Predictive characteristics of male fertility in alpacas with special reference to seminal NGF.

Recent studies document the LH-releasing pathway of nerve growth factor (NGF) in male camelids and that the LH response to seminal NGF is associated with elevated plasma testosterone concentration. Results provide rationale for the hypothesis that NGF in semen is associated with male fertility. In Experiment 1, the association between the amount of NGF in the ejaculate and characteristics of the male reproductive system was examined in alpacas. The concentration of NGF was measured by radioimmunoassay in semen samples collected from male alpacas (n = 47) and correlated with sperm morphology and motility, and measurements of the male reproductive anatomy. Most ejaculates had NGF concentrations that, based on previous studies, triggered ovulation in female camelids, however, we only found a positive correlation between NGF concentration with sperm concentration, thread formation and total NGF, and a negative correlation with pH. In Experiment 2, a retrospective analysis was carried out to determine if breeding performance during the previous season was related to recent concentrations of seminal NGF in male alpacas (n = 22). Birth rates tended to be correlated with sperm concentration and total amount of NGF in the ejaculate (P = 0.09). Experiment 3 was a prospective study to determine the relationship between seminal NGF (n = 8 male alpacas) and ovulation and pregnancy rates in a breeding trial. No association was detected between seminal NGF concentration and ovulation rate, pregnancy rate, or LH response in the female. We conclude that among the breeding males used in our study, the abundance of seminal NGF was correlated with sperm concentration and thread formation, however, it was not predictive of male fertility in alpacas. Examination of males not previously selected as breeding stock may be expected to include a broader range of seminal NGF and provide a more comprehensive understanding of the relationship between seminal NGF and male fertility.

Development and Biodistribution of a Nerve Growth Factor Radioactive Conjugate for PET Imaging.

PURPOSE: The purpose of these studies was to develop a nerve growth factor (NGF) radiometal-chelator conjugate to determine the biodistribution and brain uptake of NGF by positron emission tomography/computerized tomography (PET-CT). PROCEDURES: Purified NGF from llama seminal plasma was conjugated with FITC, and the chelator NOTA or DFO. NGF conjugates were evaluated for bioactivity. NOTA- and DFO-conjugated NGF were radiolabeled with gallium-68 or zirconium-89 ([68 Ga]GaCl3, half-life = 68 min; [89Zr]Zr(oxalate)4, half-life = 3.3 days). [89Zr]Zr-NGF was evaluated for biodistribution (0.5, 1, or 24 h), PET imaging (60 min), and brain autoradiography in mice. RESULTS: Cell-based in vitro assays confirmed that the NGF conjugates maintained NGF receptor-binding and biological activity. Zirconium-89 and gallium-68 radiolabeling showed a high efficiency; however, only[89Zr]Zr-NGF was stable in vitro. Biodistribution studies showed that, as with most small proteins < 70 kDa, [89Zr]Zr-NGF uptake was predominantly in the kidney and was cleared rapidly with almost complete elimination of NGF at 24 h. Dynamic PET imaging from 0-60 min showed a similar pattern to ex vivo biodistribution with some transient liver uptake. Interestingly, although absolute brain uptake was very low, at 24 h after treatment, cerebral cortex uptake was higher than any other brain area examined and blood. CONCLUSIONS: We conclude that conjugation of DFO to NGF through a thiourea linkage allows effective radiolabeling with zirconium-89 while maintaining NGF bioactivity. Following intravenous administration, the radiolabeled NGF targets non-neuronal tissues (e.g., kidney, liver), and although absolute brain uptake was very low, the brain uptake that was observed was restricted to the cortex.

Duct-like Recess in the Infundibular Portion of Third Ventricle Craniopharyngiomas: An MRI Sign Identifying the Papillary Type.

BACKGROUND AND PURPOSE: Papillary craniopharyngiomas (PCPs) are particularly challenging lesions requiring accurate diagnosis to plan the best therapy. Our aim was to define a narrow duct-like recess identified on MR imaging at the base of papillary craniopharyngiomas with a strict third ventricle location. MATERIALS AND METHODS: A duct-like recess at the infundibular portion of craniopharyngiomas was observed on conventional T1WI and T2WI in 3 strict third ventricle papillary craniopharyngiomas in our craniopharyngioma series (n = 125). We systematically investigated this finding on the MR imaging of 2582 craniopharyngiomas and 10 other categories of third ventricle tumors (n = 690) published in the modern era (1986-2020). The diagnostic value and significance of this finding are addressed. RESULTS: The duct-like recess was recognized in 52 papillary craniopharyngiomas, including 3 of our own cases, as a narrow canal-shaped cavity invaginated at the tumor undersurface, just behind the optic chiasm. This structure largely involves papillary craniopharyngiomas with a strict third ventricle topography (96%), follows the same diagonal trajectory as the pituitary stalk, and finishes at a closed end. The duct-like recess sign identifies the papillary craniopharyngioma type with a specificity of 100% and a sensitivity of 38% in the overall craniopharyngioma population. This finding can also establish the strictly intra-third ventricle location of the lesion with a 90% specificity and 33% sensitivity. These recesses appear as hypointense circular spots on axial/coronal T1WI and T2WI. Their content apparently corresponds to CSF freely flowing within the suprasellar cistern. CONCLUSIONS: The presence of a duct-like recess at the infundibular portion of a third ventricle tumor represents a distinctive hallmark of papillary craniopharyngiomas that can be used as a simple MR imaging sign to reliably diagnose these lesions.

