Rostral-Caudal Hippocampal Functional Convergence Is Reduced Across the Alzheimer's Disease Spectrum.

Beginning in the early stages of Alzheimer's disease (AD), the hippocampus reduces its functional connections to other cortical regions due to synaptic depletion. However, little is known regarding connectivity abnormalities within the hippocampus. Here, we describe rostral-caudal hippocampal convergence (rcHC), a metric of the overlap between the rostral and caudal hippocampal functional networks, across the clinical spectrum of AD. We predicted a decline in rostral-caudal hippocampal convergence in the early stages of the disease. Using fMRI, we generated resting-state hippocampal functional networks across 56 controls, 48 early MCI (EMCI), 35 late MCI (LMCI), and 31 AD patients from the Alzheimer's Disease Neuroimaging Initiative cohort. For each diagnostic group, we performed a conjunction analysis and compared the rostral and caudal hippocampal network changes using a mixed effects linear model to estimate the convergence and differences between these networks, respectively. The conjunction analysis showed a reduction of rostral-caudal hippocampal convergence strength from early MCI to AD, independent of hippocampal atrophy. Our results demonstrate a parallel between the functional convergence within the hippocampus and disease stage, which is independent of brain atrophy. These findings support the concept that network convergence might contribute as a biomarker for connectivity dysfunction in early stages of AD.

IMI resistance associated to crop-weed hybridization in a natural Brassica rapa population: characterization and fate.

Wild turnip (Brassica rapa) is a common weed and a close relative to oilseed rape (Brassica napus). The Clearfield® production system is a highly adopted tool which provides an alternative solution for weed management, but its efficiency is threatened by gene transfer from crop to weed relatives. Crop-weed hybrids with herbicide resistance were found in the progeny of a B. rapa population gathered from a weedy stand on the borders of an oilseed rape (B. napus) imidazolinone (IMI)-resistant crop. Interspecific hybrids were confirmed by morphological traits in the greenhouse and experimental field, survival after imazethapyr applications, DNA content through flow cytometry, and pollen viability. The transference of herbicide resistance was demonstrated even in a particular situation of pollen competition between both an herbicide-resistant crop and a non-resistant crop. However, IMI resistance was not found in further generations collected at the same location. These results verify gene transmission from oilseed rape to B. rapa in the main crop area in Argentina where resistant and susceptible varieties are found and seed loss and crop volunteers are common. Hybridization, introgression, and herbicide selection would be associated with the loss of effectiveness of IMI technology.

Preoperative progressive pneumoperitoneum and botulinum toxin type A in patients with large incisional hernia.

PURPOSE: Combination of preoperative progressive pneumoperitoneum (PPP) and botulinum toxin type A (BT) has not been previously reported in the management of large incisional hernia (LIH). METHODS: Observational study of 45 consecutive patients with LIH between June 2010 and July 2014. The diameters of the hernia sac, the volumes of the incisional hernia (VIH) and the abdominal cavity (VAC), and the VIH/VAC ratio were measured before and after PPP and BT using abdominal CT scan data. We indicated the combination of both techniques when the volume of the incisional hernia (VIH)/volume of the abdominal cavity (VAC) ratio was >20%. RESULTS: The median insufflated volume of air for PPP was 8.600 ± 3.200 cc (4.500-13.250), over a period of 14.3 ± 1.3 days (13-16). BT administration time was 40.2 ± 3.3 days (37-44). We obtained an average value of reduction of 14% of the VIH/VAC ratio after PPP and BT (p < 0.05). Complications associated with PPP were 15.5%, and with surgical technique, 26.6%. No complications occurred during the BT administration. Reconstructive technique was anterior CST and primary fascial closure was achieved in all patients. Median follow-up was 40.5 ± 19 months (12-60) and we reported 2 cases of hernia recurrence (4.4%). CONCLUSIONS: Preoperative combination of PPP and BT is feasible and a useful tool in the surgical management of LIH, although at the cost of some specific complications.

Quantification of the impact of a confounding variable on functional connectivity confirms anti-correlated networks in the resting-state.

