Did anomalous atmospheric circulation favor the spread of COVID-19 in Europe?

The current pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is having negative health, social and economic consequences worldwide. In Europe, the pandemic started to develop strongly at the end of February and beginning of March 2020. Subsequently, it spread over the continent, with special virulence in northern Italy and inland Spain. In this study we show that an unusual persistent anticyclonic situation prevailing in southwestern Europe during February 2020 (i.e. anomalously strong positive phase of the North Atlantic and Arctic Oscillations) could have resulted in favorable conditions, e.g., in terms of air temperature and humidity among other factors, in Italy and Spain for a quicker spread of the virus compared with the rest of the European countries. It seems plausible that the strong atmospheric stability and associated dry conditions that dominated in these regions may have favored the virus propagation, both outdoors and especially indoors, by short-range droplet and aerosol (airborne) transmission, or/and by changing social contact patterns. Later recent atmospheric circulation conditions in Europe (July 2020) and the U.S. (October 2020) seem to support our hypothesis, although further research is needed in order to evaluate other confounding variables. Interestingly, the atmospheric conditions during the Spanish flu pandemic in 1918 seem to have resembled at some stage with the current COVID-19 pandemic.

Impact of Physiological Signals Acquisition in the Emotional Support Provided in Learning Scenarios.

Physiological sensors can be used to detect changes in the emotional state of users with affective computing. This has lately been applied in the educational domain, aimed to better support learners during the learning process. For this purpose, we have developed the AICARP (Ambient Intelligence Context-aware Affective Recommender Platform) infrastructure, which detects changes in the emotional state of the user and provides personalized multisensorial support to help manage the emotional state by taking advantage of ambient intelligence features. We have developed a third version of this infrastructure, AICARP.V3, which addresses several problems detected in the data acquisition stage of the second version, (i.e., intrusion of the pulse sensor, poor resolution and low signal to noise ratio in the galvanic skin response sensor and slow response time of the temperature sensor) and extends the capabilities to integrate new actuators. This improved incorporates a new acquisition platform (shield) called PhyAS (Physiological Acquisition Shield), which reduces the number of control units to only one, and supports both gathering physiological signals with better precision and delivering multisensory feedback with more flexibility, by means of new actuators that can be added/discarded on top of just that single shield. The improvements in the quality of the acquired signals allow better recognition of the emotional states. Thereof, AICARP.V3 gives a more accurate personalized emotional support to the user, based on a rule-based approach that triggers multisensorial feedback, if necessary. This represents progress in solving an open problem: develop systems that perform as effectively as a human expert in a complex task such as the recognition of emotional states.

Molecular markers of putative spermatogonial stem cells in the domestic cat.

Spermatogonial stem cells (SSCs) are an important tool for fertility preservation and species conservation. The ability to expand SSCs by in vitro culture is a crucial premise for their use in assisted reproduction. Because SSCs represent a small proportion of the germ cells in the adult testis, culture success is aided by pre-enrichment through sorting techniques based on cell surface-specific markers. Given the importance of the domestic cat as a model for conservation of endangered wild felids, herein we sought to examine culture conditions as well as molecular markers for cat SSCs. Using a cell culture medium for mouse SSCs supplemented with glial cell-derived neurotrophic factor (GDNF), germ cells from prepuberal cat testes remained viable in culture for up to 43 days. Immunohistochemistry for promyelocytic leukaemia zinc finger (PLZF) protein on foetal, prepuberal and adult testis sections revealed a pattern of expression consistent with the labelling of undifferentiated spermatogonia. Fluorescence-activated cell sorting (FACS) with an antibody against epithelial cell adhesion molecule (EPCAM) was used to sort live cells. Then, the gene expression profile of EPCAM-sorted cells was investigated through RT-qPCR. Notably, EPCAM (+) cells expressed relatively high levels of CKIT (CD117), a surface protein typically expressed in differentiating germ cells but not SSCs. Conversely, EPCAM (-) cells expressed relatively high levels of POU domain class 5 transcription factor 1 (POU1F5 or OCT4), clearly a germ line stem cell marker. These results suggest that cat SSCs would probably be found within the population of EPCAM (-) cells. Future studies should identify additional surface markers that alone or in combination can be used to further enrich SSCs from cat germ cells.

