calculated. Transendothelial electrical resistance (TEER) was measured for the cells to check the monolayer formation and later to check the reduction in integrity after chemical exposure. Real time PCR was conducted to investigate the effect of chemicals on the expression BBB´s tight and adherens junction proteins. Calculated Papp value for three chemicals was in the following order: CPF>CFT>PMT, where CPF showed the highest permeation coefficient. TEER calculation showed that the integrity decreased after CPF exposure which was in concordance with Papp value whereas for other chemicals, no change in TEER after exposure was observed. In addition, the transwell study showed a higher efflux ratio (ER) (>2) of CFT indicating that CFT could be a substrate for active transport. For CPF and PMT, ER was less than 2, so no active transport seems to be involved. The evaluation of the mRNA expression analysis revealed a statistically significant decrease in Occludin (OCLN) gene expression for CPF, VE-Cadherin (CDH5) for PMT and Zonula Occludens (ZO1) expression for CFT. Our study showed that CPF has the highest potential for inducing cell death, higher permeation, and

The balance between excitatory and inhibitory neurotransmitters is essential for proper brain development. An imbalance between these two systems has been associated with neurodevelopmental disorders. On the other hand, literature also associates the massive use of pesticides with the increase of these disorders, with a particular focus on chlorpyrifos (CPF) a world-wide used organophosphate pesticide. This study was aimed at assessing social autistic-like behaviors on mice pre or postnatally exposed to CPF (0 or 1 mg/kg/day), in both sexes. In prenatal exposure, C57BL/6J pregnant mice were exposed to CPF through the diet, between gestational days (GD) 12 and 18, while a positive control group for some autistic behaviors was exposed to valproic acid (VPA) on GD 12 and 13. To assess postnatal exposure, C57BL/6J mice were orally exposed to the vehicle (corn oil) or CPF, from postnatal days (PND) 10–15. Social behavior and gene expression analysis were assessed on PND 45. Results showed social alterations only in males prenatally treated. GABA system was upregulated in CPF-treated females, whereas an increase in both systems was observed in both treated males. These findings suggest that males are more sensitive to prenatal CPF exposure, favoring the sex bias observed in ASD.

Finite element analysis (FEA) is no longer a new technique in the fields of palaeontology, anthropology, and evolutionary biology. It is nowadays a wellestablished technique within the virtual functional-morphology toolkit. However, almost all the works published in these fields have only applied the most basic FEA tools i.e., linear materials in static structural problems. Linear and static approximations are commonly used because they are computationally less expensive, and the error associated with these assumptions can be accepted. Nonetheless, nonlinearities are natural to be used in biomechanical models especially when modelling soft tissues, establish contacts between separated bones or the inclusion of buckling results. The aim of this review is to, firstly, highlight the usefulness of non-linearities and secondly, showcase these FEA tool to researchers that work in functional morphology and biomechanics, as non-linearities can improve their FEA models by widening the possible applications and topics that currently are not used in palaeontology and anthropology.

Food consumption in children with ASD, subclinical ASD and with typical development (TD), and their adequacy to dietary recommendations was studied. A school population sample of 77 children with ASD, 40 with subclinical ASD, and 333 with TD participated. Compared to children with TD, pre-schoolers with ASD consumed fewer raw vegetables and less fish and eggs, while primary school children consumed fewer legumes, raw vegetables, citrus fruits, cheese/yogurt and olive oil, and more meat. All groups consumed an excess of sugar but those with ASD consumed even a greater amount than their peers. The higher prevalence of obesity found in primary school children with ASD may be the consequence of a less healthy eating pattern sustained over time.

The goal of this work is to explore if the changes induced by d-fagomine in the gut microbiota are compatible with its effect on body weight and inflammation markers in rats. Methods: Sprague Dawley rats were fed a standard diet supplemented with d-fagomine (or not, for comparison) for 6 months. The variables measured were body weight, plasma mediators of inflammation (hydroxyeicosatetraenoic acids, leukotriene B4, and IL-6), and the concentration of acetic acid in feces and plasma. The composition and diversities of microbiota in cecal content and feces were estimated using 16S rRNA metabarcoding and high-throughput sequencing. We found that after just 6 weeks of intake d-fagomine significantly reduced body weight gain, increased the plasma acetate concentration, and reduced the plasma concentration of the pro-inflammatory biomarkers' leukotriene B4, interleukin 6 and 12 hydroxyeicosatetraenoic acids. These changes were associated with a significantly increased prevalence of Bacteroides and Prevotella feces and increased Bacteroides, Prevotella, Clostridium, and Dysgonomonas while reducing Anaerofilum, Blautia, and Oribacterium in cecal content. In conclusion, d-fagomine induced changes in the composition and diversity of gut microbiota similar to those elicited by dietary fiber and compatible with its anti-inflammatory and body-weight-reducing effects.