The effect of regressing out the global average signal (GAS) in resting state fMRI data has become a concern for interpreting functional connectivity analyses. It is not clear whether the reported anti-correlations between the Default Mode and the Dorsal Attention Networks are intrinsic to the brain, or are artificially created by regressing out the GAS. Here we introduce a concept, Impact of the Global Average on Functional Connectivity (IGAFC), for quantifying the sensitivity of seed-based correlation analyses to the regression of the GAS. This voxel-wise IGAFC index is defined as the product of two correlation coefficients: the correlation between the GAS and the fMRI time course of a voxel, times the correlation between the GAS and the seed time course. This definition enables the calculation of a threshold at which the impact of regressing-out the GAS would be large enough to introduce spurious negative correlations. It also yields a post-hoc impact correction procedure via thresholding, which eliminates spurious correlations introduced by regressing out the GAS. In addition, we introduce an Artificial Negative Correlation Index (ANCI), defined as the absolute difference between the IGAFC index and the impact threshold. The ANCI allows a graded confidence scale for ranking voxels according to their likelihood of showing artificial correlations. By applying this method, we observed regions in the Default Mode and Dorsal Attention Networks that were anti-correlated. These findings confirm that the previously reported negative correlations between the Dorsal Attention and Default Mode Networks are intrinsic to the brain and not the result of statistical manipulations. Our proposed quantification of the impact that a confound may have on functional connectivity can be generalized to global effect estimators other than the GAS. It can be readily applied to other confounds, such as systemic physiological or head movement interferences, in order to quantify their impact on functional connectivity in the resting state.

The degree of neutropenia has a prognostic impact in low risk myelodysplastic syndrome.

The severity of neutropenia in myelodysplastic syndrome (MDS) has not been completely studied. We analyzed the prognostic significance of severe neutropenia (neutrophils count <0.5×10(9)/L) at diagnosis in 1109 patients with de novo MDS and low/intermediate-1 IPSS included in the Spanish MDS Registry. Severe neutropenia was present at diagnosis in 48 of 1109 (4%). Patients with severe neutropenia were most strongly represented within the groups of refractory cytopenia with multilineage dysplasia (40%) and refractory anemia with excess of blast type 1 (29%). Severe neutropenia had negative effects on the low/intermediate-1 risk group. A significant difference in overall survival was observed between patients with severe neutropenia (28 months) and patients with a neutrophil count higher than 0.5×10(9)/L (66 months) (p<0.0001). Also, severe neutropenia predicted a significantly reduced on leukemia-free survival (p<0.0001). In the multivariate analysis, severe neutropenia retained its independent prognostic influence on overall survival [HR: 2.19, 95% CI (1.41-3.10), p<0.0001] and leukemia free survival [HR: 3.51, 95% CI (1.97-6.26), p<0.0001]. The degree of neutropenia should be considered as additional prognostic factor in low/intermediate-1 IPSS MDS.

Malignant lymphoma of the head and neck.

Malignant lymphomas represent approximately 5% of all malignant neoplasms of the head and neck area. They are classically divided into two subgroups, Hodgkin's lymphomas (HLs) and non-Hodgkin's lymphomas (NHLs). We describe the clinical characteristics of head and neck lymphomas and the methods to establish the diagnosis. The World Health Organization classification of lymphoid tissues describes more than 50 different histological types, and we analyse the most common staging system for lymphomas, the Ann Arbor staging system. Finally, the different therapeutic approaches are discussed.

Sequential hepatogenic transdifferentiation of adipose tissue-derived stem cells: relevance of different extracellular signaling molecules, transcription factors involved, and expression of new key marker genes.