Risk of tuberculosis after lung transplantation: the value of pretransplant chest computed tomography and the impact of mTOR inhibitors and azathioprine use.

BACKGROUND: It is necessary to determine the incidence and risk factors for tuberculosis (TB), as well as strategies to assess and treat latent tuberculosis infection (LTBI) in lung transplant recipients. METHODS: A retrospective cohort study of 398 lung transplant recipients was performed. Episodes of TB were studied and the incidence rate was calculated. Logistic regression analysis was used to analyze specific variables as potential risk factors for TB. RESULTS: Median follow-up was 558 days (range 1-6636). Six cases (1.5%) of TB were documented in 398 transplant patients. The incidence density of TB was 406.3 cases/10(5) patient-years (95% confidence interval [CI] 164.7-845), which is higher than in the general population (13.10 cases/10(5) person-years). All cases occurred in the period 1993-2006, when the tuberculin skin test (TST) and treatment of LTBI in positive TST patients were not part of the protocol. Pretransplant computed tomography (CT) showed residual lesions in 50% of patients who developed TB, although the TST was negative and the chest radiograph was inconclusive. Multivariate analysis identified the presence of residual lesions in the pretransplant chest CT (odds ratio [OR] 11.5, 95% CI 1.9-69.1, P = 0.008), use of azathioprine (OR 10.6, 95% CI 1.1-99.1, P = 0.038), and use of everolimus (OR 6.7, 95% CI 1.1-39.8, P = 0.036) as independent risk factors for TB. CONCLUSIONS: Residual lesions in the pretransplant chest CTs and the use of azathioprine and mTOR inhibitors are associated with the risk of TB.

Factors related to the development of CMV-specific CD8+ T cell response in CMV-seropositive solid organ transplant candidates.

This cross-sectional study analyzes factors associated with the development of CMV-specific CD8+ response, measured by IFNg production after cytomegalovirus (CMV) peptide stimulation, in CMV-seropositive solid organ transplantation candidates. A total of 114 candidates were enrolled, of whom 22.8% (26/114) were nonreactive (IFNγ < 0.2 IU/mL). Multivariate logistic regression analysis showed that age, HLA alleles and organ to be transplanted were associated with developing CMV-specific CD8+ immunity (reactive; IFNγ ≥ 0.2 IU/mL). The probability of being reactive was higher in candidates over 50 than in those under 50 (OR 6.33, 95%CI 1.93-20.74). Candidates with HLA-A1 and/or HLA-A2 alleles had a higher probability of being reactive than those with non-HLA-A1/non-HLA-A2 alleles (OR 10.97, 95%CI 3.36-35.83). Renal candidates had a higher probability of being reactive than lung (adjusted OR 8.85, 95%CI 2.24-34.92) and liver candidates (OR 4.87, 95%CI 1.12-21.19). The AUC of this model was 0.84 (p < 0.001). Positive and negative predictive values were 84.8% and 76.9%, respectively. In renal candidates longer dialysis was associated with an increased frequency of reactive individuals (p = 0.040). Therefore, although the assessment of CMV-specific CD8+ response is recommended in all R+ candidates, it is essential in those with a lower probability of being reactive, such as non-renal candidates, candidates under 50 or those with non-HLA-A1/non-HLA-A2 alleles.

[Salivaly gland tumors in childhood: importance of an early diagnosis and treatment]. / Tumores de glándulas salivales en la infancia. Importancia de un diagnóstico y tratamiento precoz.

