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Camila Folle,1 Ana M Marqués,2 Natalia Díaz-Garrido,3– 5 Paulina Carvajal-Vidal,1 Elena Sánchez López,1,6 Joaquim Suñer-Carbó,1,6 Lyda Halbaut,1,6 Mireia Mallandrich,1,6 Marta Espina,1,6 Josefa Badia,3– 5 Laura Baldoma,3– 5 Maria Luisa García,1,6 Ana Cristina Calpena1,6 1Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain; 2Department of Biology, Healthcare and Environment, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain; 3Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain; 4Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain; 5Research Institute Sant Joan De Déu (IR‑SJD), Barcelona, Spain; 6Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, Barcelona, SpainCorrespondence: Camila Folle; Elena Sánchez López, Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, 08028, Spain, Email camilafolle@ub.edu; esanchezlopez@ub.eduPurpose: Acne vulgaris is one of the most prevalent dermal disorders affecting skin health and appearance. To date, there is no effective cure for this pathology, and the majority of marketed formulations eliminate both healthy and pathological microbiota. Therefore, hereby we propose the encapsulation of an antimicrobial natural compound (thymol) loaded into lipid nanostructured systems to be topically used against acne.Methods: To address this issue, nanostructured lipid carriers (NLC) capable of encapsulating thymol, a natural compound used for the treatment of acne vulgaris, were developed either using ultrasonication probe or high-pressure homogenization and optimized using 22-star factorial design by analyzing the effect of NLC composition on their physicochemical parameters. These NLC were optimized using a design of experiments approach and were characterized using different physicochemical techniques. Moreover, short-term stability and cell viability using HaCat cells were assessed. Antimicrobial efficacy of the developed NLC was assessed in vitro and ex vivo.Results: NLC encapsulating thymol were developed and optimized and demonstrated a prolonged thymol release. The formulation was dispersed in gels and a screening of several gels was carried out by studying their rheological properties and their skin retention abilities. From them, carbomer demonstrated the capacity to be highly retained in skin tissues, specifically in the epidermis and dermis layers. Moreover, antimicrobial assays against healthy and pathological skin pathogens demonstrated the therapeutic efficacy of thymol-loaded NLC gelling systems since NLC are more efficient in slowly reducing C. acnes viability, but they possess lower antimicrobial activity against S. epidermidis, compared to free thymol.Conclusion: Thymol was successfully loaded into NLC and dispersed in gelling systems, demonstrating that it is a suitable candidate for topical administration against acne vulgaris by eradicating pathogenic bacteria while preserving the healthy skin microbiome. Keywords: lipid nanoparticles, thymol, acne vulgaris, NLC, gels, antimicrobial