Adipose tissue contains a mesenchymal stem cell (MSC) population known as adipose-derived stem cells (ASCs) capable of differentiating into different cell types. Our aim was to induce hepatic transdifferentiation of ASCs by sequential exposure to several combinations of cytokines, growth factors, and hormones. The most efficient hepatogenic protocol includes fibroblastic growth factors (FGF) 2 and 4 and epidermal growth factor (EGF) (step 1), hepatocyte growth factor (HGF), FGF2, FGF4, and nicotinamide (Nic) (step 2), and oncostatin M (OSM), dexamethasone (Dex), and insulin-tranferrin-selenium (step 3). This protocol activated transcription factors [GATA6, Hex, CCAAT/enhancer binding protein alpha and beta (CEBPalpha and beta), peroxisome proliferator-activated receptor-gamma, coactivator 1 alpha (PGC1alpha), and hepatocyte nuclear factor 4 alpha (HNF4alpha)], which promoted a characteristic hepatic phenotype, as assessed by new informative markers for the step-by-step hepatic transdifferentiation of hMSC [early markers: albumin (ALB), alpha-2-macroglobuline (alpha2M), complement protein C3 (C3), and selenoprotein P1 (SEPP1); late markers: cytochrome P450 3A4 (CYP3A4), apolipoprotein E (APOE), acyl-CoA synthetase long-chain family member 1 (ACSL1), and angiotensin II receptor, type 1 (AGTR1)]. The loss of adipose adult stem cell phenotype was detected by losing expression of Thy1 and inhibitor of DNA binding 3 (Id3). The reexpression of phosphoenolpyruvate corboxykinase (PEPCK), apolipoprotein C3 (APOCIII), aldolase B (ALDOB), and cytochrome P450 1A2 (CYP1A2) was achieved by transduction with a recombinant adenovirus for HNF4alpha and finally hepatic functionality was also assessed by analyzing specific biochemical markers. We conclude that ASCs could represent an alternative tool in clinical therapy for liver dysfunction and regenerative medicine.

[Retrospective analysis of the efficacy and tolerability of anagrelide in patients with essential thrombocytemia: Spanish registry of essential thrombocytemia]. / Análisis retrospectivo de la eficacia y la tolerabilidad de anagrelida en pacientes con trombocitemia esencial: registro español de trombocitemia esencial.

BACKGROUND AND OBJECTIVE: A retrospective analysis of a registration database was used to assess the efficacy and tolerability of anagrelide for treating essential thrombocythemia (ET). The study was conducted by analysing information on response to treatment, time to response and tolerability. PATIENTS AND METHOD: A total of 411 patients with ET from 54 centres in Spain were included in a retrospective chart review. Patients who had started treatment with anagrelide as a first- or second-line therapy before December 31, 2004 were included. RESULTS: Of 411 patients, anagrelide was given as a first-line therapy in 110 patients, following hydroxyurea in 280 patients, and following other drugs in 21 patients. Overall response (OR) with anagrelide was 81.2% (77,0-84,9; p=0,05). Complete response (platelets <400x10(9)/L) was observed in 53.6% (48,6-58,5; p=0,05) and partial response (<600x10(9)/L) in 27.6% (23,4-32,2; p=0,05) of patients. There was no significant correlation of previous treatment with OR rate (p=0.103) despite a higher OR for previously untreated patients (86.4%) than for previously treated patients (79.3%). The most frequent treatment-related adverse reactions were headache (13.1%), palpitations (10.2%) and tachycardia (7.5%). CONCLUSIONS: The observed response rates and tolerability profile are similar to those reported previously. Anagrelide is well tolerated and effective in reducing platelets to target levels in patients with ET.

Análisis retrospectivo de la eficacia y la tolerabilidad de anagrelida en pacientes con trombocitemia esencial: registro español de trombocitemia esencial / Retrospective analysis of the efficacy and tolerability of anagrelide in patients with essential thrombocytemia: Spanish registry of essential thrombocytemia