RADIOPROTECTION SURVEILLANCE OF THE TJ-II OPERATION BY TLD.

The TJ-II stellarator presently in operation at the National Laboratory of Fusion is subject to radiological surveillance in compliance with the Spanish Nuclear Regulation. During its pulsed operation hard X-rays are emitted by the runaway electrons, and soft X-rays are generated by bremsstrahlung of thermalized electrons. Inside the experimental hall, the plasma heating systems and some active diagnostics are additional sources of radiation. Outside the experimental hall, some auxiliary systems, such as high-voltage power supplies, must be checked for radiological influence. In order to verify the adequate radiological classification of the different working areas, 15 dosemeters are distributed in radiologically controlled areas close to the machine, as well as in areas of public use in the TJ-II building. The integrated dose equivalent is analyzed to help establish the range of radiological influence of the stellarator. The results of the period 2015-20 are presented and analyzed.

La Jument lighthouse: a real-scale laboratory for the study of giant waves and their loading on marine structures.

This paper presents results from an experiment designed to improve the understanding of the relationship between extreme breaking waves and their mechanical loading on heritage offshore lighthouses. The experiment, conducted at La Jument, an iconic French offshore lighthouse, featured several records of wave, current and structure accelerations acquired during severe storm conditions, with individual waves as high as 24 m. Data analysis focuses on a storm event marked by a strong peak in the horizontal accelerations measured inside La Jument. Thanks to stereo-video wave measurements synchronized to the acceleration record we were able to identify and describe the breaking wave responsible for this intense loading. Our observations suggest that this giant wave (19 m high) had a crest elevation high enough to directly hit the lighthouse tower, above the substructure. This paper reveals the potential for conducting ambitious field experiments from offshore lighthouses in order to collect valuable storm waves and wave loading observations. This offers a possible second service life for these heritage structures as in situ laboratories dedicated to the study of the coastal hydrodynamics and its interaction with marine structures. This article is part of the theme issue 'Environmental loading of heritage structures'.

Protein arginine methyltransferase 5 has prognostic relevance and is a druggable target in multiple myeloma.

Arginine methyltransferases critically regulate cellular homeostasis by modulating the functional outcome of their substrates. The protein arginine methyltransferase 5 (PRMT5) is an enzyme involved in growth and survival pathways promoting tumorigenesis. However, little is known about the biologic function of PRMT5 and its therapeutic potential in multiple myeloma (MM). In the present study, we identified and validated PRMT5 as a new therapeutic target in MM. PRMT5 is overexpressed in patient MM cells and associated with decreased progression-free survival and overall survival. Either genetic knockdown or pharmacological inhibition of PRMT5 with the inhibitor EPZ015666 significantly inhibited growth of both cell lines and patient MM cells. Furthermore, PRMT5 inhibition abrogated NF-κB signaling. Interestingly, mass spectrometry identified a tripartite motif-containing protein 21 TRIM21 as a new PRMT5-partner, and we delineated a TRIM21-dependent mechanism of NF-κB inhibition. Importantly, oral administration of EPZ015666 significantly decreased MM growth in a humanized murine model of MM. These data both demonstrate the oncogenic role and prognostic relevance of PRMT5 in MM pathogenesis, and provide the rationale for novel therapies targeting PRMT5 to improve patient outcome.

Perfil de incidencia de VIH en embarazadas atendidas en el Instituto Nacional Materno Perinatal de Lima, Perú / Incidence rate of HIV in pregnant women attended at the Instituto Nacional Materno Perinatal of Lima, Perú