Introduction Daily, moderate hypofractionation has become standard treatment for breast cancer following breast-conserving surgery, although substantial variation exists in its use. This paper describes the generation of consensus-based recommendations for the utilisation of this therapy at the healthcare system level and compares these to American Society for Radiation Oncology (ASTRO) guidelines. Materials and methods Consensus-based guidelines were developed in three steps, including a systematic literature review and involvement of radiation oncologists specialising in breast cancer in Catalonia: (a) creation of a working group and evidence review; (b) consideration of the levels of evidence and agreement on the formulation of survey questions; and (c) performance of survey and development of consensus-based recommendations. Results were compared to the ASTRO recommendations. Results Consensus was above 80% for 10 of the 14 survey items. Experts supported hypofractionated radiotherapy for all breast cancer patients aged 40 years or more; with invasive carcinoma and breast-conserving surgery; without radiation of lymph nodes; and regardless of the tumour size, histological grade, molecular subtype, breast size, laterality, other treatment characteristics, or need for a boost. Over half favoured its use in all situations, even where available scientific evidence is insufficient. The resulting recommendations and the quality of the evidence are comparable to those from ASTRO, despite some differences in the degree of consensus. Conclusion Specialists agree that hypofractionation is the standard treatment for breast cancer following breast-conserving surgery, but some specific areas require a higher level of evidence before unequivocally extending indications.

The quality of the drinking water distributed through the networks has become the main concern of most operators. This work focuses on one of the most important variables of the drinking water distribution networks (WDN) that use disinfection, chlorine. This powerful disinfectant must be dosed carefully in order to reduce disinfection byproducts (DBPs). The literature demonstrates researchers' interest in modelling chlorine decay and using several different approaches. Nevertheless, the full-scale application of these models is far from being a reality in the supervision of water distribution networks. This paper combines the use of validated chlorine prediction models with an intensive study of a large amount of data and its influence on the model's parameters. These parameters are estimated and validated using data coming from the Supervisory Control and Data Acquisition (SCADA) software, a full-scale water distribution system, and using off-line analytics. The result is a powerful methodology for calibrating a chlorine decay model on-line which coherently evolves over time along with the significant variables that influence it.

In image classification with Deep Convolutional Neural Networks (DCNNs), the number of parameters in pointwise convolutions rapidly grows due to the multiplication of the number of filters by the number of input channels that come from the previous layer. Existing studies demonstrated that a subnetwork can replace pointwise convolutional layers with significantly fewer parameters and fewer floating-point computations, while maintaining the learning capacity. In this paper, we propose an improved scheme for reducing the complexity of pointwise convolutions in DCNNs for image classification based on interleaved grouped filters without divisibility constraints. The proposed scheme utilizes grouped pointwise convolutions, in which each group processes a fraction of the input channels. It requires a number of channels per group as a hyperparameter Ch. The subnetwork of the proposed scheme contains two consecutive convolutional layers K and L, connected by an interleaving layer in the middle, and summed at the end. The number of groups of filters and filters per group for layers K and L is determined by exact divisions of the original number of input channels and filters by Ch. If the divisions were not exact, the original layer could not be substituted. In this paper, we refine the previous algorithm so that input channels are replicated and groups can have different numbers of filters to cope with non exact divisibility situations. Thus, the proposed scheme further reduces the number of floating-point computations (11%) and trainable parameters (10%) achieved by the previous method. We tested our optimization on an EfficientNet-B0 as a baseline architecture and made classification tests on the CIFAR-10, Colorectal Cancer Histology, and Malaria datasets. For each dataset, ou