Fundamento y objetivo: Se efectuó un registro retrospectivo para valorar la eficacia y la tolerabilidad de la anagrelida en el tratamiento de la trombocitemia esencial (TE). Se analizó la información de la respuesta al tratamiento, el tiempo transcurrido hasta la respuesta y la tolerabilidad. Pacientes y método: Registro retrospectivo de 411 pacientes con TE de 54 centros españoles. Se incluyó a enfermos que habían empezado a recibir anagrelida como tratamiento de primera o segunda línea antes del 31 de diciembre de 2004. Resultados: De los 411 pacientes, a 110 se les administró anagrelida como tratamiento de primera línea, a 280 después de hidroxicarbamida y a 21 después de otros fármacos. La respuesta global (RG) con anagrelida fue del 81,2% (intervalo de confianza [IC] del 95%: 77,0 a 84,9). Se observó una respuesta completa (recuento de plaquetas<400×109/l) en el 53,6% de los pacientes (IC del 95%: 48,6 a 58,5) y una respuesta parcial (<600×109/l) en el 27,6% (IC del 95%: 23,4 a 32,2). No hubo una correlación significativa entre el tratamiento previo y la tasa de RG (p=0,103), a pesar de una RG mayor en los pacientes no tratados previamente (86,4%) que en los tratados previamente (79,3%). Los acontecimientos adversos más frecuentes relacionados con el tratamiento fueron cefalea (13,1%), palpitaciones (10,2%) y taquicardia (7,5%). Conclusiones: Las tasas de respuesta y el perfil de tolerabilidad son similares a los descritos con anterioridad. La anagrelida tiene buena tolerancia y es eficaz en la reducción de las plaquetas hasta los valores deseados en los pacientes con TE

Background and objective: A retrospective analysis of a registration database was used to assess the efficacy and tolerability of anagrelide for treating essential thrombocythemia (ET). The study was conducted by analysing information on response to treatment, time to response and tolerability. Patients and method: A total of 411 patients with ET from 54 centres in Spain were included in a retrospective chart review. Patients who had started treatment with anagrelide as a first- or second-line therapy before December 31, 2004 were included. Results: Of 411 patients, anagrelide was given as a first-line therapy in 110 patients, following hydroxyurea in 280 patients, and following other drugs in 21 patients. Overall response (OR) with anagrelide was 81.2% (77,0 84,9; p=0,05). Complete response (platelets <400×109/L) was observed in 53.6% (48,6 58,5; p=0,05) and partial response (<600×109/L) in 27.6% (23,4 32,2; p=0,05) of patients. There was no significant correlation of previous treatment with OR rate (p=0.103) despite a higher OR for previously untreated patients (86.4%) than for previously treated patients (79.3%). The most frequent treatment-related adverse reactions were headache (13.1%), palpitations (10.2%) and tachycardia (7.5%). Conclusions: The observed response rates and tolerability profile are similar to those reported previously. Anagrelide is well tolerated and effective in reducing platelets to target levels in patients with ET

The role of mycoplasmas in a conservation project of the lesser kestrel (Falco naumanni).

The lesser kestrel (Falco naumanni) is one of the most endangered bird species in Europe, and a captive breeding and reintroduction project was established. A breeding project is vulnerable to pathogens, e.g., mycoplasmas, reducing the reproductive success and carrying the risk to release pathogens with the birds to the wild. Therefore, 18 infertile eggs and 43 dead in shell embryos of the breeding project, as well as 27 nestlings and 34 adult birds of the captive and three different free-ranging populations were investigated for the occurrence of mycoplasmas by culture and a Mycoplasma genus-specific polymerase chain reaction. All eggs, embryos, and hand-reared nestlings from the captive group were negative. In contrast, all parent-reared nestlings and 88% of the adults were positive. Mycoplasma falconis and unidentifiable mycoplasmas were detected in all groups. Mycoplasma buteonis was found in the captive and only in two of the three free-ranging populations. Sequencing the 16S rRNA gene of six randomly selected unidentified isolates showed that five isolates were similar and most likely had been found previously in a falcon from Germany. The remaining isolate demonstrated a very high homology to unidentified Mycoplasma isolates obtained previously from semen samples of raptors. The results suggest that these isolates might represent two new species. Mycoplasmas seem not to play a major role as pathogens in the breeding project, and there is no evidence that releasing birds poses a risk to the free-ranging population with regard to mycoplasmas. The study seems to be the first to describe the occurrence and role of mycoplasmas in the lesser kestrel.

Chronic lymphocytic leukemia with a monoclonal immunoglobulin M lambda lymphocyte agglutinin.

A case of chronic lymphocytic leukemia is described in which peripheral blood films showed lymphocyte agglutination. A serum factor responsible for the agglutination was demonstrated. The factor was dependent upon the presence of anticoagulant solutions and was more active at room temperature than at 37 degrees C. It could be identified as a monoclonal immunoglobulin M. This mechanism has not been previously described in lymphocyte agglutination.