STUDY QUESTION Does the use of preimplantation genetic testing for aneuploidies (PGT-A), personalized embryo transfer with endometrial receptivity assay (pET-ERA), or the use of donated oocytes modify the incidence of biochemical pregnancy loss (BPL) in frozen single embryo transfer (FSET)? SUMMARY ANSWER Following FSET, BPL incidence does not differ between own and donated oocytes, and the use of PGT-A with euploid embryo transfer or pET-ERA results in a similar incidence of BPL compared to cycles without embryo or endometrial analysis. WHAT IS KNOWN ALREADY BPL occurs frequently after IVF, and many factors have been associated with its incidence. The etiology of BPL is not well known, but the most probable cause seems to be either a low-quality embryo or impaired endometrial maintenance. The impact of techniques diagnosing embryonic ploidy or endometrial receptivity on BPL incidence and the BPL incidence between own and donated oocytes have not been analyzed. STUDY DESIGN, SIZE, DURATION This is a retrospective cohort study analyzing the incidence of BPL over 3741 cycles of FSET derived from own (2399 cycles) and donated (1342 cycles) oocytes between January 2013 and January 2022 in 1736 of which PGT-A, pET-ERA, or both were applied. PARTICIPANTS/MATERIALS, SETTING, METHODS We defined BPL as a pregnancy diagnosed only by serum β-hCG > 10 UI/l followed by a decrease that does not result in a clinical pregnancy. Clinical pregnancy was defined as the presence of gestational sac on transvaginal ultrasound. We compared BPL rates among patients undergoing 2399 FSETs from own oocytes, which comprised 1310 cycles of embryos analyzed by PGT-A, 950 cycles of untested embryos, 30 cycles of untested embryos with pET-ERA, and a subgroup of 109 cycles analyzed by both PGT-A and pET-ERA. We also included a total of 1342 FSET cycles from donated oocytes comprising 132, 1055, 140, and 15 cycles in the same groups, respectively. MAIN RESULTS AND THE ROLE OF CHANCE In FSET from own oocytes, the overall BPL rate per embryo transfer was 8.2% (95% CI [7.09–9.33]). In untested embryo transfers, the BPL rate was 7.5% [5.91–9.37]. In the PGT-A group, the BPL rate was 8.8% [7.32–10.47]. In the pET-ERA group, the rate was 6.7% [0.82–22.07]. In the PGT-A+ERA group, the rate was 6.5% [2.65–12.90]. No significant differences were found (P =  0.626). A multivariate analysis considering clinically meaningful variables that were significantly different among groups, taking the untested embryos/endometrium group as a reference, showed comparable incidences among groups. For PGT-A, the adjusted odds ratio (AdjOR) was 1.154 [0.768–1.735] (P  =   0.49) and for PGT-A+ERA 0.885 [0.330–2.375] (P =  0.808). Because of a low number of registered cases in the pET-ERA group, and to prevent statistical errors and convergence issues, this group was excluded from further analysis. In FSET of donated oocytes, the overall BPL rate per embryo transfer was 4.9% [3.76–6.14]. In the PGT-A group, the BPL rate was 6.8% [3.16–12.55]. In the pET-ERA group, the rate was 5.0% [2.03–10.03]. In untested embryo transfers, the rate was 4.7% [3.46–6.10]. No cases occurred in the PGT-A+ERA group, and no significant differences were found (P  =   0.578). The multivariate analysis showed comparable incidences among groups. For PGT-A the AdjOR was 1.669 [0.702–3.972] (P =  0.247) and for pET-ERA 1.189 [0.433–3.265] (P  =   0.737). The PGT-A+ERA group was eliminated from the model to prevent statistical errors and convergence issues because no BPL cases were registered in this group. In the multivariate analysis, when the sources of oocytes were compared, own versus donated, no significant differences were found in the incidence of BPL. LIMITATIONS, REASONS FOR CAUTION This was a retrospective cohort study with potential biases. In addition, we were unable to control differences among groups due to modifications in medical or laboratory protocols during this long time period, which may modify the relationships being addressed. Factors previously associated with BPL, such as immunological conditions other than thyroid autoimmunity, were not considered in this study. Limited sample sizes of some groups may limit the statistical power for finding differences that can be present in the general population. WIDER IMPLICATIONS OF THE FINDINGS BPL may be related to a mechanism not associated with the chromosomal constitution of the embryo or the transcriptome of the endometrium. More studies are needed to explore the factors associated with this reproductive issue. STUDY FUNDING/COMPETING INTEREST(S) No specific funding was available for this study. None of the authors have a conflict of interest to declare with regard to this study. TRIAL REGISTRATION NUMBER This trial was registered at clinicaltrials.gov (NCT04549909). [ABSTRACT FROM AUTHOR]

Background Bacteroides fragilis , an anaerobic gut bacterium and opportunistic pathogen, comprises two genetically divergent groups (or divisions) at the species level. Differences exist both in the core and accessory genomes and the beta-lactamase genes, with the cephalosporinase gene cep A represented only in division I and the carbapenemase gene cfi A only in division II. Methods Multidrug resistance in a clinical B. fragilis strain was examined by whole-genome sequencing. Results Strain CNM20200260 carried the antimicrobial resistance genes cep A, cfi A2, ant (6'), erm (F), mef (En2), est (T), tet (Q) and cat (A), along with 82-Phe mutation in gyr A (together with 47 amino acid changes in gyr A/B and par C/parE). bex A/B and other efflux pump genes were also observed. None of the detected insertion sequences was located upstream of cfi A2. The genome-based taxonomy coefficients (average nucleotide identity, DNA–DNA hybridization similarity and difference in genomic G + C%) with respect to genomes of the strains of B. fragilis division II and the novel species Bacteroides hominis (both cfi A-positive) met the criteria for CNM20200260 to belong to either species (>95%, >70% and <1%, respectively). No such similarity was seen with type strain NCTC 9343 or the representative genome FDAARGOS 1225 of B. fragilis (division I, cfi A-negative). Strain CNM20200260 harboured four out of nine Kyoto Encyclopedia of Genes and Genomes orthologues defined for division I and one of two defined for division II. Conclusions This is the first description of the co-occurrence of cep A and cfi A in a Bacteroides strain, confirming the complexity of the taxonomy of this species. [ABSTRACT FROM AUTHOR]

