Mars and the ESA Science Programme - the case for Mars polar science.

Current plans within the European Space Agency (ESA) for the future investigation of Mars (after the ExoMars programme) are centred around participation in the Mars Sample Return (MSR) programme led by NASA. This programme is housed within the Human and Robotic Exploration (HRE) Directorate of ESA. This White Paper, in response to the Voyage 2050 call, focuses on the important scientific objectives for the investigation of Mars outside the present HRE planning. The achievement of these objectives by Science Directorate missions is entirely consistent with ESA's Science Programme. We illustrate this with a theme centred around the study of the Martian polar caps and the investigation of recent (Amazonian) climate change produced by known oscillations in Mars' orbital parameters. Deciphering the record of climate contained within the polar caps would allow us to learn about the climatic evolution of another planet over the past few to hundreds of millions of years, and also addresses the more general goal of investigating volatile-related dynamic processes in the Solar System.

Association between depressed mood and sexual function among mid-aged Paraguayan women.

BACKGROUND: Depressive symptoms may affect female mid-life sexuality, whereas sexual problems tend to aggravate depression. Despite this, data assessing this association drawn from mid-aged Paraguayan women are scarce. OBJECTIVE: This study aimed to assess the association between depressed mood and the risk of sexual dysfunction during female mid-life. METHODS: Sexually active urban-living women from Asunción, Paraguay (n = 193, aged 40-60 years) were surveyed with the 6-item Female Sexual Function Index (FSFI-6), the 10-item Center for Epidemiological Studies Depression Scale (CESD-10), and a general questionnaire containing personal and partner information. Depressed mood was defined as a total CESD-10 score of 10 or more, and an increased risk for sexual dysfunction as an FSFI-6 total score of 19 or less. The association of depressed mood and an increased risk of sexual dysfunction was evaluated with multivariable Poisson regression. RESULTS: The mean age (±standard deviation) of surveyed woman was 48.3 ± 6.0 years and 61.1% (n = 118) were perimenopausal and postmenopausal. A total of 21.8% (n = 42) had depressed mood and 28.5% (n = 55) had an increased risk of sexual dysfunction. The final adjusted regression model determined that women with depressed mood were twice as likely to have an increased risk of sexual dysfunction, compared to women with normal mood (adjusted prevalence ratio = 2.14, 95% confidence interval 1.26-3.60). On the other hand, depressed mood was associated with a mean total FSFI-6 score that was 20% lower than that observed among women with normal mood (adjusted incidence rate ratio = 0.80, 95% confidence interval 0.68-0.93). CONCLUSION: In this mid-aged Paraguayan female sample there was a significant association between depressed mood and an increased risk of sexual dysfunction.

No correlation between the expression of FXR and genes involved in multidrug resistance phenotype of primary liver tumors.

Farnesoid X receptor (FXR) has been recently reported to enhance chemoresistance through bile acid-independent mechanisms. Thus, FXR transfection plus activation with GW4064 resulted in reduced sensitivity to cisplatin-induced toxicity. This is interesting because primary tumors of the liver, an organ where FXR is expressed, exhibit marked refractoriness to pharmacological treatment. Here we have determined whether FXR is upregulated in hepatocellular carcinoma (HCC), cholangiocarcinoma (CGC) and hepatoblastoma (HPB) and whether this is related with the expression of genes involved in mechanisms of chemoresistance. Using RT-QPCR and Taqman low density arrays we have analyzed biopsies from healthy livers or surgically removed tumors from naive patients and cell lines derived from HCC (SK-HEP-1, Alexander and Huh7), CGC (TFK1) and HPB (HepG2), before and after exposure to cisplatin at IC50 for 72 h. In liver tumors FXR expression was not enhanced but significantly decreased (healthy liver > HCC > HPB ≈ CGC). Except for CGC, this was not accompanied by changes in the proportions of FXR isoforms. Changes in 36 genes involved in drug uptake/efflux and metabolism, expression/function of molecular targets, and survival/apoptosis balance were found. Changes affecting SLC22A1, CYP2A1 and BIRC5 were shared by HCC, CGC and HPB. Similarity in gene expression profiles between cell lines and parent tumors was found. Pharmacological challenge with cisplatin induced changes that increased this resemblance. This was not dependent upon FXR expression. Thus, although FXR may play a role in inducing chemoresistance under certain circumstances, its upregulation does not seem to be involved in the multidrug resistance phenotype characteristic of HCC, CGC and HPB.