OBJECTIVE: Review of our series of salivaly gland tumors at pediatric age, given its low frequency and their higher rate of malignancy compared with the adult population. MATERIAL AND METHODS: Retrospective study of the medical records of all pediatric patients with salivaly gland tumors treated in our center between 1998 and 2013. RESULTS: We identified 12 patients. The most common site of tumor location was the parotid gland in 11 patients followed by the sublingual gland in 1 patient. Three patients had previous cancer and radiotherapy history. The diagnosis (histological or radiological) were: 4 hemangiomas, 2 pleomorphic adenomas, 4 mucoepidermoid carcinomas, one acinar cell carcinoma and 1 primitive neuroectodermal tumor (PNET). No patient had metastasis at diagnosis. Preoperative fine needle aspiration (FNA) was performed in 6 patients with solid masses, being diagnostic in all cases. Eight patients underwent surgery. In two cases of total parotidectomy initial neuroapraxia appeared but none had permanent facial paralysis. There were no cases of Frey syndrome. The aesthetic results were good. There was only one tumor recurrence and all patients, except one who died of leukemia relapse, survive today. CONCLUSIONS: Salivaly gland tumors are uncommon in pediatric age but their high rate of malignancy makes it necessary to establish a rapid diagnosis. In our experience, FNA showed a high sensitivity. For malignant tumors, definitive treatment is surgical excision, preserving the facial nerve whenever possible. For vascular tumors, surgery is reserved for cases refractory to medical treatment.

OBJETIVO: Revisión de nuestra serie de neoplasias de glándulas salivales en pediatría, dada su baja frecuencia y mayor tasa de malignidad en comparación con la población adulta. MATERIAL Y METODOS: Estudio retrospectivo de las historias clínicas de los casos pediátricos de tumores de glándulas salivales tratados en nuestro centro entre los años 1998 y 2013. RESULTADOS: Se estudian 12 pacientes. Los tumores afectaban a la glándula parótida en 11 casos y en uno a la glándula sublingual. Tres pacientes presentaban historia oncológica previa y antecedentes de radioterapia. El diagnóstico (histológico o radiológico) fue de: 4 hemangiomas, 2 adenomas pleomorfos, 4 carcinomas mucoepidermoides, 1 carcinoma de células acinares y 1 tumor primitivo neuroectodérmico (PNET). Ningún paciente presentaba metástasis al diagnóstico. Se realizó PAAF preoperatoria en 6 pacientes que presentaban masas sólidas, siendo diagnóstica en todos ellos. Ocho pacientes fueron intervenidos. En dos casos de parotidectomía total apareció neuroapraxia inicial pero ninguno tuvo parálisis facial definitiva. No hubo ningún caso de síndrome de Frey. Los resultados estéticos fueron buenos. Un solo caso presentó recidiva tumoral y todos los pacientes, excepto uno que falleció por recaída de leucemia, sobreviven en la actualidad. CONCLUSIONES: Los tumores de glándula salival son raros en pediatría pero su alta tasa de malignidad hace necesario establecer un diagnóstico rápido. En nuestra experiencia, la PAAF presentó elevada sensibilidad. En los tumores malignos el tratamiento es la exéresis, preservando el nervio facial siempre que sea posible. En los tumores vasculares la cirugía se reserva para casos refractarios al tratamiento médico.

Reconstruction of multi-animal PET acquisitions with anisotropically variant PSF.

Among other factors such as random, attenuation and scatter corrections, uniform spatial resolution is key to performing accurate quantitative studies in Positron emission tomography (PET). Particularly in preclinical PET studies involving simultaneous acquisition of multiple animals, the degradation of image resolution due to the depth of interaction (DOI) effect far from the center of the Field of View (FOV) becomes a significant concern. In this work, we incorporated a spatially-variant resolution model into a real time iterative reconstruction code to obtain accurate images of multi-animal acquisition. We estimated the spatially variant point spread function (SV-PSF) across the FOV using measurements and Monte Carlo (MC) simulations. The SV-PSF obtained was implemented in a GPU-based Ordered subset expectation maximization (OSEM) reconstruction code, which includes scatter, attenuation and random corrections. The method was evaluated with acquisitions from two preclinical PET/CT scanners of the SEDECAL Argus family: a Derenzo phantom placed 2 cm off center in the 4R-SuperArgus, and a multi-animal study with 4 mice in the 6R-SuperArgus. The SV-PSF reconstructions showed uniform spatial resolution without significant increase in reconstruction time, with superior image quality compared to the uniform PSF model.