While intensively studied, it remains unclear how the star formation (SF) in infrared dark clouds (IRDCs) compares to that of nearby clouds. We study G351.77-0.53 (henceforth G351), a cluster-forming filamentary IRDC. We begin by characterizing its young stellar object (YSO) content. Based on the average parallax of likely members, we obtain a Gaia distance of |$\sim \, 2.0\pm 0.14$|  kpc, resolving the literature distance ambiguity. Using our Herschel-derived N(H2) map, we measure a total gas mass of 10 200 M⊙ (within 11 pc2) and the average line-mass profile of the entire filament, which we model as |$\lambda =~1660 (w/\rm pc)^{0.62}\, \, {\rm M}_{\odot }\, \rm {pc}^{-1}$|⁠. At w < 0.63 pc, our λ profile is higher and has a steeper power-law index than λ profiles extracted in Orion A and most of its substructures. Based on the YSOs inside the filament area, we estimate the SF efficiency (SFE) and SF rate (SFR). We calculate a factor of 5 incompleteness correction for our YSO catalogue relative to Spitzer surveys of Orion A. The G351 SFE is ∼1.8 times lower than that of Orion A and lower than the median value for local clouds. We measure SFR and gas masses to estimate the efficiency per free-fall time, ϵff. We find that ϵff is ∼1.1 dex below the previously proposed mean local relation, and |$\sim \, 4.7\times$| below Orion A. These observations indicate that local SF-relations do not capture variations present in the Galaxy. We speculate that cloud youth and/or magnetic fields might account for the G351 inefficiency. [ABSTRACT FROM AUTHOR]

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n this paper, we present a family of iterative schemes for solving nonlinear systems with 3 real parameters. If we do not fix values for the parameters this family has order 2, but if we fix two of them we obtain order 5. Starting from the fifth-order family, we study different ways of introducing memory, thus obtaining 6 order methods. We also analyze the efficiency indices of the family and of the methods with memory obtained from it, and we compare them with each other, as well as compare them with other known classes of iterative methods with order 5 and 6. Several numerical experiments are carried out to see the behaviour of the discussed methods, including dynamical planes to compare the stability of the different iterative schemes. [ABSTRACT FROM AUTHOR]

