Obstetric and Perinatal Outcomes after Very Early Preterm Premature Rupture of Membranes (PPROM)-A Retrospective Analysis over the Period 2000-2020

Background and Objectives: Pre-term premature rupture of membranes (PPROM) responds for one third of preterm births, and it is associated with other complications that increase the risk of maternal or fetal poor outcome. To reduce uncertainty and provide accurate information to patients, the analysis of the large series is of great importance. In order to learn about the evolution over the time of the obstetric and perinatal outcomes in cases of PPROM at, or before, 28 weeks (very early PPROM) managed with an expectant/conservative protocol, we have designed the present study. Materials and Methods: We retrospectively studied all cases of very early PPROM attended in Malaga University Regional Hospital from 2000 to 2020. Results: Among 119,888 deliveries assisted, 592 cases of PPROM occurred in pregnancies at or before 28 weeks (0.49% of all deliveries, 3.9% of all preterm births and 12.9% of all cases of PPROM). The mean duration of the latency period between PPROM and delivery was 13.5 days (range 0 to 88 days), enlarging over the years. The mean gestational age at delivery was 27 weeks (SD 2.9; range 17-34). The proportion of cesarean deliveries was 52.5%. The overall perinatal mortality rate was 26.5%, decreasing over the period with a significant correlation Pearson's coefficient -0.128 (p < 0.05). Conclusions: In the period 2000-2020, there was an improvement in the outcomes of very early PPROM cases and perinatal mortality showed a clear trend to decrease.This publication was financed with funds from the University of Malaga

Mucosal Heterologous Prime/Boost Vaccination Induces Polyfunctional Systemic Immunity, Improving Protection Against Trypanosoma cruzi

There are several unmet needs in modern immunology. Among them, vaccines against parasitic diseases and chronic infections lead. Trypanosoma cruzi, the causative agent of Chagas disease, is an excellent example of a silent parasitic invasion that affects millions of people worldwide due to its progression into the symptomatic chronic phase of infection. In search for novel vaccine candidates, we have previously introduced Traspain, an engineered trivalent immunogen that was designed to address some of the known mechanisms of T. cruzi immune evasion. Here, we analyzed its performance in different DNA prime/protein boost protocols and characterized the systemic immune response associated with diverse levels of protection. Formulations that include a STING agonist, like c-di-AMP in the boost doses, were able to prime a Th1/Th17 immune response. Moreover, comparison between them showed that vaccines that were able to prime polyfunctional cell-mediated immunity at the CD4 and CD8 compartment enhanced protection levels in the murine model. These findings contribute to a better knowledge of the desired vaccine-elicited immunity against T. cruzi and promote the definition of a vaccine correlate of protection against the infection.Fil: Sanchez Alberti, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina. Helmholtz Centre for Infection Research. Department of Vaccinology and Applied Microbiology; AlemaniaFil: Bivona, Augusto Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Matos, Marina Nadia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Cerny, Natacha. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Schulze, Kai. Helmholtz Centre for Infection Research. Department of Vaccinology and Applied Microbiology; AlemaniaFil: Weißmann, Sebastian. Helmholtz Centre for Infection Research. Department of Vaccinology and Applied Microbiology; AlemaniaFil: Ebensen, Thomas. Helmholtz Centre for Infection Research. Department of Vaccinology and Applied Microbiology; AlemaniaFil: González, Germán. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología; ArgentinaFil: Morales, Celina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología; ArgentinaFil: Cardoso Landaburu, Alejandro Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Cazorla, Silvia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Guzman, Carlos A.. Helmholtz Centre for Infection Research. Department of Vaccinology and Applied Microbiology; AlemaniaFil: Malchiodi, Emilio Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentin

Mucosal Heterologous Prime/Boost Vaccination Induces Polyfunctional Systemic Immunity, Improving Protection Against Trypanosoma cruzi

