Changes in lipid metabolism driven by steroid signalling modulate proteostasis in C. elegans.

Alzheimer's, Parkinson's and Huntington's diseases can be caused by mutations that enhance protein aggregation, but we still do not know enough about the molecular players of these pathways to develop treatments for these devastating diseases. Here, we screen for mutations that might enhance aggregation in Caenorhabditis elegans, to investigate the mechanisms that protect against dysregulated homeostasis. We report that the stomatin homologue UNC-1 activates neurohormonal signalling from the sulfotransferase SSU-1 in ASJ sensory/endocrine neurons. A putative hormone, produced in ASJ, targets the nuclear receptor NHR-1, which acts cell autonomously in the muscles to modulate polyglutamine repeat (polyQ) aggregation. A second nuclear receptor, DAF-12, functions oppositely to NHR-1 to maintain protein homeostasis. Transcriptomics analyses of unc-1 mutants revealed changes in the expression of genes involved in fat metabolism, suggesting that fat metabolism changes, controlled by neurohormonal signalling, contribute to protein homeostasis. Furthermore, the enzymes involved in the identified signalling pathway are potential targets for treating neurodegenerative diseases caused by disrupted protein homeostasis.

LipidMS 3.0: an R-package and a web-based tool for LC-MS/MS data processing and lipid annotation.

MOTIVATION: LipidMS was initially envisioned to use fragmentation rules and data-independent acquisition (DIA) for lipid annotation. However, data-dependent acquisition (DDA) remains the most widespread acquisition mode for untargeted LC-MS/MS-based lipidomics. Here, we present LipidMS 3.0, an R package that not only adds DDA and new lipid classes to its pipeline but also the required functionalities to cover the whole data analysis workflow from pre-processing (i.e. peak-peaking, alignment and grouping) to lipid annotation. RESULTS: We applied the new workflow in the data analysis of a commercial human serum pool spiked with 68 representative lipid standards acquired in full scan, DDA and DIA modes. When focusing on the detected lipid standard features and total identified lipids, LipidMS 3.0 data pre-processing performance is similar to XCMS, whereas it complements the annotations returned by MS-DIAL, providing a higher level of structural information and a lower number of incorrect annotations. To extend and facilitate LipidMS 3.0 usage among less experienced R-programming users, the workflow is also implemented as a web-based application. AVAILABILITY AND IMPLEMENTATION: The LipidMS R-package is freely available at https://CRAN.R-project.org/package=LipidMS and as a website at http://www.lipidms.com. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Comparison of blastocyst euploidy rates following luteal versus follicular phase stimulation in a GnRH antagonist protocol: a prospective study with repeated ovarian stimulation cycles.