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.

Vaginal neutrophil infiltration is contingent on ovarian cycle phase and independent of pathogen infection.

The mucosa of the female reproductive tract must reconcile the presence of commensal microbiota and the transit of exogenous spermatozoa with the elimination of sexually transmitted pathogens. In the vagina, neutrophils are the principal cellular arm of innate immunity and constitute the first line of protection in response to infections or injury. Neutrophils are absent from the vaginal lumen during the ovulatory phase, probably to allow sperm to fertilize; however, the mechanisms that regulate neutrophil influx to the vagina in response to aggressions remain controversial. We have used mouse inseminations and infections of Neisseria gonorrhoeae, Candida albicans, Trichomonas vaginalis, and HSV-2 models. We demonstrate that neutrophil infiltration of the vaginal mucosa is distinctively contingent on the ovarian cycle phase and independent of the sperm and pathogen challenge, probably to prevent sperm from being attacked by neutrophils. Neutrophils extravasation is a multi-step cascade of events, which includes their adhesion through selectins (E, P and L) and integrins of the endothelial cells. We have discovered that cervical endothelial cells expressed selectin-E (SELE, CD62E) to favor neutrophils recruitment and estradiol down-regulated SELE expression during ovulation, which impaired neutrophil transendothelial migration and orchestrated sperm tolerance. Progesterone up-regulated SELE to restore surveillance after ovulation.

Fluorescence diffuse optical tomography using the split Bregman method.

PURPOSE: Standard image reconstruction methods for fluorescence Diffuse Optical Tomography (fDOT) generally make use of L2-regularization. A better choice is to replace the L2 by a total variation functional that effectively removes noise while preserving edges. Among the wide range of approaches available, the recently appeared Split Bregman method has been shown to be optimal and efficient. Furthermore, additional constraints can be easily included. We propose the use of the Split Bregman method to solve the image reconstruction problem for fDOT with a nonnegativity constraint that imposes the reconstructed concentration of fluorophore to be positive. METHODS: The proposed method is tested with simulated and experimental data, and results are compared with those yielded by an equivalent unconstrained optimization approach based on Gauss-Newton (GN) method, in which the negative part of the solution is projected to zero after each iteration. In addition, the method dependence on the parameters that weigh data fidelity and nonnegativity constraints is analyzed. RESULTS: Split Bregman yielded a reduction of the solution error norm and a better full width at tenth maximum for simulated data, and higher signal-to-noise ratio for experimental data. It is also shown that it led to an optimum solution independently of the data fidelity parameter, as long as the number of iterations is properly selected, and that there is a linear relation between the number of iterations and the inverse of the data fidelity parameter. CONCLUSIONS: Split Bregman allows the addition of a nonnegativity constraint leading to improve image quality.

[Cervical cystic lymphangioma: still a challenge]. / Linfangioma quístico cervical: todavía un reto.

INTRODUCTION: Cervical lymphangiomas can not only cause severe sequelae (aesthetic, phonatory or deglutory) but can also be life thereatening due to airway compresion or massive bleeding. This paper analyzes our surgical results, the value of prenatal diagnosis and the use of new techniques such as the EXIT procedure for airway control in sereve cases. PATIENTS AND METHODS: We retrospectively reviewed the medical record of patients with cervical lymphangiomas treated in our center between 1986 and 2009, according to our Clinical Documentation Database. Data referred to prenatal diagnosis, intrapartum airway management, surgical procedures and morbidity, sclerosing substance infiltration and long term sequelae was analyzed. RESULTS: Thirteen cases were identified. 53.8% of the patients were diagnosed by prenatal ultrasound, and MRI was performed in 46.1%. The tongue was affected in 30.7%, parotid glands in 38.4% and airway in 38.4%. Four EXIT procedures were carried out (nasotracheal intubation) and one emergency tracheotomy was needed. Five patients required more than one surgical prodedures, including partial glossectomy, with severe intraoperatory complications in 23% (bleeding, pharyngeal damage). In eight patients primary or adyuvant sclerotherapy was used. Three children with giant masses died, two due to intracystic bleeding and one from sepsis. Among the survivors, 50% have no sequelae. CONCLUSIONS: Cervical lymphangiomas are a very sereve condition, not only due to possible airway compresion or massive bleeding but also becose of the severe secualaes they may cause. Tongue or parotid gland infiltration are difficult to treat. In severe cases diagnosed prenatally a close follow up in selected centers, with multidisciplinary teams consisting of obstetricians and pediatric surgeons, trained in the EXIT procedure is warranted. Despite therapeutic efforts the prognosis of large masses is still poor.