Evaluar mediante [18F]FDG PET/RM los biomarcadores de inflamación inducidos por el VIH basal y un año postratamientos antirretrovirales (TAR). Estudio prospectivo, 14 pacientes, recién diagnosticados de VIH, asintomáticos. Se realizó [18F]FDG PET/RM (PET/MR-3.0 T, Signa™, GE) de cuerpo completo y cardiaco, basal y un año post-TAR. Valoración cualitativa vascular (referencia hepática). Valoración cuantitativa (SUVmáx) de cuerpo completo. Estimación del valor T1 y T2 en 16 segmentos miocárdicos. La resonancia magnética cardíaca (RMC) basal mostró en 3 pacientes (21,4%) una FEVI disminuida, normalizándose post-TAR. Se descartó la presencia de fibrosis (T1), sin signos de edema miocárdico (T2) basal ni post-TAR. En 4 pacientes (28,6%) se evidenció hipercaptación de [18F]FDG vascular basal, 2 en aorta torácica ascendente y 2 en aorta torácica ascendente y descendente, normalizándose post-TAR. Todos los pacientes (100%) mostraron actividad adenopática basal; supra (n:14) e infradiafragmática (n:13), laterocervical (n:14) e inguinal (n:13), variable el número de territorios (9 pacientes > 6; 64,3%). Post-TAR 7 pacientes (50%) mostraron su resolución y los otros 7 reducción en su extensión (0 pacientes > 5): 7 supra (100%) y 2 infradiafragmáticos (28,6%), 5 en axila y 2 en ingle. Todos los pacientes (100%) presentaron captación adenoidea basal persistente post-TAR, 9 (64,3%) esplénica todas resueltas post-TAR y 7 (50,5%) gástrica, persistente 3 post-TAR. Los biomarcadores cardiovasculares mediante [18F]FDG PET/RM han mostrado basalmente un 28,6% de pacientes con actividad en grandes vasos y un 21,4% una baja FEVI, normalizándose post-TAR. Los biomarcadores inflamatorios/inmunes han mostrado actividad basal en un 100% de adenopatías, 100% adenoides, 64,3% esplénica y 50,5% gástrica. Post-TAR la reducción fue del 50% adenopática, 0% adenoidea, 100% esplénica y 57,1% gástrica. To assess by [18F]FDG PET/MR the biomarkers of HIV-induced inflammation at baseline and 1 year post-antiretroviral therapy (ART). Prospective study, 14 patients, newly diagnosed HIV-positive, asymptomatic. [18F]FDG PET/MRI (PET/MR-3.0 T, Signa.GE) whole body and heart was performed, baseline and 1 year post-ART. Qualitative vascular assessment (hepatic reference). Quantitative assessment (SUVmax) of the whole body. T1 and T2 value estimation in 16 myocardial segments. Baseline CMR showed in 3 (21.4%) a decreased LVEF, normalising post-TAR. Fibrosis was ruled out (T1), with no signs of myocardial oedema (T2) at baseline or post-TAR. Four (28.6%) showed baseline vascular [18F]FDG uptake, two in ascending thoracic aorta and two in ascending and descending thoracic aorta, normalising post-TAR. All (100%) showed basal lymph-nodes activity; supra (n:14) and infradiaphragmatic (n:13), laterocervical (n:14) and inguinal (n:13), with variable number of territories (9 patients >6; 64.3%). Post-ART, 7 patients (50%) showed resolution and the other 7 reduction in extension (0 patients >5): 7 supra (100%) and 2 infradiaphragmatic (28.6%), 5 in the axilla and 2 in the groin. All (100%) had persistent basal adenoid uptake post-ART, 9 (64.3%) splenic all resolved post-ART and 7 (50.5%) gastric, persistent 3 post-ART. Cardiovascular biomarkers by [18F]FDG PET/MR have shown baseline 28.6% of patients with large vessel activity and 21.4% with low LVEF, normalising post-ART. Inflammatory/immune biomarkers showed baseline activity in 100% of lymph-nodes, 100% adenoids, 64.3% splenic and 50.5% gastric. Post-TAR the reduction was 50% lymph-nodes, 0% adenoid, 100% splenic and 57.1% gastric. [ABSTRACT FROM AUTHOR]

Muy pocas investigaciones se han realizado sobre los motivantes, destinos, resultados y tendencias de la inversión colombiana en el exterior. Este artículo presenta la estrategia de adquisiciones internacionales que ha tenido el Grupo Empresarial Bavaria en el mercado cervecero de Europa, Panamá, Ecuador y recientemente Perú. Se destaca la reacción estratégica vía inversión extranjera que una empresa colombiana ha tenido que realizar como respuesta a los cambios del entorno internacional.