STUDY QUESTION: Is there any difference in the mean number of euploid embryos following luteal phase start (LS) and follicular phase start (FS) of ovarian stimulation? SUMMARY ANSWER: The mean number of euploid blastocysts is equivalent independent of whether the inseminated oocytes are derived from FS or LS. WHAT IS KNOWN ALREADY: Starting ovarian stimulation at any time of the cycle ('random-start') is commonly used for emergency fertility preservation in cancer patients. A few retrospective studies have been published evaluating LS in women undergoing ovarian stimulation in the context of IVF, but there is a lack of robust data on the comparative efficacy of LS versus FS.Although 'random start' is commonly used in cancer survivors, few retrospective and uncontrolled studies have been published evaluating luteal phase stimulation in women undergoing ovarian stimulation in the context of IVF. Owing to this evident lack of robust data on the efficacy of LS, guidelines typically recommend the LS approach only for medical reasons and not in the context of IVF. STUDY DESIGN, SIZE, DURATION: This is a prospective, equivalence study, with repeated stimulation cycles, conducted between May 2018 and December 2021. Overall, 44 oocyte donors underwent two identical consecutive ovarian stimulation cycles, one initiated in the FS and the other in the LS. The primary outcome of the study was to evaluate whether FS and LS in the same patient would result in equivalent numbers of euploid embryos following fertilization of oocytes with the same sperm sample. PARTICIPANTS/MATERIALS, SETTING, METHODS: Overall, 44 oocyte donors underwent two consecutive ovarian stimulation protocols with 150 µg corifollitropin alpha followed by 200 IU recombinant FSH (rFSH) in a fixed GnRH antagonist protocol. The only difference between the two cycles was the day of initiation of ovarian stimulation, which was in the early follicular phase (FS) in one cycle, and in the luteal phase (LS) in the other. Forty-four oocyte recipients participated in the study receiving a mean of six metaphase II (MII) oocytes from each stimulation cycle (FS and LS). All MIIs were inseminated with the corresponding recipient's partner sperm (which had been previously frozen) or donor sperm, in order to safeguard the use of the same sample for either the FS or LS. Following fertilization and blastocyst culture, all generated embryos underwent genetic analysis for aneuploidy screening (preimplantation genetic testing for aneuploidy). MAIN RESULTS AND THE ROLE OF CHANCE: FS resulted in a significantly shorter duration of ovarian stimulation (difference between means (DBM) -1.05 (95% CI -1.89; -0.20)) and a lower total additional dose of daily rFSH was needed (DBM -196.02 (95% CI -319.92; -72.12)) compared with LS. The donors' hormonal profile on the day of trigger was comparable between the two stimulation cycles, as well as the mean number of oocytes (23.70 ± 10.79 versus 23.70 ± 8.81) (DBM 0.00 (95% CI -3.03; 3.03)) and MII oocytes (20.27 ± 9.60 versus 20.73 ± 8.65) (DBM -0.45 (95% CI -2.82; 1.91)) between FS and LS cycles, respectively. Following fertilization, the overall blastocyst formation rate was 60.70% with a euploid rate of 57.1%. Comparisons between the two stimulation cycles did not reveal any significance differences in terms of fertilization rates (71.9% versus 71.4%), blastocyst formation rates (59.4% versus 62%) and embryo euploidy rates (56.9 versus 57.3%) for the comparison of FS versus LS, respectively. The mean number of euploid blastocysts was equivalent between the FS (1.59 ± 1.30) and the LS (1.61 ± 1.17), (DBM -0.02 (90%CI -0.48; 0.44)). LIMITATIONS, REASONS FOR CAUTION: The study was performed in young, potentially fertile oocyte donors who are patients with high blastocyst euploidy rates. Although results may be extrapolated to young infertile women with good ovarian reserve, caution is needed prior to generalizing the results to infertile women of older age. WIDER IMPLICATIONS OF THE FINDINGS: The current study provides evidence that initiation of ovarian stimulation in the luteal phase in young potentially fertile women may result in a comparable number of oocytes and comparable blastocyst euploidy rates compared with follicular phase stimulation. This may imply that in case of a freeze-all protocol in young patients with good ovarian reserve, clinicians may safely consider initiation of ovarian stimulation during the luteal phase. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by an unrestricted grant from MSD/Organon. N.P.P. has received Research grants and honoraria for lectures from: Merck Serono, MSD/Organon, Ferring Pharmaceuticals, Besins Intenational, Roche Diagnostics, IBSA, Theramex, Gedeon Richter. F.M., E.C., M.R. and S.G. declared no conflict of interests. TRIAL REGISTRATION NUMBER: The study was registered at Clinical Trials Gov (NCT03555942).

LC-MS metabolomics of urine reveals distinct profiles for non-muscle-invasive and muscle-invasive bladder cancer.

