Role of the oviduct and oviduct-derived products in ruminant embryo development

Abstract The fact that embryos can be obtained in vitro undermines the role of the oviduct. However, it has been demonstrated that when in vitro produced bovine zygotes are cultured in the oviduct of sheep, cattle or mice the embryo quality is improved compared to the embryos produced in vitro. Thus the oviduct is not simply a passive organ required only for transporting the embryo to the uterus but also provides a suitable microenvironment for the early embryo. The study of physiological mechanisms and interactions between the embryo and the oviductal environment is essential to understand the correct processes of early embryo developmental. This knowledge can be used to improve current in vitro procedures providing high quality embryos capable of continued development and implantation, and resulting in viable births

Onomatopoeia, gestures, actions and words: How do caregivers use multimodal cues to communicate with their children

Most research on how children learn the mapping between words and world has assumed that language is arbitrary, and has investigated language learning in contexts in which objects referred to are present in the environment. Here, we report analyses of a semi-naturalistic corpus of caregivers talking to their 2-3 year-old. We focus on caregivers’ use of non-arbitrary cues across different expressive channels: both iconic (onomatopoeia and representational gestures) and indexical (points and actions with objects). We ask if these cues are used differently when talking about objects known or unknown to the child, and when the referred objects are present or absent. We hypothesize that caregivers would use these cues more often with objects novel to the child. Moreover, they would use the iconic cues especially when objects are absent because iconic cues bring to the mind’s eye properties of referents. We find that cue distribution differs: all cues except points are more common for unknown objects indicating their potential role in learning; onomatopoeia and representational gestures are more common for displaced contexts whereas indexical cues are more common when objects are present. Thus, caregivers provide multimodal non-arbitrary cues to support children’s vocabulary learning and iconicity – specifically – can support linking mental representations for objects and labels

Onomatopoeia, gestures, actions and words: how do caregivers use multimodal cues in their communication to children?

Most research on how children learn the mapping between words and world has assumed that language is arbitrary, and has investigated language learning in contexts in which objects referred to are present in the environment. Here, we report analyses of a semi-naturalistic corpus of caregivers talking to their 2-3 year-old. We focus on caregivers’ use of non-arbitrary cues across different expressive channels: both iconic (onomatopoeia and representational gestures) and indexical (points and actions with objects). We ask if these cues are used differently when talking about objects known or unknown to the child, and when the referred objects are present or absent. We hypothesize that caregivers would use these cues more often with objects novel to the child. Moreover, they would use the iconic cues especially when objects are absent because iconic cues bring to the mind’s eye properties of referents. We find that cue distribution differs: all cues except points are more common for unknown objects indicating their potential role in learning; onomatopoeia and representational gestures are more common for displaced contexts whereas indexical cues are more common when objects are present. Thus, caregivers provide multimodal non-arbitrary cues to support children’s vocabulary learning and iconicity – specifically – can support linking mental representations for objects and labels

Sexually dimorphic gene expression in bovine conceptuses at the initiation of implantation

In cattle, maternal recognition of pregnancy occurs on Day 16 via secretion of interferon tau (IFNT) by the conceptus. The endometrium can distinguish between embryos with different developmental competencies. In eutherian mammals, X-chromosome inactivation (XCI) is required to ensure an equal transcriptional level of most X-linked genes for both male and female embryos in adult tissues, but this process is markedly different in cattle than mice. We examined how sexual dimorphism affected conceptus transcript abundance and amino acid composition as well as the endometrial transcriptome during the peri-implantation period of pregnancy. Of the 5132 genes that were differentially expressed on Day 19 in male compared to female conceptuses, 2.7% were located on the X-chromosome. Concentrations of specific amino acids were higher in the uterine luminal fluid of male compared to female conceptuses, while female conceptuses had higher transcript abundance of specific amino acid transporters (SLC6A19 and SLC1A35). Of note, the endometrial transcriptome was not different in cattle gestating a male or a female conceptus. These data support the hypothesis that, far from being a blastocyst specific phenomenon, XCI is incomplete before and during implantation in cattle. Despite differences in transcript abundance and amino acid utilization in male versus female conceptuses, the sex of the conceptus itself does not elicit a different transcriptomic response in the endometrium

IHCV: Discovery of Hidden Time-Dependent Control Variables in Non-Linear Dynamical Systems

Discovering non-linear dynamical models from data is at the core of science. Recent progress hinges upon sparse regression of observables using extensive libraries of candidate functions. However, it remains challenging to model hidden non-observable control variables governing switching between different dynamical regimes. Here we develop a data-efficient derivative-free method, IHCV, for the Identification of Hidden Control Variables. First, the performance and robustness of IHCV against noise are evaluated by benchmarking the IHCV method using well-known bifurcation models (saddle-node, transcritical, pitchfork, Hopf). Next, we demonstrate that IHCV discovers hidden driver variables in the Lorenz, van der Pol, Hodgkin-Huxley, and Fitzhugh-Nagumo models. Finally, IHCV generalizes to the case when only partial observational is given, as demonstrated using the toggle switch model, the genetic repressilator oscillator, and a Waddington landscape model. Our proof-of-principle illustrates that utilizing normal forms could facilitate the data-efficient and scalable discovery of hidden variables controlling transitions between different dynamical regimes and non-linear models.Comment: 12 pages, 2 figure

