Double versus single stimulation in young low prognosis patients followed by a fresh embryo transfer: a randomized controlled trial (DUOSTIM-fresh).

STUDY QUESTION: Does double stimulation, followed by a fresh embryo transfer (DUOSTIM fresh) give a higher number of good-quality blastocysts as compared with a single stimulation in young low prognosis patients? SUMMARY ANSWER: Compared to single stimulation, DUOSTIM fresh leads to a significantly higher number of good quality blastocysts, without hindering fresh embryo transfer outcomes. WHAT IS KNOWN ALREADY: DUOSTIM (ovarian stimulation both in the follicular and luteal phase of the same cycle) is an innovative strategy to retrieve a higher number of oocytes in a shorter time frame, thus it is particularly appealing for poor ovarian responders. Three current limitations of dual stimulation are: (i) it is unclear whether outcomes of the second (luteal) wave result from the second stimulation, or a carry-over effect from previous follicular stimulation; (ii) the desynchronization between endometrium and ovaries and, (iii) lack of robust evidence. No previous studies explored DUOSTIM starting from the luteal phase, and with a fresh embryo transfer (DUOSTIM fresh). STUDY DESIGN, SIZE, DURATION: This study is a randomized, controlled, single-center, superiority clinical trial comparing two different ovarian stimulation protocols: a double stimulation cycle versus a single stimulation cycle followed by fresh embryo transfer. The primary outcome was the number of good quality blastocysts obtained, while secondary outcomes included results from fresh embryo transfer (clinical pregnancy, miscarriage). A total of 120 women were enrolled in this study between October 2020 and October 2022, with a 1:1 allocation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Only young (<40 years old) low prognosis (anti-Müllerian hormone <1.2 ng/ml) patients were recruited in the Reproductive Medicine Department of Dexeus University Hospital. In the investigational group, DUOSTIM fresh, the first stimulation was initiated in the luteal phase (Day 18-21 cycle) followed by a second stimulation 5 days post first oocyte retrieval, initiated in the follicular phase and a fresh embryo transfer of the best blastocyst generated (first or second cycle). The control group performed a follicular phase single stimulation cycle with a fresh embryo transfer. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 107 patients were analyzed, 53 in the investigational (DUOSTIM fresh) and 54 in the control arm (single stimulation). DUOSTIM fresh resulted in a significantly higher number of good quality blastocysts as compared to single stimulation (difference of mean 0.81, 95% CI 0.12-1.49). The mean percentage of cycles with embryo transfer was comparable (62.3% and 51.9%, respectively for double versus single stimulation). No significant differences were found for clinical outcomes following fresh embryo transfer with an ongoing pregnancy rate of 24.5% for DUOSTIM fresh versus 22.2%, for conventional IVF. Of interest comparisons between different stimulation cycles (A: luteal-phase DUOSTIM fresh, B: follicular-phase DUOSTIM fresh, and C: single stimulation) did not demonstrate any significant difference in terms of ovarian response with the mean (SD) number of mature oocytes being (A: 3.3 (2.9), B: 3.4 (3.4), and C: 3.5 (2.9), respectively). LIMITATIONS, REASONS FOR CAUTION: Study sample size was calculated to detect differences on the mean number of good quality blastocysts. Therefore, results for secondary outcomes (embryo transfer rates and clinical pregnancy rates) should be interpreted with caution as exploratory findings that deserve future investigations. WIDER IMPLICATIONS OF THE FINDINGS: Although DUOSTIM fresh results in a higher number of blastocysts as compared with a single stimulation in young low prognosis patients, the decision of performing dual stim should be evaluated with caution, considering that whether this may improve embryo transfers rate and pregnancy outcomes is still unclear. Results on cumulative-live-birth-rate are warranted. STUDY FUNDING/COMPETING INTEREST(S): The study was an investigator-initiated study supported by an unrestricted grant by Organon. N.P.P. has received grants from Merck Serono, Organon, Ferring Pharmaceutical, Theramex, and Besins Healthcare. N.P.P. has received consulting fees from Merck Serono, Organon, Besins Healthcare, and IBSA. N.P.P. has received honoraria for lectures from Merck Serono, Organon, Theramex, Roche Diagnostics, IBSA, Besins Healthcare, and Ferring. A.R. has received Research grants, honoraria for lectures from Merck Serono, MSD/Organon, Ferring Pharmaceuticals, Besins International, IBSA, Guerbet. The other authors declare that there is no conflict of interest to disclose with respect to the content of this article. TRIAL REGISTRATIO NUMBER: NCT04446845. TRIAL REGISTRATION DATE: 25 June 2020. DATE OF FIRST PATIENT'S ENROLMENT: 30 October 2020.

