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Introduction. Understanding the origin and evolution of Phobos and Deimos is the goal of the coming Martian Moons eXploration mission (MMX) led by JAXA [1, 2, 3]. This mission will be launched in 2024 to the Martian system and return samples from Phobos. Before sample return operations, a rover of 25 kg approximately will be delivered to the surface carrying four instruments: a Raman spectrometer (RAX), a radiometer (miniRad), a stereo pair of cameras looking forwards (NavCams), and two cameras looking at the wheel-surface interface, (WheelCams) [4]. The RAX instrument. The RAman spectrometer for MMX, RAX, has been developed together by DLR, INTA/UVA, and JAXA/UTo [5]. It consists of three elements: I) The RAX Laser Assembly (RLA), which was originally designed for the RLS instrument of the ExoMars mission, and includes a laser emitting at 532 nm; II) The RAX Spectrometer Module (RSM), comprising a sophisticated confocal optical assembly and a CMOS detector that covers a spectral range of up to 4000 cm-1 with a spectral resolution of ̴ 10 cm-1; III) The Autofocus System (AFS) to measure with high precision at different positions onto the ground. RAX will in situ examine the minerals of the surface and their formation conditions at rover sampling spots. By analysing the vibrational modes of the substances, RAX will be capable to characterize the igneous phases, volatiles, organic species, and secondary alteration minerals at grain scale. RAX’s targets may be correlated, on the one hand to the orbital data to better approach the spatial distribution and stratigraphic relationship between the Phobos’ blue and red material units, and on the other hand to the mineral and rock types observed on the Mars’ surface by other Raman spectrometers to link their genesis (or not) (e.g. RLS [6], or Supercam [7]). The identified mineral assemblages can be used to determine whether Phobos is a captured asteroid rich in carbon and water, or is a remnant body of a giant impact to Mars. In addition, the information may also support the sample return selection and provide context information of the materials once they are in terrestrial laboratories. References. [1] T. Usui, et al., Space Sci. Rev. 216:49, 2020; [2] S. L. Murchie, D. T. Britt, C. M. Pieters., Space Science 102, 2014, 176–182; [3] C.M. Pieters, S. L. Murchie, N. Thomas, and D. Britt, Planetary and Space Science 102, 2014, 144-151; [4] P. Michel, et al., Earth, Planets and Space 74: 2, 2022; [5] Y. Cho et al., Earth, Planets and Space 73:232, 2021; [6] F. Rull et al., Astrobiology 17 (6-7), 2017, 627–654; [7] S. Maurice et al., Space Sci. Rev. 217, 2021.

The María de Maeztu Academy of the Centro de Astrobiología is a two year-long (2019-2020, 2020-2021), tailor-made capacity-building activity implemented within the frame of the “Maria de Maeztu” excellence programme. It aims to strengthen and develop new capacities and stimulate the training of young researchers. The first edition of the transdisciplinary challenges is a training activity of the María de Maeztu Academy intended to develope new skills and generating relevant scientific-technical solutions in the field of Astrobiology. The training program started in September 2021 by forming teams with volunteers from different CAB and INTA departments and different areas of expertise. Throughout 2020-2021, several periodic reviews of the proposals were carried out, passing different milestones and receiving expert comments in each evaluation. Then, the CAB’s MdM Executive Committee decided to financially support the four teams to develop the proposed projects in the 2021/2022 academic year, until the end of the María de Maeztu programme. One of those challenges is “NEXT (iN situ EXploration of planeTary objects): EUROPA” and its objective is to identify the optimal Raman technique for the exploration of the surface of Jupiter´s moon Europa in future missions: conducting tests of various Raman techniques (using both commercial and flight models) on representative samples from Europa characterizing these samples with the different Raman techniques generating a database of pros and cons of each technique, which can minimize risks and optimize expected results Figure 1 - “NEXT (iN situ EXploration of planeTary objects): EUROPA” logo In the search for life on other bodies within the Solar System, the top candidates are the icy moons, including Saturn’s moon Enceladus and Europa. These icy moons are target of study as they will help us in the task of assessing possible habitability zones in our neighborhood. The choice of instruments that can answer these questions and also allow us to understand other factors is key. Raman spectroscopy has the versatility to be used to obtain those answers. It has been widely used in the analysis of terrestrial and planetary samples due to its advantages in rapid and non-destructive analysis of the mineralogy and mineral chemistry of rock and/or soil samples. For planetary explorations it exhibits great potentials for unambiguous phase identification due to its narrow and non-overlapping peak profiles, fast analysis without sample preparations, robust behavior and low mass, etc. To achieve the stated objectives, a work plan has been established in different stages, subdivided into three phases: Samples preparation Tests conduction of various Raman techniques on the samples (first is carried out exclusively at the INTA facilities and in the second, the collaborating laboratories will take part) Analysis of the test results and database generation of pros and cons of each technique The samples prepared consist in a saline solution with a molecular organic component. The salt used was MgSO4 that was detected by the Galileo mission [1]. The organic molecule selected was the amino-acid alanine. This amino-acid was discovering in several meteorites as the Murchison meteorite [2]. The sample solutions were prepared with proportions in weight of 5, 10 and 17 % for the salt, and 0.5, 1.0 and 1.5 for the alanine. The following figures show the multisamples compositions of the nine samples (1 to 9), as a result of the prepared sample vials. Figure 2 - Multisamples concentrations Figure 3 - Prepared multisamples vials In the second phase, the prepared samples will be analysed in liquid and frozen state with different Raman technologies in four laboratories including the ExoMars RLS [3] Flight Spare model located at INTA. RLS [4] was the first Raman spectrometer qualified for space applications. This phase will be completed in June 2022. The laboratories where the tests will take place together with the Raman technology to be tested are as follows: Centro de Astrobiología (CAB): iHR550 Horiba with an in-situ 532nm laser and portable i-Raman BWTEK with an in-situ 532nm laser INTA: ExoMars RLS Flight Spare (in-situ visible green laser). GSE (control and scientific analysis) automated by SW University of Valladolid: Raman in-situ Exemplar® Plus LS High Performance Spectrometer with an 785nm (IR) laser and Raman with remote pulsed laser Instituto de Micro y Nanotecnología (IMN): LabRaman HR with two possibilities: 532 nm Solid State Diode Laser and 632 nm (HeNe) Solid State Diode Laser Figure 4 - portable i-Raman BWTEK at CAB facilities Figure 5 - RLS Flight Spare Model at INTA facilities With all the information provided by the Raman tests with Raman technology, an analysis of the results will be carried out in July 2022 and conclusions will be issued on the different techniques used to determine and argue which technology (remote or in-situ Raman technology, which excitation laser wavelength: visible / infrared spectrum) would be the most suitable for meet the scientific requirements to address whether life exists or has ever existed in Europa. [1] Thomas B. McCord, Gary B. Hansen, Jean-Philippe Combe, Paul Hayne, Hydrated minerals on Europa’s surface: An improved look from the Galileo NIMS investigation, Icarus, Volume 209, Issue 2, 2010, Pages 639-650 [2] Engel, M., Nagy, B. Distribution and enantiomeric composition of amino acids in the Murchison meteorite. Nature 296, 837–840 (1982) [3] Rull, F., et al, The Raman Laser Spectrometer for the ExoMars Rover Mission to Mars, Astrobiology, 2017, vol. 17(6-7), 627-654 [4] Moral, A.G., et al, A Raman Spectrometer for the ExoMars 2020 Rover, European Planetary Science Congress 2017, 17-22 September, 2017, Riga Latvia, id. EPSC2017-1001

