Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative Expression Profiling Reveals an Essential Role for Raldh2 in Epimorphic Regeneration*

Zebrafish have the remarkable ability to regenerate body parts including the heart and fins by a process referred to as epimorphic regeneration. Recent studies have illustrated that similar to adult zebrafish, early life stage larvae also possess the ability to regenerate the caudal fin. A comparative microarray analysis was used to determine the degree of conservation in gene expression among the regenerating adult caudal fin, adult heart, and larval fin. Results indicate that these tissues respond to amputation/injury with strikingly similar genomic responses. Comparative analysis revealed raldh2, a rate-limiting enzyme for the synthesis of retinoic acid, as one of the most highly induced genes across the three regeneration platforms. In situ localization and functional studies indicate that raldh2 expression is critical for the formation of wound epithelium and blastema. Patterning during regenerative outgrowth was considered to be the primary function of retinoic acid signaling; however, our results suggest that it is also required for early stages of tissue regeneration. Expression of raldh2 is regulated by Wnt and fibroblast growth factor/ERK signaling.
Clinical Outcome of Patients with Previous Myocardial Infarction and Left Ventricular Dysfunction Assessed with Myocardial 99mTc-MIBI SPECT and 18F-FDG PET

UNLABELLED Myocardial viability was assessed by (99m)Tc-methoxyisobutylisonitrile (MIBI) SPECT and (18)F-FDG PET to evaluate the prognosis and treatment strategy of patients with myocardial infarction (MI) and left ventricular (LV) dysfunction. METHODS One hundred twenty-three consecutive patients with previous MI and LV dysfunction (LV ejection fraction [EF], 35% +/- 6% [mean +/- SD]) who underwent (99m)Tc-MIBI SPECT and FDG PET were followed-up for 26 +/- 10 mo (mean +/- SD). Distributions of the 2 radiotracers in myocardial segments were classified into 2 patterns: myocardial perfusion-metabolism mismatch (MM) and match (M). LV EF and LV end-diastolic diameter (EDD) were measured by echocardiography at baseline, 3 mo (Pos1), and 6 mo (Pos2) after revascularization. Cardiac death, acute MI, unstable angina, and late revascularization (>3 mo) experienced by the patients during follow-up were defined as cardiac events. RESULTS Sixty-seven patients underwent revascularization and 56 patients were treated medically. Of the 72 patients with > or =2 MM segments, 42 underwent revascularization (group A1) and 30 were treated medically (group A2). Of the 51 patients with 0.05). During the follow-up, 22 patients (17.9%) suffered from cardiac events, including 11 cardiac deaths, 4 acute MI, 6 late coronary artery bypass grafting, and 1 unstable angina pectoris. The cardiac event rate in group A2 (50%) was significantly higher than that of groups A1 (2.4%; chi(2) = 23.08; P 2 viable myocardial segments.
Multicenter prospective trial evaluating the tolerability of imatinib for Japanese patients with chronic myelogenous leukemia in the chronic phase: Does body weight matter?

Imatinib at a daily dose of 400 mg is the standard treatment for chronic myelogenous leukemia in the chronic phase. However, the feasibility of this dose for small Japanese adults has not been clarified. We prospectively investigated the toxicity and efficacy of this dose in adult Japanese patients. Among the 89 evaluable patients with a median body weight of 62.8 kg, imatinib therapy was held in 40 subjects (45%), due to Grade 3–4 toxicities in 30 patients (75%) and Grade 2 toxicities at the discretion of the attending physician in 10 patients (25%). However, treatment was resumed and the dose was gradually increased until 62 of the 89 patients tolerated a maintenance dose of 400 mg. Older age and lower body weight were significant independent risk factors for discontinuation of imatinib. After a median follow‐up period of 31 months, 84 patients were alive without progression. The complete cytogenetic response rate was 60 and 90% at 6 months and 1 year after starting imatinib, respectively. Older patients and those with a lower body weight were less likely to achieve a complete cytogenetic response. These findings suggest that the body weight has a significant influence on the toxicity and efficacy of imatinib in patients with a small body size, although dose reduction in proportion to weight may result in an inadequate response to imatinib. Am. J. Hematol. , 2008. © 2008 Wiley‐Liss, Inc.
Influence of body mass index and sedentary lifestyle in clinical control and health related quality of life in moderate and severe asthmatics