Resumen OBJETIVO Determinar la incidencia de la infección por VIH en mujeres embarazadas atendidas en el Instituto Nacional Materno Perinatal de Lima, Perú (2007-2016). MATERIAL Y MÉTODOS Estudio observacional, descriptivo y retrospectivo. Revisión de los resultados de los exámenes diagnósticos de VIH de mujeres embarazadas efectuados según la normativa nacional vigente que incluye las pruebas de tamizaje (inmunocromatografía o ELISA). Los reportes positivos se corroboran con exámenes confirmatorios (inmunofluorescencia indirecta y western blot). Determinación de la incidencia de VIH de acuerdo con la tendencia anual; aplicación de la correlación de Pearson y prueba de χ2 para comparar las características del perfil de incidencia. RESULTADOS Se tamizaron 113,258 mujeres embarazadas y la incidencia obtenida fue de 2.9 por cada mil. La tendencia anual fue errática, excepto entre 2014 y 2016 años en los que se advirtió una tendencia a disminuir. Solo se tamizó a 22.7% de las parejas masculinas en quienes la seroconcordancia fue 10.3%, y la serodiscordancia 12.4%. La frecuencia de seroconcordancia se correlacionó directamente con el porcentaje de parejas tamizadas e inversamente con la frecuencia de VIH (p<0.05). La condición de convivencia o madre soltera se asoció con mayor frecuencia a la falta de tamizaje de la pareja (p<0.001). CONCLUSIONES La incidencia de VIH confirmado fue errática (2007-2016). Deben proponerse estrategias para incrementar el tamizaje en las parejas de las embarazadas infectadas, teniendo en cuenta la alta frecuencia de inestabilidad de ese tipo de unión.

Abstract OBJECTIVE To determine the incidence of HIV infection in pregnant women treated at the National Maternal and Perinatal Institute (Lima, Peru), between 2007-2016. MATERIAL AND METHODS Observational, descriptive and retrospective study. The results of the diagnostic tests of HIV in pregnant women were reviewed, carried out according to current national regulations, which includes the screening tests (immunochromatography and / or ELISA), which in case of being reactive were corroborated by confirmatory tests (indirect immunofluorescence and Western Blot). The incidence of HIV was measured according to the annual trend, and the Pearson correlation and χ2 test were applied to compare the characteristics of the incidence profile. RESULTS 113,258 pregnant women were screened, obtaining an incidence of 2.91 per thousand pregnant women, the annual trend was erratic, except between 2014 and 2016 where there was a tendency to decrease. Only 22.73% of the couples of the pregnant women were screened, the seroconcordance was 10.3%, and the serodiscordance was 12.42%. The frequency of seroconcordance correlated directly with the percentage of sifted couples and inversely with the frequency of HIV (p <0.05). The condition of coexistence or single mother was associated more frequently with the lack of screening of the couple (p <0.001). CONCLUSIONS The confirmed incidence of HIV was erratic (2007-2016). Strategies should be elaborated to increase the screening in the pairs of the infected pregnant women, taking into account the high frequency of the instability of said union.

Fiebre-fobia nosocomial: un miedo contagioso / Nosocomial fever phobia: an infectious fear

Introducción: En 1980, Schmitt introdujo el término «fiebre-fobia» para referirse al miedo injustificado que los padres presentaban ante la fiebre de los niños. Más de 35 años después, el temor infundado persiste. El objetivo principal de este trabajo era realizar una encuesta a los trabajadores de cuatro hospitales públicos y analizar el grado de conocimiento sobre la fiebre en niños. Pacientes y métodos: Estudio descriptivo, transversal y multicéntrico. Se enviaron 4.830 encuestas anónimas por correo electrónico a los participantes, entre el 15 de septiembre y el 15 de octubre de 2015. Se llevó a cabo un análisis estadístico mediante el programa SPSS v22.0. Se estimó como suficiente un tamaño muestral de 450 respuestas, con un error <4,4% y un intervalo de confianza del 95% (heterogeneidad del 50%). Resultados: Se obtuvieron 462 respuestas de los participantes. Un 75% eran mujeres, un 56% tenían menos de 35 años, un 81% eran profesionales sanitarios y un 60% tenían hijos. Respecto al conocimiento sobre la fiebre, un 83% cree que deben usarse las medidas físicas (no recomendado), un 60% piensa que el tratamiento precoz previene las convulsiones (falso), un 56% considera que siempre se debe tratar aunque el niño se encuentre bien (erróneo) y un 41% cree que se deben combinar antitérmicos (incorrecto). Un 86% de los encuestados reconoce que la fiebre-fobia existe. Hay diferencias significativas en los resultados entre sanitarios y no sanitarios, entre encuestados con hijos y sin hijos, e incluso entre sexos. Conclusiones: Un importante porcentaje de los trabajadores hospitalarios, médicos y pediatras incluidos, desconocen las actuales recomendaciones sobre la fiebre en niños. Este desconocimiento favorece la persistencia de la fiebre-fobia, un miedo contagioso que da lugar a tratamientos innecesarios. Se requiere una adecuada transmisión de la información a las familias, pero cualquier esfuerzo será ímprobo mientras los sanitarios no nos creamos nuestras propias recomendaciones (AU)