Kisspeptius, the products of the KISS-1 gene acting via G protein-coupled receptor 54 (GPR54), have recently emerged as pivotal signals in the hypothalamic network triggering the preovulatory surge of gonadotropins and, hence, ovulation. Additional actions of kisspeptins at other levels of the hypothalamic-pituitary-ovarian axis have been suggested but remain to date scarcely studied. We report herein the pattern of expression of KISS-1 and GPR54 in the human and nonhuman primate ovary and evaluate changes in ovarian KiSS-1 expression in a rat model of ovulatory dysfunction. KISS-1 and GPR54 mRNAs were detected in human ovarian tissue and cultured granulosa-lutein cells. In good agreement, kisspeptin immunoreactivity was observed in cyclic human and marmoset ovaries, with prominent signals in the theca layer of growing follicles, corpora lutea, interstitial gland, and ovarian surface epithelium. GPR54 immunoreactivity was also found in human theca and luteal cells. Administration of indomethacin to cyclic female rats disturbed ovulation and resulted in a dramatic drop in ovarian KiSS-1, but not GPR54, cyclooxygenase-2 (COX-2), or progesterone receptor, mRNA levels at the time of ovulation; an effect mimicked by the selective COX-2 inhibitor NS398 and rescued by coadministration of [PGE.sub.2]. Likewise, the stimulatory effect of human choriogonadotropin on ovarian KISS-1 expression was partially blunted by indomethacin. In contrast, KISS-1 mRNA levels remained unaltered in another model of ovulatory failure, i.e., the RU486-treated rat. In summary, we document for the first time the expression of KISS-1/kisspeptin and GPR54 in the human and nonhuman primate ovary. In addition, we provide evidence for the ability of inhibitors of COX-2, known to disturb follicular rupture and ovulation, to selectively alter the expression of KISS-1 gene in rat ovary. Altogether, our results are suggestive of a conserved role of local KISS-1 in the direct control of ovarian functions in mammals. G protein-coupled receptor 54; follicle; ovulation; rat

En este artículo, utilizando una técnica ideada por Thayse, se introduce una generalización del concepto de potenciación reticular y como subproducto se ofrece una presentación más uniforme de aspectos de la estructura reticular de las funciones discretas, incluyendo algunos resultados adicionales.

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Copyright of Avances en Odontoestomatologia is the property of Ediciones Avances SL and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Avances en Odontoestomatologia is the property of Ediciones Avances SL and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Study Question: What is the risk of developing intracavitary fluid (ICF) during ovarian stimulation in patients with an isthmocele after previous caesarean section (CS) delivery?Summary Answer: In patients with an existing isthmocele, the risk of developing ICF during hormonal stimulation for IVF is almost 40%; therefore, special attention has to be paid to exclude fluid accumulation during stimulation and particularly at the time of transfer, in which case the reproductive outcomes of frozen embryo transfer (FET) cycles appear to be uncompromised.What Is Known Already: Lately, there is an increasing focus on the long-term impact of CS delivery on the health and future fertility of the mother. Development of an isthmocele is one of the sequelae of a CS delivery. The presence of ICF in combination with an isthmocele has been described previously, and the adverse effect of endometrial fluid on implantation is well recognised by reproductive medicine specialists. Accumulation of ICF has been previously described in patients with hydrosalpinx, less commonly in patients with polycystic ovary syndrome undergoing ovarian stimulation for IVF/ICSI, and even in some patients without any identifiable reason. Assisted reproductive techniques (ARTs) are a means to overcome infertility. Reproductive medicine specialists commonly see patients with secondary infertility with a history of having had one or more previous CS and with ultrasound confirmation of an isthmocele. However, the available data pertaining to the prevalence of intracavitary fluid during ovarian stimulation in patients with ultrasound confirmation of an isthmocele is limited. Furthermore, data on the influence of ICF in a stimulated cycle on the ART outcome of a subsequent FET cycle is scarce and merits further studies.Study Design, Size, Duration: A prospective observational exploratory study was performed in IVI Middle East Fertility Clinic, Abu Dhabi, from June 2018 to March 2019, and retrospective analysis of the reproductive outcomes was performed until July 2019.Participants/materials, Setting, Methods: Patients with secondary infertility, defined as a minimum of 1 year of infertility after a previous successful pregnancy, undergoing ovarian stimulation for IVF/ICSI and having a history of one or more previous CS with ultrasonographic visible isthmocele, were included (n = 103). Patients were monitored as a clinical routine with vaginal ultrasound examinations during ovarian stimulation for IVF/ICSI treatment. All patients included in the study were asked to complete a questionnaire regarding their previous obstetric history. Development of ICF was recorded as well as changes in the measurements of the isthmocele during the course of ovarian stimulation. Reproductive outcomes of FET cycles of the patients with an isthmocele were retrospectively compared to those of patients with infertility and without isthmocele in our clinic during the same time period.Main Results and the Role Of Chance: Patients with an existing isthmocele after previous CS have a risk of ~40% of developing ultrasonographic visible fluid in the endometrial cavity during the course of ovarian stimulation. Development of ICF was significantly correlated with the depth of the isthmocele on Day 2/3 (P = 0.038) and on the day of trigger (-1/-2 days) (P = 0.049), circumference of the isthmocele on the day of trigger (-1/-2 days) (P = 0.040), distance from the C-scar to the external os (P = 0.036), number of children delivered (P = 0.047) and number of previous CS (P = 0.035). There was a statistically significant increase in the parameters related to the size of the isthmocele during ovarian stimulation. No significant differences in the reproductive outcome (pregnancy rate and rates of biochemical and ectopic pregnancies, miscarriages and ongoing/delivered pregnancies) after FET were found between the patients with and without an isthmocele, when ICF was excluded prior to embryo transfer procedure.Large-scale Data: NA.Limitations, Reasons For Caution: This study was not primarily designed to investigate the causes of ICF during ovarian stimulation or to evaluate the reproductive outcomes. Further, the small number of reported reproductive outcomes may be seen as a limitation.Wider Implications Of the Findings: The data highlights the need for an increased awareness on the part of reproductive medicine specialists towards the potentially adverse impact of an isthmocele on ART treatment, as there is a potential to develop intracavitary fluid during ovarian stimulation for IVF. The increase in the circumference of the isthmocele may increase embryo transfer difficulty.Study Funding/competing Interest(s): No funding of the study has to be reported. The authors have no competing interests.Trial Registration Number: This prospective study was registered with clinicaltrials.gov. under the number NCT03518385. [ABSTRACT FROM AUTHOR]