A sedentary lifestyle has been associated with obesity in general population. In addition, obese asthmatics have worse clinical control and health related quality of life (HRQL) than non-obese; however, the influence of sedentary lifestyle in asthmatics remains unknown. Aim: To assess the influence of daily life physical activity (DLPA) and body mass index in clinical control and HRQL in moderate and severe asthmatic adults. Methods: This cross sectional study assessed asthmatic patients for body mass index (BMI, kg/m2), DLPA during 5 days (accelerometer Power Walker-610, Yamax), clinical control (asthma control questionnaire, ACQ) and HRQL (asthma quality of life questionnaire). Patients were analyzed categorically according to DLPA, BMI and ACQ and the comparison between groups was evaluated by t-test. Results: Sedentary patients (7,166±1,736steps/day) presented a higher number of asthmatics with non-controlled status (ACQ=1.7±0.9 vs. 1.4±0.9score) and had higher BMI (33.7±6.2 vs. 29.2±4.8kg/m2) compared to physically active patients (14,416±3,999steps/day), respectively. In addition, obese asthmatics (36.1±2.7kg/m2) presented higher number of sedentary (8,801±3,143 vs. 12,630±5,591steps/day) and non-controlled patients (ACQ=1.7±0.9 vs. 1.3±0.8score) than non-obese asthmatics (25.3±2,8kg/m2), respectively. HRQL was influenced by clinical control (4.7±1,0 in controlled vs. 3.6±1,2score in non-controlled patients) but not by obesity or DLPA. Conclusion: Our data suggest that sedentary lifestyle and BMI influence in clinical control in patients with moderate and severe asthma.
Are We Speaking the Same Language? Finding Theoretical Coherence and Precision in "Mindfulness-Based Mechanisms" in Chronic Pain.

Objective Over the past 50 years, the field of chronic pain has witnessed an evolution of psychological approaches with some notable success. Some of this evolution has included "mindfulness-based interventions" (MBIs), now regarded as having encouraging partial support for their effectiveness. However, several theoretical challenges remain that may inhibit the progress of MBIs. These challenges include a lack of clarity surrounding the mindfulness construct itself, the proliferation of purported underlying mechanisms arising from different theories, and limited evidence for the mechanisms through which MBIs work. The current conceptual review provides a critique of existing theoretical models of mindfulness that have been applied to understanding and treating chronic pain. Design A conceptual narrative review was conducted. Setting Treatment programs for people with chronic pain. Patients Individuals with any type of chronic pain. Interventions MBIs for chronic pain. Outcome Measures Mindfulness-based mechanisms explored in relation to several domains of functioning. Results and Conclusions Based on this assessment, a summary of available evidence for a particular contextual behavioral theory of "mindfulness"-psychological flexibility-is outlined. Findings show the need for further integration of existing mindfulness constructs to better guide development and evaluation of mindfulness-based treatment methods in the future.
Activation of the Liver X Receptor Stimulates Trans-intestinal Excretion of Plasma Cholesterol*

Recent studies have indicated that direct intestinal secretion of plasma cholesterol significantly contributes to fecal neutral sterol loss in mice. The physiological relevance of this novel route, which represents a part of the reverse cholesterol transport pathway, has not been directly established in vivo as yet. We have developed a method to quantify the fractional and absolute contributions of several cholesterol fluxes to total fecal neutral sterol loss in vivo in mice, by assessing the kinetics of orally and intravenously administered stable isotopically labeled cholesterol combined with an isotopic approach to assess the fate of de novo synthesized cholesterol. Our results show that trans-intestinal cholesterol excretion significantly contributes to removal of blood-derived free cholesterol in C57Bl6/J mice (33% of 231 μmol/kg/day) and that pharmacological activation of LXR with T0901317 strongly stimulates this pathway (63% of 706 μmol/kg/day). Trans-intestinal cholesterol excretion is impaired in mice lacking Abcg5 (−4%), suggesting that the cholesterol transporting Abcg5/Abcg8 heterodimer is involved in this pathway. Our data demonstrate that intestinal excretion represents a quantitatively important route for fecal removal of neutral sterols independent of biliary secretion in mice. This pathway is sensitive to pharmacological activation of the LXR system. These data support the concept that the intestine substantially contributes to reverse cholesterol transport.
Actualidad en la patología y tratamiento de los gangliogliomas: un tumor no tan benigno

