Transcriptional landscape of human trophoblast cells treated with calcitriol and TGF-ß1.

Calcitriol and transforming growth factor beta 1 (TGF-ß1) are unrelated molecules that regulate biological processes according to the genetic target, cell type, and context. Several studies have shown independent effects of calcitriol and TGF-ßs on the placenta, but there is no information regarding the impact of their combination on these cells. Therefore, this study analyzed the effects of calcitriol, TGF-ß1, and their combination in primary cultures of human trophoblast cells using a whole genome expression microarray. Data analysis revealed a set of differentially expressed genes induced by each treatment. Enrichment pathway analysis identified modulatory effects of calcitriol on genes related to metabolic processes such as vitamin D, steroid, and fat-soluble vitamins as well as antimicrobial and immune responses. In relation to TGF-ß1, the analysis showed a few differentially expressed genes that were mainly associated with the neutrophil immune response. Lastly, the analysis revealed that the combination of calcitriol and TGF-ß1 up-regulated genes involving both immunologic processes and the biosynthesis of unsaturated fatty acids, eicosanoids, and lipoxins, among others. In contrast, pathways down-regulated by the combination were mostly associated with the catabolic process of acylglycerols and peptides, PPAR signaling pathway, cellular response to low-density lipoprotein stimulus, renin angiotensin system and digestion, mobilization and transport of lipids. Consistent with these results, the combined treatment on human trophoblast cells induced the accumulation of intracellular neutral lipid droplets and stimulated both gene and protein expression of 15-hydroxyprostaglandin dehydrogenase. In conclusion, the results revealed that differentially expressed genes induced by the combination modified the transcriptional landscape compared to each treatment alone, mainly altering the storage, activity and metabolism of lipids, which might have an impact on placental development.

Effects of calcitriol upon TGF-ßs and their receptors in trophoblast cells.

Calcitriol levels increase during pregnancy, contributing to the hormonal and immunological balance, but its deficiency has been associated with problems during this period. Meanwhile, transforming growth factors-ß (TGF-ßs) play an important role in the maintenance of fetal-maternal immune tolerance; however, exacerbated concentrations of this growth factor are associated with complicated pregnancies. Therefore, we studied the effects of calcitriol on TGF-ßs and their receptors in trophoblast cells. Term placentas from uncomplicated pregnancies after cesarean sections were used for cell cultures. Basal gene expression and the effect of calcitriol upon TGF-ß1, TGF-ß2, TGF-ß3, and their receptors TGF-ßR1 and TGF-ßR2 were assessed using real-time PCR from trophoblast cells. The presence of TGF-ß1, 2, 3, and TGF-ßR1 were evaluated by immunofluorescence, and the protein abundance and secretion of TGF-ß1 were assessed by Western blot and ELISA, respectively. Basal gene expression of TGF-ß1 in trophoblast from term placentas was higher than TGF-ß2 and TGF-ß3, while TGF-ßR2 was higher than TGF-ßR1. The presence and cellular localization of TGF-ß1, 2, 3, and TGF-ßR1 were detected in the cytoplasm of syncytiotrophoblast, with TGF-ß1 showing the highest intensity. Calcitriol significantly inhibited gene expression of TGF-ß1, TGF-ß2, and TGF-ßR1. Likewise, calcitriol decreased the secretion and abundance of TGF-ß1. In conclusion, results indicate that calcitriol is a regulator of TGF-ßs in cultured trophoblast cells from term placentas and therefore may be an important player in the development of healthy pregnancies.

Gene Expression Changes in the Ovary Mediate Non-Anovulatory Mechanisms of Contraception with Levonorgestrel.