Solar photovoltaic (PV) systems have drawn significant attention over the last decade. One of the most critical obstacles that must be overcome is distributed energy generation. This paper presents a comprehensive quantitative bibliometric study to identify the new trends and call attention to the evolution within the research landscape concerning the integration of solar PV in power networks. The research is based on 7146 documents that were authored between 2000-2021 and downloaded from the Web of Science database. Using an in-house bibliometric tool, Bibliometrix R-package, and the open-source tool VOSviewer we obtained bibliometric indicators, mapped the network analysis, and performed a multivariate statistical analysis. The works that were based on solar photovoltaics into power networks presented rapid growth, especially in India. The co-occurrence analysis showed that the five main clusters, classified according to dimensions and significance, are (i) power quality issues that are caused by the solar photovoltaic penetration in power networks; (ii) algorithms for energy storage, demand response, and energy management in the smart grid; (iii) optimization, techno-economic analysis, sensitivity analysis, and energy cost analysis for an optimal hybrid power system; (iv) renewable energy integration, self-consumption, energy efficiency, and sustainable development; and (v) modeling, simulation, and control of battery energy storage systems. The results revealed that researchers pay close attention to "renewable energy", "microgrid", "energy storage", "optimization", and "smart grid", as the top five keywords in the past four years. The results also suggested that (i) power quality; (ii) voltage and frequency fluctuation problems; (iii) optimal design and energy mana

To analyse women's stated preferences for establishing the relative importance of each attribute of shared decision-making (SDM) and their willingness to pay (WTP) for more participatory care in breast cancer screening programmes (BCSP).A discrete choice experiment was designed with 12 questions (choice tasks). It included three attributes: 'How the information is obtained', regarding benefits and harms; whether there is a 'Dialogue for scheduled mammography' between the healthcare professional and the woman; and, 'Who makes the decision', regarding participation in BCSP. Data were obtained using a survey that included 12 choice tasks, 1 question on WTP and 7 socioeconomic-related questions. The analysis was performed using conditional mixed-effect logit regression and stratification according to WTP.Data collection related to BCSP was conducted between June and November 2021 in Catalonia, Spain.Sixty-five women aged between 50 and 60.Women's perceived utility of each attribute, trade-off on these attributes and WTP for SDM in BCSP.The only significant attribute was 'Who makes the decision'. The decision made alone (coefficient=2.879; 95% CI=2.297 to 3.461) and the decision made together with a healthcare professional (2.375; 95% CI=1.573 to 3.177) were the options preferred by women. The former contributes 21% more utility than the latter. Moreover, 52.3% of the women stated a WTP of €10 or more for SDM. Women's preferences regarding attributes did not influence their WTP.The participant women refused a current paternalistic model and preferred either SDM or informed decision-making in BCSP.© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.

The scientific literature has already shown that health information is a factor that contributes to reduce health disparities, improving the situation of vulnerable groups, such as homeless people. However, less is known about the ways that health information has been spread by social workers and related professionals to homeless people in the first moments of the COVID-19 pandemic. This work analyses some social work actions related to health information addressed to homeless people and to identify its impact during the lockdown in Barcelona. This qualitative study is based on semi-structured interviews with social workers and related professionals involved in developing interventions related to health information with homeless people in Barcelona. The data analysis is based on the communicative methodology to identify exclusionary and transformative dimensions. The results show the improvement in the health information of homeless people during the pandemic through the design and development of actions facilitated and promoted by some social workers and related professionals. The findings demonstrate the role that some social workers and related professionals have played in the improvement of health information of homeless people during the lockdown in Barcelona.

Secreted frizzled-related protein 5 (SFRP5) is an anti-inflammatory adipocytokine secreted by adipocytes that seems to be linked with nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the role of the SFRP5-wingless-MMTV integration site family member 5a (WNT5A) pathway, closely related to adipogenesis, in subcutaneous (SAT) and visceral adipose tissues (VAT) and its relationship with obesity-related NAFLD. Our cohort was composed of 60 women with morbid obesity (MO), who underwent hypocaloric diet, subclassified according to their hepatic histopathology and 15 women with normal weight. We observed increased SFRP5 mRNA expression in VAT and lower WNT5A expression in SAT in MO compared to normal weight. We found elevated SFRP5 expression in nonalcoholic steatohepatitis (NASH) in SAT and in mild simple steatosis (SS) and NASH in VAT. We observed higher WNT5A expression in SS compared to normal liver in SAT, and a peak of WNT5A expression in mild SS. To conclude, we reported increased SFRP5 mRNA expression in SAT and VAT of NAFLD-related to obesity subjects, suggesting an implication of the SFRP5-WNT5A pathway in NAFLD pathogenesis, probably due to the adipose tissue-liver axis. Since the mechanisms by which this potential interaction takes place remain elusive, more research in this field is needed.