SUMMARY Gangliogliomas (GG) are defined as mixed tumors compose from glia and neurons usually with a benign biological behavior. However, there are reports of GG that differentiate toward high grade glioblastoma. This change is observed more frequently in the glial component but neuronal part could be also involved. Pathophysiology is better understood currently, part of this is represented by the identification of changes in genes at p53 and the definition of tumoral markers like Ki 67, both of them important at the moment of prognosis definition and therapeutic decisions. Treatment of these tumors implies broad surgical resection due to high morbidity of them. Chemotherapy and radiotherapy are options which improve survival of patients who suffer anaplastic varieties. This paper review recent changes in histological classification and recent contributions on histology, inmunochemistry, genetics and treatment. In addition we discuss two cases in two different ages and stages showing the usual benign behavior and the transformation to a multiform gliobastoma, along with a detailed pathological review.
Survival in young patients with intermediate‐/high‐risk myelofibrosis: Estimates derived from databases for non transplant patients

Recent studies have suggested that allogenic stem cell transplantation (allo‐SCT) might be a better treatment option, compared to drug therapy, for young patients with high‐/intermediate‐risk primary myelofibrosis (PMF). However, there are no controlled studies that validate this contention and allo‐SCT is associated with a substantial risk of procedure‐related mortality and morbidity. In a retrospective analysis of nontransplant PMF patients, who were both young (age <60 years) and with high‐/intermediate‐risk disease, 1‐ and 3‐year survival estimates were 87% and 55%, 95% and 77%, 71% and 58%, respectively, involving patients seen at three different centers with expertise in PMF; these data did not appear to be inferior to those published in the context of either myeloablative or reduced‐intensity conditioning allo‐SCT. These observations underscore the need for controlled studies to accurately assess the value of allo‐SCT in PMF. AM. J. Hematol. 2009. © 2008 Wiley‐Liss, Inc.
TRPC5 Is a Ca2+-activated Channel Functionally Coupled to Ca2+-selective Ion Channels*

TRPC5 forms non-selective cation channels. Here we studied the role of internal Ca2+ in the activation of murine TRPC5 heterologously expressed in human embryonic kidney cells. Cell dialysis with various Ca2+ concentrations (Ca2+i) revealed a dose-dependent activation of TRPC5 channels by internal Ca2+ with EC50 of 635.1 and 358.2 nm at negative and positive membrane potentials, respectively. Stepwise increases of Ca2+i induced by photolysis of caged Ca2+ showed that the Ca2+ activation of TRPC5 channels follows a rapid exponential time course with a time constant of 8.6 ± 0.2 ms at Ca2+i below 10 μm, suggesting that the action of internal Ca2+ is a primary mechanism in the activation of TRPC5 channels. A second slow activation phase with a time to peak of 1.4 ± 0.1 s was also observed at Ca2+i above 10 μm. In support of a Ca2+-activation mechanism, the thapsigargin-induced release of Ca2+ from internal stores activated TRPC5 channels transiently, and the subsequent Ca2+ entry produced a sustained TRPC5 activation, which in turn supported a long-lasting membrane depolarization. By co-expressing STIM1 plus ORAI1 or the α1C and β2 subunits of L-type Ca2+ channels, we found that Ca2+ entry through either calcium-release-activated-calcium or voltage-dependent Ca2+ channels is sufficient for TRPC5 channel activation. The Ca2+ entry activated TRPC5 channels under buffering of internal Ca2+ with EGTA but not with BAPTA. Our data support the hypothesis that TRPC5 forms Ca2+-activated cation channels that are functionally coupled to Ca2+-selective ion channels through local Ca2+ increases beneath the plasma membrane.
Adiponectin Inhibits Pro-inflammatory Signaling in Human Macrophages Independent of Interleukin-10*