Up-regulation of FXR isoforms is not required for stimulation of the expression of genes involved in the lack of response of colon cancer to chemotherapy.

Several mechanisms are involved in the poor response of colorectal adenocarcinoma (CRAC) to pharmacological treatment. Since preliminary evidences have suggested that the enhanced expression of farnesoid X receptor (FXR) results in the stimulation of chemoresistance, we investigated whether FXR up-regulation is required for the expression of genes that characterize the multidrug resistance (MDR) phenotype of CRAC. Samples of tumours and adjacent healthy tissues were collected from naive patients. Using Taqman Low-Density Arrays, the abundance of mRNA of 87 genes involved in MDR was determined. Relevant changes were re-evaluated by conventional RT-QPCR. In healthy tissue the major FXR isoforms were FXRα2(+/-) (80%). In tumours this predominance persisted (91%) but was accompanied by a consistent reduction (3-fold) in total FXR mRNA. A lower FXR expression was confirmed by immunostaining, in spite of which there was a significant change in the expression of MDR genes. Pharmacological challenge was simulated "in vitro" using human CRAC cells (LS174T cells). Short-term (72h) treatment with cisplatin slightly increased the almost negligible expression of FXR in wild-type LS174T cells, whereas long-term (months) treatment induced a cisplatin-resistant phenotype (LS174T/R cells), which was accompanied by a 350-fold up-regulation of FXR, mainly FXRα1(+/-). However, the changed expression of MDR genes in LS174T/R cells was not markedly affected by incubation with the FXR antagonist Z-guggulsterone. In conclusion, although the enhanced expression of FXR may be involved in the stimulation of chemoresistance that occurs during pharmacological treatment, FXR up-regulation is not required for the presence of the MDR phenotype characteristic of CRAC.

Experience with botulinum toxin in chronic migraine. / Experiencia con toxina botulínica en la migraña crónica.

OBJECTIVE: The purposes of this study were to describe our 16-month experience with onabotulinumtoxinA (OnabotA) for the treatment of chronic migraine (CM) in the Spanish province of Segovia, evaluate its benefits, and determine clinical markers of good response to treatment. PATIENTS AND METHODS: Prospective study of patients with CM who received OnabotA for 16 months. The effectiveness of OnabotA was evaluated based on the reduction in the number of headache days, pain intensity, and side effects. We used two-way analysis of variance (ANOVA) to assess the effects of treatment according to the time factor. We studied the correlation between treatment effects and other variables using a linear regression model to establish the clinical markers of good response to treatment. RESULTS: We included 69 patients who met the diagnostic criteria for CM. Patients underwent an average of 2 infiltrations. Mean age was 43 years; 88.4% were women. The number of headache days and pain intensity decreased significantly (P < .005); improvements remained over time. We found a negative correlation between the reduction in pain intensity and the number of treatments before OnabotA. CONCLUSION: The beneficial effects of OnabotA for CM continue over time. OnabotA is a safe and well-tolerated treatment whose use for refractory CM should not be delayed since early treatment provides greater benefits.

Papillary serous carcinoma of the tunica vaginalis testis.

This is a case report of a testicular papillary serous carcinoma of ovarian type (PSCOT) diagnosed in a 50-year-old man. The tumor presented in the form of multiple papillary exophytic excrescencies on the visceral tunica vaginalis testis lining the inner surface of a hydrocele sac. The tumor was histologically a papillary serous carcinoma with numerous psammoma bodies, indistinguishable from similar tumors arising on the surface of the ovary. Following the tumor's surgical removal, the patient was treated with the same drugs used to treat ovarian serous carcinomas, and he is alive two years after the initial diagnosis. PSCOT must be distinguished from mesothelioma of the tunica vaginalis testis, a tumor with a most unfavorable prognosis. As shown here, immunohistochemical findings can be useful for formulating the correct diagnosis of PSCOT.

[The effect neutron irradiation of Uranium 235 on the venom of Lachesis muta muta (Ofidia: Viperidae)]. / Efectos de la irradiación neutrónica del Uranio 235 sobre el veneno de Lachesis muta muta (Ofidia: Viperidae).