The third-generation anaplastic lymphoma tyrosine kinase inhibitor (ALK-TKI) lorlatinib has a unique side effect profile that includes hypercholesteremia and hypertriglyceridemia in >80% of lung cancer patients. Here, we tested the hypothesis that lorlatinib might directly promote the accumulation of cholesterol and/or triglycerides in human hepatic cells. We investigated the capacity of the hepatoprotectant silibinin to modify the lipid-modifying activity of lorlatinib. To predict clinically relevant drug-drug interactions if silibinin were used to clinically manage lorlatinib-induced hyperlipidemic effects in hepatic cells, we also explored the capacity of silibinin to interact with and block CYP3A4 activity using in silico computational descriptions and in vitro biochemical assays. A semi-targeted ultrahigh pressure liquid chromatography accurate mass quadrupole time-of-flight mass spectrometry with electrospray ionization (UHPLC-ESI-QTOF-MS/MS)-based lipidomic approach revealed that short-term treatment of hepatic cells with lorlatinib promotes the accumulation of numerous molecular species of cholesteryl esters and triglycerides. Silibinin treatment significantly protected the steady-state lipidome of hepatocytes against the hyperlipidemic actions of lorlatinib. Lipid staining confirmed the ability of lorlatinib to promote neutral lipid overload in hepatocytes upon long-term exposure, which was prevented by co-treatment with silibinin. Computational analyses and cell-free biochemical assays predicted a weak to moderate inhibitory activity of clinically relevant concentrations of silibinin against CYP3A4 when compared with recommended (rosuvastatin) and non-recommended (simvastatin) statins for lorlatinib-associated dyslipidemia. The elevated plasma cholesterol and

Introducción: los trastornos de la conducta alimentaria (TCA) son un grupo de afecciones en las cuales las creencias negativas sobre la comida, la forma del cuerpo y el peso corporal se acompañan de conductas que incluyen restricción de la ingesta, atracones, realización excesiva de ejercicio, provocación del vómito y uso de laxantes. Pueden llegar a ser graves, repercutir sobre la calidad de vida y conducir a múltiples complicaciones físicas y psiquiátricas, incluso con desenlace fatal. El propósito de este artículo es describir las características, la epidemiología y las tendencias de los TCA con información actualizada a partir de las publicaciones más recientes. Métodos: se ha realizado una búsqueda sistemática de la literatura en Medline, EMBASE, Cochrane y Web of Science. Los términos de búsqueda fueron “anorexia nervosa”, “bulimia nervosa”, “binge eating disorders” and “epidemiology” en título y resumen. Resultados y conclusiones: los TCA se presentan generalmente en adolescentes y adultos jóvenes. Los mejor caracterizados son la anorexia nerviosa (AN), la bulimia nerviosa (BN) y el trastorno por atracón (TA). Los estudios de prevalencia indican amplias diferencias en función del grupo de edad y el sexo, muy superior en las mujeres jóvenes (AN: 0,1-2 %; BN: 0,37-2,98 %; TA: 0,62-4,45 %). La prevalencia de los TCA es del 2,2 % (0,2-13,1 %) en Europa, del 3,5 % (0,6-7,8 %) en Asia y del 4,6 % (2,0-13,5 %) en América. La comorbilidad es elevada con problemas psiquiátricos como la depresión, la ansiedad, el déficit de atención e hiperactividad, el trastorno obsesivo-compulsivo y los trastornos de personalidad.