Neuregulin 1 (NRG1) and its receptor ERBB4 are schizophrenia (SZ) risk genes that control the development of both excitatory and inhibitory cortical circuits. Most studies focused on the characterization ErbB4 deficient mice. However, ErbB4 deletion concurrently perturbs the signaling of Nrg1 and Neuregulin 3 (Nrg3), another ligand expressed in the cortex. In addition, NRG1 polymorphisms linked to SZ locate mainly in non-coding regions and they may partially reduce Nrg1 expression. Here, to study the relevance of Nrg1 partial loss-of-function in cortical circuits we characterized a recently developed haploinsufficient mouse model of Nrg1 (Nrg1tm1Lex). These mice display SZ-like behavioral deficits. The cellular and molecular underpinnings of the behavioral deficits in Nrg1tm1Lex mice remain to be established. With multiple approaches including Magnetic Resonance Spectroscopy (MRS), electrophysiology, quantitative imaging and molecular analysis we found that Nrg1 haploinsufficiency impairs the inhibitory cortical circuits. We observed changes in the expression of molecules involved in GABAergic neurotransmission, decreased density of Vglut1 excitatory buttons onto Parvalbumin interneurons and decreased frequency of spontaneous inhibitory postsynaptic currents. Moreover, we found a decreased number of Parvalbumin positive interneurons in the cortex and altered expression of Calretinin. Interestingly, we failed to detect other alterations in excitatory neurons that were previously reported in ErbB4 null mice suggesting that the Nrg1 haploinsufficiency does not entirely phenocopies ErbB4 deletions. Altogether, this study suggests that Nrg1 haploinsufficiency primarily affects the cortical inhibitory circuits in the cortex and provides new insights into the structural and molecular synaptic impairment caused by NRG1 hypofunction in a preclinical model of SZ., The project was supported by the Spanish Ministry of Economy and Competitiveness, grants RYC-2014-16410 (PF) and SAF2017-89020-R (PF, CNG, ARP, AGM, YDC), PRE2018-083562 (ARP); Generalitat Valenciana (GVA) fellowship ACIF/2019/015 (AGM). We would like to thank Encarnaci ́on Fern ́andez Valle, from the Nuclear Magnetic Reso-nance Unit (Bioimage Research Support Center, Complutense University of Madrid), for her technical support with spectra processing. We thank Miguel Gonz ́alez Manteiga for helping with the volumetric analysis. We also thank, Victoria Moreno Manzano, Dunja Luckovich and Deborah Burks for sharing useful reagents. Part of the equipment employed in this work has been funded by GVA and co-financed with ERDF funds (OP ERDF of Comunitat Valenciana 2014-2020). We also thank the support of the Conselleria de Sanitat of the GVA which is funding the salary of CNG via the Centro de Investigaci ́on Príncipe Felipe, facilities and structural support.

The Raman Laser Spectrometer (RLS) is one of the Pasteur Payload instruments within ESA’s ExoMars mission to Mars. The RLS instrument scientific goal consists of performing Raman spectroscopy over different mineral powder samples of the Mars subsoil, been able to detect organic samples if they exist. The laser unit contained in RLS is one of the most critical parts of the instrument and must meet a series of requirements and functionalities that guarantee compliance with the scientific requirements. The flight unit was thoroughly characterized, obtaining a 2D mapping of its optical properties. Since the laser modules are hermetically sealed, this characterization was performed in ambient conditions. But what if the internal pressure conditions changed? How would performances be affected? Leak rate requirement was calculated in order to guarantee high internal pressure levels up to end-of-life but a sealing failure leading to a slow degradation or a depressurization event may still be feasible. Two batch of tests were carried out in order to know how the laser unit behaves if a depressurization occurs by chance. The first test phase consisted of characterizing unsealed laser units both in ambient pressure and in vacuum, so that we could see the contrast between both cases. In the second phase of tests, the pressure profile was varied while monitoring both the power and the spectral behavior, in order to study the evolution of performances of these units. This work summarizes the outcome of these test sessions.

Given the growing interest in fluorine, it is necessary to develop new multi-tuned RF coils. Therefore, our objective is to design a simple and versatile double-tuned RF coil that can be used as a transmitter and receiver double-tuned coil (1H and 19F) or as transmitter-only double-tuned coil. A high-pass eight-element birdcage coil was built for 1H and 19F for a 7 T scanner. PIN diodes and cable traps to block unwanted common mode currents in cables were introduced to confer more flexibility to the coil. S-parameters and quality factor were measured in workbench and signal to noise ratio as well as signal intensity profiles in imaging experiments. Bench measurements show S11 values less than − 33 dB, S21 lower than − 13 dB and quality factors ratio of the order of 1.8 that are in agreement with good performances of a RF coil, as well as values of − 39 dB for 19F and − 30 dB for 1H as good detuning values. Signal intensity profiles prove excellent homogeneity at 1H and 19F. We present a simple structure of a double-tuned high-pass birdcage coil tuned to 1H and 19F that shows a great uniformity and sensitivity for 19F.

Mesenchymal stem cell (MSC)-based therapy is a promising therapeutic approach in the management of several pathologies, including central nervous system diseases. Previously, we demonstrated the therapeutic potential of human adipose-derived MSCs for neurological sequelae of oncological radiotherapy using the intranasal route as a non-invasive delivery method. However, a comprehensive investigation of the safety of intranasal MSC treatment should be performed before clinical applications. Here, we cultured human MSCs in compliance with quality control standards and administrated repeated doses of cells into the nostrils of juvenile immunodeficient mice, mimicking the design of a subsequent clinical trial. Short- and long-term effects of cell administration were evaluated by in vivo and ex vivo studies. No serious adverse events were reported on mouse welfare, behavioral performances, and blood plasma analysis. Magnetic resonance study and histological analysis did not reveal tumor formation or other abnormalities in the examined organs of mice receiving MSCs. Biodistribution study reveals a progressive disappearance of transplanted cells that was further supported by an absent expression of human GAPDH gene in the major organs of transplanted mice. Our data indicate that the intranasal application of MSCs is a safe, simple and non-invasive strategy and encourage its use in future clinical trials, This work was funded by grants from the Andalusian Regional Ministry of Health (PI- 0272-2017 to V.C.-G), the Institute of Health Carlos III co-funded by Fondos FEDER (PI20/00341, CP19/00046 to V.C.-G; PI18/01590, CPII19/00023 to A.M.-M.), the Fundación Científica de la Asociación Española Contra el Cáncer (IDEAS20051CAPI to V.C.-G.), the crowdfunding platform PRECIPITA of the Spanish Foundation for Science and Technology (2018-000237 to V.C.-G.), and the Asociación Pablo Ugarte (+ VIDA project to V.C.-G).