El fracaso académico en las asignaturas relacionadas con las Matemáticas en la Facultad de Ciencias Empresariales de la Universidad de Huelva es una realidad ampliamente contrastada. La falta de una base sólida para afrontar los nuevos conocimientos, unida a la ausencia de un esfuerzo personal diario y a una aversión generalizada entre nuestros alumnos hacia las Matemáticas, sean quizás las causas principales de esos resultados adversos. Hemos realizado un estudio, mediante un cuestionario elaborado para tal fin y contestado por los alumnos el primer día de clase, sobre los conocimientos matemáticos básicos con los que llegan éstos al primer curso de nuestra Facultad. El objetivo es establecer un marco de actuación adecuado para enfrentarnos a la docencia de nuestras asignaturas e intentar paliar, en lo posible, las carencias del alumnado.

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The valorisation of chicken feathers waste was researched in this work through the preparation of composites using ground chicken feathers as a filler (20% vol/vol) and polypropylene or low-density polyethylene matrices. In order to improve the compatibility between chicken feathers and the matrices, two different strategies were followed: first, by the chemical modification of the chicken feathers by either acetylation or silanization and second, by the addition of adhesion promoters like maleated polypropylene and maleated polyethylene. The effect of those treatments on the physical, mechanical and structural properties of the thermoplastic-chicken feathers biocomposites, which are mainly related to the fibre–matrix compatibility, was analysed. Results show that the addition of 20% (vol/vol) of unmodified chicken feathers to the thermoplastic matrices results in a significant decrease of the tensile strength associated to a weak interfacial adhesion as it was demonstrated by scanning electron microscopy. However, when the adhesion promoters were added to the mixture, a significant increase in the tensile strength was noticed, particularly when the composites were obtained by a process at 180℃. On the contrary, acetylation and silane treatments of the chicken feathers did not result in any practical improvement of the macroscopic properties of the biocomposites. [ABSTRACT FROM AUTHOR]