A new method based on dispersive solid phase microextraction with commercial MOFs coupled to LC-MS/MS for the determination of isoflavones in soy drinks.

For the first time, a method based on dispersive solid phase microextraction (D-µSPE) using commercial metal-organic frameworks coupled to liquid chromatography-triple quadrupole tandem mass spectrometry (LC-MS/MS) has been proposed for the determination of isoflavones in soy drinks. The use of commercial sorbents simplifies the sample treatment procedure and allows their application to routine analysis. Optimization of the parameters involved in the microextraction process was carried out using a Box-Behnken experimental design. Under the optimized conditions, the limits of detection ranged between 2 and 7 µg L-1; the intra-day and inter-day precision were <10 and 20%, respectively, and the recoveries were in the range of 61-120%. No significant matrix effect was found, which allowed the use of external standard calibration method. The method was successfully applied to the determination of isoflavones in commercial soy milk samples.

CardioHotspots: a database of mutational hotspots for cardiac disorders.

Mutational hotspots are DNA regions with an abnormally high frequency of genetic variants. Identifying whether a variant is located in a mutational hotspot is critical for determining the variant's role in disorder predisposition, development, and treatment response. Despite their significance, current databases on mutational hotspots are limited to the oncology domain. However, identifying mutational hotspots is critical for any disorder in which genetics plays a role. This is true for the world's leading cause of death: cardiac disorders. In this work, we present CardioHotspots, a literature-based database of manually curated hotspots for cardiac diseases. This is the only database we know of that provides high-quality and easily accessible information about hotspots associated with cardiac disorders. CardioHotspots is publicly accessible via a web-based platform (https://genomics-hub.pros.dsic.upv.es:3099/). Database URL: https://genomics-hub.pros.dsic.upv.es:3099/.

Analysis of SIRT1 genetic variants in young Mexican individuals: relationships with overweight and obesity.

The high prevalence of obesity in Mexico starting from the early stages of life is concerning and represents a major public health problem. Genetic association studies have reported that single nucleotide variants (SNVs) in SIRT1, an NAD+-dependent deacetylase that plays an important role in the regulation of metabolic cellular functions, are associated with multiple metabolic disorders and the risk of obesity. In the present study, we analyzed the effect that the SNVs rs1467568 and rs7895833 of the SIRT1 gene may have on cardiometabolic risk factors in a young adult population from Mexico. A cross-sectional study was carried out with young adults between the ages of 18 and 25 who had a body mass index (BMI) greater than 18.5 kg/m2. This study included 1122 young adults who were classified into the normal weight (n = 731), overweight group (n = 277), and obesity group (n = 114) according to BMI of whom 405 and 404 volunteers were genotyped for rs1467568 and rs7895833 respectively using TaqMan probes through allelic discrimination assays. We found that the male sex carrying the G allele of rs7895833 had slightly lower BMI levels (p = 0.009). Furthermore, subjects carrying rs1467568 (G allele) showed a 34% lower probability of presenting with hyperbetalipoproteinemia where female carrying rs1467568 had lower levels of total cholesterol (p = 0.030), triglycerides (p = 0.026) and LDL cholesterol (p = 0.013). In conclusion, these findings suggest that the presence of both SNVs could have a non-risk effect against dyslipidemia in the Mexican population.

Impact of mediterranean diet promotion on environmental sustainability: a longitudinal analysis.

OBJECTIVE: This article aims to estimate the differences in environmental impact (greenhouse gas [GHG] emissions, land use, energy used, acidification and potential eutrophication) after one year of promoting a Mediterranean diet (MD). METHODS: Baseline and 1-year follow-up data from 5800 participants in the PREDIMED-Plus study were used. Each participant's food intake was estimated using validated semi-quantitative food frequency questionnaires, and the adherence to MD using the Dietary Score. The influence of diet on environmental impact was assessed through the EAT-Lancet Commission tables. The influence of diet on environmental impact was assessed through the EAT-Lancet Commission tables. The association between MD adherence and its environmental impact was calculated using adjusted multivariate linear regression models. RESULTS: After one year of intervention, the kcal/day consumed was significantly reduced (-125,1 kcal/day), adherence to a MD pattern was improved (+0,9) and the environmental impact due to the diet was significantly reduced (GHG: -361 g/CO2-eq; Acidification:-11,5 g SO2-eq; Eutrophication:-4,7 g PO4-eq; Energy use:-842,7 kJ; and Land use:-2,2 m2). Higher adherence to MD (high vs. low) was significantly associated with lower environmental impact both at baseline and one year follow-up. Meat products had the greatest environmental impact in all the factors analysed, both at baseline and at one-year follow-up, in spite of the reduction observed in their consumption. CONCLUSIONS: A program promoting a MD, after one year of intervention, significantly reduced the environmental impact in all the factors analysed. Meat products had the greatest environmental impact in all the dimensions analysed.