Objectives Preoperative breast magnetic resonance imaging (MRI) can inform surgical planning but might cause overtreatment by increasing the mastectomy rate. The Multicenter International Prospective Analysis (MIPA) study investigated this controversial issue. Methods This observational study enrolled women aged 18–80 years with biopsy-proven breast cancer, who underwent MRI in addition to conventional imaging (mammography and/or breast ultrasonography) or conventional imaging alone before surgery as routine practice at 27 centers. Exclusion criteria included planned neoadjuvant therapy, pregnancy, personal history of any cancer, and distant metastases. Results Of 5896 analyzed patients, 2763 (46.9%) had conventional imaging only (noMRI group), and 3133 (53.1%) underwent MRI that was performed for diagnosis, screening, or unknown purposes in 692/3133 women (22.1%), with preoperative intent in 2441/3133 women (77.9%, MRI group). Patients in the MRI group were younger, had denser breasts, more cancers ≥ 20 mm, and a higher rate of invasive lobular histology than patients who underwent conventional imaging alone (p p p p Conclusions Clinicians requested breast MRI for women with a higher a priori probability of receiving mastectomy. MRI was associated with 11.3% more mastectomies, and with 3.2% fewer reoperations in the breast conservation subgroup. Key Points • In 19% of patients of the MIPA study, breast MRI was performed for screening or diagnostic purposes. • The current patient selection to preoperative breast MRI implies an 11% increase in mastectomies, counterbalanced by a 3% reduction of the reoperation rate. • Data from the MIPA study can support discussion in tumor boards when preoperative MRI is under consideration and should be shared with patients to achieve informed decision-making.

Contains fulltext : 225795.pdf (Publisher’s version ) (Closed access) Despite its high diagnostic performance, the use of breast MRI in the preoperative setting is controversial. It has the potential for personalized surgical management in breast cancer patients, but two of three randomized controlled trials did not show results in favor of its introduction for assessing the disease extent before surgery. Meta-analyses showed a higher mastectomy rate in women undergoing preoperative MRI compared to those who do not. Nevertheless, preoperative breast MRI is increasingly used and a survey from the American Society of Breast Surgeons showed that 41% of respondents ask for it in daily practice. In this context, a large-scale observational multicenter international prospective analysis (MIPA study) was proposed under the guidance of the European Network for the Assessment of Imaging in Medicine (EuroAIM). The aims were (1) to prospectively and systematically collect data on consecutive women with a newly diagnosed breast cancer, not candidates for neoadjuvant therapy, who are offered or not offered breast MRI before surgery according to local practice; (2) to compare these two groups in terms of surgical and clinical endpoints, adjusting for covariates. The underlying hypotheses are that MRI does not cause additional mastectomies compared to conventional imaging, while reducing the reoperation rate in all or in subgroups of patients. Ninety-six centers applied to a web-based call; 36 were initially selected based on volume and quality standards; 27 were active for enrollment. On November 2018, the target of 7000 enrolled patients was reached. The MIPA study is presently at the analytic phase. Key Points • Breast MRI has a high diagnostic performance but its utility in the preoperative setting is controversial. • A large-scale observational multicenter prospective study was launched to compare women receiving with those not receiving preoperative MRI. • Twenty-seven centers enrolled more than 7000 patients. The study is presently at the analytic phase.

The morphological changes that occur in the central nervous system of patients with severe acute intermittent porphyria (AIP) have not yet been clearly established. The aim of this work was to analyse brain involvement in patients with severe AIP without epileptic seizures or clinical posterior reversible encephalopathy syndrome, as well as in a mouse model receiving or not liver-directed gene therapy aimed at correcting the metabolic disorder. We conducted neuroradiologic studies in 8 severely affected patients (6 women) and 16 gender- and age-matched controls. Seven patients showed significant enlargement of the cerebral ventricles and decreased brain perfusion was observed during the acute attack in two patients in whom perfusion imaging data were acquired. AIP mice exhibited reduced cerebral blood flow and developed chronic dilatation of the cerebral ventricles even in the presence of slightly increased porphyrin precursors. While repeated phenobarbital-induced attacks exacerbated ventricular dilation in AIP mice, correction of the metabolic defect using liver-directed gene therapy restored brain perfusion and afforded protection against ventricular enlargement. Histological studies revealed no signs of neuronal loss but a denser neurofilament pattern in the periventricular areas, suggesting compression probably caused by imbalance in cerebrospinal fluid dynamics. In conclusion, severely affected AIP patients exhibit cerebral ventricular enlargement. Liver-directed gene therapy protected against the morphological consequences of the disease seen in the brain of AIP mice. The observational study was registered at Clinicaltrial.gov as NCT02076763.

Introduction: The objective of this study was to evaluate the association between the type of initial fluid therapy used (isotonic or hypotonic solutions) and the development of hyponatremia, the plasma chlorine values and the tolerance of venous access. Patients and Method: Retrospective cohort study in a Pediatric Intensive Care Unit (PICU) of a high complexity hospital. There were included children younger than 15 years old hospitalized during the first semester of 2010 and 2013 who received intravenous maintenance fluid therapy, excluding patients undergoing cardiac surgery, kidney transplant and admissions that lasted less than 24 hours. Epidemiological, comorbidity and admission related data were collected, including type of solution received, sodium and chlorine values in the first 72 hours of hospitalization and the incidence of extravasation of peripheral intravenous lines. Results: 111 children were included; 68 children (61.3%) were treated with hypotonic solutions and 43 (38.7%) with isotonic solutions. There were no differences in pathology and severity, and also in the volume of fluid received. Among the patients who received hypotonic solutions, 28 (41.2%) developed hyponatremia, wich was moderate (Na

The importance of atherosclerosis is driving research to create improved diagnostic tools based on molecular imaging. Pretargeted imaging is the use of bioorthogonal probes that selectively accumulate upon reaction with a pre-modified biomolecule in vivo. To date, this very promising approach has not been applied to atherosclerosis. Neither has been the use of a single nano-radiomaterial for PET / T-MR imaging of atherosclerosis. Here, we synthesized bioorthogonal nano-radiomaterials for in vivo pretargeted molecular imaging in a mouse model of atherosclerosis. Based on tetrazine-ligation, these functionalized Ga iron oxide nano-radiomaterials provide simultaneous PET and T-MRI signals and selectively accumulate in atherosclerotic plaques in mice sequentially injected with trans-cyclooctene-modified antibodies against oxidized LDL followed by the hybrid nano-radiomaterial. Our results demonstrate the ability of this approach to unambiguously detect atherosclerosis. Furthermore, we show the first example of how hybrid imaging can be used for pretargeted bioorthogonal molecular imaging with nanomaterials., This work was funded by the Spanish Ministry for Economy and Competitiveness (MEyC) (grant number: SAF2016-79593-P and SAF2017-84494-C2-R) and Carlos III Health Institute (grant number: DTS16/00059). L.G. was funded by Ramon y Cajal grant (RYC-2014-15512).