PURPOSE: Bladder cancer (BC) is among the most frequent malignancies worldwide. Novel non-invasive markers are needed to diagnose and stage BC with more accuracy than invasive procedures like cystoscopy. To date, no study has identified urine metabolites characteristic of all BC stages. To discover novel urine metabolomic profiles to diagnose and stage non-muscle-invasive (NMIBC) and muscle-invasive (MIBC) patients using mass spectrometry-based metabolomics. METHODS: We prospectively recruited 198 BC patients and 98 age- and sex-matched healthy volunteers without evidence of renal or bladder condition confirmed by ultrasound, from whom we collected a first morning urine sample (before surgery in patients). In a discovery stage, an untargeted metabolomic analysis was conducted in urine samples of a selection of 64 BC patients (19 TaG1, 11 TaG3, 20 T1G3, 12 T2G3, 1 T2G2, 1 T3G3) and 20 controls to identify dysregulated metabolites. Next, after exhaustive multivariate analysis, confirmed dysregulated metabolites were validated in an independent cohort of 134 BC patients (19 TaG1, 62 TaG2, 9 TaG3, 15 T1G2, 16 T1G3, 4 T2G2, 9 T2G3) and 78 controls. RESULTS: We validated p-cresol glucuronide as potential diagnostic biomarker for BC patients compared to controls (AUC = 0.79). For NMIBC, p-cresol glucuronide was valuable as staging biomarker (AUC = 0.803). And among NMIBCs, p-coumaric acid may be a potential specific staging biomarker for the TaG1 NMIBC; however, future validation experiments should be conducted once the precise version of the standard is commercially available. Remarkably, for MIBC we validated spermine as potential specific staging biomarker (AUC = 0.882). CONCLUSION: Ours is the first metabolomics study conducted in urine of a thoroughly characterized cohort comprising all stages of NMIBC, MIBC and healthy controls in which we identified non-invasive diagnostic and staging biomarkers. These may improve BC management, thus reducing the use of current harmful diagnostic techniques.

Impact of Acetate versus Citrate Dialysates on Intermediary Metabolism-A Targeted Metabolomics Approach.

Acetate is widely used as a dialysate buffer to avoid the precipitation of bicarbonate salts. However, even at low concentrations that wouldn't surpass the metabolic capacity of the Krebs tricarboxylic acid (TCA) cycle, other metabolic routes are activated, leading to undesirable clinical consequences by poorly understood mechanisms. This study aims to add information that could biologically explain the clinical improvements found in patients using citrate dialysate. A unicentric, cross-over, prospective targeted metabolomics study was designed to analyze the differences between two dialysates, one containing 4 mmol/L of acetate (AD) and the other 1 mmol/L of citrate (CD). Fifteen metabolites were studied to investigate changes induced in the TCA cycle, glycolysis, anaerobic metabolism, ketone bodies, and triglyceride and aminoacidic metabolism. Twenty-one patients completed the study. Citrate increased during the dialysis sessions when CD was used, without surpassing normal values. Other differences found in the next TCA cycle steps showed an increased substrate accumulation when using AD. While lactate decreased, pyruvate remained stable, and ketogenesis was boosted during dialysis. Acetylcarnitine and myo-inositol were reduced during dialysis, while glycerol remained constant. Lastly, glutamate and glutarate decreased due to the inhibition of amino acidic degradation. This study raises new hypotheses that need further investigation to understand better the biochemical processes that dialysis and the different dialysate buffers induce in the patient's metabolism.

Characterization of anaphylaxis reveals different metabolic changes depending on severity and triggers.

BACKGROUND: Despite the increasing incidence of anaphylaxis, its underlying molecular mechanisms and biomarkers for appropriate diagnosis remain undetermined. The rapid onset and potentially fatal outcome in the absence of managed treatment prevent its study. Up today, there are still no known biomarkers that allow an unequivocal diagnosis. Therefore, the aim of this study was to explore metabolic changes in patients suffering anaphylactic reactions depending on the trigger (food and/or drug) and severity (moderate and severe) in a real-life set-up. METHODS: Eighteen episodes of anaphylaxis, one per patient, were analysed. Sera were collected during the acute phase (T1), the recovery phase (T2) and around 2-3 months after the anaphylactic reaction (T0: basal state). Reactions were classified following an exhaustive allergological evaluation for severity and trigger. Sera samples were analysed using untargeted metabolomics combining liquid chromatography coupled to mass spectrometry (LC-MS) and proton nuclear magnetic resonance spectroscopy (1 H-NMR). RESULTS: 'Food T1 vs T2' and 'moderate T1 vs T2' anaphylaxis comparisons showed clear metabolic patterns during the onset of an anaphylactic reaction, which differed from those induced by drugs, food + drug or severe anaphylaxis. Moreover, the model of food anaphylaxis was able to distinguish the well-characterized IgE (antibiotics) from non-IgE-mediated anaphylaxis (nonsteroidal anti-inflammatory drugs), suggesting a differential metabolic pathway associated with the mechanism of action. Metabolic differences between 'moderate vs severe' at the acute phase T1 and at basal state T0 were studied. Among the altered metabolites, glucose, lipids, cortisol, betaine and oleamide were observed altered. CONCLUSIONS: The results of this exploratory study provide the first evidence that different anaphylactic triggers or severity induce differential metabolic changes along time or at specific time-point, respectively. Besides, the basal status T0 might identify high-risk patients, thus opening new ways to understand, diagnose and treat anaphylaxis.