Introduction: In 1980, Schmitt was the first to coin the term "fever phobia" to describe parents’ unrealistic fears about fever. More than 35 years later, this unfounded fear remains. A survey is conducted in Spain to the workers of four public hospitals. Knowledge about fever in children is analyzed, being the main aim of the study. Patients and methods: A descriptive, cross-sectional and multicenter study was conducted from 15th September 2015 to 15th October 2015. 4,830 anonymous surveys were sent by e-mail. A sample size of 450 replies was estimated as sufficient, with a miscalculation <4.4% and a confidence interval of 95% (50% heterogeneity). SPSS v22.0 was used for statistical data analysis. Results: Out of 462 responses were received. Seventy five per cent were women, 56% were under 35 years old, 81% were healthcare professionals and 60% were parents. Results concerning fever knowledge were: 83% affirm that physical methods should be used (not recommended), 60% think that seizures could be prevented with early treatment of fever (false), 56% support that fever should always be treated, even if the child is healthy (wrong) and 41% encourage that antipyretics should be alternated (incorrect). Eighty six per cent of the workers recognized that the fever phobia exists. There are significant differences in responses depending on healthcare and non-healthcare professionals, on being parents or not, and even on gender. Conclusions: A significant percentage of hospital workers, including doctors and pediatricians, are unaware of the existing recommendations on fever in children. This ignorance favors the persistence of fever-phobia, an infectious fear that leads to unnecessary treatments. Adequate transmission of information to families is needed, but every effort will be arduous while healthcare professionals do not believe their own recommendations (AU)

[Hydrocephalus due to hyperplasia of the choroid plexuses in a patient with trisomy 9 mosaicism. A real diagnostic and therapeutic challenge]. / Hidrocefalia por hiperplasia de plexos coroideos en un paciente con mosaicismo de trisomia 9. Un verdadero reto diagnostico y terapeutico.

INTRODUCTION: Trisomy 9 is an unusual chromosome abnormality in live-born patients, which is frequently accompanied by functional and structural anomalies of the central nervous system. Among many other alterations, several studies have been published in the English-speaking literature that show an association between chromosome 9 abnormality and pathologies affecting the choroid plexuses. CASE REPORT: We report the case of a 4-month-old male with trisomy 9 mosaicism associated to hydrocephalus secondary to choroid plexus hyperplasia, who was referred due to a clinical picture of intracranial hypertension. The cerebrospinal fluid (CSF) drainage procedure that was initially chosen caused massive ascites due to an excessive production of CSF, and led to a cascade of multiple surgical interventions, which included endoscopic and drainage procedures. CONCLUSIONS: This is another example of an association between choroid plexus pathologies and chromosome 9 abnormality. Due to its scarce incidence, diagnosis of hydrocephalus secondary to plexus hyperplasia is difficult, as is selecting its most suitable treatment. In this type of hydrocephalus there is a double pathophysiological mechanism, which involves an increase in CSF production and a decrease in its reabsorption. Despite taking these considerations into account, the treatment of hydrocephalus secondary to plexus hyperplasia is a real challenge that usually leads to multiple surgical interventions ranging from plexectomy or coagulation of the choroid plexuses to the implantation of CSF drainage devices.

TITLE: Hidrocefalia por hiperplasia de plexos coroideos en un paciente con mosaicismo de trisomia 9. Un verdadero reto diagnostico y terapeutico.Introduccion. La trisomia 9 es una cromosomopatia inusual en pacientes nacidos vivos, que frecuentemente se acompaña de anomalias funcionales y estructurales del sistema nervioso central. Entre otras muchas alteraciones, varios trabajos en la bibliografia anglosajona demuestran una asociacion entre cromosomopatia 9 y patologia de los plexos coroideos. Caso clinico. Varon de 4 meses de vida con mosaicismo de trisomia 9 asociado a hidrocefalia secundaria a hiperplasia de los plexos coroideos, que fue remitido por clinica de hipertension intracraneal. El procedimiento derivativo de liquido cefalorraquideo por el que optamos inicialmente provoco una ascitis masiva debida a la produccion desmesurada de liquido cefalorraquideo, y desemboco en una cascada de multiples intervenciones quirurgicas, entre las que se incluyeron procedimientos endoscopicos y derivativos. Conclusiones. Se trata de un ejemplo mas de asociacion entre patologia de los plexos coroideos y cromosomopatia 9. Debido a su escasa incidencia, es dificil establecer el diagnostico de hidrocefalia secundaria a hiperplasia de los plexos y, por tanto, el tratamiento mas adecuado. En este tipo de hidrocefalia existe un doble mecanismo fisiopatologico, que implica un aumento de produccion de liquido cefalorraquideo y una disminucion de su reabsorcion. A pesar de tener en cuenta dicha consideracion, el tratamiento de la hidrocefalia secundaria a hiperplasia de los plexos supone un verdadero reto que habitualmente pasa por multiples procedimientos quirurgicos, desde la plexectomia o coagulacion de los plexos coroideos hasta la implantacion de dispositivos de derivacion de liquido cefalorraquideo.