Introduction: Total hip and knee arthroplasty (THA/TKA) are surgical procedures with proven benefits. Although the literature reports outcomes of fusion of the lumbar spine comparable to those of THA/TKA in general health-related quality-of-life (HRQoL) questionnaires, functional assessment is nevertheless needed for these results to be of use in clinical practice and management. Aim of our study was to prove that lumbar spinal fusion has similar if not better outcomes than THA/TKA using intervention-specific HRQoL questionnaires and functional assessment questionnaires. Materials and methods: Observational, ambispective, multicentre study of three cohorts undergoing lumbar spinal fusion (n = 115), THA (n = 119) and TKA (n = 253). Patients were evaluated using the Short-Form-12 (SF-12), Harris–Hip-Score, Hospital for Special Surgery Scale (HSS) and Oswestry Low Back Pain Disability questionnaires. A minimum follow-up of two years was conducted. Results: The SF-12 showed significant improvement in all groups. The SF-12 physical component summary score indicated a more severe pre-operative status (p = 0.031) in the THA cohort. The mental component summary score indicated a less severe pre-operative status in the TKA cohort (p = 0.008) and greater post-operative improvement in the TKA and THA cohorts across follow-up (six months p = 0.021; one year p = 0.012; two years p = 0.042). Functional assessment indicated greater pre-operative disability in the THA group. At two years of follow-up, functional improvement according to the Harris, HSS and Oswestry questionnaires were 152.01%, 50.07% and 41.14% respectively. Conclusions: This study demonstrates that lumbar spinal fusion and total knee and hip arthroplasty are comparable in terms of functional improvement when thoroughly studied with health, quality-of-life and functional assessment questionnaires.

Given the growing interest in fluorine, it is necessary to develop new multi-tuned RF coils. Therefore, our objective is to design a simple and versatile double-tuned RF coil that can be used as a transmitter and receiver double-tuned coil (A high-pass eight-element birdcage coil was built forBench measurements show S11 values less than - 33 dB, S21 lower than - 13 dB and quality factors ratio of the order of 1.8 that are in agreement with good performances of a RF coil, as well as values of - 39 dB forWe present a simple structure of a double-tuned high-pass birdcage coil tuned to

Meningoencephalitis of unknown origin (MUO) is a common inflammatory disease of the central nervous system. Several studies investigated finding prognostic factors, but results are contradictory. The aim of this study was to determine the concentrations of blood lactate (Blood-L) and cerebrospinal fluid lactate (CSF-L) in dogs with MUO for prognostic purposes. A total of 45 dogs with MUO (MUO group) and 11 with idiopathic epilepsy (IE group) were included. In the MUO group, 22 dogs were treated with prednisolone + cytosine arabinoside, 17 with prednisolone ± cyclosporine, and six received no treatment. In the MUO group, there was a strong-moderate positive correlation between Blood-L and CSF-L (ρ = 0.63557; P 0.0001), a strong-moderate negative correlation between survival and CSF-L (ρ= -0.50210; P 0.0004), and a weak negative correlation between survival and Blood-L (ρ= -0.35685; P 0.0220). Dogs with a favourable response to treatment at 1 month had lower initial concentrations of Blood-L and CSF-L (P 0.0010; P 0.0037), and those with a worse response had higher values (P 0.0497; P 0.0004). Dogs that remained stable with treatment showed lower CSF-L concentrations (P 0.0013). Dogs with Blood-L4 mmol/L (P 0.03) and/or CSF-L4 mmol/L (P 0.009) had lower survival rates with the latter also showing more severe signs, probably indicating severe neuronal damage. These findings suggest that concentrations of CSF-L and Blood-L in dogs with MUO could be used as prognostic indicators.

Nowadays, the technology has become necessary in daily aspects of everyday life, included healthcare and healthy lifestyle. Thus, in the last years has taken place an important development of Body Sensor Networks (BSN) to let a continuous monitoring. Security is becoming increasingly important in all areas related to Information Technology, and becomes even more important when patient’s health is involved. Confiability and privacy are necessary requirements for patients to feel secure with the sensors, but the reliability is necessary too, because if all measured data are lost or damage before reaching their destination, it cannot be made an adequate monitor or make the best diagnosis. The aim of this work is to provide a review of the security for BSN applied to the healthcare, in order to enable the development of applications to improve the patient's diagnosis and treatment with chronic diseases.Keywords: BSN, healthcare,confiability, reliability, chronic diseases.

The use of click chemistry reactions for the functionalization of nanoparticles is particularly useful to modify the surface in a well-defined manner and to enhance the targeting properties, thus facilitating clinical translation. Here it is demonstrated that olefin metathesis can be used for the chemoselective functionalization of iron oxide nanoparticles with three different examples. This approach enables, in one step, the synthesis and functionalization of different water-stable magnetite-based particles from oleic acid-coated counterparts. The surface of the nanoparticles was completely characterized showing how the metathesis approach introduces a large number of hydrophilic molecules on their coating layer. As an example of the possible applications of these new nanocomposites, a focus was taken on atherosclerosis plaques. It is also demonstrated how the in vitro properties of one of the probes, particularly its Ca(2+) -binding properties, mediate their final in vivo use; that is, the selective accumulation in atherosclerotic plaques. This opens promising new applications to detect possible microcalcifications associated with plaque vulnerability. The accumulation of the new imaging tracers is demonstrated by in vivo magnetic resonance imaging of carotids and aorta in the ApoE(-/-) mouse model and the results were confirmed by histology.

The objective of this study was to evaluate the association between the type of initial fluid therapy used (isotonic or hypotonic solutions) and the development of hyponatremia, the plas ma chlorine values and the tolerance of venous access.Retrospective cohort study in a Pediatric Intensive Care Unit (PICU) of a high complexity hospital. There were included children younger than 15 years old hospitalized during the first semester of 2010 and 2013 who recei ved intravenous maintenance fluid therapy, excluding patients undergoing cardiac surgery, kidney transplant and admissions that lasted less than 24 hours. Epidemiological, comorbidity and admis sion-related data were collected, including type of solution received, sodium and chlorine values in the first 72 hours of hospitalization and the incidence of extravasation of peripheral intravenous lines.111 children were included; 68 children (61.3%) were treated with hypotonic solutions and 43 (38.7%) with isotonic solutions. There were no differences in pathology and severity, and also in the volume of fluid received. Among the patients who received hypotonic solutions, 28 (41.2%) de veloped hyponatremia, wich was moderate (Na130 mEq/Kg) in 11 cases, compared with 8 children (18.6%) who received isotonic solutions, with only one case of moderate hyponatremia (p = 0.027). No cases of hypernatremia were recorded, and there were no differences in plasma chlorine values. There was also no increased frequency of venous access loss in patients treated with isotonic solutions (4.7% versus 7.4%, p = 0.704).Treatment with initial isotonic solutions in children hos pitalized in PICU is associated with a lower incidence and severity of hyponatremia, without changes in the plasma chlorine values and it is well tolerated by peripheral intravenous lines.