Mild Muscle Mitochondrial Fusion Distress Extends Drosophila Lifespan through an Early and Systemic Metabolome Reorganization.

In a global aging population, it is important to understand the factors affecting systemic aging and lifespan. Mitohormesis, an adaptive response caused by different insults affecting the mitochondrial network, triggers a response from the nuclear genome inducing several pathways that promote longevity and metabolic health. Understanding the role of mitochondrial function during the aging process could help biomarker identification and the development of novel strategies for healthy aging. Herein, we interfered the muscle expression of the Drosophila genes Marf and Opa1, two genes that encode for proteins promoting mitochondrial fusion, orthologues of human MFN2 and OPA1. Silencing of Marf and Opa1 in muscle increases lifespan, improves locomotor capacities in the long term, and maintains muscular integrity. A metabolomic analysis revealed that muscle down-regulation of Marf and Opa1 promotes a non-autonomous systemic metabolome reorganization, mainly affecting metabolites involved in the energetic homeostasis: carbohydrates, lipids and aminoacids. Interestingly, the differences are consistently more evident in younger flies, implying that there may exist an anticipative adaptation mediating the protective changes at the older age. We demonstrate that mild mitochondrial muscle disturbance plays an important role in Drosophila fitness and reveals metabolic connections between tissues. This study opens new avenues to explore the link of mitochondrial dynamics and inter-organ communication, as well as their relationship with muscle-related pathologies, or in which muscle aging is a risk factor for their appearance. Our results suggest that early intervention in muscle may prevent sarcopenia and promote healthy aging.

Psychometric properties of instruments measuring quality and satisfaction in mental health: A systematic review.

AIM: To identify the methodological quality of each study and analyse the psychometric properties of instruments measuring quality and satisfaction with care from the perspective of mental health patients and professionals. BACKGROUND: In recent years, interest in rigorously assessing quality of care in mental health and nursing has increased. Health professionals and researchers should select the most adequate instrument based on knowledge of its measurement properties. REVIEW DESIGN: A psychometric review was conducted of the instruments from the perspectives of both patients and professionals according to the COnsensus-based Standards for the selection of health Measurement INstruments panel (COSMIN). DATA SOURCES: Articles published from January 2005 - September 2016 were identified in a search of MEDLINE, CINAHL, and SCOPUS. We included studies in English, Spanish, and Portuguese. REVIEW METHODS: Inclusion criteria were applied to all articles validated and reviewed by a second independent reviewer. The analysis included the use of the COSMIN checklist and the Terwee quality criteria. RESULTS: In the 34 studies selected, a total of 22 instruments which measure quality and satisfaction with care provided, according to patients and/or professionals, were identified. Most are instruments with sound, contemporary theoretical foundations. They vary to the extent to which they have been used in empirical studies and with respect to evaluation of their validity and reliability, although five instruments stand out as yielding good-excellent values in quality criteria. CONCLUSION: The present psychometric review found that five of the instruments met valid psychometric criteria. In light of the current economic situation, future reviews should include analysis of the usefulness of instruments based on cost-effectiveness, acceptability, and educational impact.

Distributions and determinants of urinary biomarkers of organophosphate pesticide exposure in a prospective Spanish birth cohort study.