BACKGROUND: Emergency contraception with levonorgestrel (LNG) is a viable option to prevent unintended pregnancies. Although the efficacy of LNG as an anovulatory agent decreases as treatment approaches ovulation, it still provides some contraceptive benefits. AIM: To better understand the contraceptive mechanisms of LNG in ovulatory subjects. METHODS: We conducted a study on Wistar rats that received a single dose of LNG (0.01 or 0.05 mg/kg) on the morning of proestrus before ovulation and evaluated its effects on ovarian gene expression, ovulation, and implantation. RESULTS: Our findings showed changes in the expression of genes involved in follicular development and oocyte quality. Pregnancy rates - as an indicator of ovulation - and embryo implantation were significantly lower than those in the control group. CONCLUSIONS: This study suggests that LNG alters regulatory factors in the ovary that are essential for the development of competent fertilizable oocytes, highlighting the non-anovulatory mechanisms by which levonorgestrel may regulate fertility and suggesting that it could be a novel observation that contributes to the understanding of emergency contraception in humans.

Analytical reference framework to analyze non-COVID-19 events.

BACKGROUND: The COVID-19 pandemic has disrupted the healthcare system, leading to delays in detection of other non-COVID-19 diseases. This paper presents ANE Framework (Analytics for Non-COVID-19 Events), a reliable and user-friendly analytical forecasting framework designed to predict the number of patients with non-COVID-19 diseases. Prior to 2020, there were analytical models focused on specific illnesses and contexts. Then, most models have focused on understanding COVID-19 behavior. There is a lack of analytical frameworks that enable disease forecasting for non-COVID-19 diseases. METHODS: The ANE Framework utilizes time series analysis to generate forecasting models. The framework leverages daily data from official government sources and employs SARIMA models to forecast the number of non-COVID-19 cases, such as tuberculosis and suicide attempts. RESULTS: The framework was tested on five different non-COVID-19 events. The framework performs well across all events, including tuberculosis and suicide attempts, with a Mean Absolute Percentage Error (MAPE) of up to 20% and the consistency remains independent of the behavior of each event. Moreover, a pairwise comparison of averages can lead to over or underestimation of the impact. The disruption caused by the pandemic resulted in a 17% gap (2383 cases) between expected and reported tuberculosis cases, and a 19% gap (2464 cases) for suicide attempts. These gaps varied between 20 and 64% across different cities and regions. The ANE Framework has proven to be reliable for analyzing several diseases and exhibits the flexibility to incorporate new data from various sources. Regular updates and the inclusion of new associated data enhance the framework's effectiveness. CONCLUSIONS: Current pandemic shows the necessity of developing flexible models to be adapted to different illness data. The framework developed proved to be reliable for the different diseases analyzed, presenting enough flexibility to update with new data or even include new data from different databases. To keep updated on the result of the project allows the inclusion of new data associated with it. Similarly, the proposed strategy in the ANE framework allows for improving the quality of the obtained results with news events.

Dynamic curvature sensing using time expanded ΦOTDR.

Shape sensing can be accomplished using optical fiber sensors through different interrogation principles such as fiber Bragg gratings, optical frequency-domain reflectometry (OFDR), or optical time-domain reflectometry (OTDR). These techniques are either not entirely distributed, have poor performance in dynamic sensing, or are only valid for few-meter-long fibers. Here, we present a system able to perform distributed curvature sensing with a range of 125 m, 10-cm resolution, and a sampling rate of 50 Hz. This is done by interrogating three cores of a multi-core fiber (MCF) with the novel, to the best of our knowledge, time-expanded phase-sensitive (TE-Φ)OTDR technique. This system fills a performance gap in fiber shape sensors, opening the door to applications in civil engineering, medicine, or seismology.

Impaired Carbohydrate Metabolism and Excess of Lipid Accumulation in Offspring of Hyperandrogenic Mice.

Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder of unknown etiology. Hyperandrogenism (HA) is the main diagnostic criteria for PCOS, in addition to being a risk factor for developing several disorders throughout the patient's life, including pregnancy. However, the impact on offspring is little known. Therefore, the aim of this work was to evaluate the effect of maternal HA on glucose metabolism and hepatic lipid accumulation in adult offspring. We used Balb/c mice treated with dehydroepiandrosterone (DHEA) for 20 consecutive days. The ovary of DHEA-treated mice showed hemorrhagic bodies, an increased number of atretic follicles, and greater expression of genes related to meiotic cell cycle and DNA repair. The DHEA offspring (O-DHEA) had low birth weight, and some pups showed malformations. However, O-DHEA individuals gained weight rapidly, and the differences between them and the control group became significantly greater in adulthood. Moreover, O-DHEA presented higher serum glucose after a 6 h fast and a larger area under glucose, insulin, and pyruvate tolerance test curves. Oil Red O staining showed a more significant accumulation of fat in the liver but no changes in serum cholesterol and triacylglycerol levels. In summary, our results show that HA, induced by DHEA, affects gene expression in oocyte, which in turn generates defects in embryonic development, insulin resistance, and alteration in hepatic gluconeogenesis and lipid metabolism in O-DHEA, thereby increasing the risk of developing metabolic diseases.

Optical fiber point sensors based on forward Brillouin scattering.

Forward Brillouin scattering interactions support the sensing and analysis of media outside the cladding boundaries of standard fibers, where light cannot reach. Quantitative point-sensing based on this principle has yet to be reported. In this work, we report a forward Brillouin scattering point-sensor in a commercially available, off-the-shelf multi-core fiber. Pump light at the inner, on-axis core of the fiber is used to stimulate a guided acoustic mode of the entire fiber cross-section. The acoustic wave, in turn, induces photoelastic perturbations to the reflectivity of a Bragg grating inscribed in an outer, off-axis core of the same fiber. The measurements successfully analyze refractive index perturbations on the tenth decimal point and distinguish between ethanol and water outside the centimeter-long grating. The measured forward Brillouin scattering linewidths agree with predictions. The acquired spectra are unaffected by forward Brillouin scattering outside the grating region. The results add point-analysis to the portfolio of forward Brillouin scattering optical fiber sensors.

The EDIT Survey: Identifying Emergency Department Information Technology Knowledge and Training Gaps.

OBJECTIVE: To review Emergency Department internet connectivity, cyber risk factors, perception of risks and preparedness, security policies, training and mitigation strategies. METHODS: A validated targeted survey was sent to Canadian ED physicians and nurses between March 5, 2019 and April 28, 2019. RESULTS: There were 349 responses, with physicians making up 84% of the respondents (59% urban teaching, 35% community teaching, 6% community non-teaching hospitals). All had multiple passwords, 93% had more than 1 user account, over 90% had to log repeatedly each workday, 52% had to change their passwords every 3 months, 75% had multiple methods of authentication and 53% reported using a terminal where someone else was already logged in. Passwords were used to review laboratory and radiology data, access medical records and manage patient flow. Majority of the respondents (51%) did not know if they worked with internet linked devices. Only 7% identified an 'air gapped' computer in their facility and 76% used personal devices for patient care, with less than a third of those allowing the IT department to review their device. A total of 26 respondents received no cyber security training. CONCLUSION: This paper revealed significant computer-human interface dysfunctionality and readiness gaps in the event of an IT failure. These stemmed from poor system design, poor planning and lack of training. The paper identified areas with technical or training solutions and suggested mitigation strategies.

Polycystic ovarian syndrome: signs and feedback effects of hyperandrogenism and insulin resistance.