El siguiente artículo invita a realizar una reflexión sobre algunos términos como "comunidad" "identidad y diferencia", "ciudadanía y democracia", "tejidos social y multiculturalismo", entre otros. Optaré por comprender lo palabra comunidad en el sentido de la organización, la identidad y la acción comunitaria, de esta manera se entiende que una comunidad es un sistema sociocultural, y así se está dando la posibilidad del reconocimiento de lo propio que lo constituye y aunque no se puede afirmar que existen parámetros completamente homogéneos de definición, sí se puede pensar que hay elementos comunes que la definen y que la hacen dinámica y es justamente desde las dinámicas propias de las comunidades o grupos comunitarios desde donde resulta posible la acción que conllevo o fortalecer o restablecer el tejido social que no se limita únicamente a una vecindad espacial, sino a la significación y construcción de sus formas de vida.Así, al analizar las zonas marginadas desde su entramado social y su cohesión, se daría paso al reconocimiento positivo que a través del diálogo, que establece la relación con el otro y permite la vinculación de mis intereses con los de aquél, lo que derivará en una acción dialogada conjunta, que reconoce la identidad y la diferencia y que genera procesos de participación.

Objective To assess the contribution of mammography and ultrasound in men with nipple discharge. Materials and methods All men with nipple discharge who underwent mammography and/or ultrasound between 1993 and 2011 in our hospital were retrospectively evaluated. Radiological findings were classified according to BI-RADS lexicon. The final diagnosis was made based on histopathological results or clinical–radiological follow-up. The diagnostic performance of physical examination, mammography and ultrasound was calculated and compared. Results 26 men with 21 mammograms and 19 ultrasounds were reviewed. The final diagnoses were: 6 carcinomas (23.1%), 10 gynaecomastias, 2 pseudogynaecomastias and 8 normal breast tissues. Mammograms and ultrasounds performed on all five patients with infiltrating carcinoma showed a mass (categories 4 and 5). In all these patients except one, a breast mass was also noted and the physical examination was positive or suspected malignancy. In the patient with carcinoma in situ, the only conspicuous clinical sign was bloody nipple discharge and the mammography showed calcifications (category 4) that were not visible on ultrasound. Radiological findings of all patients without malignancy were classified as categories 1 and 2. The diagnostic performance of physical examination was lower than mammography and ultrasound (P > 0.05). Mammography was more sensitive than ultrasound (100% vs. 83.3%). Both techniques showed the same specificity (100%). Conclusions Men with nipple discharge have a high incidence of breast carcinoma. Nipple discharge may be the only clinical sign of carcinoma in situ. Mammography and ultrasound are useful in the evaluation of men with nipple discharge, diagnosing carcinoma in initial stages, avoiding unnecessary biopsies.

An 82-year-old male with a history of high blood pressure, COPD, chronic myeloid leukemia, and stage-4 chronic renal failure. Admitted to hospital for lower-limb cellulitis and severe COPD exacerbation, he received antibiotic therapy and bronchodilators. During his hospital stay he developed severe anemia and had an hematochezia event with no diarrhea. A complete colonoscopy found small (4-7 mm) nacreous elevated lesions, circumferential in shape, in the cecum and ascending colon with some bleeding stigmata and submucosal bleeding suggestive of infectious colitis; stool culture was negative and Clostridium difficile toxins were positive. The condition was histologically confirmed.

Porphobilinogen deaminase (PBGD) haploinsufficiency (acute intermittent porphyria, AIP) is characterized by neurovisceral attacks when hepatic heme synthesis is activated by endogenous or environmental factors including fasting. While the molecular mechanisms underlying the nutritional regulation of hepatic heme synthesis have been described, glucose homeostasis during fasting is poorly understood in porphyria. Our study aimed to analyse glucose homeostasis and hepatic carbohydrate metabolism during fasting in PBGD-deficient mice. To determine the contribution of hepatic PBGD deficiency to carbohydrate metabolism, AIP mice injected with a PBGD-liver gene delivery vector were included. After a 14 h fasting period, serum and liver metabolomics analyses showed that wild-type mice stimulated hepatic glycogen degradation to maintain glucose homeostasis while AIP livers activated gluconeogenesis and ketogenesis due to their inability to use stored glycogen. The serum of fasted AIP mice showed increased concentrations of insulin and reduced glucagon levels. Specific over-expression of the PBGD protein in the liver tended to normalize circulating insulin and glucagon levels, stimulated hepatic glycogen catabolism and blocked ketone body production. Reduced glucose uptake was observed in the primary somatosensorial brain cortex of fasted AIP mice, which could be reversed by PBGD-liver gene delivery. In conclusion, AIP mice showed a different response to fasting as measured by altered carbohydrate metabolism in the liver and modified glucose consumption in the brain cortex. Glucose homeostasis in fasted AIP mice was efficiently normalized after restoration of PBGD gene expression in the liver.

Trabajo fin de Grado presentado por Leticia Marina Benito para optar al Grado de Educación Infantil por la Universidad de Valladolid, Facultad de Educación y Trabajo Social: Departamento de Biología Celular, Histología y Farmacología., [ES]: El aprendizaje por indagación y experimentación tiene como objetivo que los alumnos sean capaces de interiorizar los conocimientos científicos de manera significativa, para descubrir el mundo que les rodea. Así formaremos ciudadanos con pensamiento crítico, y resolutivos ante cualquier situación que se les plantee, ya sea escolar o de su vida cotidiana. El presente trabajo pretende analizar diferentes documentos que apoyan la indagación como metodología en el aula de infantil y alguna propuesta acerca de cómo llevarla a cabo. Además también se explica una propuesta didáctica para realizar con alumnos de Educación Infantil. De esta propuesta se detallan las actividades que se han llevado a cabo con niños de 1º de Educación Infantil (3 años) del C.E.I.P. García Quintana, expresando sus reacciones ante ellas., [EN]: The aim of the inquiry based learning and experimentation is that students are able to internalize scientific knowledge significantly, to discover the world around them. So we educate citizens with critical thinking, and problem-solving in any situation that is raised before them, whether school or everyday life. The following work analyzes different documents that supporting the inquiry like a classroom methodology and any ideas about how to carry it out. In addition a didactic proposal also explains how to perform with kindergarten students. In this proposal the activities have been conducted with children from Early Childhood Education (3 years old) of C.E.I.P. Garcia Quintana, expressing their reactions to them.

Resumen En los ultimos anos, los cambios en la demanda de asistencia sanitaria relacionada con la patologia mamaria, y en concreto con el cancer de mama, unidos a las nuevas tendencias diagnosticas y terapeuticas, han impulsado el desarrollo de equipos multidisciplinarios dedicados a esta enfermedad. En la mayoria de los centros sanitarios que atienden patologia mamaria se han creado unidades multidisciplinarias de mama siguiendo las directrices de determinadas instituciones y sociedades cientificas. En el presente trabajo se revisan las recomendaciones mas importantes al respecto, se valoran la experiencia y los aspectos organizativos que han permitido adaptarse a esta nueva situacion, y se plantean estrategias futuras.

La generación de formas de apropiación territorial en América latino están ligados a las formas de representación europea de territorio que se introducen en la colonia, estas formas generan imaginarios culturales que unidos a los particulares procesos de mestizaje que se llevaron a cabo, dan paso a un fuerte sentimiento de añoranza de lo que no se es, otorgando el poder de representación o elementos externos a la misma América latino, sin embargo, de estos mismos procesos surgen las propuestas para mirarse y hacerse notar no como simple marginalidad, sino como marginalidad empoderada que se reterritorializa culturalmente, lo cual implica un cambio epistemológico en la auto-representación y por tanto en la hetero-representación.