Relationship between diabetic peripheral neuropathy and adherence to the Mediterranean diet in patients with type 2 diabetes mellitus: an observational study.

PURPOSE: The main study goal is to assess the relationship between adherence to the mediterranean diet (MD) and the presence of diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (T2DM). METHODS: Observational pilot study of 174 patients diagnosed with T2DM. Sociodemographic and anthropometric variables, physical activity, smoking habits, blood biochemical parameters and comorbidities were recorded. The presence of alterations in sensitivity to pressure, pain, thermal and vibration was explored. Good MD adherence was a score ≥ 9 the 14-point MD adherence questionnaire (MEDAS-14). RESULTS: The study population consisted of 174 patients (61.5% men and 38.5% women), with a mean age of 69.56 ± 8.86 years; 19% of these patients adhered to the MD. The score obtained in the MEDAS-14 was higher in patients who did not present alterations in sensitivity to pressure (p = 0.047) or vibration (p = 0.021). The patients without diabetic peripheral neuropathy were more likely to comply with the MD and had a higher score on the MEDAS-14 (p = 0.047). However, multivariate analysis showed that only altered sensitivity to pressure was associated with adherence to the MD (altered sensitivity OR = 2.9; 95%CI 1.02-8.22; p = 0.045). CONCLUSIONS: Although the patients with DPN had lower scores on the MEDAS questionnaire and therefore poorer adherence to the mediterranean diet, the only parameter significantly associated with the MD was that of sensitivity to pressure (monofilament test).

The consequences of data dispersion in genomics: a comparative analysis of data sources for precision medicine.

BACKGROUND: Genomics-based clinical diagnosis has emerged as a novel medical approach to improve diagnosis and treatment. However, advances in sequencing techniques have increased the generation of genomics data dramatically. This has led to several data management problems, one of which is data dispersion (i.e., genomics data is scattered across hundreds of data repositories). In this context, geneticists try to remediate the above-mentioned problem by limiting the scope of their work to a single data source they know and trust. This work has studied the consequences of focusing on a single data source rather than considering the many different existing genomics data sources. METHODS: The analysis is based on the data associated with two groups of disorders (i.e., oncology and cardiology) accessible from six well-known genomic data sources (i.e., ClinVar, Ensembl, GWAS Catalog, LOVD, CIViC, and CardioDB). Two dimensions have been considered in this analysis, namely, completeness and concordance. Completeness has been evaluated at two levels. First, by analyzing the information provided by each data source with regard to a conceptual schema data model (i.e., the schema level). Second, by analyzing the DNA variations provided by each data source as related to any of the disorders selected (i.e., the data level). Concordance has been evaluated by comparing the consensus among the data sources regarding the clinical relevance of each variation and disorder. RESULTS: The data sources with the highest completeness at the schema level are ClinVar, Ensembl, and CIViC. ClinVar has the highest completeness at the data level data source for the oncology and cardiology disorders. However, there are clinically relevant variations that are exclusive to other data sources, and they must be considered in order to provide the best clinical diagnosis. Although the information available in the data sources is predominantly concordant, discordance among the analyzed data exist. This can lead to inaccurate diagnoses. CONCLUSION: Precision medicine analyses using a single genomics data source leads to incomplete results. Also, there are concordance problems that threaten the correctness of the genomics-based diagnosis results.

Prevalence and severity of molar-incisor hypomineralization, is there an association with socioeconomic status? A cross-sectional study in Chilean schoolchildren.