Polycystic ovary syndrome (PCOS) is a disease whose diagnosis is based on the detection of hyperandrogenism (HA) and ovulatory dysfunction. Women with PCOS frequently develop insulin resistance (IR), which generates a metabolic condition that involves a decrease in the action of insulin at the cellular level and is linked to compensatory hyperinsulinemia (HI). In PCOS, the ovary remains sensitive to the action of insulin. Additionally, it has been observed that the main effect of insulin in the ovary is the stimulation of androgen synthesis, resulting in HA, one of the fundamental characteristics of the PCOS. In this sense, the excess of androgens favors the development of IR, thus perpetuating the cycle of IR-HI-HA, and therefore PCOS. Moreover, mitochondrial dysfunction is present in PCOS patients and is a common feature in both IR and HA. This review places electron transfer as a key element in HA and IR development, with emphasis on the relationship between androgen biosynthesis and mitochondrial function. Indeed, metformin has been involved in repair mitochondrial dysfunction, decrease of oxidative stress, reduction of androgens levels and the enhancing of insulin sensitivity. Therefore, we propose that treatment with metformin could decrease HI and consequently HA, restoring, at least in part, the metabolic and hormonal disorders of PCOS.

Regulation of anti-tumorigenic pathways by the combinatory treatment of calcitriol and TGF-ß in PC-3 and DU145 cells.

Calcitriol and transforming growth factors beta (TGF-ß) are involved in several biological pathways such as cell proliferation, differentiation, migration and invasion. Their cellular effects could be similar or opposite depending on the genetic target, cell type and context. Despite the reported association of calcitriol deficiency and disruption of the TGF-ß pathway in prostate cancer and the well-known independent effects of calcitriol and TGF-ßs on cancer cells, there is limited information regarding the cellular effects of calcitriol and TGF-ß in combination. In this study, we in vitro analyze the combinatory effects of calcitriol and TGF-ß on cell growth and apoptosis using PC-3 and DU145 human prostate cancer cell lines. Using high-throughput microarray profiling of PC-3 cells upon independent and combinatory treatments, we identified distinct transcriptional landscapes of each intervention, with a higher effect established by the combinatorial treatment, following by TGF-ß1 and later by calcitriol. A set of genes and enriched pathways converge among the treatments, mainly between the combinatory scheme and TGF-ß1, but the majority were treatment-specific. Of note, CYP24A1, IGFBP3, CDKN1A, NOX4 and UBE2D3 were significantly up-regulated upon the combinatorial treatment whereas CCNA1, members of the CT45A and APOBEC3 family were down-regulated. By public RNA signatures, we were able to confirm the regulation by the co-treatment over cell proliferation and cell cycle. We finally investigated the possible clinical impact of genes modulated by the combinatorial treatment using benchmark prostate cancer data. This comprehensive analysis reveals that the combinatory treatment impairs cell growth without affecting apoptosis and their combinatory actions might synergize and improved their individual effects to reprogram prostate cancer signaling.

An organotin indomethacin derivative inhibits cancer cell proliferation and synergizes the antiproliferative effects of lapatinib in breast cancer cells.

It is known that an inflammatory condition in different types of cancer provides a sustained microenvironment that favors tumor growth, invasion, and metastasis. Non-steroidal anti-inflammatory drugs such as indomethacin have demonstrated chemo-preventive, anti-proliferative and cytotoxic effects in a variety of tumors. The aim of this study was to investigate the effects of an organotin indomethacin derivative (OID) on the proliferation of breast and prostate cancer cell lines and the possible mechanisms of action of this compound. Different cancer cell lines were treated in the presence of OID and cell proliferation was measured by quantification of the DNA content, changes in the cell cycle profile and the activation of caspase 3 were evaluated by flow cytometry, interleukin 6 (IL-6) gene expression was evaluated by qPCR and protein expression was analyzed by ELISA and Western blot assays. OID inhibited the cell proliferation of a panel of cancer cell lines in a concentration-dependent manner. Moreover, the addition of OID to lapatinib treatment, targeted therapy for breast cancer, significantly enhanced its antiproliferative response. The effects on cell proliferation of these compounds involved, among others, the induction of apoptosis, the downregulation of IL-6 and a decrease of the MAPK activation pathway. Our results suggest that the use of OID alone or in combination with tyrosine kinase inhibitors could be considered as adjuvants in the treatment of cancer.

Gene transcription profiling of astheno- and normo-zoospermic sperm subpopulations.