The effect of irradiation of the aqueous solution of L. m. muta venom was evaluated with thermic neutrons from Uranium-235 employing doses of 1.61 to 5.19 Gray. The venom was examined for protein content by the Folin Lowry Method modified by Stauffer; for acute toxicity by intraperitoneal route estimation in mice and for immunochemical tests by the antigen-antibody reactions evaluation. Neutronic radiation affects all evaluated parameters in venom (decrease in protein content levels, increase of LD50 values and decrease in the number of precipitating antigen-antibody) as shown by immunodiffusion and immunoelectrophoresis.

Experiencia con toxina botulínica en la migraña crónica / Experience with botulinum toxin in chronic migraine

OBJETIVO: Describir la experiencia con la administración de toxina botulínica tipo A (OnabotA) en el tratamiento de la migraña crónica (MC) en Segovia durante 16 meses, evaluar su beneficio y buscar marcadores clínicos que sirvan para predecir una mejor respuesta al tratamiento. PACIENTES Y MÉTODOS: Estudio prospectivo de pacientes con MC que recibieron infiltraciones con OnabotA durante 16 meses. Se evaluó la eficacia de OnabotA comparando la reducción en el número de días de cefalea, en la intensidad y efectos adversos. Se comparó el efecto del tratamiento con el factor tiempo mediante un análisis de la varianza de dos vías (ANOVA). Se estudió la correlación del efecto del tratamiento con el resto de las variables mediante un modelo de regresión lineal para buscar marcadores clínicos que sirvan para predecir una mejor respuesta. RESULTADOS: Se incluyó a 69 pacientes que cumplían criterios de MC. Se les realizó una media de 2 infiltraciones. La edad media fue de 43 años, el 88,4% fueron mujeres. La frecuencia de los días de cefalea y su intensidad se redujeron de forma significativa (p < 0,005) y esta mejoría se mantuvo a lo largo del tiempo. Se encontró una correlación negativa entre la reducción de la intensidad y el número de tratamientos previos a la administración de la toxina. CONCLUSIÓN: El efecto beneficioso de la OnabotA en la MC se mantiene en el tiempo, siendo un tratamiento seguro y bien tolerado. No debe retrasarse su uso en MC refractaria, ya que su beneficio podría ser mayor cuanto antes se administre

OBJECTIVE: The purposes of this study were to describe our 16-month experience with onabotulinumtoxinA (OnabotA) for the treatment of chronic migraine (CM) in the Spanish province of Segovia, evaluate its benefits, and determine clinical markers of good response to treatment. PATIENTS AND METHODS: Prospective study of patients with CM who received OnabotA for 16 months. The effectiveness of OnabotA was evaluated based on the reduction in the number of headache days, pain intensity, and side effects. We used two-way analysis of variance (ANOVA) to assess the effects of treatment according to the time factor. We studied the correlation between treatment effects and other variables using a linear regression model to establish the clinical markers of good response to treatment. RESULTS: We included 69 patients who met the diagnostic criteria for CM. Patients underwent an average of 2 infiltrations. Mean age was 43 years; 88.4% were women. The number of headache days and pain intensity decreased significantly (P < .005); improvements remained over time. We found a negative correlation between the reduction in pain intensity and the number of treatments before OnabotA. CONCLUSION: The beneficial effects of OnabotA for CM continue over time. OnabotA is a safe and well-tolerated treatment whose use for refractory CM should not be delayed since early treatment provides greater benefits

Exposure to Sarcocystis spp. in horses from Spain determined by Western blot analysis using Sarcocystis neurona merozoites as heterologous antigen.