Blockade of deubiquitylating enzyme Rpn11 triggers apoptosis in multiple myeloma cells and overcomes bortezomib resistance.

Proteasome inhibition is an effective therapy for multiple myeloma (MM) patients; however, the emergence of drug resistance is common. Novel therapeutic strategies to overcome proteasome inhibitor resistance are needed. In this study, we examined whether targeting deubiquitylating (DUB) enzymes upstream of 20S proteasome overcomes proteasome inhibitor resistance. Gene expression analysis, immunohistochemical studies of MM patient bone marrow, reverse transcription-PCR and protein analysis show that Rpn11/POH1, a DUB enzyme upstream of 20S proteasome, is more highly expressed in patient MM cells than in normal plasma cells. Importantly, Rpn11 expression directly correlates with poor patient survival. Loss-of-function studies show that Rpn11-siRNA knockdown decreases MM cell viability. Pharmacological inhibition of Rpn11 with O-phenanthroline (OPA) blocks cellular proteasome function, induces apoptosis in MM cells and overcomes resistance to proteasome inhibitor bortezomib. Mechanistically, Rpn11 inhibition in MM cells activates caspase cascade and endoplasmic stress response signaling. Human MM xenograft model studies demonstrate that OPA treatment reduces progression of tumor growth and prolongs survival in mice. Finally, blockade of Rpn11 increases the cytotoxic activity of anti-MM agents lenalidomide, pomalidomide or dexamethasone. Overall, our preclinical data provide the rationale for targeting DUB enzyme Rpn11 upstream of 20S proteasome to enhance cytotoxicity and overcome proteasome inhibitor resistance in MM.

Biologic therapies for refractory juvenile dermatomyositis: five years of experience of the Childhood Arthritis and Rheumatology Research Alliance in North America.

BACKGROUND: The prognosis of children with juvenile dermatomyositis (JDM) has improved remarkably since the 1960's with the use of corticosteroid and immunosuppressive therapy. Yet there remain a minority of children who have refractory disease. Since 2003 the sporadic use of biologics (genetically-engineered proteins that usually are derived from human genes) for inflammatory myositis has been reported. In 2011-2016 we investigated our collective experience of biologics in JDM through the Childhood Arthritis and Rheumatology Research Alliance (CARRA). METHODS: The JDM biologic study group developed a survey on the CARRA member experience using biologics for Juvenile DM utilizing Delphi consensus methods in 2011-2012. The survey was completed online by the CARRA members interested in JDM in 2012. A second survey was similarly developed that provided more opportunity to describe their experiences with biologics in JDM in detail and was completed by CARRA members in Feb 2013. During three CARRA meetings in 2013-2015, nominal group techniques were used for achieving consensus on the current choices of biologic drugs. A final survey was performed at the 2016 CARRA meeting. RESULTS: One hundred and five of a potential 231 pediatric rheumatologists (42%) responded to the first survey in 2012. Thirty-five of 90 had never used a biologic for Juvenile DM at that time. Fifty-five of 91 (denominators vary) had used biologics for JDM in their practice with 32%, 5%, and 4% using rituximab, etanercept, and infliximab, respectively, and 17% having used more than one of the three drugs. Ten percent used a biologic as monotherapy, 19% a biologic in combination with methotrexate (mtx), 52% a biologic in combination with mtx and corticosteroids, 42% a combination of a biologic, mtx, corticosteroids (steroids), and an immunosuppressive drug, and 43% a combination of a biologic, IVIG and mtx. The results of the second survey supported these findings in considerably more detail with multiple combinations of drugs used with biologics and supported the use of rituximab, abatacept, anti-TNFα drugs, and tocilizumab in that order. One hundred percent recommended that CARRA continue studying biologics for JDM. The CARRA meeting survey in 2016 again supported the study and use of these four biologic drug groups. CONCLUSIONS: Our CARRA JDM biologic work group developed and performed three surveys demonstrating that pediatric rheumatologists in North America have been using multiple biologics for refractory JDM in numerous scenarios from 2011 to 2016. These survey results and our consensus meetings determined our choice of four biologic therapies (rituximab, abatacept, tocilizumab and anti-TNFα drugs) to consider for refractory JDM treatment when indicated and to evaluate for comparative effectiveness and safety in the future. Significance and Innovations This is the first report that provides a substantial clinical experience of a large group of pediatric rheumatologists with biologics for refractory JDM over five years. This experience with biologic therapies for refractory JDM may aid pediatric rheumatologists in the current treatment of these children and form a basis for further clinical research into the comparative effectiveness and safety of biologics for refractory JDM.