Sexually dimorphic gene expression in bovine conceptuses at the initiation of implantation

In cattle, maternal recognition of pregnancy occurs on Day 16 via secretion of interferon tau (IFNT) by the conceptus. The endometrium can distinguish between embryos with different developmental competencies. In eutherian mammals, X-chromosome inactivation (XCI) is required to ensure an equal transcriptional level of most X-linked genes for both male and female embryos in adult tissues, but this process is markedly different in cattle than mice. We examined how sexual dimorphism affected conceptus transcript abundance and amino acid composition as well as the endometrial transcriptome during the peri-implantation period of pregnancy. Of the 5132 genes that were differentially expressed on Day 19 in male compared to female conceptuses, 2.7% were located on the X-chromosome. Concentrations of specific amino acids were higher in the uterine luminal fluid with male compared to female conceptuses, while female conceptuses had higher transcript abundance of specific amino acid transporters (SLC6A19 and SLC1A35). Of note, the endometrial transcriptome was not different in cattle gestating a male or a female conceptus. These data support the hypothesis that, far from being a blastocyst specific phenomenon, XCI is incomplete before and during implantation in cattle. Despite differences in transcript abundance and amino acid utilization in male versus female conceptuses, the sex of the conceptus itself does not elicit a different transcriptomic response in the endometrium

Base de datos multicéntrica de hemorragia subaracnoidea espontánea del Grupo de Trabajo de Patología Vascular de la Sociedad Española de Neurocirugía: presentación,criterios de inclusión y desarrollo de una base de datos en internet = Spontaneous Subarachnoid Haemorrhage multicenter database from the Group for the Study of Vascular Pathology of the Spanish Society for Neurosurgery: Presentation, inclusion criteria and development of an internet-based registry

Introducción. La hemorragia subaracnoidea (HSA) continúa siendo una de las enfermedades de interés neuroquirúrgico de más alta morbilidad y mortalidad. Su estudio es clave a la hora de mejorar la atención de estos enfermos en nuestro medio. Con este fin el Grupo de Trabajo de Patología Vascular de la SENEC decidió la creación de una base de datos multicéntrica para su estudio. Material y métodos. Se incluyen en esta base de datos todos los casos de hemorragia subaracnoidea espontánea ingresados en los centros participantes de forma prospectiva desde Noviembre del año 2004 hasta Noviembre del 2007. Se decidieron de forma consensuada los campos a recoger incluyendo edad, antecedentes personales, características clínicas, características radiológicas y del aneurisma, tipo de tratamiento y complicaciones de la enfermedad, evolución según la escala de evolución de Glasgow (GOS) al alta y a los seis meses así como el resultado angiográfico del tratamiento. Todos los campos se recogieron en un formulario rellenable a través de una página web segura. Resultados. En los tres años en los que ha estado activa la base se han recogido un total de 1149 casos de HSA espontánea recogidos por 14 centros participantes. Se ha estimado que es necesario aproximadamente un tiempo de 3.4 minutos para rellenar cada caso. En cuanto a sus características generales la serie es similar a otras series hospitalarias no seleccionadas. La edad media de los enfermos incluidos es de unos 55 años y la relación mujer:hombre 4:3. En cuanto a la gravedad del sagrado inicial un 32% de los enfermos se encontraba en mal grado clínico (WFNS = 4 ó 5). El 5% de los pacientes fallecieron antes de realizarse una angiografía que confirmara el origen aneurismático del sangrado. Se confirmó el origen aneurismático en el 76% de los pacientes mientras que en el 19% no se encontró ninguna lesión vascular responsable del sangrado, siendo clasificados como HSA idiopática. En los pacientes en los que se detectó un aneurisma su tratamiento fue endovascular en el 47% de los casos, quirúrgico en el 39, mixto en el 3% y no recibieron tratamiento de su aneurisma el 11% de los pacientes por fallecimiento precoz. En cuanto a su evolución, la mortalidad global de la serie se sitúa en el 22%. Sólo el 40% de los enfermos con HSA aneurismática presentaron una buena evolución (GOS=5). Conclusiones. La HSA espontánea continúa siendo una enfermedad con alta morbilidad y mortalidad. Esta base de datos puede ser un instrumento para conocer mejor sus características en nuestro medio y mejorar sus resultados, ya que se trata de una serie multicéntrica hospitalaria no seleccionada. Sería pues recomendable que esta base constituyera el germen de un registro nacional de HSA espontánea. Introduction. Subarachnoid haemorrhage is one of the most severe neurosurgical diseases. Its study is crucial for improving the care of these patients in our environment. With this goal the Group for the Study of Neurovascular Pathology of the Spanish Society for Neurosurgery (SENEC) decided to create a multicenter registry for the study of this disease. Materials and methods. In this database we have prospectively included all cases with spontaneous subarachnoid haemorrhage admitted to the participant hospitals from November 2004 to November 2007. The fields to be included in the database were selected by consensus, including age, past medical history, clinical characteristics at admission, radiological characteristics including presence or absence of an aneurysm and its size and location, type and complications of the aneurysm treatment, outcome assessed by the Glasgow Outcome Scale (GOS) at discharge and six months after the bleeding as well as the angiographic result of the aneurysm treatment. All fields were collected by means of an electronic form posted in secure web page. Results. During the three years of study a total of 1149 patients have been included by 14 Hospitals. The time needed to fill in a patient in the registry is approximately 3.4 minutes. This series of patients with spontaneous SAH is similar to other non-selected in-hospital series of SAH. The mean age of the patients is 55 years and there is a 4:3 female to male ratio. In relation to the severity of the bleeding 32% of the patients were in poor clinical grade at admission (WFNS 4 or 5). 5% of the patients died before angiography could be performed. An aneurysm was confirmed as the origin of the bleeding in 76% of the patients (aSAH), while in 19% of the patients no lesion was found in the angiographic studies and were thus classified as idiopathic subarachnoid hemorrhage (ISAH). Of those patients with aSAH, 47% were treated endovascularly, 39% surgically, 3% received a combined treatment and 11% did not receive any treatment for their aneurysm because of early death. Regarding outcome, there is a 22% mortality in the series. Only 40% of the patients with aSAH reached a good outcome at discharge (GOS = 5). Conclusions. Spontaneous SAH continues to be a disease with high morbidity and mortality. This database can be an ideal instrument for improving the knowledge about this disease in our environment and to achieve better results. It would be desirable that this database could in the future be the origin of a national registry of spontaneous SAH