Detection of visual activation in the rat brain using 2-deoxy-2-[(18)F]fluoro-D: -glucose and statistical parametric mapping (SPM).

PURPOSE: This study was designed to assess changes in brain glucose metabolism in rats after visual stimulation. MATERIALS AND METHODS: We sought to determine whether visual activation in the rat brain could be detected using a small-animal positron emission tomography (PET) scanner and 2-deoxy-2-[(18)F]fluoro-D: -glucose (FDG). Eleven rats were divided into two groups: (a) five animals exposed to ambient light and (b) six animals stimulated by stroboscopic light (10 Hz) with one eye covered. Rats were injected with FDG and, after 45 min of visual stimulation, were sacrificed and scanned for 90 min in a dedicated PET tomograph. Images were reconstructed by a three-dimensional ordered subset expectation maximization algorithm (1.8 mm full width at half maximum). A region-of-interest (ROI) analysis was performed on 14 brain structures drawn on coronal sections. Statistical parametric mapping (SPM) adapted for small animals was also carried out. Additionally, the brains of three rats were sliced into 20-microm sections for autoradiography. RESULTS: Analysis of ROI data revealed significant differences between groups in the right superior colliculus, right thalamus, and brainstem (p < or = 0.05). SPM detected the same areas as the ROI approach. Autoradiographs confirmed the existence of hyperactivation in the left superior colliculus and auditory cortex. CONCLUSIONS: To our knowledge, this is the first report that uses FDG-PET and SPM analysis to show changes in rat brain glucose metabolism after a visual stimulus.

Sinogram bow-tie filtering in FBP PET reconstruction.

Low-pass filtering of sinograms in the radial direction is the most common practice to limit noise amplification in filtered back projection (FBP) reconstruction of positron emission tomography studies. Other filtering strategies have been proposed to prevent the loss in resolution due to low-pass radial filters, although results have been diverse. Using the well-known properties of the Fourier transform of a sinogram, the authors defined a binary mask that matches the expected shape of the support region in the Fourier domain of the sinogram ("bow tie"). This mask was smoothed by a convolution with a ten-point Gaussian kernel which not only avoids ringing but also introduces a pre-emphasis at low frequencies. A new filtering scheme for FBP is proposed, comprising this smoothed bow-tie filter combined with a standard radial filter and an axial filter. The authors compared the performance of the bow-tie filtering scheme with that of other previously reported methods: Standard radial filtering, angular filtering, and stackgram-domain filtering. All the quantitative data in the comparisons refer to a baseline reconstruction using a ramp filter only. When using the smallest size of the Gaussian kernel in the stackgram domain, the authors achieved a noise reduction of 33% at the cost of degrading radial and tangential resolutions (14.5% and 16%, respectively, for cubic interpolation). To reduce the noise by 30%, the angular filter produced a larger degradation of contrast (3%) and tangential resolution (46% at 10 mm from the center of the field of view) and showed noticeable artifacts in the form of circular blurring dependent on the distance to the center of the field of view. For a similar noise reduction (33%), the proposed bow-tie filtering scheme yielded optimum results in resolution (gain in radial resolution of 10%) and contrast (1% increase) when compared with any of the other filters alone. Experiments with rodent images showed noticeable image quality enhancement when using the proposed bow-tie filtering scheme.