There are several unmet needs in modern immunology. Among them, vaccines against parasitic diseases and chronic infections lead. Trypanosoma cruzi, the causative agent of Chagas disease, is an excellent example of a silent parasitic invasion that affects millions of people worldwide due to its progression into the symptomatic chronic phase of infection. In search for novel vaccine candidates, we have previously introduced Traspain, an engineered trivalent immunogen that was designed to address some of the known mechanisms of T. cruzi immune evasion. Here, we analyzed its performance in different DNA prime/protein boost protocols and characterized the systemic immune response associated with diverse levels of protection. Formulations that include a STING agonist, like c-di-AMP in the boost doses, were able to prime a Th1/Th17 immune response. Moreover, comparison between them showed that vaccines that were able to prime polyfunctional cell-mediated immunity at the CD4 and CD8 compartment enhanced protection levels in the murine model. These findings contribute to a better knowledge of the desired vaccine-elicited immunity against T. cruzi and promote the definition of a vaccine correlate of protection against the infection.Fil: Sanchez Alberti, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina. Helmholtz Centre for Infection Research. Department of Vaccinology and Applied Microbiology; AlemaniaFil: Bivona, Augusto Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Matos, Marina Nadia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Cerny, Natacha. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Schulze, Kai. Helmholtz Centre for Infection Research. Department of Vaccinology and Applied Microbiology; AlemaniaFil: Weißmann, Sebastian. Helmholtz Centre for Infection Research. Department of Vaccinology and Applied Microbiology; AlemaniaFil: Ebensen, Thomas. Helmholtz Centre for Infection Research. Department of Vaccinology and Applied Microbiology; AlemaniaFil: González, Germán. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología; ArgentinaFil: Morales, Celina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología; ArgentinaFil: Cardoso Landaburu, Alejandro Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Cazorla, Silvia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Guzman, Carlos A.. Helmholtz Centre for Infection Research. Department of Vaccinology and Applied Microbiology; AlemaniaFil: Malchiodi, Emilio Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentin

Transmitted Fetal Immune Response in Cases of SARS-CoV-2 Infections during Pregnancy

(1) Background: Little is known about the effects of SARS-CoV-2 on the placenta, and whether the maternal inflammatory response is transmitted vertically. This research aims to provide information about the effects of SARS-CoV-2 infection on maternal and fetal immunity. (2) Methods: We have studied placental changes and humoral and cellular immunity in maternal and umbilical cord blood (UCB) samples from a group of pregnant women delivering after the diagnosis of SARS-CoV-2 infection during pregnancy. IgG and IgM SARS-CoV-2 antibodies, Interleukin 1b (IL1b), Interleukin 6 (IL6), and gamma-Interferon (IFN-γ), have been studied in the UCB samples. Lymphocyte subsets were studied according to CD3, CD8, CD4, CD34, and invariant natural Killer T cells (iNKT) markers. We used in situ hybridization techniques for the detection of viral RNA in placentas. (3) Results: During the study period, 79 pregnant women and their corresponding newborns were recruited. The main gestational age at the time of delivery was 39.1 weeks (SD 1.3). We did not find traces of the SARS-CoV-2 virus RNA in any of the analyzed placental samples. Detectable concentrations of IgG anti-SARS-CoV-2 antibodies, IL1b, IL6, and IFN-γ, in UCB were found in all cases, but IgM antibodies anti-ARS-CoV-2 were systematically undetectable. We found significant correlations between fetal CD3+ mononuclear cells and UCB IgG concentrations. We also found significant correlations between UCB IgG concentrations and fetal CD3+/CD4+, as well as CD3+/CD8+ T cells subsets. We also discovered that fetal CD3+/CD8+ cell counts were significantly higher in those cases with placental infarctions. (4) Conclusion: we have not verified the placental transfer of SARS-CoV-2. However, we have discovered that a significant immune response is being transmitted to the fetus in cases of SARS-CoV-2 maternal infection.Partial funding for open access charge: Universidad de Málaga. This research was funded by Ferring COVID-19 Investigational Grant Placental injury and immune reaction transmitted to the neonates in cases of SARS-CoV-2 infections during pregnancy. Study on placental and blood cord samples. The APC was funded by University of Málaga. Funding institutions did not participate in the design, recruitment, analysis, or interpretation of the results

Mood state at the beginning of the pregnancy and its influence on obstetric and perinatal outcomes

Aim: We designed this study to ascertain the prevalence of depressive disorders and anxiety at the beginning of the pregnancy, studying possible associated factors and assessing the influence of mood disorders on perinatal outcomes. Methods: A representative sample of 191 pregnant women at first trimester of their pregnancies completed a questionnaire that included the Whooley´s questions, the Spanish version of the Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory and a series of questions related to health status, general mood and sociodemographic variables. Later, we prospectively evaluated the influence of anxiety and depression on the perinatal and obstetric results in 145 of them. Results: More than 20% of pregnant women presented high levels of anxiety. The mean values of the state and trait anxiety scores were 38.7 (SD 9.8) and 34.5 (SD 9.5). The mean BDI score was 5.97 (SD 4.9), with 9.5% of participants achieving scores compatible with depression, (61% mild in, 22.2% moderate, and 16.6% severe). BDI scores were significantly lower in women who became pregnant after assisted reproductive techniques. We observed an association between depression and trait anxiety scores with an infant’s low birth weight. The multivariate analysis showed that the feeling of happiness at the beginning of pregnancy was the best predictor of foetal weight. Conclusion: The prevalence of emotional disorders in the first trimester of pregnancy is high, with more than 20% of pregnant women presenting high levels of anxiety, and more than 9.5% presenting depression. During the first trimester, depression and anxiety were associated with low birth weight