Horses serve as an intermediate host for several species of Sarcocystis, all of which utilize canids as the definitive host. Sarcocystis spp. infection and formation of latent sarcocysts in horses often appears to be subclinical, but morbidity can occur, especially when the parasite burden is large. A serological survey was conducted to determine the presence of antibodies against Sarcocystis spp. in seemingly healthy horses from the Galicia region of Spain. Western blot analyses using Sarcocystis neurona merozoites as heterologous antigen suggested greater than 80% seroprevalance of Sarcocystis spp. in a sample set of 138 horses. The serum samples were further tested with enzyme-linked immunosorbent assays (ELISAs) based on recombinant S. neurona-specific surface antigens (rSnSAGs). As expected for horses from the Eastern Hemisphere, less than 4% of the serum samples were positive when analyzed with either the rSnSAG2 or the rSnSAG4/3 ELISAs. An additional 246 horses were tested using the rSnSAG2 ELISA, which revealed that less than 3% of the 384 samples were seropositive. Collectively, the results of this serologic study suggested that a large proportion of horses from this region of Spain are exposed to Sarcocystis spp. Furthermore, the anti-Sarcocystis seroreactivity in these European horses could be clearly distinguished from anti-S. neurona antibodies using the rSnSAG2 and rSnSAG4/3 ELISAs.

El espectro clínico de las demencias frontotemporales: un caso de demencia rápidamente progresiva / The clinical spectrum of frontotemporal dementia: a case of rapidly progressive dementia

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Overview of the molecular bases of resistance to chemotherapy in liver and gastrointestinal tumours.

Primary malignancies of the liver and the gastrointestinal tract constitute one of the main health problems worldwide. Together, these types of tumour are the first cause of death due to cancer, followed by lung and breast cancer respectively. One important limitation in the treatment of these tumours is that, with a few exceptions, they exhibit marked resistance to currently available drugs. Moreover, most of them develop chemoresistance during treatment. The mechanisms responsible for drug refractoriness in gastrointestinal tumours include a reduction in drug uptake; enhanced drug export; intracellular inactivation of the effective agent; alteration of the molecular target; an increase in the activity of the target route to be inhibited or the appearance or stimulation of alternative routes; enhanced repair of drug-induced modifications in the target molecules, and the activation/inhibition of intracellular signalling pathways, which leads to a negative balance between the apoptosis/survival of tumour cells. A better understanding of these mechanisms is needed in order to develop accurate tests to predict the lack of response to chemotherapy and novel approaches aimed at overcoming resistance to anticancer agents. The purpose of the present review is to offer an updated overview of the molecular mechanisms of resistance to cytostatic drugs in the most frequent types of primary malignant tumour affecting the liver and gastrointestinal tract.

Sexo y sexualidad, complejidad de la identidad humana / Sex, sexuality, complexity of human identity / Sexo e sexualidade, a complexidade da identidade humana

En este artículo se presenta un proceso diagnóstico de necesidades en salud sexual y reproductiva de los estudiantes \r\nde VII semestre de Enfermería en una institución de educación superior en la ciudad de Bogotá, que hacen su rotación \r\nde Salud Pública en Salud Sexual y Reproductiva. Esto fue la base práctica para elaborar un proyecto de educación \r\nsexual, dirigida a la población estudiantil adolescente de educación básica secundaria (edad promedio 16 años). A \r\npartir de aquí se plantea una postura foucaultiana, que desde la arqueología, contribuya a una nueva perspectiva sobre \r\nla sexualidad en nuestras sociedades en Occidente.\r\nAdemás se analiza cómo la sexualidad es un fenómeno complejo que no se puede dividir y que tiene su punto de \r\ninflexión en el proceso formativo familiar y en el proceso educativo académico, en las enseñanzas del maestro hacia \r\nel educando y, cómo a su vez, este retroalimenta la interacción con las construcciones personales desde su propio \r\ncontexto. Estas múltiples posibilidades del Homo eroticus se organizan en una intrincada red de creencias, emociones, \r\ngustos, deseos, gestos, mociones estéticas, conceptos, prácticas o actividades sociales que demuestran la complejidad \r\ny dinámica cambiante del erotismo, como una fuente inagotable del sentido humano.