Neglected Tropical Diseases outside the Tropics

Neglected Tropical Diseases (NTDs) have been targeted due to their prevalence and the burden of disease they cause globally, but there has been no significant focus in the literature on the subject of NTDs as a group in immigrants and travelers, and no specific studies on the emerging phenomenon of imported NTDs. We present the experience of a Tropical Medicine Unit in a major European city, over a 19-year period, describing and comparing NTDs diagnosed amongst immigrants, travelers and travelers visiting friends and relatives (VFRs). NTDs were diagnosed outside tropical areas and occurred more frequently in immigrants, followed by VFR travelers and then by other travelers. The main NTDs diagnosed in immigrants were onchocerciasis, Chagas disease and ascariasis; most frequent NTDs in travelers were schistosomiasis, onchocerciasis and ascariasis, and onchocerciasis and schistosomiasis in VFRs. Issues focusing on modes of transmission outside endemic areas and how eradication programs for some NTDs in endemic countries may have an impact in non-tropical Western countries by decreasing disease burden in immigrants, are addressed. Adherence to basic precautions such as safe consumption of food/water and protection against arthropod bites could help prevent many NTDs in travelers

Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial

IMPORTANCE: Immune dysregulation contributes to poorer outcomes in COVID-19. OBJECTIVE: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and December 2021. INTERVENTIONS: Single infusion of abatacept (10 mg/kg; maximum dose, 1000 mg) or infliximab (5 mg/kg) or a 28-day oral course of cenicriviroc (300-mg loading dose followed by 150 mg twice per day). MAIN OUTCOMES AND MEASURES: The primary outcome was time to recovery by day 28 evaluated using an 8-point ordinal scale (higher scores indicate better health). Recovery was defined as the first day the participant scored at least 6 on the ordinal scale. RESULTS: Of the 1971 participants randomized across the 3 substudies, the mean (SD) age was 54.8 (14.6) years and 1218 (61.8%) were men. The primary end point of time to recovery from COVID-19 pneumonia was not significantly different for abatacept (recovery rate ratio [RRR], 1.12 [95% CI, 0.98-1.28]; P = .09), cenicriviroc (RRR, 1.01 [95% CI, 0.86-1.18]; P = .94), or infliximab (RRR, 1.12 [95% CI, 0.99-1.28]; P = .08) compared with placebo. All-cause 28-day mortality was 11.0% for abatacept vs 15.1% for placebo (odds ratio [OR], 0.62 [95% CI, 0.41-0.94]), 13.8% for cenicriviroc vs 11.9% for placebo (OR, 1.18 [95% CI 0.72-1.94]), and 10.1% for infliximab vs 14.5% for placebo (OR, 0.59 [95% CI, 0.39-0.90]). Safety outcomes were comparable between active treatment and placebo, including secondary infections, in all 3 substudies. CONCLUSIONS AND RELEVANCE: Time to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04593940