Macrophages participate pivotally in the pathogenesis of many chronic inflammatory diseases including atherosclerosis. Adiponectin, a vasculoprotective molecule with insulin-sensitizing and anti-atherogenic properties, suppresses pro-inflammatory gene expression in macrophages by mechanisms that remain incompletely understood. This study investigated the effects of adiponectin on major pro-inflammatory signaling pathways in human macrophages. We demonstrate that pretreatment of these cells with adiponectin inhibits phosphorylation of nuclear factor κB inhibitor (IκB), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK), induced by either lipopolysaccharide (LPS) or tumor necrosis factor (TNF) α, as well as STAT3 phosphorylation induced by interleukin-6 (IL6). Antagonism of IL10 by either neutralizing antibodies or siRNA-mediated silencing did not abrogate the anti-inflammatory actions of adiponectin, indicating that the ability of adiponectin to render human macrophages tolerant to various pro-inflammatory stimuli does not require this cytokine. A systematic search for adiponectin-inducible genes with established anti-inflammatory properties revealed that adiponectin augmented the expression of A20, suppressor of cytokine signaling (SOCS) 3, B-cell CLL/lymphoma (BCL) 3, TNF receptor-associated factor (TRAF) 1, and TNFAIP3-interacting protein (TNIP) 3. These results suggest that adiponectin triggers a multifaceted response in human macrophages by inducing the expression of various anti-inflammatory proteins that act at different levels in concert to suppress macrophage activation.
Silencing cAMP-response Element-binding Protein (CREB) Identifies CYR61 as a Tumor Suppressor Gene in Melanoma*

Metastatic progression of melanoma is associated with overexpression and activity of cAMP-response element-binding protein (CREB). However, the mechanism by which CREB contributes to tumor progression and metastasis remains unclear. Here, we demonstrate that stably silencing CREB expression in two human metastatic melanoma cell lines, A375SM and C8161-c9, suppresses tumor growth and experimental metastasis. Analysis of cDNA microarrays revealed that CREB silencing leads to increased expression of cysteine-rich protein 61 (CCN1/CYR61) known to mediate adhesion, chemostasis, survival, and angiogenesis. Promoter analysis and chromatin immunoprecipitation assays demonstrated that CREB acts as a negative regulator of CCN1/CYR61 transcription by directly binding to its promoter. Re-expression of CREB in CREB-silenced cells rescued the low CCN1/CYR61 expression phenotype. CCN1/CYR61 overexpression resulted in reduced tumor growth and metastasis and inhibited the activity of matrix metalloproteinase-2. Furthermore, its overexpression decreased melanoma cell motility and invasion through Matrigel, which was abrogated by silencing CCN1/CYR61 in low metastatic melanoma cells. Moreover, a significant decrease in angiogenesis as well as an increase in apoptosis was seen in tumors overexpressing CCN1/CYR61. Our results demonstrate that CREB promotes melanoma growth and metastasis by down-regulating CCN1/CYR61 expression, which acts as a suppressor of melanoma cell motility, invasion and angiogenesis.
Mash1 is required for neuroendocrine cell development in the glandular stomach

In the epithelium of the developing glandular stomach, neuroendocrine cells differentiate from common progenitors, but the mechanism of how these cells are specified remains to be determined. Here, we show that the basic helix–loop–helix (bHLH) gene, mammalian achaete‐scute homologue 1 (Mash1), is highly expressed in the glandular stomach epithelium. In Mash1‐null mice, almost all gastric neuroendocrine cells are missing, whereas development of non‐neuroendocrine cells is not significantly affected. The bHLH gene Neurogenin3 (Ngn3), which is known to regulate formation of subsets of gastric neuroendocrine cells (gastrin‐, glucagon‐ and somatostatin‐producing cells), is expressed normally in the Mash1‐null stomach. Thus, Ngn3 alone is not sufficient but Mash1 is additionally required for the differentiation of these neuroendocrine cells. Taken together, these results indicate that formation of gastrin‐, glucagon‐ and somatostatin‐producing cells depends on both Mash1 and Ngn3, while that of other neuroendocrine cells depends on Mash1 alone, suggesting that combinations of bHLH genes may contribute to cell type diversity.
Nuevas evidencias en la susceptibilidad a la infección por dengue asociadas al polimorfismo HH del receptor FcgRIIa