Detección del déficit de alfa-1 antitripsina: estudio en pacientes con enfermedad pulmonar obstructiva crónica diagnosticados en atención primaria / Detection of alpha-1 antitrypsin deficiency: a study on patients diagnosed with chronic obstructive pulmonary disease in primary health care

La enfermedad pulmonar obstructiva crónica (EPOC) tiene una prevalencia en España del 10,2%. El principal factor etiológico es el tabaco. La exposición al humo de biomasa y el déficit de alfa-1 antitripsina (DAAT) también se relacionan con su desarrollo. El DAAT es una condición genética en la que subyace el 2-3% de los pacientes con EPOC. El objetivo de este estudio descriptivo transversal fue descartar el DAAT en pacientes con EPOC del CS Culleredo, A Coruña. Para ello se realizó la prueba de la gota de sangre gruesa en papel secante y el estudio de variantes PI*S y PI*Z del gen SERPINA1 mediante análisis de curvas de desnaturalización tras amplificación simultánea por reacción en cadena de la polimerasa. El estudió analizó 80 pacientes entre 40-80 años. Un 30% eran portadores de un alelo deficitario en heterocigosis, que en el 80% de ellos se trataba del alelo S. Se detectó un caso PiSZ (1,25%) y ninguno PiZZ. Esto representa una frecuencia alélica de 3,1% para el PiZ y 13,1% para el PiS. Las frecuencias alélicas detectadas son superiores a las descritas previamente para la población española. Este trabajo excluye el déficit grave de AAT en el 98,75% de la población estudiada. El caso con genotipo Pi*SZ fue diagnosticado en una fase precoz de la enfermedad. El estudio cumple con uno de los indicadores de calidad asistencial recomendados por GesEPOC y constata una elevada frecuencia alélica PiS y PiZ en la zona, que será referencia de futuros estudios en Galicia (AU)

The prevalence of chronic obstructive pulmonary disease (COPD) in Spain is 10.2%. Although tobacco is the main aetiological factor, biomass smoke exposure and alpha-1 antitrypsin deficiency (AATD) have also been related to its development. AATD is a genetic condition which could be causing 2-3% of COPD cases. The aim of this cross-sectional descriptive study was to exclude the existence of AATD in a population of COPD patients from CS Culleredo, A Coruña. The thick blood drop test on blotting paper, as well as the analysis of the mutations PI*S and PI*Z of the gene SERPINA 1 by the analysis of denaturing gradients after simultaneous amplification related to PCR (polymerase chain reaction). The study population included 80 patients between 40-80 years old, of whom 30% were carriers of a deficient allele (heterozygous), and 80% of them were the allele PiS. Only one PiSZ (1.25%) individual and no PiZZ was detected. This represents an allelic frequency of 3.1% (PiZ), and 13.1% (PiS). The detected allelic frequencies are higher than previously reported in the Spanish population. Severe AATD has been excluded in 98.75% of the study population. The Pi*SZ patient has been diagnosed in an early stage of the disease. We have also achieved one of the quality indicators recommended by GesEPOC. Our area has shown a high PiS and PiZ frequency, thus our study could be used as a reference for further research in the Galician population (AU)

The first sixty-five craniopharyngioma operations in France.

Craniopharyngiomas (CPs) are benign epithelial tumors that develop along the hypothalamus-hypophyseal axis and were first described by Jakob Erdheim in 1904. These tumors have represented a challenge for surgeons since the rise of modern neurosurgery. The study of CPs is linked to the development of this surgical discipline in parallel with neuroendocrinology within the French school of neurology, led by Joseph Babinski. For the present study, all CP cases published in the French scientific literature before the development of modern neuroradiology were gathered, and 65 cases that underwent surgical procedures between 1921 and 1973 were selected. From our analysis of them, useful information has been obtained that can be applied to the management of CPs today. Most tumors were adamantinomatous CPs (62 patients) with an infundibulo-tuberal location (40.6%). The most frequent surgical route employed was subfrontal (69%). Selection of the surgical approach and degree of removal did not appear to have been influenced by the presumed topography of the tumor, and resulted in a poor outcome in 47% of patients. However, the authors were able to recognize the presence of symptoms indicating that the tumor had caused hypothalamic and/or infundibular damage, such as seen in the infundibulo-tuberal syndrome, first described by Claude and Lhermitte in 1917. At present, the optimal surgical approach and degree of removal are still the subject of debate, although the presence of clinical signs pointing to hypothalamic involvement by CPs should always be preoperatively accurately assessed to improve surgical outcomes.

[Detection of alpha-1 antitrypsin deficiency: A study on patients diagnosed with chronic obstructive pulmonary disease in primary health care]. / Detección del déficit de alfa-1 antitripsina: estudio en pacientes con enfermedad pulmonar obstructiva crónica diagnosticados en atención primaria.