PURPOSE: Data about molar-incisor hypomineralization (MIH) prevalence and its severity remains limited for some Latin American countries. Furthermore, its association with socioeconomic status (SES) is still unclear. Thus, this study aims to determine the prevalence and severity of MIH in Santiago, Chile and explore its association with SES. METHODS: A cross-sectional study with schoolchildren between 6 and 12 years was conducted. Children were evaluated using the European Academy of Paediatric Dentistry to diagnose MIH, and the Mathu-Muju and Wright criteria to determine its severity. RESULTS: A total of 1,270 children were included. The MIH prevalence was 12.8% without association with gender (p = 0.609). Prevalence was higher among schoolchildren ages 8 and 9 (p = 0.002), and in lower SES (p = 0.007). MIH mild cases were the most prevalent (63%), and severity was not related to gender (p = 0.656), age (p = 0.060), or SES (p = 0.174). CONCLUSIONS: The prevalence of MIH in the province of Santiago, Chile is 12.8% and was found to have a higher incidence in 8-9-year-old students and among those categorized by low SES. Furthermore, MIH prevalence was associated with low SES. IMPLICATIONS: Public health policies to address MIH in Chile should start with schoolchildren aged 8 to 9, and with low SES.

Anaesthetic management of thyroid storm in a patient with Friederich's ataxia. A case report.

A 26-year-old patient with Friederich's ataxia with hypertrophic obstructive cardiomyopathy undergoing total thyroidectomy due to persistent amiodarone-induced thyrotoxicosis (despite high doses of antithyroid drugs and corticosteroids), presented an intraoperative episode suggestive of thyroid storm. Thyroid storm is an endocrine emergency that is associated with high morbidity and mortality. Early diagnosis and treatment, which is of vital importance to improve survival, includes symptomatic treatment, treatment of cardiovascular, neurological, and/or hepatic manifestations and thyrotoxicosis, measures to suppress or avoid triggering stimuli, and definitive treatment.

Glycemia and associated factors in a pediatric population in Mexico.

Aims: In this study, we evaluated the association of sociodemographic, lifestyle and cardiometabolic factors with blood glucose levels in children and adolescents in Mexico. Methods: An analytical cross-sectional study of 642 children and adolescents aged 6 to 19 years from different educational centers located in municipalities of the state of San Luis Potosí, Mexico, was carried out. Pearson χ2 and Spearman correlation tests and multiple linear regression models were used to evaluate the associations of the variables with glycemia. Results: The prevalence of prediabetes was 8.0% in both sexes. Male participants were more likely to develop hyperglycemia than female participants (OR 2.7, 95% CI: 1.5-5.0). The variables associated with glucose levels were male sex, high socioeconomic status, inadequate diet, high blood pressure, and increased total cholesterol, LDL cholesterol, and triglycerides, which also explained up to 15.6% (p < 0.05) of the variability in glucose concentrations. Conclusion: The detection of sociodemographic, lifestyle and cardiometabolic factors in children and adolescents will contribute to the implementation of prevention strategies for cardiometabolic diseases, among which prediabetes is common.

Evaluation of polycyclic aromatic hydrocarbons in sediments of Balsas River Mouth, Pacific Coast, Mexico: Sources, risks, and genotoxicity.

Polycyclic aromatic hydrocarbons (PAHs) were assessed in sediments (n = 7) collected from the mouth of the Balsas River, Pacific Coast, Mexico. The total PAH levels ranged between 142.1 and 3944.07 µg kg-1 in the summer and 137.65-3967.38 µg kg-1 in the winter, probably reflecting the anthropogenic activities of the region. Calculation of the four analytical ratios of [Anthracene/(Anthracene + Phenanthrene)]: [Fluoranthene/(Fluoranthene + Pyrene)], [Fluoranthene/Pyrene: Fluoranthene/(Fluoranthene + Pyrene)], [Indeno [123-cd]Pyrene/(Indeno [123-cd]Pyrene + Benzo [ghi]Perylene)]: [Benzo [a]anthracene/(Benzo [a]Anthracene + Chrysene)], and [Anthracene/Phenanthrene]: [Fluoranthene/(Fluoranthene + Pyrene)] revealed a mixed PAH source, from petroleum and biomass combustion. Significant statistical correlations (r2 = 0.90) between the 4 and 5 ringed PAHs denote that adsorption is the principal mechanism for accumulation in sedimentary archives. Ecotoxicological indices (Mean Effect Range Medium Quotient and Mean Probable Effect Level Quotient) indicated moderate pollution with adverse biological impacts on ambient benthonic organisms. The calculations of Toxicity Equivalent Quotient and Mutagen Equivalent Quotient values proposed that the region is highly polluted by mutagenic and carcinogenic PAH compounds. The genotoxic evaluation of Lutjanus guttatus (Spotted rose snapper) presented significant DNA damage and discrepancies in Ethoxyresorufin-O-Deethylase activity. Based on the toxicological and genotoxicological evaluation of PAHs in sediments, the region was observed to be largely impacted from biological damage.

