Micronized natural progesterone (Seidigestan®) vs GnRH antagonists for preventing the LH surge during controlled ovarian stimulation (PRO_NAT study): study protocol of a randomized clinical trial.

Introduction: Progesterone-primed cycles effectively suppress the pituitary LH surge during ovarian stimulation in oocyte donors and in the infertile population. Particularly in oocyte donors, the use of synthetic progesterone (progestins) has been explored in prospective clinical trials, showing mixed results. This trial was designed to determine whether the use of micronized natural progesterone is as effective as the GnRH-antagonist protocol in terms of the number of mature oocytes (MII) retrieved in oocyte donation cycles as a primary outcome, and it also aims to explore the corresponding results in recipients as a secondary outcome. Methods: We propose a prospective, open-label, non-inferiority clinical trial to compare a novel approach for oocyte donors with a control group, which follows the standard ovarian stimulation protocol used in our institution. A total of 150 donors (75 in each group) will be recruited and randomized using a computer algorithm. After obtaining informed consent, participants will be randomly assigned to one of two ovarian stimulation protocols: either the standard GnRH antagonist or the oral micronized natural progesterone protocol. Both groups will receive recombinant gonadotropins tailored to their antral follicle count and prior donation experiences, if any. The primary outcome is the number of mature metaphase II (MII) oocytes. Secondary measures include treatment duration, pregnancy outcomes in recipients, as well as the economic cost per MII oocyte obtained in each treatment regimen. Analyses for the primary outcome will be conducted in both the intention-to-treat (ITT) and per-protocol (PP) populations. Each donor can participate only once during the recruitment period. The estimated duration of the study is six months for the primary outcome and 15 months for the secondary outcomes. Discussion: The outcomes of this trial have the potential to inform evidence-based adjustments in the management of ovarian stimulation protocols for oocyte donors. Clinical trial registration: ClinicalTrials.gov, identifier, NCT05954962.

Brain MRI without anesthesia in children less than 3 months old.

INTRODUCTION: The use of general anesthesia in infants involves both short-term and long-term risks. The aim of this study is to evaluate the efficacy of brain MRI without anesthesia in infants younger than 3-month-old immobilized with a pillow. PATIENTS AND METHODS: This prospective case-control study was done in 2019. Cases were stable patients less than 3 months old who did not require ventilatory support for whom brain MRI was indicated. Patients were fed so they would fall asleep and placed in the scanner with an immobilizing pillow. Controls were clinically unstable patients matched for age and sex referred for brain MRI under general anesthesia. Three pediatric radiologists evaluated the success of the MRI study (whether it answered the clinical question), recorded whether it was necessary to repeat the study, and rated the presence of motion artifacts on a scale ranging from 1 to 4. RESULTS: A total of 47 cases were included (28 boys and 19 girls; mean age, 31 days). Of these, 42 (89%) MRI studies were considered successful. The proportion of successful MRI studies was lower in outpatients than in inpatients (p = 0.02). The quality of MRI in cases was considered optimal in 60% and suboptimal (motion artifacts in one or two sequences) in 30%. No safety issues related with the technique were detected. The mean duration of the studies was 16.6 min (range, 6-30 min). All of the MRI studies in controls were considered successful; quality was considered optimal in 89% and suboptimal in 11%. In the first year in which we used this technique, we avoided the use of general anesthesia in 47 MRI studies in 42 newborns. CONCLUSION: Brain MRI using the feed and sleep technique in infants younger than 3-month-old immobilized with a pillow can be done safely and efficaciously without general anesthesia.

Neuroinvasive disease due to West Nile virus: Clinical and imaging findings associated with a re-emerging pathogen.

The West Nile virus (WNV) is an arbovirus than can infect human beings and cause severe neuroinvasive disease. Taking the outbreak that occurred in Spain in 2020 as a reference, this article reviews the clinical and imaging findings for neuroinvasive disease due to WNV. We collected demographic, clinical, laboratory, and imaging (CT and MRI) variables for 30 patients with WNV infection diagnosed at our center. The main clinical findings were fever, headache, and altered levels of consciousness. Neuroimaging studies, especially MRI, are very useful in the diagnosis and follow-up of these patients. The most common imaging findings were foci of increased signal intensity in the thalamus and brainstem in T2-weighted sequences; we illustrate these findings in cases from our hospital.