Plaque development has been extensively studied using magnetic resonance imaging (MRI) in animal models of rapidly progressing atherosclerosis, such as apolipoprotein E-knockout (apoE-KO) mice. Preclinical MRI plays a significant role in the study of experimental atherosclerosis. Currently, MRI is capable of detecting luminal narrowing, plaque size, and morphology with high accuracy and reproducibility, providing reliable measurements of plaque burden. Therefore, MRI offers a noninvasive approach to serially monitor the progression of the disease. Compared with other imaging modalities, MRI appears to have the greatest potential for plaque characterization, through the use of multiple contrast weightings (e.g., T1, T2, and proton density). Here, we illustrate a standard procedure to image the aorta of atherosclerotic mice using noninvasive MRI.

Plaque development has been extensively studied using magnetic resonance imaging (MRI) in animal models of rapidly progressing atherosclerosis, such as apolipoprotein E-knockout (apoE-KO) mice. Preclinical MRI plays a significant role in the study of experimental atherosclerosis. Currently, MRI is capable of detecting luminal narrowing, plaque size, and morphology with high accuracy and reproducibility, providing reliable measurements of plaque burden. Therefore, MRI offers a noninvasive approach to serially monitor the progression of the disease. Compared with other imaging modalities, MRI appears to have the greatest potential for plaque characterization, through the use of multiple contrast weightings (e.g., T1, T2, and proton density). Here, we illustrate a standard procedure to image the aorta of atherosclerotic mice using noninvasive MRI.

A fast and reproducible microwave-driven process has allowed us to synthesise neridronate-functionalised nanoparticles. Contrary to tradition, the phosphate groups decorate the outside layer of the particles providing Ca2+ binding properties in vitro and selective accumulation in vivo in the atheroma plaque. In vivo and ex vivo detection by T2-weighted MRI is demonstrated and validated by histology. The accumulation in the plaque takes place in less than one hour following the intravenous injection, which is particularly suitable for clinical applications.

We provide an integrative interpretation of neuroglial metabolic coupling including the presence of subcellular compartmentation of pyruvate and monocarboxylate recycling through the plasma membrane of both neurons and glial cells. The subcellular compartmentation of pyruvate allows neurons and astrocytes to select between glucose and lactate as alternative substrates, depending on their relative extracellular concentration and the operation of a redox switch. This mechanism is based on the inhibition of glycolysis at the level of glyceraldehyde 3-phosphate dehydrogenase by NAD+ limitation, under sufficiently reduced cytosolic NAD+/NADH redox conditions. Lactate and pyruvate recycling through the plasma membrane allows the return to the extracellular medium of cytosolic monocarboxylates enabling their transcellular, reversible, exchange between neurons and astrocytes. Together, intracellular pyruvate compartmentation and monocarboxylate recycling result in an effective transcellular coupling between the cytosolic NAD+/NADH redox states of both neurons and glial cells. Following glutamatergic neurotransmission, increased glutamate uptake by the astrocytes is proposed to augment glycolysis and tricarboxylic acid cycle activity, balancing to a reduced cytosolic NAD+/NADH in the glia. Reducing equivalents are transferred then to the neuron resulting in a reduced neuronal NAD+/NADH redox state. This may eventually switch off neuronal glycolysis, favoring the oxidation of extracellular lactate in the lactate dehydrogenase (LDH) equilibrium and in the neuronal tricarboxylic acid cycles. Finally, pyruvate derived from neuronal lactate oxidation, may return to the extracellular space and to the astrocyte, restoring the basal redox state and beginning a new loop of the lactate/pyruvate transcellular coupling cycle. Transcellular redox coupling operates through the plasma membrane transporters of monocarboxylates, similarly to the intracellular redox shuttles coupling the cytosolic and mitochondrial redox states through the transporters of the inner mitochondrial membrane. Finally, transcellular redox coupling mechanisms may couple glycolytic and oxidative zones in other heterogeneous tissues including muscle and tumors. © 2006 Elsevier Ltd. All rights reserved., The present work was supported in part by grants SAF 2001-2245 and SAF 2004-03197 from the Spanish Ministry of Education and Science, and grants FISss C03/08, C03/155, C03/10, PI051530 and PI051845 from the Institute of Health Carlos III to S.C. and M.L.G.M., respectively. Justesa Imagen S.A. provided a core grant supporting the NMR Facility. M.B. and A.S. were predoctoral fellows from CSIC and UNED, respectively. T.B.R., C.P.F. and L.L.F. hold fellowships from the Fundação para a Ciência e Tecnologia/Ministério da Inovação, Ciência e Ensino Superior (Portugal). M.L.G.M. holds a young investigator award Ramón y Cajal at CSIC.

We report the synthesis of micellar phosphatidylcholine-coated superparamagnetic iron oxide nanoparticles as a new long circulation contrast agents for magnetic resonance imaging. Oleic acid-coated Fe3 O4 nanoparticles were first prepared through thermal degradation and then encapsulated into small clusters with a phosphatidylcholine coating to obtain hydrophilic nanomicelles. A thorough characterization confirmed the chemical nature of the coating and the excellent colloidal stability of these nanomicelles in aqueous media. Magnetization and relaxivity properties proved their suitability as magnetic resonance imaging (MRI) contrast agent and in vitro cell viability data showed low toxicity. Vascular lifetime and elimination kinetics in the liver were assessed by blood relaxometry and by in vivo MRI in rats and compared with "control" particles prepared with a polyethylene glycol derivative. These micellar particles had a lifetime in blood of more than 10 h, much longer than the control nanoparticles (≈2 h), which is remarkable considering that the coating molecule is a small biocompatible zwitterionic phospholipid. The protein corona was characterized after incubation with rat serum at different times by high-throughput proteomics, showing a higher proportion of bound apolipoproteins and other dysopsonins for the phosphatidylcholine particles. The antibiofouling properties of this corona and its resistance to the adsorption of proteins corroborate the observed enhanced stability and prolonged systemic circulation. This study is supported by a grant from FP7 Marie Curie, Pulmonary imaging network (PINET), by Fundacio La Maratode TV3 (70/C/2012) and by a grant from the Comunidad de Madrid (S2010/BMD-2326, Inmunothercan-CM) and by Spanish Economy Ministry (MAT2013-47303-P). We thank E. Urones (Centro Nacional de Microscopia de la Universidad Complutense de Madrid) for the transmission electronic microscopy imaging; P. Morales (Instituto de Ciencia de Materiales de la Universidad Autonoma de Madrid) for the thermogravimetric and magnetization analysis and B. Salinas (Fundacion Centro Nacional de Investigaciones Cardiovasculares and CIBER de Enfermedades Respiratorias) for the TEM picture of oleic acid coated Fe3 O4. The authors declare no competing financial interests. Sí

Este escrito está dividido en tres momentos: en el primero, se muestra de manera general por qué Heidegger considera que el humanismo es otra metafísica, o mejor, que todo humanismo se ha fundamentado metafísicamente. De ahí surge la necesidad del giro, de la KEHRE, para buscar lo verdaderamente fundante. El segundo, examinará la idea de la ciencia moderna como lo fundamental de la existencia y si realmente es ella lo más fundante de la existencia humana. El último se refiere a la reflexión sobre lo que Heidegger considera el verdadero habitar como lo fundante. This piece is divided in three phases: the first evaluates in general terms why Heidegger considers that humanism is another metaphysics or that all humanism was metaphysically established; from this the KHERE theory emerges consecutively to explore the fundamental requirements. The second phase studies the concept of modern science as the vital element of existence and, if in fact, it is the most vital element for the human existence. The last phase refers to Heidegger 's notion of a true dwelling.