New therapeutic options are needed in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Lenalidomide-based schedules can reverse rituximab refractoriness in lymphoma.In the phase II R2-GDP trial, 78 patients unsuitable for autologous stem cell transplant received treatment with the following schedule: lenalidomide 10 mg Days (D)1-14, rituximab 375 mg/m2 D1, cisplatin 60 mg/m2 D1, gemcitabine 750 mg/m2 D1 and D8, and dexamethasone 20 mg D1-3, up to 6 cycles (induction phase), followed by lenalidomide 10 mg (or last lenalidomide dose received) D1-21 every 28 days (maintenance phase). Primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and monitorization of key circulating immune biomarkers (EU Clinical Trials Register number: EudraCT 2014-001620-29).After a median follow-up of 37 months, ORR was 60.2% [37.1% complete responses (CR) and 23.1% partial responses (PR)]. Median OS was 12 months (47 vs. 6 months in CR vs. no CR); median PFS was 9 months (34 vs. 5 months in CR vs. no CR). In the primary refractory population, ORR was 45.5% (21.2% CR and 24.3% PR). Most common grade 3-4 adverse events were thrombocytopenia (60.2%), neutropenia (60.2%), anemia (26.9%), infections (15.3%), and febrile neutropenia (14.1%). Complete responses were associated with a sharp decrease in circulating myeloid-derived suppressor cells and regulatory T cells.R2-GDP schedule is feasible and highly active in R/R DLBCL, including the primary refractory population. Immune biomarkers showed differences in responders versus progressors.©2022 The Authors; Published by the American Association for Cancer Research.

Background: Over the last decade, transcranial direct current stimulation (tDCS) has set promise contributing to post-stroke gait rehabilitation. Even so, results are still inconsistent due to low sample size, heterogeneity of samples, and tDCS design differences preventing comparability. Nonetheless, updated knowledge in post-stroke neurophysiology and stimulation technologies opens up opportunities to massively improve treatments. Objective: The current systematic review aims to summarize the current state-of-the-art on the effects of tDCS applied to stroke subjects for gait rehabilitation, discuss tDCS strategies factoring individual subject profiles, and highlight new promising strategies. Methods: MEDLINE, SCOPUS, CENTRAL, and CINAHL were searched for stroke randomized clinical trials using tDCS for the recovery of gait before 7 February 2022. In order to provide statistical support to the current review, we analyzed the achieved effect sizes and performed statistical comparisons. Results: A total of 24 records were finally included in our review, totaling n = 651 subjects. Detailed analyses revealed n = 4 (17%) studies with large effect sizes (≥0.8), n = 6 (25%) studies with medium ones (≥0.5), and n = 6 (25%) studies yielding low effects sizes (≤ 0.2). Statistically significant negative correlations (rho = −0.65, p = 0.04) and differences (p = 0.03) argued in favor of tDCS interventions in the sub-acute phase. Finally, significant differences (p = 0.03) were argued in favor of a bifocal stimulation montage (anodal M1 ipsilesional and cathodal M1 contralesional) with respect to anodal ipsilesional M1. Conclusion: Our systematic review highlights the potential of tDCS to contribute to gait recovery following stroke, although also the urgent need to improve current

The increase and indiscriminate use of personal care products, food products, fertilizers, pesticides, and health products, among others, have resulted/are resulting in extensive environmental contamination. Most of these products contain traces of widespread chemicals, usually known as emerging pollutants (EPs) or pollutants of emerging concern (PEC). The Latin American (LA) region comprises 20 countries with different social and cultural aspects, with 81 % of the population living in urban areas. The LA region has some countries on the top list of users/consumers of EPs, from pesticides and fertilizers to personal care products. However, there is a gap in information related to the distribution of EPs in the environment of this region, with very few existing review texts exploring this issue. Therefore, this present paper advances this approach. An exhaustive literature review, with the selection of 176 documents, provided unique up-to-date information on the presence/distribution of 17 classes of legacy or emerging pollutants in different food and environmental matrices (soil, sediment, water, and air). The study shows that the wide distribution and recorded levels of these pollutants in the continental environment are potential risks to human health, mainly through food and drinking water ingestion. Polycyclic aromatic hydrocarbons are pollutants of deep public concern since they show carcinogenic properties. Several classes of pollutants, like endocrine disruptors, have caused harmful effects on humans and the environment. Besides that, pharmaceutical products and pesticides are compounds of high consumption worldwide, being environmental contamination a real and ongoing possibility. Finally, gaps and future research needs are deeply pointed out.Copyright © 2022. P

Los trastornos de la alimentación son poco frecuentes en las edades de la etapa escolar, siendo predominantes en el sexo femenino. Los principales factores predictivos en esta edad son similares a los de otros grupos de edad, siendo particularmente importante la influencia de los cambios corporales, sobre todo en las niñas. Aunque los programas preventivos en este grupo de edad son escasos, los centrados principalmente en la aceptación de la imagen corporal, la internalización del ideal de apariencia y la alfabetización mediática han observado cierta eficacia. No obstante, son necesarias nuevas investigaciones que confirmen los enfoques con mejores resultados.