Resonancia magnética cerebral sin anestesia en niños menores de 3 meses / Brain MRI without anesthesia in children less than 3 months old

Introducción: El uso de anestesia general en niños pequeños conlleva riesgos, a corto y largo plazo. El objetivo de este estudio fue evaluar la eficacia de la técnica de resonancia magnética (RM) cerebral sin anestesia mediante fijación con colchón en niños menores de 3 meses. Pacientes y métodos: Estudio prospectivo de casos y controles realizado en el año 2019. Los casos fueron pacientes menores de 3 meses con indicación de RM craneal, estables y sin soporte ventilatorio; las resonancias se realizaron usando la técnica de dar de comer y dormir y un colchón inmovilizador. Los controles fueron pacientes de la misma edad y sexo, inestables clínicamente, derivados para realizar RM craneal con anestesia general. Tres radiólogos pediátricos evaluaron el éxito de la RM (si respondía a la pregunta clínica), si era necesario repetirla y calificaron la presencia de artefactos de movimiento en una escala del 1 al 4. Resultados: 47 casos fueron incluidos en este estudio (28 niños, 19 niñas; media: 31 días de vida), de los cuales (89%) 42 RM fueron llevadas a cabo de manera exitosa. Los estudios realizados de manera ambulatoria se asociaron a mayor posibilidad de fallo de la técnica que los realizados a ingresados (valor de p 0,02). El 60% de las RM de los casos realizados tuvieron calidad óptima y el 30%, subóptima (artefacto de movimiento en una o dos secuencias). No se detectaron problemas de seguridad con esta técnica. La media de duración de los estudios fue de 16,6 minutos (rango 6-30 minutos). El 100% de las RM de los controles bajo anestesia general se llevaron a cabo con éxito, con una calidad óptima en el 89% y subóptima en el 11% restante. En el primer año de experiencia con esta técnica, de 47 RM realizadas, se evitó el uso de anestesia general a 42 recién nacidos. Conclusión: La técnica de dar de comer y dormir y fijación con colchón neumático para realizar RM sin anestesia puede realizarse de forma eficaz y segura en niños menores de 3 meses.(AU)

Introduction: The use of general anesthesia in infants involves both short-term and long-term risks. The aim of this study is to evaluate the efficacy of brain MRI without anesthesia in infants younger than 3-month-old immobilized with a pillow. Patients and methods: This prospective case-control study was done in 2019. Cases were stable patients less than 3 months old who did not require ventilatory support for whom brain MRI was indicated. Patients were fed so they would fall asleep and placed in the scanner with an immobilizing pillow. Controls were clinically unstable patients matched for age and sex referred for brain MRI under general anesthesia. Three pediatric radiologists evaluated the success of the MRI study (whether it answered the clinical question), recorded whether it was necessary to repeat the study, and rated the presence of motion artifacts on a scale ranging from 1 to 4. Results: A total of 47 cases were included (28 boys and 19 girls; mean age, 31 days). Of these, 42 (89%) MRI studies were considered successful. The proportion of successful MRI studies was lower in outpatients than in inpatients (p=0.02). The quality of MRI in cases was considered optimal in 60% and suboptimal (motion artifacts in one or two sequences) in 30%. No safety issues related with the technique were detected. The mean duration of the studies was 16.6minutes (range, 6-30minutes). All of the MRI studies in controls were considered successful; quality was considered optimal in 89% and suboptimal in 11%. In the first year in which we used this technique, we avoided the use of general anesthesia in 47 MRI studies in 42 newborns. Conclusion: Brain MRI using the feed and sleep technique in infants younger than 3-month-old immobilized with a pillow can be done safely and efficaciously without general anesthesia.(AU)

Enfermedad neuroinvasiva por el virus del Nilo Occidental: características clínicas y en neuroimagen de un patógeno reemergente / Neuroinvasive disease due to West Nile virus: clinical and imaging findings associated with a re-emerging pathogen