The prevalence of chronic obstructive pulmonary disease (COPD) in Spain is 10.2%. Although tobacco is the main aetiological factor, biomass smoke exposure and alpha-1 antitrypsin deficiency (AATD) have also been related to its development. AATD is a genetic condition which could be causing 2-3% of COPD cases. The aim of this cross-sectional descriptive study was to exclude the existence of AATD in a population of COPD patients from CS Culleredo, A Coruña. The thick blood drop test on blotting paper, as well as the analysis of the mutations PI*S and PI*Z of the gene SERPINA 1 by the analysis of denaturing gradients after simultaneous amplification related to PCR (polymerase chain reaction). The study population included 80 patients between 40-80 years old, of whom 30% were carriers of a deficient allele (heterozygous), and 80% of them were the allele PiS. Only one PiSZ (1.25%) individual and no PiZZ was detected. This represents an allelic frequency of 3.1% (PiZ), and 13.1% (PiS). The detected allelic frequencies are higher than previously reported in the Spanish population. Severe AATD has been excluded in 98.75% of the study population. The Pi*SZ patient has been diagnosed in an early stage of the disease. We have also achieved one of the quality indicators recommended by GesEPOC. Our area has shown a high PiS and PiZ frequency, thus our study could be used as a reference for further research in the Galician population.

Conocimiento, aceptación y uso de medicina tradicional peruana y de medicina alternativa/complementaria en usuarios de consulta externa en Lima Metropolitana / Knowdlege, aceptation and use of peruvian traditional medicine and complementary/alternative medicine in users from outpatient services in Lima Metropolitana

Objetivo: Determinar los conocimientos, aceptación y uso de la Medicina Tradicional Peruana y la Medicina Alternativa/Complementaria en usuarios de consulta externa de en establecimientos de salud de Lima Metropolitana. Materiales y Métodos: Se realizó una encuesta validada en 351 usuarios de consulta externa de ocho establecimientos de salud pertenecientes al Ministerio de Salud (MINSA) y Seguro Social de Salud (EsSalud) donde se evaluaron los patrones de uso, conocimiento y aceptación de terapias de Medicina Tradicional Peruana (MTC) y Medicina Complementaria/Alternativa (MAC). Resultados: La terapia de MTP más conocida, aceptada y usada fue la pasada de huevo (71.5%, 67.5% y 58.1%) mientras que en el caso de las terapias de MAC fue la fitoterapia (63.8%, 72.1% y 59.5%), La MTP mayormente fue usada solo 1-2 veces y un 29.6% refirió el uso de MAC, como la fitoterapia, en todos sus episodios de enfermedad. La razón más frecuente de aceptación es la "integración a la medicina convencional" (20.5% en MTP y 29.9% en MAC) y las de no aceptación fueron el no tener bases científicas (14.8% en MTP) o no estar reconocida legalmente (29.9% en MAC). Conclusión: La terapia de MTP más conocida, aceptada y usada fue la pasada de huevo, mientras que en el caso de MAC fue la fitoterapia. Las terapias de MTP suelen ser menos usadas que las terapias MAC por los encuestados. Estos procedimientos suelen ser realizados en el domicilio del paciente y son aceptados por la posibilidad de integración con la medicina convencional.

Ovulation-inducing factor (OIF/NGF) in seminal plasma: a review and update.

The ovulation-inducing effect of seminal plasma was first reported in Bactrian camels over 30 years ago, and the entity responsible was dubbed 'ovulation-inducing factor' (OIF). More recent studies, primarily in llamas and alpacas, characterized the biological and chemical properties of OIF and ultimately identified it as ßNGF. This recent discovery has allowed a convergence of knowledge previously separated by discipline and by mechanism; that is, neurobiology and reproductive biology, and autocrine/paracrine vs endocrine. To preserve this link, we have referred to the seminal factor as OIF/NGF. As a highly conserved protein, the implications of discoveries related to OIF/NGF in reproductive tissues extend beyond the camelid species, and results of recent studies show that the presence and function of OIF/NGF in seminal plasma are conserved among species considered to be induced ovulators as well as those considered to be spontaneous ovulators. The abundance of OIF/NGF in seminal plasma and the effects of seminal plasma on ovarian function strongly support the idea of an endocrine mode of action (i.e. systemic distribution with distant target tissues). This review is intended to provide an update on the progress in our understanding of the nature of OIF/NGF in seminal plasma and its effects on reproductive function in the female, including the effects of dose and route of administration, evidence for ovarian effects in other species, tissue sources of OIF/NGF and early findings related to the mechanism of action of OIF.