Maternal short-chain fatty acids (SCFAs) play a critical role in fetal development and metabolic programming. However, an important gap in the analysis of such relationships is the lack of reference values in pregnant women. Therefore, we establish serum SCFA percentile reference ranges both early and later in pregnancy in a population from a Mediterranean region of Northern Spain. A population-based follow-up study involving 455 healthy pregnant women (mean age 30.6 +/- 5.0 years) from the ECLIPSES study is conducted. Sociodemographic, obstetric, anthropometric, lifestyle, dietary variables and blood samples were collected in the first and third trimesters. Serum SCFA concentrations were measured by LC-MS/MS. The 2.5/97.5 percentiles of the reference interval for serum acetic, propionic, isobutyric, and butyric acids were 16.4/103.8 mu mol/L, 2.1/5.8 mu mol/L, 0.16/1.01 mu mol/L and 0.32/1.67 mu mol/L in the first trimester of pregnancy, respectively. In the third trimester, butyrate levels increased with most of the maternal factors and categories studied, while acetic acid and isobutyric acid decreased only in some maternal categories. Propionic acid was not affected by maternal factors. Reference ranges did not vary with maternal age, body weight, social class or diet, but decreased with smoking, high physical activity, low BMI and primiparity. This study establishes for the first-time SCFAs reference ranges in serum for women in our region in both early and late pregnancy. This information can be useful to monitor pregnancy follow-up and detect risk values.

The COVID-19 pandemic has prompted the re-emergence of staycations to the fore, as many people were forced to spend their vacations at or close to home due to travel restrictions. This phenomenon first went mainstream during the 2008 financial crisis, and has now been further accelerated by the COVID-19 pandemic. This study investigated the growth and practice of staycations during the first two years of the pandemic by analyzing social media and internet search data using Latent Dirichlet Allocation (LDA) topic modeling and Google Trends analytics. Key findings suggest that, while spatially close to home, people tried to achieve a psychological distance away from home. This was demonstrated by a strong global search interest in spending staycations at hotels close to home. The optimal LDA topic model produced 38 topics which were classified under four aggregate dimensions of antecedents, attributes, activities, and consequences of staycations. The findings provide useful insights to managers and policymakers on boosting revenue through this practice, and the role of staycations in promoting leisure activities close to home and sustainable tourism.

There is little evidence regarding the role that consuming a Mediterranean diet (MedDiet) during pregnancy plays in foetal growth. We therefore examined the relationship between maternal MedDiet adherence during pregnancy and anthropometric measures and small-for-gestational-age (SGA) at birth in a Spanish population on the north-eastern Mediterranean coast of Spain. Prospective analysis involved 614 mother-newborn pairs from the ECLIPSES study. Diet during pregnancy was assessed using a validated food frequency questionnaire, and a relative MedDiet score (rMedDiet) was calculated. Neonatal information, including weight, length, head circumference and SGA (< 10th percentile) at birth, was recorded. Multivariable logistic regression analyses were performed. The mean rMedDiet score was 9.8 (SD 2.1), ranging from 5 to 16 points. In the sample, 45% of the women had low (<= 9 points), 32% had medium (10-11 points), and 22% had high (>= 12 points) adherence to the rMedDiet. There was no association between rMedDiet and birth weight, length, head circumference or anthropometric indices (weight/length ratio and ponderal index). Pregnant women with a high rMedDiet score had a lower risk of delivering a SGA baby for weight (high vs low, OR = 0.36; 95% CI 0.16-0.79) and head circumference (high vs low, OR = 0.39; 95% CI 0.18-0.86), and a nonsignificant decrease in risk of SGA for length (high vs low, OR = 0.57; 95% CI 0.28-1.17). In conclusion, closer adherence to the MedDiet during pregnancy may have beneficial effects on foetal growth.