El virus del Nilo Occidental es un arbovirus que puede infectar al ser humano y causar una enfermedad neuroinvasiva grave. Tomando como referencia el brote que tuvo lugar en España en 2020, se ha realizado una revisión clínica y de neuroimagen de dicha patología. Para ello, se han recogido datos demográficos, clínicos, analíticos y pruebas de imagen (tomografía computarizada y resonancia magnética) de 30 pacientes diagnosticados de infección por virus del Nilo Occidental en nuestro centro. Las principales manifestaciones clínicas fueron fiebre, cefalea y alteración del nivel de conciencia. Los estudios de neuroimagen, especialmente la resonancia, son de gran importancia para el diagnóstico y seguimiento. Los hallazgos más frecuentes fueron focos de aumento de señal en T2 en el tálamo y tronco del encéfalo, que ilustramos en esta revisión con casos de nuestro centro hospitalario.(AU)

The West Nile virus (WNV) is an arbovirus than can infect human beings and cause severe neuroinvasive disease. Taking the outbreak that occurred in Spain in 2020 as a reference, this article reviews the clinical and imaging findings for neuroinvasive disease due to WNV. We collected demographic, clinical, laboratory, and imaging (CT and MRI) variables for 30 patients with WNV infection diagnosed at our center. The main clinical findings were fever, headache, and altered levels of consciousness. Neuroimaging studies, especially MRI, are very useful in the diagnosis and follow-up of these patients. The most common imaging findings were foci of increased signal intensity in the thalamus and brainstem in T2-weighted sequences; we illustrate these findings in cases from our hospital.(AU)

Neuroinvasive disease due to West Nile virus: clinical and imaging findings associated with a re-emerging pathogen. / Enfermedad neuroinvasiva por el virus del Nilo Occidental: características clínicas y en neuroimagen de un patógeno reemergente.

The West Nile virus (WNV) is an arbovirus than can infect human beings and cause severe neuroinvasive disease. Taking the outbreak that occurred in Spain in 2020 as a reference, this article reviews the clinical and imaging findings for neuroinvasive disease due to WNV. We collected demographic, clinical, laboratory, and imaging (CT and MRI) variables for 30 patients with WNV infection diagnosed at our center. The main clinical findings were fever, headache, and altered levels of consciousness. Neuroimaging studies, especially MRI, are very useful in the diagnosis and follow-up of these patients. The most common imaging findings were foci of increased signal intensity in the thalamus and brainstem in T2-weighted sequences; we illustrate these findings in cases from our hospital.

Brain MRI without anesthesia in children less than 3 months old. / Resonancia magnética cerebral sin anestesia en niños menores de 3 meses.

INTRODUCTION: The use of general anesthesia in infants involves both short-term and long-term risks. The aim of this study is to evaluate the efficacy of brain MRI without anesthesia in infants younger than 3-month-old immobilized with a pillow. PATIENTS AND METHODS: This prospective case-control study was done in 2019. Cases were stable patients less than 3 months old who did not require ventilatory support for whom brain MRI was indicated. Patients were fed so they would fall asleep and placed in the scanner with an immobilizing pillow. Controls were clinically unstable patients matched for age and sex referred for brain MRI under general anesthesia. Three pediatric radiologists evaluated the success of the MRI study (whether it answered the clinical question), recorded whether it was necessary to repeat the study, and rated the presence of motion artifacts on a scale ranging from 1 to 4. RESULTS: A total of 47 cases were included (28 boys and 19 girls; mean age, 31 days). Of these, 42 (89%) MRI studies were considered successful. The proportion of successful MRI studies was lower in outpatients than in inpatients (p=0.02). The quality of MRI in cases was considered optimal in 60% and suboptimal (motion artifacts in one or two sequences) in 30%. No safety issues related with the technique were detected. The mean duration of the studies was 16.6minutes (range, 6-30minutes). All of the MRI studies in controls were considered successful; quality was considered optimal in 89% and suboptimal in 11%. In the first year in which we used this technique, we avoided the use of general anesthesia in 47 MRI studies in 42 newborns. CONCLUSION: Brain MRI using the feed and sleep technique in infants younger than 3-month-old immobilized with a pillow can be done safely and efficaciously without general anesthesia.