In this article we present an assessment of needs in sexual \r\nand reproductive health as part of the practice of students \r\nin VII semester of Nursing at a Higher Education Institu\r\n-\r\ntion in the City of Bogotá, who make rotations of Public \r\nHealth in sexual and reproductive health, which was the \r\npractical basis for the development of a sex education \r\nproject aimed at high school student (approximate mean \r\nage 16 years). From here there is a Foucauldian stance, \r\nthat from archeology contributes to a new perspective on \r\nsexuality in our societies in the West.\r\nWe also consider how sexuality is a "complex pheno\r\n-\r\nmenon " that can not be divided, has a point of inflection \r\nin the family formation process and in the academic \r\neducational process, from the professor's teachings to the \r\nstudent and how this student, in turn, provides feedback \r\nwith personal ideas from their own point of view. These \r\nmultiple possibilities of homo eroticus are organized \r\nin an intricate web of beliefs, emotions, tastes, desires, \r\ngestures, motions, aesthetic concepts, practices or social \r\nactivities that demonstrate the complexity and changing \r\ndynamics of eroticism, as an inexhaustible source of \r\nhuman consciousness.

Nesta palestra, apresentamos um processo de avaliação \r\ndas necessidades na saúde sexual e reprodutiva como \r\nparte da prática dos alunos no VII semestre de enfer\r\n-\r\nmagem de uma instituição de ensino superior na cidade de \r\nBogotá. Esta clinica é parte da rotação de Saúde Pública \r\n/ Saúde Sexual e Reprodutiva, que serve de base para o \r\ndesenvolvimento de um projeto de educação sexual diri\r\n-\r\ngida à população de estudantes adolecentes do ensino \r\nsecundário com idade média de 16 anos. A partir deste \r\nponto há uma postura foucaultiana, da arqueologia, que \r\ncontribui para uma perspectiva nova sobre a sexualidade \r\nem nossas sociedades ocidentais.\r\nAlem diso e proposto que a sexualidade é um fenômeno \r\n«complexo¼ por tanto não pode ser dividido. Ele começa \r\ncomo profesor em direção ao aluno que por sua vez da \r\nfeedback com o que ele controi no seu próprio contexto. \r\nEstas múltiplas possibilidades de homo eroticus são orga\r\n-\r\nnizadas em uma intrinca teia de crenças, emoções, gostos, \r\ndesejos, gestos, movimentos estéticos, conceitos, práticas \r\nou atividades sociais que demonstram a complexidade \r\ne a mudança dinâmica do erotismo, como uma fonte \r\ninesgotável da consciência humana. Vivemos uma sexua\r\n-\r\nlidade deformada, silenciada e mutilada.

[A kinetic model for heparin dosing in patients on chronic hemodialysis]. / Modelo cinetico de heparina para individualizar su dosificacion en pacientes hemodializados cronicos.

The quality of anticoagulation was evaluated in 5 patients receiving heparin during chronic hemodialysis. 50 kinetic studies were performed using 2 monitoring tests, TTPK and TCK. Basal and intradialysis measurements were used to estimate sensitivity and the elimination constant according to formulae described by Milthorpe. Mean basal TTPK time was 27.3 sec and TCK time was 211 sec. Mean initial intradialysis TTPK time was 107.5 sec and after correction applying the kinetic model it was 62 sec. Intradialysis TCK time varied from 806 to 683 sec after correction. At the end of the study, mean intradialysis TTPK time was 61 sec not significantly different from the target time of 55 sec. TCK time, however, was significantly greater than target (684 vs 434 sec).

Recombinant human chromosomal proteins HMG-14 and HMG-17.

Vectors for expressing human chromosomal proteins HMG-14 and HMG-17 in bacterial cultures under the control of the temperature-inducible lambda PL promoter have been constructed. The open reading frames of the cDNAs have been amplified by the polymerase chain reaction (PCR), utilizing amplimers containing desired restriction sites, thereby facilitating precise location of the initiation codon downstream from a ribosomal binding site. Expression of the recombinant proteins does not significantly affect bacterial growth. The rate of synthesis of the recombinant proteins is maximal during the initial stages of induction and slows down appreciably with time. After an initial burst of protein synthesis, the level of the recombinant protein in the bacterial extracts remains constant at different times following induction. Methods for rapid extraction and purification of the recombinant proteins are described. The recombinant proteins are compared to the proteins isolated from eucaryotic cells by electrophoretic mobility, Western analysis and nucleosome core mobility-shift assays. The ability of the proteins to shift the mobility of the nucleosome cores, but not that of DNA, can be used as a functional assay for these HMG proteins. A source for large quantities of human chromosomal proteins HMG-14 and HMG-17 will facilitate studies on their structure, cellular function and mechanism of interaction with nucleosomes.