The time elapsed between assessments of blood metabolome and live weight affects associations between the abundance of metabolites and growth rate in beef cattle.

INTRODUCTION: This study aimed to assess the associations between the relative abundance (RA) of blood metabolites and growth rate (i.e., live weight change, LWC) calculated using different intervals of time between live weight (LW) measurements from the metabolome assessment. METHODS: Grazing beef cattle were raised for 56 days and blood samples from each animal were taken on day 57. Live weight was continuously measured using an automatic in-paddock weighing scale. The RA of plasma metabolites were determined using proton nuclear magnetic resonance (NMR). Live weight data were filtered for outliers and one LW record was selected every 1, 7, 14, 21, 28, 35, 42, 49 and 56 days before the metabolome assessment (LWC1 to LWC56, respectively). Live weight change was then re-calculated for each interval between LW data selected. RESULTS: Associations between LWC calculations and the RA of metabolites were greatly affected by the interval of time between LW data selected. Thus, the number of significant associations decreased from 9 for LWC1 to 5 for LWC35 whereas no significant associations were found for LWC56 (P > 0.05). There were 7 metabolites negatively associated with LWC1 including leucine, 2-hydroxybutyrate, valine, creatinine, creatine, phenylalanine and methylhistidine; however, correlations were positive for 2 lipids. The strength of the correlation coefficients decreased as the length of the interval between LW measures increased although this reduction was greater for some metabolites such as leucine compared to others such as lipids. Our findings suggest that the time frame in which a particular response variable, such as LWC, is measured and metabolomic samples are taken could largely impact associations and thus conclusions drawn. CONCLUSIONS: Depending on the variable to be explored, rapid changes in cattle metabolome may not be reflected in correlations if they are not assessed close in time. Our findings suggest that LWC should be measured for a period shorter than 28 days before the metabolome assessment as the number of significant associations decreases when LWC is measured for longer periods.

Prognostic utility of pulse pressure in patients with heart failure with preserved ejection fraction: The RICA Registry.

BACKGROUND AND AIMS: The prognostic role of pulse pressure (PP) in heart failure (HF) patients with preserved left ventricular ejection fraction (LVEF) is not well understood. Our aim was to evaluate it in acute and stable HF. MATERIAL AND METHODS: This work is a retrospective observational study of patients included in the RICA registry between 2008 and 2021. Blood pressure was collected on admission (decompensation) and 3 months later on an outpatient basis (stability). Patients were categorized according to whether the PP was greater or less than 50mmHg. All-cause mortality was assessed at 1year after admission. RESULTS: A total of 2291 patients were included, with mean age 80.1±7.7 years. 62.9% were women and 16.7% had a history of coronary heart disease. In the acute phase, there was no difference in mortality according to PP values, but in the stable phase PP<50mmHg was independently associated with all-cause mortality at 1-year follow-up (HR 1.57, 95% CI 1.21-2.05, p=0.001), after adjusting for age, sex, New York Heart Association functional class, previous HF, chronic kidney disease, valvular heart disease, cerebrovascular disease, score on the Barthel and Pfeiffer scales, hemoglobin and sodium levels. CONCLUSIONS: Low stable-phase PP was associated with increased all-cause mortality in HF patients with preserved LVEF. However, PP was not useful as a prognostic marker of mortality in acute HF. Further studies are needed to assess the relationship of this variable with mortality in HF patients.

Impact of a specific consultation for patients with progressive forms of multiple sclerosis on the response to their unmet care needs: a cross-sectional study.

BACKGROUND: As their disease evolves, most patients with progressive forms of multiple sclerosis (MS) develop particular healthcare needs that are not always addressed with usual follow-up. To adapt neurological care to these patients, we created a specific consultation for patients with progressive MS in our centre in 2019. OBJECTIVES: To explore the main unmet care needs of patients with progressive MS in our setting, and to establish the usefulness of the specific consultation to address them. METHODS: Literature review and interviews with patients and healthcare professionals were conducted to identify the main unmet needs in routine follow-up. Two questionnaires were developed, assessing the importance of the unmet needs identified and the usefulness of the consultation to meet them, for patients under follow-up in the specific consultation and their informal caregivers. RESULTS: Forty-one patients and nineteen informal caregivers participated. The most important unmet needs were the information about the disease, access to social services and coordination between specialists. A positive correlation was found between the importance of these unmet needs and the responsiveness to each of them in the specific consultation. CONCLUSIONS: The creation of a specific consultation may improve attention to the healthcare needs of patients with progressive MS.