Mujer fértil con rectorragia periódica / Fertile woman with periodic rectal bleeding

No disponible

[Dynamic magnetic resonance imaging in the diagnosis of tumors and pseudotumors of the musculoskeletal system]. / Resonancia magnética dinámica en el diagnóstico de las lesiones tumorales y seudotumorales del sistema musculoesquelético.

The greater temporal resolution provided in ultrafast dynamic contrast-enhanced magnetic resonance imaging sequences makes it possible to know the physiological phenomenon of the distribution of the contrast material through a time-signal intensity curve. Analyzing these curves enables us to deduce information relevant to the vascularization and perfusion of tissues, capillary permeability, and the interstitial space in the tumor. A steep curve with early washout in a space-occupying lesion greatly increases the possibility of histological malignancy, although this type of curve is not rare in benign lesions and relatively flat curves are not rare in malignant tumors. Nevertheless, dynamic studies of the uptake of contrast material provide important information for the characterization of neoplasms that, together with the usual signs, can help to differentiate between benign and malignant tumors of adipocyte, chondroid, or neural lineage, clearing up diagnostic uncertainty in certain benign lesions such as osteoid osteoma and ischemic musculoskeletal disease. Furthermore, it enables the accurate determination of the response to chemotherapy, detecting recurrence within the treated tumor early, delimiting more precisely the margins between the tumor and peritumoral edema, and helping in diagnostic planning by determining the most vascularized areas of the tumor, which are more likely to be malignant.

Resonancia magnética dinámica en el diagnóstico de las lesiones tumorales y seudotumorales del sistema musculoesquelético / Dynamic magnetic resonance imaging in the diagnosis of tumors and pseudotumors of the musculoskeletal system

La mayor resolución temporal que ofrece la secuencia de imágenes ultrarrápidas de la resonancia magnética contrastada dinámica (RMD), permite conocer el fenómeno fisiológico de la distribución del contraste mediante una curva de intensidad de señal-tiempo (TIC), de cuyo análisis puede deducirse información relevante sobre la vascularización y perfusión tisular, la permeabilidad capilar y el espacio intersticial del tumor. El hallazgo de una curva de pendiente elevada con lavado precoz de contraste en una lesión ocupante de espacio aumenta sensiblemente la posibilidad de malignidad histológica, aunque no es raro el hallazgo de curvas de este tipo en lesiones histológicamente benignas y de curvas de perfil relativamente plano en tumores de reconocida malignidad. A pesar de todo, los estudios dinámicos de captación pueden aportar información de gran interés en el proceso de caracterización de las lesiones neoformativas, ayudando a los restantes datos semiológicos habituales a diferenciar las formas malignas de las benignas en las tumoraciones de estirpe adipocítica, condroide o neural, confirmando dudas diagnósticas en determinadas lesiones benignas como el osteoma osteoide y la patología isquémica osteomuscular, permitiendo determinar con precisión el grado de respuesta a la quimioterapia, detectando con precocidad la recidiva en el seno del tumor tratado, delimitando con mayor exactitud los márgenes del tumor frente al edema peritumoral y ayudando a la planificación diagnóstica al determinar las áreas más vascularizadas y, por tanto, más probablemente malignas del tumor (AU)

The greater temporal resolution provided in ultrafast dynamic contrast-enhanced magnetic resonance imaging sequences makes it possible to know the physiological phenomenon of the distribution of the contrast material through a time-signal intensity curve. Analyzing these curves enables us to deduce information relevant to the vascularization and perfusion of tissues, capillary permeability, and the interstitial space in the tumor. A steep curve with early washout in a space-occupying lesion greatly increases the possibility of histological malignancy, although this type of curve is not rare in benign lesions and relatively flat curves are not rare in malignant tumors. Nevertheless, dynamic studies of the uptake of contrast material provide important information for the characterization of neoplasms that, together with the usual signs, can help to differentiate between benign and malignant tumors of adipocyte, chondroid, or neural lineage, clearing up diagnostic uncertainty in certain benign lesions such as osteoid osteoma and ischemic musculoskeletal disease. Furthermore, it enables the accurate determination of the response to chemotherapy, detecting recurrence within the treated tumor early, delimiting more precisely the margins between the tumor and peritumoral edema, and helping in diagnostic planning by determining the most vascularized areas of the tumor, which are more likely to be malignant (AU)