Spermatozoa contain a repertoire of RNAs considered to be potential functional fertility biomarkers. In this study, the gene expression of human sperm subpopulations with high (F1) and low (F2) motility from healthy normozoospermic (N) and asthenozoospermic (A) individuals was evaluated using RNA microarray followed by functional genomic analysis of differentially expressed genes. Results from A-F1 versus N-F1, A-F2 versus N-F2, N-F1 versus N-F2, and A-F1 versus A-F2 comparisons showed a considerably larger set of downregulated genes in tests versus controls. Gene ontology (GO) analysis of A-F1 versus N-F1 identified 507 overrepresented biological processes (BPs), several of which are associated with sperm physiology. In addition, gene set enrichment analysis of the same contrast showed 110 BPs, 36 cellular components, and 31 molecular functions, several of which are involved in sperm motility. A leading-edge analysis of selected GO terms resulted in several downregulated genes encoding to dyneins and kinesins, both related to sperm physiology. Furthermore, the predicted activation state of asthenozoospermia was increased, while fertility, cell movement of sperm, and gametogenesis were decreased. Interestingly, several downregulated genes characteristic of the canonical pathway protein ubiquitination were involved in asthenozoospermia activation. Conversely, GO analysis of A-F2 versus N-F2 did not identify overrepresented BPs, although the gene set enrichment analysis detected six enriched BPs, one cellular component, and two molecular functions. Overall, the results show differences in gene transcription between sperm subpopulations from asthenozoospermic and normozoospermic semen samples and allowed the identification of gene sets relevant to sperm physiology and reproduction.

Multicore optical fiber shape sensors suitable for use under gamma radiation.

We have designed and implemented a fiber optic shape sensor for high-energy ionizing environments based on multicore optical fibers. We inscribed two fiber Bragg gratings arrays in a seven-core optical fiber. One of the arrays has been inscribed in a hydrogen-loaded fiber and the other one in an unloaded fiber in order to have two samples with very different radiation sensitivity. The two samples were coiled in a metallic circular structure and were exposed to gamma radiation. We have analyzed the permanent radiation effects. The radiation-induced Bragg wavelength shift (RI-BWS) in the hydrogen-loaded fiber is near ten times higher than the one observed for the unloaded fiber, with a maximum wavelength shift of 415 pm. However, the use of the multiple cores permits to make these sensors immune to RI-BWS obtaining a similar curvature error in both samples of approximately 1 cm without modifying the composition of the fiber, pre-irradiation or thermal treatment.

Isocitrate dehydrogenase type 2 (IDH2) is part of a multiprotein complex for placental steroidogenesis.

BACKGROUND: Human syncytiotrophoblast mitochondria require the activity of the isocitrate dehydrogenase type 2 (IDH2) to obtain reduced coenzymes for progesterone (P4) synthesis. Data from the literature indicate that mitochondrial steroidogenic contact sites transform efficiently cholesterol into P4. In this research, we identified the IDH2 as a member of the steroidogenic contact site and analyzed the steroidogenic role of its activity. METHOD: Human syncytiotrophoblast mitochondria were isolated by differential centrifugation, and steroidogenic contact sites were obtained by osmotic shock and sucrose gradient ultracentrifugation. In-gel native activity assay, mass spectroscopy, and western blot were used to identify the association of proteins and their activities. P4 was determined by immunofluorescence. RESULTS: The IDH2 was mainly identified in steroidogenic contact sites, and its activity was associated with a complex of proteins with an apparent molecular mass of ~590 kDa. Mass spectroscopy showed many groups of proteins with several metabolic functions, including steroidogenesis and ATP synthesis. The IDH2 activity was coupled to P4 synthesis since in the presence of Ca2+ or Na2SeO3, inhibitors of the IDH2, the P4 production decreased. CONCLUSIONS: The human syncytiotrophoblast mitochondria build contact sites for steroidogenesis. The IDH2, a non-membrane protein, supplies the NADPH required for the synthesis of P4 in a complex (steroidosome) that associate the proteins required to transform efficiently cholesterol into P4, which is necessary in pregnancy to maintain the relationship between mother and fetus. GENERAL SIGNIFICANCE: The IDH2 is proposed as a check point in the regulation of placental steroidogenesis.