La evidencia científica apoya un modelo interactivo de influencias biopsicosociales en la etiología de los trastornos de la conducta alimentaria (TCA). Los nuevos estudios de asociación de genoma completo sugieren una base de desregulación metabólica en la anorexia nerviosa. Entre los factores psicológicos, la insatisfacción corporal (IC) puede considerarse el predictor más consistente, principalmente en el género femenino. Baja autoestima, afecto negativo e interiorización del ideal de delgadez determinan la IC. Ciertos rasgos de personalidad y otros factores individuales como un alto índice de masa corporal, problemas emocionales y algunas enfermedades, metabólicas y digestivas, factores sociales como algunas actividades deportivas o profesionales centradas en la presión por la figura corporal, características del entorno familiar, y presiones sociales y del grupo de pares por estar delgada, mediado actualmente por el uso/abuso de las redes sociales, actúan como condicionantes de riesgo en los TCA. La mayoría de los programas de prevención se dirigen a las mujeres adolescentes en educación secundaria y jóvenes. Son escasas las intervenciones en edades tempranas, en adultos y en varones. Los programas con buenos resultados se centran en uno o más factores de riesgo, se basan en enfoques cognitivos o conductuales e incluyen contenido sobre alimentación saludable o nutrición, alfabetización mediática o presiones socioculturales y aceptación corporal o satisfacción corporal. Incorporan nuevas tecnologías y son interactivos. Se necesitan más investigación y programas de prevención de los TCA innovadores para niños pequeños, adultos y varones.

Nuclear magnetic resonance (NMR)-based advanced lipoprotein tests have demonstrated that LDL and HDL particle numbers (LDL-P and HDL-P) are more powerful cardiovascular (CV) risk biomarkers than conventional cholesterol markers. Of interest, in people living with HIV (PLHIV), predictors of preclinical atherosclerosis and vascular dysfunction may be associated with impaired immune function. We previously stated that immunological non-responders (INR) were at higher CV risk than immunological responders (IR) before starting antiretroviral therapy (ART). Using Liposcale (R) tests, we characterized the lipoprotein profile from the same cohort of PLHIV at month 12 and month 36 after starting ART, intending to explore what happened with these indicators of CV risk during viral suppression. ART initiation dissipates the differences in lipoprotein-based CV risk markers between INR and IR, and only an increase in the number of HDL-P was found in INR + IR when compared to controls (p = 0.047). Interestingly, CD4(+) T-cell counts negatively correlated with medium HDL-P concentrations at month 12 in all individuals (p = -0.335, p = 0.003). Longitudinal analyses showed an important increase in LDL-P and HDL-P at month 36 when compared to baseline values in both IR and INR. A proper balance between a proatherogenic and atherogenic environment may be related to the reconstitution of CD4(+) T-cell count in PLHIV.

BACKGROUND: During the COVID-19 pandemic, different non-validated tests were proposed to simplify the diagnosis of gestational diabetes (GDM). AIM: To analyse the effects of replacing the two-step approach for Early-GDM and GDM diagnosis, with a fasting plasma glucose test. MATERIAL AND METHODS: This is a cohort study consisting of 3200 pregnant women: 400 with Early-GDM, 800 with GDM and 2000 with Non-GDM diagnosed using the two-step approach. Using fasting plasma glucose for Early-GDM and GDM diagnosis, according to the recommendations of Spain, Australia, Italy and the UK during the pandemic, the rates of missed and new Early-GDM and GDM were calculated and perinatal outcomes were analysed. RESULTS: Using fasting plasma glucose in the first trimester >100 mg/dL for Early-GDM diagnosis, the rates of post-COVID missed and new Early-GDM were 79.5% and 3.2%, respectively. Using fasting plasma glucose at 24-28 weeks <84 or >92, 95 or 100 mg/dL for GDM diagnosis, the rates of missed GDM were 50.4%, 78%, 82.6% and 92.4%, respectively, and 8.6%, 5.6% and 2.3% women with Non-GDM were diagnosed with new GDM. CONCLUSION: Fasting plasma glucose is not a good test for the diagnosis of GDM either in the first trimester or at 24-28 weeks.