Varicocele, leucocitospermia y su impacto en la fragmentación del ADN espermático / Varicocele, leukocytospermia and its impact on the spermatic DNA fragmentation

Introducción: El estrés oxidativo en una de las causas que puede explicar la presencia de unos niveles elevados de daño en la molécula de ADN. En 2 cuadros clínicos que afectan a la línea germinal del varón, la leucocitospermia y el varicocele, se reconoce la incidencia de niveles elevados de estrés oxidativo. Objetivos: En el presente trabajo se compararon 2 cuadros clínicos, varicocele y leucocitospermia, con objeto de comprobar si existe una intensidad diferencial de la fragmentación del ADN espermático. Material y métodos: Se incluyeron como controles externos donantes de espermatozoides con fertilidad probada y pacientes con factor masculino no determinado. A diferencia de otros estudios de fragmentación del ADN espermático, en este caso, se consideraron tanto los niveles de fragmentación absolutos (SDF), como la proporción de espermatozoides degradados en el total de fragmentados (índice de degradación [ID]) de acuerdo con la información obtenida tras la aplicación del test Halosperm. Resultados: Se demostró un aumento muy significativo de la fragmentación del ADN espermático en las muestras seminales de pacientes con varicocele y con leucocitospermia. Los pacientes con varicocele mostraron un ID 2 veces mayor que el observado en pacientes con factor masculino no determinado o en pacientes con leucocitospermia, y 6 veces mayor que en los donantes. Discusión: La presencia de unos niveles de estrés oxidativo elevados podría ser una explicación asumible para justificar los altos niveles de daño observado en los espermatozoides de los pacientes tanto con varicocele como con leucocitospermia, pero probablemente estos niveles sean más elevados en el caso del varicocele ya que los niveles de degradación del ADN espermático son superiores a los observados en cuadros de leucocitospermia... (AU)

Introduction: High levels of oxidative stress can explain the presence of high levels of damage in the DNA molecule. The impact of high levels of oxidative stress in 2 clinical circumstances affecting the male germ line has been well established: leukocytospermia and varicocele. Objective: To assess sperm DNA fragmentation in patients diagnosed with leukocytospermic and varicocele. Material and methods: Leukocytospermic and varicocele patients and external controls (donors with proven fertility and patients with undetermined male factor). Unlike in other studies of sperm DNA fragmentation, in this study both the proportion of damaged sperm after using the sperm chromatin dispersion test (Halosperm), and the proportion of degraded sperm in total fragmented (degradation index [DI]) were taken into consideration. Results: A highly significant increase in sperm DNA fragmentation has been observed in semen samples of patients with varicocele and leukocytospermia. Varicocele patients showed a DI twice as high as that observed in patients with undetermined male factor or in patients with leukocytospermia, and 6 times as high as that observed in the donors. Discussion: The presence of high levels of oxidative stress could be an acceptable explanation for the high levels of damage observed in the spermatozoa of varicocele patients or with leukocytospermia; the level of sperm degradation is higher in the case of varicocele than those observed in leukocytospermia. Conclusions: SDF levels in patients with leukocytospermia and varicocele are significantly higher than those observed in donors or men with undetermined male factor. The DI in sperm samples from patients with varicocele is the highest of all the samples studied in this analysis. The routine determination of the DI may have a practical value, by guiding the patient towards the potential diagnosis of varicocele, even when this is subclinical (AU)

Factor masculino: tratamiento del varón o del semen / No disponible

No disponible

Changes in thymus volume in adult HIV-infected patients under HAART: correlation with the T-cell repopulation.