BACKGROUND: Prenatal exposure to organophosphate pesticides (OPs) has been associated with impaired child development. Pesticide exposure determinants need to be studied in order to identify sources and pathways of pesticide exposure. The aim of this paper is to describe prenatal exposure to OPs and evaluate the associated factors in pregnant women. METHODS: The study population consisted of pregnant women (n = 573) who participated in the INMA birth cohort study in Valencia (Spain, 2003-2006). OP metabolites were analyzed in maternal urine at the 32nd week of gestation using a liquid chromatography-high resolution mass spectrometry method. The analysis included non-specific (diethyl phosphate [DEP], diethyl thiophosphate [DETP], dimethyl thiophosphate [DMTP], dimethyl dithiophosphate [DMDTP]) and specific metabolites (2-diethylamino-6-methyl-4-pyrimidinol [DEAMPY], 2-isopropyl-4-methyl-6-hydroxypyrimidine [IMPY], para-nitrophenol [PNP], and 3,5,6-trichloro-2-pyridinol [TCPY]). Information about the sociodemographic, environmental, and dietary characteristics was obtained by questionnaire. The association between log-transformed OPs and covariates was analyzed using multivariable interval censored regression. RESULTS: The detection frequencies were low, DMTP and TCPY being the most frequently detected metabolites (53.8% and 39.1%, respectively). All the OP metabolites were positively associated with maternal intake of fruits and vegetables. Other maternal characteristics related to the OPs were body mass index (BMI) before pregnancy and smoking habit during pregnancy. Women with lower BMI and those who did not smoke presented higher OP concentrations. Moreover, mothers who had a yard or garden with plants at home or who lived in an urban area were also more exposed to OPs. CONCLUSIONS: The OP detection frequencies and the concentrations observed in our study population were low, compared with most of the previously published studies. Given the high vulnerability of the fetus to neurotoxicant exposure, further research on the determinants of the body burden of OPs during pregnancy would be necessary. The knowledge gained from such studies would enhance the effectiveness of public health control and future recommendations in order to reduce the risk to both the health of pregnant women and the health and development of their children.

Echographic features and perinatal outcomes in fetuses with congenital absence of ductus venosus.

INTRODUCTION: The purpose of this study was to describe the echographic features and perinatal outcomes of fetuses with absence of ductus venosus. MATERIAL AND METHODS: Retrospective review of 10 cases with absence of ductus venosus diagnosed by prenatal ultrasonography between January 2014 and February 2016 at a single referral center. Prenatal findings, umbilical shunting type, perinatal outcomes, and autopsy reports were reviewed. RESULTS: A total of 11 491 fetuses underwent a first- and second-trimester screening during the study period. Ten cases of absence of ductus venosus were diagnosed. All of the fetuses presented an extrahepatic shunt: three fetuses from the umbilical vein to the right atrium and the seven remaining fetuses from the umbilical vein to the inferior vena cava. Major structural defects and fetal effusions were detected in six fetuses. There were two cases of chromosomal abnormalities. Five patients underwent legal termination of pregnancy and five decided to carry to term. In two of these, the absence of ductus venosus anomaly was isolated and had a normal outcome. In the remaining three cases, a follow up of the children showed a variety of adverse outcomes. CONCLUSIONS: The absence of ductus venosus is associated with high rates of adverse perinatal outcomes. The prognosis for this group of anomalies depends on the additional findings with targeted ultrasound. This pathology should lead to a detailed anatomical study and affected fetuses should be closely monitored for signs of congestive heart failure.

Biomonitoring exposure assessment to contemporary pesticides in a school children population of Spain.