Human mesenchymal stem cells from adipose tissue: Differentiation into hepatic lineage.

Adipose tissue represents an accessible source of mesenchymal stem cells (ADSCs), with similar characteristics to bone marrow-derived stem cells. The aim of this work was to investigate the transdifferentiation of ADSCs into hepatic lineage cells in vitro. ADSCs were obtained from human adipose tissue from lipectomy. Cells were grown in medium containing 15% AB human serum. Cultures were serum deprived for two days and exposed to a two-step protocol with two different media using growth factors and cytokines. Hepatic differentiation was assessed by RT-PCR of liver-marker genes. ADSCs exhibited a fibroblastic morphology that changed to a cuboidal shape when cells differentiated. Expression of liver genes increased when using one of the two studied media consisting of DMEM supplemented with HGF, bFGF and nicotinamide for 14 days. The results indicate that, under certain specific inducing conditions, ADSCs can be induced to differentiate into hepatic lineage in vitro. Adipose tissue may be an ideal source of high amounts of autologous stem cells.

Classification and scoring systems in myelodysplastic syndromes: a retrospective analysis of 311 patients.

The main objective of this study was to evaluate the role of the recent World Health Organization (WHO) classification for assessing prognosis in patients with myelodysplastic syndromes (MDS). To this effect, we analyzed the prognostic impact of the WHO and French-American-British (FAB) morphologic classifications and of four different scoring systems in a series of 311 patients with primary MDS diagnosed between October 1990 and June 2001. Both the FAB and WHO classifications identified groups with different prognoses (p<0.0001), those presenting refractory anemia (RA) and refractory anemia with ringed sideroblasts (RARS) showing the best prognosis. The WHO classification subdivided RA into RA with only red cell dysplasia, and refractory cytopenia with multilineage dysplasia (RCMD), and RARS into RARS plus refractory cytopenia with multilineage dysplasia and ringed sideroblast (RCMD-RS). In our population, we have shown that the two subtypes characterized by dysplasia affecting exclusively the erythroid population (RA and RARS) have a better prognosis, with a median survival of 122.2 and 81.9 months, respectively, than those with multilineage dysplasia (RCMD and RCMD-RS) with a median survival of 32.3 and 43.2 months, respectively. There were no significant differences in median survival comparing RA with RAS (p<0.95), or comparing RCMD with RSCMD (p<0.97). Besides, the four scoring systems discriminated our MDS patients in terms of survival, and an increase in prognostic capacity was achieved on adding the score to the morphological classifications. Risk scoring had a greater prognostic impact than the FAB and WHO classifications. Prognostic scoring systems may be an important tool for risk stratification in hematological practice, and add significance to morphological classification. Combined application of the WHO classification and score system is useful for improving the identification of patients with a poorer prognosis. The WHO classification establishes more homogeneous subcategories than the FAB classification and is also able to identify groups with different prognoses.

Randomized comparison of dexamethasone combined with melphalan versus melphalan with prednisone in the treatment of elderly patients with multiple myeloma.

Melphalan-prednisone (MP) has been the gold standard treatment for more than 30 years in elderly multiple myeloma (MM) patients. In order to assess whether the combination of dexamethasone with melphalan (MD) could improve on the efficacy of MP, we have carried out a randomized trial comparing both treatment approaches. A total of 201 patients >/=70 years old were included in the study. The overall response rate was similar after six cycles (MP: 67.9%versus MD: 64.5%) and after 12 cycles (MP: 49.4%versus MD: 46.1%). However, the proportion of complete responses (CR) was higher in the MD arm, particularly after 12 cycles (MD: 22.4%versus MP: 9.1%; P < 0.05). There was no significant difference in event-free survival (MP: 15.9 months versus MD: 23.3 months). The median overall survival in both arms was almost identical (MP: 29.4 months versus MD: 27.2 months; P = 0.63). No significant differences in haematological toxicity were observed, but non-haematological toxicity was significantly higher in the MD arm. According to these results MP remains as the gold standard for treatment of MM and should be the reference for comparison of new therapeutic approaches involving novel agents.