Tuberculosis, los errores que cometemos: experiencia del Hospital San Juan de Dios / Tuberculosis, our mistakes: the experience at San Juan de Dios Hospital

Tuberculosis is an infectious disease that in Chile is far from eradicated. To ask what improvements we could make, we must recognize from our experience at San Juan de Dios Hospital, the major mistakes which many of us do, both in the diagnosis and management of the disease. Possibly the most important, common and serious mistake, is to believe that tuberculosis is eradicated, because if we believe it does no longer exists, then we do not seek it, and leave undiagnosed infectious cases, keeping the reservoirs of the disease.

La tuberculosis es una enfermedad infecciosa que en Chile está lejos de ser eliminada. Para plantear qué mejoras podríamos realizar para su control es necesario conocer los principales errores que según nuestra experiencia, en el Hospital San Juan de Dios, muchos de nosotros cometemos, tanto en el diagnóstico como en el manejo de la enfermedad. El más común y grave, posiblemente sea el de creer que la tuberculosis está erradicada, porque si creemos que ya no existe, no la buscaremos y dejaremos casos sin diagnosticar, manteniendo los reservorios que trasmiten la enfermedad.

Estilo de apego, riesgo relacional y depresión en gestantes adolescentes de los Consultorios de Atención Primaria de Valparaíso / Attachment, relational risk and depression in pregnant adolescents of the Primary Health Care System of Valparaiso

La Gestación adolescente puede traer consecuencias negativas para la díada. Su aparición, podría relacionarse con el estilo de apego de la joven madre, y a su vez dicho patrón relacionarse con la presencia de depresión prenatal y de dificultad en la vinculación con su bebé. Estudio tipo caso-control cuyo objetivo fue comparar el estilo de apego de las gestantes adolescentes versus adultas y su relación con el riesgo relacional de la díada y sintomatología depresiva en ambos grupos. Se les aplicó Escala Edinburgo, Instrumento De Lazos Parentales y Escala De Riesgo Relacional Prenatal. La muestra estuvo compuesta por 29 casos y 29 controles. Las gestantes adolescentes, resultaron tener menor porcentaje de apego seguro con su figura de apego primaria (17,2% v/s 44,8%), mayor riesgo de depresión prenatal (41,33% v/s 17,2%) y alto riesgo relacional (51,7% v/s 24%), todas diferencias estadísticamente significativas. Se justifica la necesidad de diseñar intervenciones preventivas enfocadas en minimizar estos riesgos. Palabras Claves: Apego, Gestación Adolescente, depresión prenatal, riesgo relacional.

Adolescent pregnancy can have negative consequences for the dyad. Its appearance could be related to the attachment style of the young mother, and that pattern be related to the presence of prenatal depression and difficulty in bonding with their baby.This is a case-control study where the aim was to compare the style of attachment of adolescents versus adult pregnant women and their relationship with the relational risk of the dyad and depressive symptoms in both groups. We applied the Edinburg Scale, the Parental Bonding Instrument and the Prenatal Relational Risk Scale. The sample consisted of 29 cases and 29 controls. Pregnant teenagers were found to have a lower percentage of secure attachment with their primary attachment figure (17.2% v / s 44.8%), increased risk of prenatal depression (41.33% v / s 17.2%) and high relational risk (51.7% v / s 24%). All differences were statistically significant. The need to design preventive interventions focused on minimizing these risks are justified.Keywords: Attachment, Adolescent Pregnancy, Prenatal Depression, Relational Risk.

Targeting proteasome ubiquitin receptor Rpn13 in multiple myeloma.

Proteasome inhibitor bortezomib is an effective therapy for relapsed and newly diagnosed multiple myeloma (MM); however, dose-limiting toxicities and the development of resistance can limit its long-term utility. Recent research has focused on targeting ubiquitin receptors upstream of 20S proteasome, with the aim of generating less toxic therapies. Here we show that 19S proteasome-associated ubiquitin receptor Rpn13 is more highly expressed in MM cells than in normal plasma cells. Rpn13-siRNA (small interfering RNA) decreases MM cell viability. A novel agent RA190 targets Rpn13 and inhibits proteasome function, without blocking the proteasome activity or the 19S deubiquitylating activity. CRISPR/Cas9 Rpn13-knockout demonstrates that RA190-induced activity is dependent on Rpn13. RA190 decreases viability in MM cell lines and patient MM cells, inhibits proliferation of MM cells even in the presence of bone marrow stroma and overcomes bortezomib resistance. Anti-MM activity of RA190 is associated with induction of caspase-dependent apoptosis and unfolded protein response-related apoptosis. MM xenograft model studies show that RA190 is well tolerated, inhibits tumor growth and prolongs survival. Combining RA190 with bortezomib, lenalidomide or pomalidomide induces synergistic anti-MM activity. Our preclinical data validates targeting Rpn13 to overcome bortezomib resistance, and provides the framework for clinical evaluation of Rpn13 inhibitors, alone or in combination, to improve patient outcome in MM.