Copyright of RPDI - Revista Portuguesa de Doenças Infecciosas is the property of Sociedade Portuguesa de Doencas Infecciosas e Microbiologia Clinica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Study Question: Is endometrial recurrent implantation failure (RIF) only a matter of an asynchronous (displaced) window of implantation (WOI), or could it also be a pathological (disrupted) WOI?Summary Answer: Our predictive results demonstrate that both displaced and disrupted WOIs exist and can present independently or together in the same RIF patient.What Is Known Already: Since 2002, many gene expression signatures associated with endometrial receptivity and RIF have been described. Endometrial transcriptomics prediction has been applied to the human WOI in two previous studies. One study describes endometrial RIF to be the result of a temporal displacement of the WOI. The other indicates that endometrial RIF can also result from a molecularly disrupted WOI without temporal displacement.Study Design, Size, Duration: Retrospective analysis was undertaken to compare WOI endometrial transcriptomics predictions in controls (n = 72) and RIF patients (n = 43). RIF was clinically designated by the absence of implantation after four or more transfers of high quality embryos or after the placement of 10 or more embryos in multiple transfers. Endometrial tissue samples were collected from LH + 5 to LH + 8. We compared the two molecular causes of RIF to signatures currently described in the literature. We propose a new transcriptomic RIF taxonomy to fill the gap between the two hypotheses and to guide the development of clinical detection and determination of both types of RIF.Participants/materials, Setting, Methods: Utilizing 115 gene expression profiles, two different predictive designs were developed: one considering RIF versus controls removing menstrual cycle timing, called the disrupted or pathological model, and another stratifying the WOI in transcriptomic profiles related to timing for predicting displacements. The predictive value of each model was compared between all signatures selected. We propose a new genomic approach that distinguishes between both types of RIF in the same sample cohort.Main Results and the Role Of Chance: From the 16 signatures analysed, we clearly predicted two causes of RIF-both a displaced WOI and an on-time but pathologically disrupted WOI. A high predictive value related to WOI profiles associated with menstrual cycle timing was found in most of the signatures. Specifically, 69% of the signatures analysed presented an accuracy higher than expected by chance in a range from 0.87 to 0.97. Displacements and disruptions were not molecularly independent, as some signatures were moderately associated with both causes. The gene and functional comparison between signatures revealed that they were not similar, although we did find functions in common and a cluster of moderate functional concordance between some of the signatures that predicted displacements (the highest Cohen's Kappa index were between 0.55 and 0.62 depending on the functional database). We propose a new transcriptomic RIF taxonomy to fill the gap between these prior studies and to establish methodology for detecting and distinguishing both types of RIF in clinical practice. Our findings indicate these two phenotypes could present independently or together in the same RIF patient. RIF patients designated by clinical criteria have been stratified transcriptomically as 18.6% with only a displaced WOI, 53.5% with a displaced and pathological WOI, 23.3% with only a disrupted WOI, and 4.7% could be a clinical RIF with non-endometrial origin. The new RIF transcriptomic taxonomy avoids menstrual cycle timing as a confounding variable that should be controlled for, distinguishing clearly between a disrupted and a displaced WOI for precision medicine in RIF.Limitations Reasons For Caution: The main objective of this study was to use transcriptomics to detect both RIF causes and to understand the role of transcriptomic signatures in these phenotypes. The predictive value in absolute terms for each signature was not indicative in these prediction designs; instead, the comparison between signatures was most important for prediction capability in the same sample cohort for both RIF causes. Clinical follow up of the RIF taxonomies proposed has not been analysed in this study, so further prospective clinical studies are necessary to determine the prevalence and penetrance of these phenotypes.Wider Implications Of the Findings: The main insight from this study is a new understanding of RIF taxonomy. Understanding how to classify RIF patients to distinguish clinically between a patient who could benefit from a personalized embryo transfer day and a patient with a disrupted WOI will enable identification and stratification for the research and development of new treatments. In addition, we demonstrate that basic research designs in endometrial transcriptomics cause masking of the study variable by the menstrual cycle timing.Study Funding/competing Interest(s): This research has been funded by IVI-RMA; the authors do not have any competing interests. [ABSTRACT FROM AUTHOR]

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Copyright of Archivos de Zootecnia is the property of Archivos de Zootecnia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Archivos de Zootecnia is the property of Archivos de Zootecnia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)