PeneloPET, a Monte Carlo PET simulation tool based on PENELOPE: features and validation.

Monte Carlo simulations play an important role in positron emission tomography (PET) imaging, as an essential tool for the research and development of new scanners and for advanced image reconstruction. PeneloPET, a PET-dedicated Monte Carlo tool, is presented and validated in this work. PeneloPET is based on PENELOPE, a Monte Carlo code for the simulation of the transport in matter of electrons, positrons and photons, with energies from a few hundred eV to 1 GeV. PENELOPE is robust, fast and very accurate, but it may be unfriendly to people not acquainted with the FORTRAN programming language. PeneloPET is an easy-to-use application which allows comprehensive simulations of PET systems within PENELOPE. Complex and realistic simulations can be set by modifying a few simple input text files. Different levels of output data are available for analysis, from sinogram and lines-of-response (LORs) histogramming to fully detailed list mode. These data can be further exploited with the preferred programming language, including ROOT. PeneloPET simulates PET systems based on crystal array blocks coupled to photodetectors and allows the user to define radioactive sources, detectors, shielding and other parts of the scanner. The acquisition chain is simulated in high level detail; for instance, the electronic processing can include pile-up rejection mechanisms and time stamping of events, if desired. This paper describes PeneloPET and shows the results of extensive validations and comparisons of simulations against real measurements from commercial acquisition systems. PeneloPET is being extensively employed to improve the image quality of commercial PET systems and for the development of new ones.

Design and performance evaluation of a coplanar multimodality scanner for rodent imaging.

This work reports on the development and performance evaluation of the VrPET/CT, a new multimodality scanner with coplanar geometry for in vivo rodent imaging. The scanner design is based on a partial-ring PET system and a small-animal CT assembled on a rotatory gantry without axial displacement between the geometric centers of both fields of view (FOV). We report on the PET system performance based on the NEMA NU-4 protocol; the performance characteristics of the CT component are not included herein. The accuracy of inter-modality alignment and the imaging capability of the whole system are also evaluated on phantom and animal studies. Tangential spatial resolution of PET images ranged between 1.56 mm at the center of the FOV and 2.46 at a radial offset of 3.5 cm. The radial resolution varies from 1.48 mm to 1.88 mm, and the axial resolution from 2.34 mm to 3.38 mm for the same positions. The energy resolution was 16.5% on average for the entire system. The absolute coincidence sensitivity is 2.2% for a 100-700 keV energy window with a 3.8 ns coincident window. The scatter fraction values for the same settings were 11.45% for a mouse-sized phantom and 23.26% for a rat-sized phantom. The peak noise equivalent count rates were also evaluated for those phantoms obtaining 70.8 kcps at 0.66 MBq/cc and 31.5 kcps at 0.11 MBq/cc, respectively. The accuracy of inter-modality alignment is below half the PET resolution, and the image quality of biological specimens agrees with measured performance parameters. The assessment presented in this study shows that the VrPET/CT system is a good performance small-animal imager, while the cost derived from a partial ring detection system is substantially reduced as compared with a full-ring PET tomograph.

[Identification of genetic alterations by multiple ligation-dependent probe amplification (MLPA) analysis in oligodendrogliomas]. / Identificación de alteraciones genéticas en oligodendrogliomas mediante amplificación dependiente de ligasa de múltiples sondas (MLPA) (multiple ligation-dependent probe amplification).