An important thymus role has been suggested in T-cell repopulation after HAART in adult HIV-1 infected patients. Thymus volume increase after treatment has been described in HIV-1 infected children but not in adult patients. The objective of this work was to evaluate the effect of HAART on the thymic volume of adult HIV-1 infected patients and its relation with the T-cell repopulation. Twenty-one adult patients following 24 weeks under HAART were included in the study. All patients underwent a thoracic computed tomography (CT) evaluation for the measurement of thymic volumes at weeks 0, 12 and 24. Baseline thymus volume showed a significant correlation with the patient's age. Thymic volume significantly increased after 24 weeks of HAART. Besides, a significant correlation between changes in the thymus volume and changes in both total and naïve CD4+ cell counts was found. Only patients with increases > or =100 CD4+ cell counts after treatment significantly increased the thymic volume. These data show the first evidence of an early change in thymic volume of adult HIV-1 infected patients under HAART. This increase was related to the rise of both total and naïve CD4+ cell counts suggesting a functional role of thymic volume increase.

Salmonella enterica serovar Typhimurium response involved in attenuation of pathogen intracellular proliferation.

Salmonella enterica serovar Typhimurium proliferates within cultured epithelial and macrophage cells. Intracellular bacterial proliferation is, however, restricted within normal fibroblast cells. To characterize this phenomenon in detail, we investigated the possibility that the pathogen itself might contribute to attenuating the intracellular growth rate. S. enterica serovar Typhimurium mutants were selected in normal rat kidney fibroblasts displaying an increased intracellular proliferation rate. These mutants harbored loss-of-function mutations in the virulence-related regulatory genes phoQ, rpoS, slyA, and spvR. Lack of a functional PhoP-PhoQ system caused the most dramatic change in the intracellular growth rate. phoP- and phoQ-null mutants exhibited an intracellular growth rate 20- to 30-fold higher than that of the wild-type strain. This result showed that the PhoP-PhoQ system exerts a master regulatory function for preventing bacterial overgrowth within fibroblasts. In addition, an overgrowing clone was isolated harboring a mutation in a previously unknown serovar Typhimurium open reading frame, named igaA for intracellular growth attenuator. Mutations in other serovar Typhimurium virulence genes, such as ompR, dam, crp, cya, mviA, spiR (ssrA), spiA, and rpoE, did not result in pathogen intracellular overgrowth. Nonetheless, lack of either SpiA or the alternate sigma factor RpoE led to a substantial decrease in intracellular bacterial viability. These results prove for the first time that specific serovar Typhimurium virulence regulators are involved in a response designed to attenuate the intracellular growth rate within a nonphagocytic host cell. This growth-attenuating response is accompanied by functions that ensure the viability of intracellular bacteria.

Protein kinase C mu selectively activates the mitogen-activated protein kinase (MAPK) p42 pathway.

Here we show that human protein kinase C mu (PKC mu) activates the mitogen-activated protein kinase (MAPK). Transient expression of constitutive active PKC mu leads to an activation of Raf-1 kinase as demonstrated by in vitro phosphorylation of MAPK. PKC mu enhances transcriptional activity of a basal thymidine kinase promotor containing serum response elements (SREs) as shown by luciferase reporter gene assays. SRE driven gene activation by PKC mu is triggered by the Elk-1 ternary complex factor. PKC mu-mediated activation of SRE driven transcription can be inhibited by the MEK1 inhibitor PD98059. In contrast to the activation of the p42/ERK1 MAPK cascade, transient expression of constitutive active PKC mu does neither affect c-jun N-terminal kinase nor p38 MAPK.

Inhibition of Salmonella intracellular proliferation by non-phagocytic eucaryotic cells.

Salmonella typhimurium is an intracellular pathogen capable of proliferating within vacuolar compartments of non-phagocytic eucaryotic cells. This process has been shown to be essential for virulence in the mouse typhoid model (Leung and Finlay, Proc. Natl. Acad. Sci. USA, 88, 11470-11474, 1990). Here we present evidence that certain non-phagocytic eucaryotic cell lines, such as 3T3 (mouse fibroblasts) and NRK (rat fibroblasts) cells, are not permissive for S. typhimurium intracellular proliferation. Moreover, viability of intracellular bacteria residing within both cell types notably decreases at late postinfection times (72 h). These results clearly demonstrate that non-phagocytic eucaryotic cells are capable of destroying intracellular S. typhimurium. Experimentation with 3T3 and NRK cell lines might provide an appropriate in vitro model for identifying new bacterial and/or eucaryotic factors regulating Salmonella intracellular proliferation within vacuoles of the host eucaryotic cell.