INTRODUCTION: polymorphic variants of FcgammaRIIa receptor have been associated to susceptibility to develop several infectious diseases. The relationship between the polymorphism of this receptor and the susceptibility to dengue hemorrhagic fever was recently reported. OBJECTIVES: to explore whether the association of the homocygotic variants of the receptor to susceptibility to or protection from a disease could be also related with the IgG antibody titters and the exposure to a number of infections. METHODS: a retrospective analytical study was performed on individuals who had been infected with the dengue virus 4 during the 2006 epidemic in the City of Havana and were tracked down in 2008. A total number of 97 individuals were recruited of whom 68 had suffered dengue fever and 29 had had dengue hemorrhagic fever. A 10-mL blood sample was taken from each of them and then placed in EDTA anticoagulant for DNA isolation and 5 mL placed in dry tubes to obtain serum. The genetic polymorphism of FcgammaRIIa receptor, the total anti-dengue IgG antibody titers and the antecedent of dengue infection were determined. RESULTS: it was interesting to note that there was very significant direct relation (p< 0.0001) between high anti-dengue IgG antibodies titers and the number of infections suffered by these people. This behaviour was present in those individuals with the HH homocygotic variant. CONCLUSION: it seems that those individuals with polymorphism in FCgammaRIIa-H/H receptor would tend to non-elimination of IgG antibodies through this receptor, which is associated to the number of infections suffered by the individual.
International Consensus on Diagnostic Criteria and Clinical Considerations of Myofascial Trigger Points: A Delphi Study

Objective There is no consensus on the essential diagnostic criteria for diagnosing a trigger point (TrP). In fact, a variety of diagnostic criteria are currently being used. Our aim was to conduct a Delphi panel to achieve an international consensus on the cluster of criteria needed for the TrP diagnosis to reach a consensus on the definition of active and latent TrPs and to clarify different clinical considerations about TrPs. Methods Following international guidelines, an international three-round Delphi survey was conducted. Questions were created based on a systematic literature search of the diagnostic criteria for TrPs. Results Sixty experts from 12 countries completed all rounds of the survey. A cluster of three diagnostic criteria was proposed as essential for the TrP diagnosis: a taut band, a hypersensitive spot, and referred pain. Eighty percent of the experts agreed that the referred pain elicited by a TrP can include different sensory sensations and not just pain, that is, pain spreading to a distant area, deep pain, dull ache, tingling, or burning pain. Eighty-four percent of the international experts consistently answered that the main clinical differences between active and latent TrPs are the reproduction of any of the symptoms experienced by a patient and the recognition of pain. No specific location of the pain referral area and TrP location should be expected. Conclusions This Delphi panel has produced an expert-based standardized definition of a TrP with a discussion of the clinical components, including the definition of referred pain and the difference between active and latent TrPs, thereby providing a foundation for future research in MPS.
hScrib, a human homologue of Drosophila neoplastic tumor suppressor, is a novel death substrate targeted by caspase during the process of apoptosis

hScrib, human homologue of Drosophila neoplastic tumor suppressor, was identified as a target of human papillomavirus E6 oncoprotein for the ubiquitin‐mediated degradation. Here, we report that hScrib is a novel death substrate targeted by caspase. Full‐length hScrib was cleaved by caspase during death ligands‐induced apoptosis, which generates a p170 C‐terminal fragments in Hela cells. In vitro cleavage assay using recombinant caspases showed that hScrib is cleaved by the executioner caspases. DNA damage‐induced apoptosis caused loss of expression of full‐length hScrib, which was recovered by addition of capase‐3 inhibitor in HaCat cells. TUNEL positive apoptotic cells, which were identified 4 h after UV irradiation in HaCat cells, showed loss of hScrib expression at the adherens junction. Mutational analysis identified the caspase‐dependent cleavage site of hScrib at the position of Asp‐504. Although MDCK cells transfected with GFP‐fused wild‐type hScrib showed loss of E‐cadherin expression and shrinkage of cytoplasm by UV irradiation, cells transfected with hScrib with Ala substitution of Asp‐504 showed resistance to caspase‐dependent cleavage of hScrib and intact expression of E‐cadherin. These results indicate that caspase‐dependent cleavage of hScrib is a critical step for detachment of cell contact during the process of apoptosis.