Concurrent deletion at 1p/19q is a common signature of oligodendrogliomas, and it may be identified in low-grade tumours (grade II) suggesting it represents an early event in the development of these brain neoplasms. Additional non-random changes primarily involve CDKN2A, PTEN and EGFR. Identification of all of these genetic changes has become an additional parameter in the evaluation of the clinical patients' prognosis, including good response to conventional chemotherapy. Multiple ligation-dependent probe amplification (MLPA) analysis is a new methodology that allows an easy identification of the oligodendrogliomas' abnormalities in a single step. No need of the respective constitutional DNA from each patient is another advantage of this method. We used MLPA kits P088 and P105 to determine the molecular characteristics of a series of 40 oligodendrogliomas. Deletions at l p and 19q were identified in 45% and 65% of cases, respectively. Alterations of EGFR, CDKN2A, ERBB2, PTEN and TP53 were also identified in variable frequencies among 7% to 35% of tumours. These findings demonstrate that MLPA is a reliable technique to the detection of molecular genetic changes in oligodendrogliomas.

[Pro-inflammatory cytokines in the knee fat pad and subcutaneous fat of the thigh in osteoarthritic patients]. / Citoquinas proinflamatorias en la grasa articular y subcutánea del muslo en pacientes artrósicos.

OBJECTIVE: To analyze the level of pro-inflammatory cytokines in osteoarthritis knee joint fat pad in relation to the subcutaneous fat of the thigh. MATERIAL AND METHODS: We performed a study of fat of the knee joint adipose affected of osteoarthritis and subcutaneous fat of the thigh of the same side to the greater distance of the joint in six patients with severe gonarthrosis, with a mean age of 68 years (range: 55-81 years). From the fat samples the progenitor mesenchymal cells were obtained. The supernatants of mesenchymal cells obtained to analyze inflammatory factors (IL-1b, IL6, IL9, IL1ra, IL12, IL13, IL15) and angiogenic (VEGF, PDGF bb) and immunomodulatory cytokines (IP-10 and INF-) means of two samples. RESULTS: Quantitative analysis revealed a significant (p 0.05) decrease in IL-1b, IL6, IL8, IL9, IL1ra, IL12, IL13 and increase of IL15 in Hoffa fat pad versus subcutaneous adipose tissue. Likewise, the analysis of angiogenic factors such as VEGF and PDGF, as well as factors IP-10 and INF- presented a significant decrease (p 0.05) in Hoffa fat pad versus subcutaneous adipose tissue. DISCUSSION: Mesenchymal cells from the adipose tissue of the severe osteoarthritic knee show a significant decrease in inflammatory cytokines even in the chronic state and a significant decrease in angiogenic factors and immunomodulatory cytokines (IP10 and INF).

OBJETIVO: Analizar el nivel de citoquinas proinflamatorias en la grasa articular del paquete adiposo en pacientes con gonartrosis, en relación con la grasa subcutánea del muslo. MATERIAL Y MÉTODOS: Efectuamos un estudio de grasa del paquete adiposo articular de la rodilla afectada de artrosis y de la grasa subcutánea del muslo del mismo lado, a la mayor distancia de la articulación en seis pacientes con gonartrosis grave, con una edad media de 68 años (rango: 55-81 años). De las muestras de grasa se obtuvieron las células mesenquimales progenitoras. Los sobrenadantes de células mesenquimales obtenidas se utilizaron para analizar factores inflamatorios (IL-1b, IL6, IL8, IL9, IL1ra, IL12, IL13, IL15) y angiogénicos (VEGF, PDGF bb), así como citoquinas inmunomoduladoras (IP-10 e INF-) y se compararon las medias de dos muestras. RESULTADOS: El análisis cuantitativo reveló una disminución significativa (p 0.05) de IL-1b, IL6, IL8, IL9, IL1ra, IL12, IL13 y un aumento de IL15 en la grasa de Hoffa frente al tejido adiposo subcutáneo. Del mismo modo, el análisis de factores angiógenicos como VEGF y PDGF bb, al igual que los factores IP-10 e INF- presentaron una disminución significativa en la grasa de Hoffa (p 0.05) frente al tejido adiposo subcutáneo. DISCUSIÓN: Las células mesenquimales del paquete adiposo articular de la rodilla artrósica grave muestran una disminución significativa de citoquinas inflamatorias, aun en el estado crónico, y una disminución significativa de factores angiogénicos y citoquinas inmunomoduladoras (IP10 e INF).