The exposure to pesticides amongst school-aged children (6-11 years old) was assessed in this study. One hundred twenty-five volunteer children were selected from two public schools located in an agricultural and in an urban area of Valencia Region, Spain. Twenty pesticide metabolites were analyzed in children's urine as biomarkers of exposure to organophosphate (OP) insecticides, synthetic pyrethroid insecticides, and herbicides. These data were combined with a survey to evaluate the main predictors of pesticide exposure in the children's population. A total of 15 metabolites were present in the urine samples with detection frequencies (DF) ranging from 5% to 86%. The most frequently detected metabolites with DF>53%, were 3,5,6-trichloro-2-pyridinol (TCPy, metabolite of chlorpyrifos), diethyl phosphate (DEP, generic metabolite of OP insecticides), 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMPY, metabolite of diazinon) and para-nitrophenol (PNP, metabolite of parathion and methyl parathion). The calculated geometric means ranged from 0.47 to 3.36 µg/g creatinine, with TCPy and IMPY showing the higher mean concentrations. Statistical significant differences were found between exposure subgroups (Mann-Whitney test, p<0.05) for TCPy, DEP, and IMPY. Children living in the agricultural area had significantly higher concentrations of DEP than those living in the urban area. In contrast, children aged 6-8 years from the urban area, showed statistically higher IMPY levels than those from agricultural area. Higher levels of TCPy were also found in children with high consumption of vegetables and higher levels of DEP in children whose parents did not have university degree studies. The multivariable regression analysis showed that age, vegetable consumption, and residential use of pesticides were predictors of exposure for TCPy, and IMPY; whereas location and vegetable consumption were factors associated with DEP concentrations. Creatinine concentrations were the most important predictors of urinary TCPy and PNP metabolites.

Brain areas lipidomics in female transgenic mouse model of Alzheimer's disease.

Lipids are the major component of the brain with important structural and functional properties. Lipid disruption could play a relevant role in Alzheimer's disease (AD). Some brain lipidomic studies showed significant differences compared to controls, but few studies have focused on different brain areas related to AD. Furthermore, AD is more prevalent in females, but there is a lack of studies focusing on this sex. This work aims to perform a lipidomic study in selected brain areas (cerebellum, amygdala, hippocampus, entire cortex) from wild-type (WT, n = 10) and APPswe/PS1dE9 transgenic (TG, n = 10) female mice of 5 months of age, as a model of early AD, to identify alterations in lipid composition. A lipidomic mass spectrometry-based method was optimized and applied to brain tissue. As result, some lipids showed statistically significant differences between mice groups in cerebellum (n = 68), amygdala (n = 49), hippocampus (n = 48), and the cortex (n = 22). In addition, some lipids (n = 15) from the glycerolipid, phospholipid, and sphingolipid families were statistically significant in several brain areas simultaneously between WT and TG. A selection of lipid variables was made to develop a multivariate approach to assess their discriminant potential, showing high diagnostic indexes, especially in cerebellum and amygdala (sensitivity 70-100%, sensibility 80-100%).

Glucose 6 phosphate dehydrogenase overexpression rescues the loss of cognition in the double transgenic APP/PS1 mouse model of Alzheimer's disease.

Mice models of Alzheimer's disease (APP/PS1) typically experience cognitive decline with age. G6PD overexpressing mice (G6PD-Tg) exhibit better protection from age-associated functional decline including improvements in metabolic and muscle functions as well as reduced frailty compared to their wild-type counterparts. Importantly G6PD-Tg mice show diminished accumulation of DNA oxidation in the brain at different ages in both males and females. To further explore the potential benefits of modulating the G6PD activity in neurodegenerative diseases, triple transgenic mice (3xTg G6PD) were generated, overexpressing APP, PSEN1, and G6PD genes. The cognitive decline characteristic of APP/PS1 mice was prevented in 3xTg G6PD mice, despite similar amyloid-ß (Aß) levels in the hippocampus. This challenges the dominant hypothesis in Alzheimer's disease (AD) etiology and the majority of therapeutic efforts in the field, based on the notion that Aß is pivotal in cognitive preservation. Notably, the antioxidant properties of G6PD led to a decrease in oxidative stress parameters, such as improved GSH/GSSG and GSH/CysSSG ratios, without major changes in oxidative damage markers. Additionally, metabolic changes in 3xTg G6PD mice increased brain energy status, countering the hypometabolism observed in Alzheimer's models. Remarkably, a higher respiratory exchange ratio suggested increased carbohydrate utilization. The relative failures of Aß-targeted clinical trials have raised significant skepticism on the amyloid cascade hypothesis and whether the development of Alzheimer's drugs has followed the correct path. Our findings highlight the significance of targeting glucose-metabolizing enzymes rather than solely focusing on Aß in Alzheimer's research, advocating for a deeper exploration of glucose metabolism's role in cognitive preservation.