We report a novel ((13)C, (2)H) nuclear magnetic resonance (NMR) procedure to investigate lactate recycling through the monocarboxylate transporter of the plasma membrane of cells in culture. C6 glioma cells were incubated with [3-(13)C]lactate in Krebs-Henseleit Buffer containing 50% (2)H(2)O (vol/vol) for up to 30 hr. (13)C NMR analysis of aliquots progressively taken from the medium, showed: (1) a linearly decreasing singlet at approximately 20.85 parts per million (ppm; -0.119 micromol/mg protein/hr) derived from the methyl carbon of [3-(13)C]lactate; and (2) an exponentially increasing shifted singlet at approximately 20.74 ppm (0.227 micromol/ mg protein/hr) from the methyl carbon of [3-(13)C, 2-(2)H]lactate. The shifted singlet appears because during its transit through the cytosol, [3-(13)C]lactate generates [3-(13)C, 2-(2)H]lactate in the lactate dehydrogenase (LDH) equilibrium, which may return to the incubation medium through the reversible monocarboxylate carrier. The methyl group of [3-(13)C, 2-(2)H]lactate is shifted -0.11 ppm with respect to that of [3-(13)C]lactate, making it possible to distinguish between both molecules by (13)C NMR. During incubations with 2.5 mM [1-(13)C]glucose and 3.98 mM [U-(13)C(3)]lactate or with 2.5 mM [1-(13)C]glucose and 3.93 mM [2-(13)C]pyruvate, C2-deuterated lactate was produced only from [1-(13)C]glucose or [U-(13)C(3)]lactate, revealing that this deuteration process is redox sensitive. When [1-(13)C]glucose and [U-(13)C(3)]lactate were used as substrates, no significant [3-(13)C]lactate production from [1-(13)C]glucose was detected, suggesting that glycolytic lactate production may be stopped under the high lactate concentrations prevailing under mild hypoxic or ischemic episodes or during cerebral activation.

A number of metabolites have signaling properties by acting through G-protein–coupled receptors. Succinate, a Krebs cycle intermediate, increases after dysregulated energy metabolism and can bind to its cognate receptor succinate receptor 1 (Sucnr1, or GPR91) to activate downstream signaling pathways. We show that Sucnr1 is highly expressed in the white adipose tissue (WAT) compartment of mice and regulates adipose mass and glucose homeostasis. Sucnr1−/− mice were generated, and weight gain was monitored under basal and nutritional stress (high-fat diet [HFD]) conditions. On chow diet, Sucnr1−/− mice had increased energy expenditure, were lean with a smaller WAT compartment, and had improved glucose buffering. Lipolysis measurements revealed that Sucnr1−/− mice were released from succinate-induced inhibition of lipolysis, demonstrating a function of Sucnr1 in adipose tissue. Sucnr1 deletion also protected mice from obesity on HFD, but only during the initial period; at later stages, body weight of HFD-fed Sucnr1−/− mice was almost comparable with wild-type (WT) mice, but WAT content was greater. Also, these mice became progressively hyperglycemic and failed to secrete insulin, although pancreas architecture was similar to WT mice. These findings suggest that Sucnr1 is a sensor for dietary energy and raise the interesting possibility that protocols to modulate Sucnr1 might have therapeutic utility in the setting of obesity.

16 páginas, 9 figuras, 1 tabla, Adult neurogenesis is restricted to specific brain regions. Although involved in the continuous supply of interneurons for the olfactory function, the role of neural precursors in brain damage-repair remains an open question. Aiming to in vivo identify endogenous neural precursor cells migrating towards a brain damage site, the monoclonal antibody Nilo2 recognizing cell surface antigens on neuroblasts, was coupled to magnetic glyconanoparticles (mGNPs). The Nilo2-mGNP complexes allowed, by magnetic resonance imaging in living animals, the in vivo identification of endogenous neural precursors at their niche, as well as their migration to a lesion site (induced brain tumor), which was fast (within hours) and orderly. Interestingly, the rapid migration of neuroblasts towards a damage site is a characteristic that might be exploited to precisely localize early damage events in neurodegenerative diseases. In addition, it might facilitate the study of regenerative mechanisms through the activation of endogenous neural cell precursors. A similar approach, combining magnetic glyconanoparticles linked to appropriate antibodies could be applied to flag other small cell subpopulations within the organism, track their migration, localize stem cell niches, cancer stem cells or even track metastatic cells, This work was supported by CSIC (PIF200620F0041), MICINN (SAF2009-07974; RD06/0010/1010 from the Instituto de Salud Carlos III, CTQ2008-04638) and the Department of Industry, Innovation and Technology of the Basque Country (grant ETORTEK)

Proceedings of: 2011 IEEE Nuclear Science Symposium and Medical Imaging Conference (NSS/MIC). Valencia, Spain, 23-29 October 2011 Dynamic cardiac magnetic resonance imaging in small animals is an important tool in the study of cardiovascular diseases. The reduction of the long acquisition times required for cardiovascular applications is crucial to achieve good spatiotemporal resolution and signal-to-noise ratio. Nowadays there are many acceleration techniques which can reduce acquisition time, including compressed sensing technique. Compressed sensing allows image reconstruction from undersampled data, by means of a non linear reconstruction which minimizes the total variation of the image. The recently appeared Split Bregman methodology has proved to be more computationally efficient to solve this problem than classic optimization methods. In the case of dynamic magnetic resonance imaging, compressed sensing can exploit time sparsity by the minimization of total variation across both space and time. In this work, we propose and validate the Split Bregman method to minimize spatial and time total variation, and apply this method to accelerate cardiac cine acquisitions in rats. We found that applying a quasi-random variable density pattern along the phase-encoding direction, accelerations up to a factor 5 are possible with low error. In the future, we expect to obtain higher accelerations using spatiotemporal undersampling. This work is supported in part by Ministerio de Ciencia e Innovacion (Red RECA VA), Comunidad de Madrid and Fondos FEDER (ARTEMIS project S2009DPI 1802). Publicado

Background & aim: Uptake, cytotoxicity and interaction of improved superparamagnetic iron oxide nanoparticles were studied in cells, tissues and organs after single and multiple exposures. Material & method: We prepared dimercaptosuccinic acid-coated iron oxide nanoparticles by thermal decomposition in organic medium, resulting in aqueous suspensions with a small hydrodynamic size (< 100 nm), high saturation magnetization and susceptibility, high nuclear magnetic resonance contrast and low cytotoxicity. Results: In vitro and in vivo behavior showed that these nanoparticles are efficient carriers for drug delivery to the liver and brain that can be combined with MRI detection.