Physical Activity in Work and Leisure Time during Pregnancy, and Its Influence on Maternal Health and Perinatal Outcomes

Background: Physical inactivity during pregnancy has been shown to be linked to an increased risk of complications. However, during pregnancy, doubts arise about what type, intensity and frequency of physical activity are most recommended. Objective: Our main objective was to know the level of physical activity (PA) and sedentary lifestyle in a representative sample of pregnant women in Málaga, one of the most populated cities in Spain. Also, we aimed to find out the effects of PA on obstetric and perinatal outcomes and on the mental health of pregnant women, differentiated according to PA intensity and domain. Methods: Five hundred and forty full-term pregnant women who had their obstetric checks in the maternity ward of the Regional University Hospital of Málaga were recruited through consecutive sampling. Participants answered a questionnaire that included the WHO Global Physical Activity Questionnaire (GPAQ), the Edinburgh Depression Scale (EDS), the Generalized Anxiety Disorder Scale (GAD-7) and some other sociodemographic and health-related questions. Subsequently, information about perinatal outcomes was obtained after birth. Results: Only 50.8% of women followed the WHO recommendations on activity. We found a high proportion of obese pregnant women and a direct effect of a sedentary lifestyle on the rate of cesarean sections and vulvovaginal tears in spontaneous births, as well as on the mental health of future mothers. Women’s age, the number of children, BMI at the beginning of pregnancy and leisure time physical activity (LTPA) explained anxiety scores, and age, LTPA, BMI at the end of pregnancy and intense work-related physical activity (WTPA) predicted depression scores. Conclusions: LTPA improves obstetric outcomes, helping to reduce the rate of cesarean sections and vulvovaginal tears, as well as reducing prenatal anxiety and depression.University of Malaga’s Research Plan: Funds for Research Initiation Grant

Assessment of the attitude towards childbirth in health sciences students - development and validation of the questionnaire Cave-St

BACKGROUND: The purpose of this study is to report on the validation process of the Spanish version of a questionnaire that explores health science students’ attitudes towards women’s childbirth experiences. This questionnaire could help inform education programs to enhance the quality of woman-professional interactions, and to improve women’s experiences of childbirth. METHODS: A standardised procedure for the development and validation of the questionnaire included: item development and psychometric pre-validation, Cronbach’s Alpha and split-half coefficients calculation, test–retest and item-total correlation for the reliability analysis. Content validity was undertaken by Delphi method with sixteen panelists over two rounds. We determined the factor structure and refined and validated the questionnaire according to the responses of a cohort of 160 students using principal components factor analysis with varimax rotation. RESULTS: A 52-items questionnaire CAVE-st: (acronym for cuestionario de actitudes sobre vivencias y experiencias en el parto) was developed and validated. The questionnaire had a high construct validity, with a Cronbach´s alpha > 0.92. The intraclass correlations (0.80) indicated adequate test–retest reliability. The results of the exploratory factor analysis revealed fourteen latent components that explained more than the 70% of the observed total variance. CONCLUSIONS: The Spanish version of the questionnaire CAVE-st has been developed and validated. Its psychometrics indicate that it is a valid and reliable tool to assess health sciences students’ attitude towards women´s childbirth experience. Further work to translate and adapt the instrument in other cultures and languages will be undertaken

Arabidopsis thaliana root colonization by the nematophagous fungus Pochonia chlamydosporia is modulated by jasmonate signaling and leads to accelerated flowering and improved yield

· Pochonia chlamydosporia has been intensively studied in nematode control of different crops. We have investigated the interaction between P. chlamydosporia and the model system Arabidopsis thaliana under laboratory conditions in the absence of nematodes. · This study demonstrates that P. chlamydosporia colonizes A. thaliana. Root colonization monitored with green fluorescent protein-tagged P. chlamydosporia and quantitative PCR (qPCR) quantitation methods revealed root cell invasion. Fungal inoculation reduced flowering time and stimulated plant growth, as determined by total FW increase, faster development of inflorescences and siliques, and a higher yield in terms of seed production per plant. · Precocious flowering was associated with significant expression changes in key flowering-time genes. In addition, we also provided molecular and genetic evidence that point towards jasmonate signaling as an important factor to modulate progression of plant colonization by the fungus. · Our results indicate that P. chlamydosporia provides benefits to the plant in addition to its nematophagous activity. This report highlights the potential of P. chlamydosporia to improve yield in economically important crops.This research was funded by grants from the Spanish Ministry of Economy and Competitiveness (AGL2015-66833-R to L.V.LL., and BIO2014-56321-P to A.V. and A.M-L.)