Effect of providing citrus pulp-integrated diet on fecal microbiota and serum and fecal metabolome shifts in crossbred pigs.

The study aimed to assess the impact of dehydrated citrus pulp (DCP) on growth performance, fecal characteristics, fecal bacterial composition (based on 16S rRNA analysis), and fecal and serum metabolomic profiles in crossbred pigs. 80 finishing pigs Duroc × (Landrace × Large White) were fed either a control diet (C) or a diet with 240 g/kg DCP (T) for six weeks. Including DCP in diets tended to decrease feed intake, increased (p < 0.05) the concentrations of acetic and heptanoic acids and decreased (p < 0.05) fecal butyric and branched-chain fatty acid concentrations in feces. Animals fed DCP exhibited a lower abundance of the genera Clostridium and Romboutsia, while Lachnospira significantly increased. Orthogonal partial least squares discriminant analysis plotted a clear separation of fecal and serum metabolites between groups. The main discriminant fecal metabolites were associated with bacterial protein fermentation and were downregulated in T-fed pigs. In serum, DCP supplementation upregulated metabolites related to protein and fatty acids metabolism. In conclusion, the addition of DCP as an environmentally friendly source of nutrients in pig diets, resulted in modifications of fecal bacterial composition, fermentation patterns, and overall pig metabolism, suggesting improvements in protein metabolism and gut health.

Impact of perceived discrimination and coping strategies on well-being and mental health in newly-arrived migrants in Spain.

OBJECTIVES: To explore how perceived discrimination impacts the emotional well-being and mental health of newly-arrived migrants in Spain; and to identify the coping strategies and behavioral changes used to deal with perceived discrimination. DESIGN: 102 individual audio-recorded in-depth qualitative interviews were conducted. The interviews were transcribed and analyzed through content analysis. RESULTS: Negative emotions related to perceived discrimination included disgust, sadness, fear, loneliness, humiliation, sense of injustice, rage, feeling undervalued or vulnerable, and mixed emotions. Change in behaviors due to perceived discrimination comprised westernization or cultural assimilation, creating a good image, avoiding going out or leaving alone, hypervigilance, stop participating in politics, self-sufficiency, a positive adaptation, and paradoxically, becoming an oppressor. The identified coping strategies to deal with perceived discrimination were ignoring or not responding, isolation, self-medication, engagement in intellectual activities, leisure and sport, talking or insulting the oppressor, denouncement, physical fight or revenge, seeking comfort, increasing solidarity with others, crying, or using humor. Discrimination-related stress and related mental health problems were conveyed, as challenges related to substance abuse and addictive behaviors, mood, and anxiety. CONCLUSIONS: Findings establish initial evidence of the great impact of perceived discrimination on the health, emotional well-being, and behavior of newly-arrived migrants in Spain, alerting to the need for targeted policies and services to address the effects of discrimination in this population. Further research is needed to explore more closely the causes and effects of perceived discrimination on mental health, to develop more targeted and effective interventions.

The imperative for metrics in training.

A twenty-first century model for the training and assessment of cardiac interventionists' skills, outlined by Prof. John Morgan FRCP FESC.

Plasma Lipidomics Approach in Early and Specific Alzheimer's Disease Diagnosis.