To assess clinical variables that may be useful in differentiating gynaecomastia from carcinoma and to analyse the contribution of mammography and ultrasound to the evaluation of male breast disease.All men who underwent mammography and/or ultrasound between 1993 and 2006 in our hospital were retrospectively evaluated. Clinical characteristics in patients with gynaecomastia and those with carcinoma were compared. Radiological findings were classified according to the BI-RADS (Breast Imaging Reporting and Data System) criteria. The diagnostic performance of physical examination, mammography and ultrasound was determined and compared.A total of 628 patients with 518 mammograms and 423 ultrasounds were reviewed. The final diagnoses were: 19 carcinomas, 526 gynaecomastias, 84 other benign conditions and 25 normal. There were statistically significant differences in age, bilateral involvement, clinical presentation and physical examination between patients with carcinoma and those with gynaecomastia. The diagnostic performance of physical examination was lower than that of mammography and ultrasound (p0.05 for specificity). Mammography was the most sensitive (94.7%) and ultrasound the most specific (95.3%) for detection of malignancy (p0.05). We propose an algorithm for the use of mammography and ultrasound in men.Mammography and ultrasound, with a negative predictive value close to 100%, make it possible to avoid very many unnecessary surgical procedures in men.

Preoperative diagnosis of axillary metastases in breast cancer patients enables treatment planning. We aimed to evaluate the diagnostic accuracy of axillary ultrasonography and percutaneous biopsy, both alone and in combination, in detecting axillary metastases in patients with breast cancer and to assess the impact of these techniques on the patients’ management. Materials and methods Retrospective study of consecutive patients with suspected breast cancer examined between October 2006 and December 2008. The diagnosis of a primary tumor was histologically confirmed in all patients. All patients underwent axillary ultrasonography and percutaneous core biopsy (14G) of suspicious lymph nodes. We evaluated the morphological characteristics of the lymph nodes by ultrasonography. We calculated the diagnostic accuracy of ultrasonography and of core biopsy, and assessed the impact of these techniques on patients’ treatment. Results We evaluated 675 axillary regions and performed 291 core biopsies of axillary lymph nodes in 662 patients. In 650 patients, breast cancer was histologically confirmed and in 12 patients malignant tumors in other locations were confirmed. The sensitivity and specificity of axillary ultrasonography were 63.2% and 88.7%, respectively. The absence of a fatty hilum within the lymph node was the ultrasonographic finding with the highest positive predictive value for malignancy (93.1%). The sensitivity and specificity of axillary core biopsy were 69.1% and 100%, respectively. Sentinel lymph node biopsy was avoided in 33% of initial candidates and immediate breast reconstruction was undertaken in 35.1% of the patients with mastectomy and negative axillary core biopsy. Conclusions Ultrasonography and axillary core biopsy enable adequate pretreatment staging in patients with breast cancer and has a positive impact on their management.

[ES]: Se revisan los diversos métodos de medida de pH que utilizan espectroscopía e imagen por resonancia magnética y su potencial repercusión diagnóstica. La revisión comienza con una breve descripción de la regulación del pH intra y extracelular en condiciones fisiológicas y patológicas. Posteriormente se presentan los principales procedimientos basados en espectroscopía de resonancia magnética de 31P ó 1H, basados en la dependencia del pH de los desplazamientos químicos del fosfato inorgánico intracelular intrínseco o del protón H2 del imidazol en indicadores extrínsecos. Finalmente se describen los procedimientos que utilizan imagen por resonancia magnética, empleando como herramienta principal la dependencia del pH de (i) la relajatividad de determinados agentes de contraste paramagnéticos o (ii) de los procesos de transferencia de magnetización entre moléculas diamagnéticas (DIACEST) o paramagnéticas (PARACEST) y el agua libre de los tejidos. Se ilustran brevemente las potenciales aplicaciones clínicas de estos nuevos procedimientos., [EN]: We review the different methods for measuring pH by magnetic resonance imaging and magnetic resonance spectroscopy and discuss their potential diagnostic repercussions. We begin with a brief description of intra- and extracellular pH regulation in physiological and pathological conditions. Then we present the main 31P or 1H magnetic resonance spectroscopy procedures, which are based on the dependence of the pH on the chemical displacements of the intrinsic intracellular inorganic phosphate or of the H2 proton of imidazole in extrinsic indicators. Finally, we describe the procedures that use magnetic resonance imaging, whose main tool is the dependence of the pH (i) on the relaxivity of certain paramagnetic contrast agents, or (ii) on the processes of magnetic transference between diamagnetic molecules (DIACEST) or paramagnetic molecules (PARACEST) and the free water in the tissues. We briefly illustrate the potential clinical applications of these new procedures., Este trabajo se ha financiado en parte con los proyectos SAF2001-2245, SAF2004-03197 del Ministerio de Educación y Ciencia y FISss PI051530 del Instituto de Salud Carlos III a SC, SAF2003-01810 y CTQ2006-06505/BQU del Ministerio de Educación y Ciencia a PB y CM-S-BIO/0170/2006 de la Comunidad de Madrid a SC y PB.

et al., The acidity of the tumor microenvironment aids tumor growth, and mechanisms causing it are targets for potential therapies. We have imaged extracellular pH (pHe) in C6 cell gliomas in rat brain using 1H magnetic resonance spectroscopy in vivo. We used a new probe molecule, ISUCA [(±)2- (imidazol-1-yl)succinic acid], and fast imaging techniques, with spiral acquisition in k-space. We obtained a map of metabolites [136 ms echo time (TE)] and then infused ISUCA in a femoral vein (25 mmol/kg body weight over 110 min) and obtained two consecutive images of pHe within the tumor (40 ms TE, each acquisition taking 25 min). pHe (where ISUCA was present) ranged from 6.5 to 7.5 in voxels of 0.75 μL and did not change detectably when [ISUCA] increased. Infusion of glucose (0.2 mmol/kg·min) decreased tumor pHe by, on average, 0.150 (SE, 0.007; P < 0.0001, 524 voxels in four rats) and increased the mean area of measurable lactate peaks by 54.4 ± 3.4% (P < 0.0001, 287 voxels). However, voxel-by-voxel analysis showed that, both before and during glucose infusion, the distributions of lactate and extracellular acidity were very different. In tumor voxels where both could be measured, the glucose-induced increase in lactate showed no spatial correlation with the decrease in pHe. We suggest that, although glycolysis is the main source of protons, distributed sites of proton influx and efflux cause pHe to be acidic at sites remote from lactate production. ©2007 American Association for Cancer Research., Grant support: Institut National de la Santé et de la Recherche Médicale-Consejo Superior de Investigaciones Cientificas Collaborative Grant; Association pour la Recherche sur le Cancer; Cancéropôle Région Rhône-Alpes; Région Rhône-Alpes; Institute of Health Carlos III, Spain, PI051845 and PI051530 (M.L. García-Martín and S. Cerdán); Ministry of Education and Science, Spain SAF 2004-03197 and NAN2004- 09125-C07-03 (S. Cerdán); and Institut National de Cancer (C. Rémy).