Palladium catalyzes the cydclopropanation of 2-substituted 1,1-diborylalkenes with (trimethylsilyl)diazomethane. The relative stereoselectivity is controlled via a carbene insertion sequence generating an exclusive anti conformation between the R and SiMe3 substituents. Mixed 1,1-diborylalkenes also contributed to the formation of stereoselective B, B, Si-cyclopropanes. Orthogonal activation with (NaOBu)-Bu-t gives protodeborylation preferentially on the boron moiety syn to the aryl group. Further oxidation gives access to polyfunctional cycloopropyl alcohols with controlled enantioselectivity when chiral boryl motifs are involved.

Four novel mixed-mode zwitterionic silica-based functionalized with strong moieties sorbents were synthesized and evaluated through solid-phase extraction (SPE) to determine acidic and basic drugs in environmental water samples. All sorbents had the same functionalization: quaternary amine and sulfonic groups and C18 chains so that hydrophobic and strong cationic exchange (SCX) and strong anionic exchange (SAX) interactions could be exploited, in addition, two of them had carbon microparticles embedded. All sorbents retained both acidic and basic compounds in the preliminary assays but only the basic compounds were retained selectively through ionic exchange interactions when a clean-up step was introduced. The SPE method was therefore optimized to promote the selective retention of the basic compounds, initially with the two best-performing sorbents. After optimization of the SPE protocol, these sorbents were evaluated for the analysis of environmental water samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method with the best-performing sorbent was then validated with 100 mL of river samples and 50 mL of effluent wastewater samples in terms of apparent recoveries (%Rapp) spiking samples at 50 ng/L (river) and 200 ng/L (river and effluent), matrix effect, linear range, method quantification and detection limits, repeatability, and reproducibility. It should be highlighted that %Rapp ranged from 40 to 85% and matrix effects ranged from -17 to -4% for spiked river samples. When the method was applied to river and effluent wastewater samples, most compounds were found in the range from 24 to 1233 ng/L with detection limits from 1 to 5 ng/L.

In this study, a novel catalyst is introduced based on the immobilization of palladium onto dipyrido (3,2-a:2 ',3 '-c) phenazine-modified mesoporous silica nanoparticles. The dipyrido (3,2-a:2 ',3 '-c) phenazine (Py(2)PZ) ligand is synthesized in a simple method from the reaction of 1,10-phenanthroline-5,6-dione and 3,4-diaminobenzoic acid as starting materials. The ligand is used to functionalize mesoporous silica nanoparticles (MSNs) and modify their surface chemistry for the immobilization of palladium. The palladium-immobilized dipyrido (3,2-a:2 ',3 '-c) phenazine-modified mesoporous silica nanoparticles (Pd@Py(2)PZ@MSNs) are synthesized and characterized by several characterization techniques, including TEM, SEM, FT-IR, TGA, ICP, XRD, and EDS analyses. After the careful characterization of Pd@Py(2)PZ@MSNs, the activity and efficiency of this catalyst is examined in carbon-carbon bond formation reactions. The results are advantageous in water and the products are obtained in high isolated yields. In addition, the catalyst showed very good reusability and did not show significant loss in activity after 10 sequential runs.

Context DNA methylation in the diagnosis of gestational diabetes. Objective To assess the value of DNA methylation in the diagnosis of gestational diabetes (GDM) and in the prediction of maternal postpartum glucose disturbances. Methods Two-stage observational study performed between July 2006 and December 2010, at University Hospital. Forty-eight randomly selected pregnant women formed the discovery cohort (24 with GDM and 24 controls) and 252 pregnant women (94 with GDM and 158 controls) formed the replication cohort. GDM women were re-evaluated 4 years postpartum. The main outcome measures were GDM, type 2 diabetes or prediabetes at 4 years postpartum. Results We identified 3 CpG sites related to LINC00917, TRAPPC9, and LEF1 that were differentially methylated in women with GDM and abnormal glucose tolerance; and sites associated with LINC00917 and TRAPPC9 were independently associated with an abnormal glucose tolerance status 4 years postpartum after controlling for clinical variables. Moreover, the site associated with LINC00917 and the combination of the 3 sites had the highest predictive values. Conclusion Our results suggest that some of these sites may be implicated in the development of GDM and postpartum abnormal glucose tolerance.