Sampled true time delay line operation by inscription of long period gratings in few-mode fibers.

We propose and experimentally demonstrate distributed microwave photonics signal processing over a few-mode fiber link by implementing 4-sample true time delay line operation. The inscription of a set of long period gratings at specific locations along the few-mode fiber allows the excitation of the higher-order modes while adjusting the individual sample group delays and amplitudes that are required for sampled true time delay line behavior. Since solely the injection of the fundamental mode at the few-mode fiber input is required, we render this signal processing system independent of any preceding fiber link that may be required in addition to distribute the signal. We experimentally validate the performance of the implemented true time delay line when applied to radiofrequency signal filtering.

Calcitriol Inhibits the Proliferation of Triple-Negative Breast Cancer Cells through a Mechanism Involving the Proinflammatory Cytokines IL-1ß and TNF-α.

Triple-negative breast cancer (TNBC) is one of the most aggressive tumors, with poor prognosis and high metastatic capacity. The aggressive behavior may involve inflammatory processes characterized by deregulation of molecules related to the immunological responses in which interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) are involved. It is known that calcitriol, the active vitamin D metabolite, modulates the synthesis of immunological mediators; however, its role in the regulation of IL-1ß and TNF-α in TNBC has been scarcely studied. In the present study, we showed that TNBC cell lines SUM-229PE and HCC1806 expressed vitamin D, IL-1ß, and TNF-α receptors. Moreover, calcitriol, its analogue EB1089, IL-1ß, and TNF-α inhibited cell proliferation. In addition, we showed that synthesis of both IL-1ß and TNF-α was stimulated by calcitriol and its analogue. Interestingly, the antiproliferative activity of calcitriol was significantly abrogated when the cells were treated with anti-IL-1ß receptor 1 (IL-1R1) and anti-TNF-α receptor type 1 (TNFR1) antibodies. Furthermore, the combination of calcitriol with TNF-α resulted in a greater antiproliferative effect than either agent alone, in the two TNBC cell lines and an estrogen receptor-positive cell line. In summary, this study demonstrated that calcitriol exerted its antiproliferative effects in part by inducing the synthesis of IL-1ß and TNF-α through IL-1R1 and TNFR1, respectively, in TNBC cells, highlighting immunomodulatory and antiproliferative functions of calcitriol in TNBC tumors.

Steroid hormones and pregnancy.

Pregnancy is associated with physiological adjustments in order to allow adequate growth and fetal development. In particular, steroids are necessary to maintain in balance numerous functions during gestation. Steroidogenesis in the maternal, placental and fetal compartments and the biological effects of progestins and estrogens that play a pivotal role before and during pregnancy are described. Although it is well-known that androgens are considered as substrate for estrogens biosynthesis, their biosynthesis and functionality in placental and other tissues have been questioned. As compared with healthy pregnancy, steroid hormones levels have been found altered in complicated pregnancies and hormonal treatments have been used is some pathologies. Therefore, the aim of this work was to review the biosynthesis, function and regulation of progestins, androgens and estrogens during gestation. Furthermore, steroid hormones concentrations during healthy and complicated pregnancy as well hormonal therapies for the prevention of miscarriages and preterm deliveries are discussed in the present review.