BACKGROUND: The brain is rich in lipid content, so a physiopathological pathway in Alzheimer's disease (AD) could be related to lipid metabolism impairment. The study of lipid profiles in plasma samples could help in the identification of early AD changes and new potential biomarkers. METHODS: An untargeted lipidomic analysis was carried out in plasma samples from preclinical AD (n = 11), mild cognitive impairment-AD (MCI-AD) (n = 31), and healthy (n = 20) participants. Variables were identified by means of two complementary methods, and lipid families' profiles were studied. Then, a targeted analysis was carried out for some identified lipids. RESULTS: Statistically significant differences were obtained for the diglycerol (DG), lysophosphatidylethanolamine (LPE), lysophosphatidylcholine (LPC), monoglyceride (MG), and sphingomyelin (SM) families as well as for monounsaturated (MUFAs) lipids, among the participant groups. In addition, statistically significant differences in the levels of lipid families (ceramides (Cer), LPE, LPC, MG, and SM) were observed between the preclinical AD and healthy groups, while statistically significant differences in the levels of DG, MG, and PE were observed between the MCI-AD and healthy groups. In addition, 18:1 LPE showed statistically significant differences in the targeted analysis between early AD (preclinical and MCI) and healthy participants. CONCLUSION: The different plasma lipid profiles could be useful in the early and minimally invasive detection of AD. Among the lipid families, relevant results were obtained from DGs, LPEs, LPCs, MGs, and SMs. Specifically, MGs could be potentially useful in AD detection; while LPEs, LPCs, and SM seem to be more related to the preclinical stage, while DGs are more related to the MCI stage. Specifically, 18:1 LPE showed a potential utility as an AD biomarker.

The metabolomic differential plasma profile between dialysates. Pursuing to understand the mechanisms of citrate dialysate clinical benefits.

Background: Currently, bicarbonate-based dialysate needs a buffer to prevent precipitation of bicarbonate salts with the bivalent cations, and acetate at 3-4 mmol/L is the most used. However, citrate is being postulated as a preferred option because of its association with better clinical results by poorly understood mechanisms. In that sense, this hypothesis-generating study aims to identify potential metabolites that could biologically explain these improvements found in patients using citrate dialysate. Methods: A unicentric, cross-over, prospective untargeted metabolomics study was designed to analyze the differences between two dialysates only differing in their buffer, one containing 4 mmol/L of acetate (AD) and the other 1 mmol/L of citrate (CD). Blood samples were collected in four moments (i.e., pre-, mid-, post-, and 30-min-post-dialysis) and analyzed in an untargeted metabolomics approach based on UPLC-Q-ToF mass spectrometry. Results: The 31 most discriminant metabolomic variables from the plasma samples of the 21 participants screened by their potential clinical implications show that, after dialysis with CD, some uremic toxins appear to be better cleared, the lysine degradation pathway is affected, and branched-chain amino acids post-dialysis levels are 9-10 times higher than with AD; and, on its part, dialysis with AD affects acylcarnitine clearance. Conclusion: Although most metabolic changes seen in this study could be attributable to the dialysis treatment itself, this study successfully identifies some metabolic variables that differ between CD and AD, which raise new hypotheses that may unveil the mechanisms involved in the clinical improvements observed with citrate in future research.

Factors Associated with Depression and Anxiety Symptoms among Migrant Population in Spain during the COVID-19 Pandemic.

Migrants are likely to experience mental health conditions, being one of the most vulnerable groups during the COVID-19 pandemic. The present study aims to: (1) estimate the prevalence of depressive and anxious symptoms and (2) examine the impact of risk and protective factors on this symptomatology. A sample of 129 migrants living in Spain during the COVID-19 pandemic completed an anonymous online survey, including information on sociodemographic and individual characteristics, migration, basic needs, social environment and perceived health domains. Multiple Poisson regression models analysed the effects of risk and protective factors on depression and anxiety symptoms. The prevalence of depressive and anxiety symptoms was 22.3% and 21.4%, respectively. Risk factors such as living in a rented house and previous mental health conditions were associated with higher depression symptoms, whereas unemployment was related to anxiety symptoms. Conversely, older age, better self-esteem, and higher levels of social support were associated with fewer depression symptoms. Older age and better quality of life were related to fewer anxiety symptoms. These findings addressing risk and protective factors (e.g., social support, self-esteem) help to design culturally effective programs, particularly in migrants with pre-existing mental health conditions, adjusting the organisation of mental healthcare services in difficult times in Spain.