Random field-union intersection tests for EEG/MEG imaging.

Electrophysiological (EEG/MEG) imaging challenges statistics by providing two views of the same spatiotemporal data: topographic and tomographic. Until now, statistical tests for these two situations have developed separately. This work introduces statistical tests for assessing simultaneously the significance of spatiotemporal event-related potential/event-related field (ERP/ERF) components and that of their sources. The test for detecting a component at a given time instant is provided by a Hotelling's T(2) statistic. This statistic is constructed in such a manner to be invariant to any choice of reference and is based upon a generalized version of the average reference transform of the data. As a consequence, the proposed test is a generalization of the well-known Global Field Power statistic. Consideration of tests at all time instants leads to a multiple comparison problem addressed by the use of Random Field Theory (RFT). The Union-Intersection (UI) principle is the basis for testing hypotheses about the topographic and tomographic distributions of such ERP/ERF components. The performance of the method is illustrated with actual EEG recordings obtained from a visual experiment of pattern reversal stimuli.

Brain potentials reflect residual face processing in a case of prosopagnosia.

Here, ERPs were employed to characterise the residual face processing of FE, a patient with extensive damage to the ventral temporal-occipital cortex and a dense prosopagnosia. Alarge N170 was present in FE and he performed well in tests of face structural processing. Covert recognition of the faces of personal acquaintances was demonstrated with P300 oddball experiments. The onset latency of the P300 effect was normal, indicating fast availability of covert memory. The scalp topography of this component in FE was different from that of the P3b, presenting a centro-frontal maximum. FE also presented larger skin conductance responses to familiar than to unfamiliar faces. The amplitudes of both the single-trial P300s and the SCRs triggered by familiar faces were positively correlated with the degree of person-familiarity that FE had for the poser. He performed at chance when asked to select between the face of a familiar person and that of an unfamiliar person on the basis of explicit recognition, whereas he selected more the previously known face if the forced choice was based on trustworthiness or a vague sense of familiarity. The results suggest that in FE, early face processing was relatively intact and covert recognition was fast. Neural structures involved in the processing of emotional or social cues possibly mediate the covert recognition present in FE.

[Our experience with extranodal lymphomas of the ORL region]. / Nuestra experiencia en linfomas extranodales del área ORL.

Head and neck extranodal lymphomas are rare. Waldeyer lymphatic ring is the most common localisation of these lymphomas, followed by oral cavity and parothoid glands. We have done a retrospective study of patients with extranodal lymphomas diagnosed in our hospital between 1991 and 1999. We have included in this study 23 patients, 15 males and 9 females. We have used the REAL classification. All of them have been non-Hodgkin lymphomas. The rhinopharynx has been the most affected region, followed by the palatine tonsils and oral cavity. Most of them were of medium degree and they were in the initial stages. The presentation symptoms varied depending on the localisation. The age, stage and histologic degree were important for the treatment election.

Nuestra experiencia en linfomas extranodales del área ORL / Our experience with extranodal lymphomas in ear, nose and throat practice

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Nuestra experiencia en linfomas extranodales del área ORL / Our experience with extranodal lymphomas in ear, nose and throat practice

Los linfomas extranodales de cabeza y cuello son una entidad clínica poco común. El anillo linfático de Waldeyer es la localización más frecuente de estos linfomas, seguida de la cavidad oral y glándulas parótidas. Se ha realizado un estudio retrospectivo de pacientes diagnosticados de linfomas extranodales, entre los años 1991 al 1999 en nuestro Hospital. Se incluyeron en el estudio 23 pacientes, 15 hombres y 9 mujeres. Se empleó la clasificación REAL para su catalogación. Todos lo linfomas fueron linfomas de tipo no-Hodgkin. El cavum fue el lugar más afectado, seguido de amígdalas palatinas y cavidad oral. La mayor parte de los linfomas eran de grado intermedio y se encontraban en estados iniciales. Los síntomas de presentación variaban según la localización. La edad del paciente, estadio y grado histológico fueron importantes para la elección del tratamiento (AU)

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