Selección de hospital destino para el traslado de urgencia de pacientes / Selecting the Destination Hospital to Carry Emergency Patients / Escolha de hospital alvo para traslado de urgência de pacientes

Resumen El tiempo total de atención prehospitalaria (APH) es el tiempo que transcurre desde que ingresa la llamada al operador hasta que la ambulancia queda disponible para atender otra emergencia. Esta investigación pretende demostrar que la selección del hospital destino afecta de manera significativa el tiempo total de APH, lo que influye en la supervivencia del paciente que es trasladado y en el tiempo de liberación del recurso (ambulancias). En consecuencia, se propone una técnica de selección de hospital destino que incluye dimensiones relacionadas con el paciente (diagnóstico, especialidad y asegurador) y el hospital (ocupación y cercanía). Se evalúa su desempeño por medio de una simulación de eventos discretos y se concluye que la técnica propuesta obtiene un mejor tiempo de APH en el 73% de los casos estudiados, con una reducción media entre 40 y 80 minutos, en comparación con la técnica más comúnmente usada (selección hospital más cercano).

Abstract Total time of prehospital care (PHC) is the time elapsing from the inbound call up to the moment when the ambulance is available for serve in another emergency event. This research aims to show that selecting the destination hospital impacts significantly the total PHC time, which influences the survival of the patient being transported as well as the time to make the resource available again (the ambulance). Consequently, a technique for selecting the destination hospital is proposed herein including some dimensions related both to the patient (diagnosis, specialty and insurance company) and to the hospital (occupancy and closeness). The performance was evaluated based on a simulation of discrete events. It is concluded that the proposed technique provides a better PHC time in 73% of the studied cases, with a mean decrease between 40 and 80 minutes as compared to the most commonly used technique (selecting the closest hospital).

Resumo O tempo total de atendimento pré-hospitalar (APH) é o tempo decorrente desde que a ligação for feita para o telefonista até a ambulância se disponibilizar para atender outra emergência. Esta pesquisa visa demostrar que a escolha do hospital alvo afeta significativamente o tempo total de APH, o que influi na sobrevida do paciente trasladado e no tempo de liberação do recurso (ambulâncias). Consequentemente, propõe-se uma técnica de escolha de hospital alvo que inclui dimensões relacionadas com paciente (diagnóstico, especialidade e assegurador) e hospital (ocupação e proximidade). Avalia-se o desempenho por meio de simulação de eventos discretos e conclui-se que a técnica proposta obtém melhor tempo de APH em 73% dos casos estudados com redução media entre 40 e 80 minutos, em comparação com a técnica mais comumente usada (escolha hospital mais próximo).

Few-mode fiber true time delay lines for distributed radiofrequency signal processing.

We report, for the first time to our knowledge, distributed radiofrequency signal processing built upon true time delay operation on a step-index few-mode fiber. Two 3-sample configurations with different time delay properties are implemented over the same 60-meter 4-LP-mode fiber link. The inscription of a long period grating at a specific fiber position converts part of the LP01 mode into the LP02, permitting sample time delay engineering. Delay line performance is experimentally demonstrated when applied to radiofrequency signal filtering, example of fiber-distributed processing functionality exhibiting one order or magnitude gain in terms of compactness.

A single preovulatory administration of ulipristal acetate affects the decidualization process of the human endometrium during the receptive period of the menstrual cycle.

In order to get further information on the effects of ulipristal acetate (UPA) upon the process of decidualization of endometrium, a functional analysis of the differentially expressed genes in endometrium (DEG) from UPA treated-versus control-cycles of normal ovulatory women was performed. A list of 1183 endometrial DEG, from a previously published study by our group, was submitted to gene ontology, gene enrichment and ingenuity pathway analyses (IPA). This functional analysis showed that decidualization was a biological process overrepresented. Gene set enrichment analysis identified LIF, PRL, IL15 and STAT3 among the most down-regulated genes within the JAK STAT canonical pathway. IPA showed that decidualization of uterus was a bio-function predicted as inhibited by UPA. The results demonstrated that this selective progesterone receptor modulator, when administered during the periovulatory phase of the menstrual cycle, may affect the molecular mechanisms leading to endometrial decidualization in response to progesterone during the period of maximum embryo receptivity.