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Find video protocols related to scientific articles indexed in Pubmed.
Successful mortality reduction and control of co-morbidities in patients with acromegaly followed at a highly specialized multidisciplinary clinic.
J. Clin. Endocrinol. Metab.
PUBLISHED: 09-12-2014
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Context: Acromegaly is usually due to the excessive secretion of GH by a pituitary adenoma. It is frequently accompanied by co-morbidities which compromise quality of life and results in elevated mortality rates. Objective: To evaluate mortality and morbidity in patients with acromegaly receiving multimodal care. Setting: Tertiary care center. Design, patients and methods: Retrospective evaluation of 442 patients (65.4% women, mean age 43.5 ± 13.1 years) followed for a median of 6 years (IQR 3-10). Results: Twenty-two patients died during the study period (4.9%), representing a total standardized mortality ratio (SMR) of 0.72 (95% CI 0.41-1.03). SMR were 1.5 and 0.44, for patients whose last GH was above and below 2.5 ng/mL, respectively; 1.17 and 0.16 for those whose last GH was above and below 1 ng/mL, respectively; and 0.94 and 0.46 for those whose last IGF-1 was above and below 1.2 times the upper limit of normal (x ULN), respectively. The prevalence of diabetes mellitus, hypertension, heart disease and cancer was 30%, 35%, 8% and 4.7%, respectively. The most common cause of death was cancer. On multivariate analysis, diabetes, heart disease and cancer were related to a baseline GH >10 ng/mL; the presence of cancer and the last IGF-1 were significant predictors of mortality. Survival decreased as the latest GH levels increased from <1 ng/mL to >5 ng/mL and as IGF-1 increased from <1.2 to >2 x ULN. Conclusions: Mortality in acromegaly can be successfully reduced, provided patients are treated using a multimodal approach with careful management of co-morbidities.
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Drinking Water Quality in a Mexico City University Community: Perception and Preferences.
Ecohealth
PUBLISHED: 09-02-2014
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A transversal study was conducted at the University City campus of the National Autonomous University of Mexico (UNAM) in Mexico City, with the goal of estimating the university community preference for drinking either tap water or bottled water and the reasons for their selection. A representative sample of three university community subpopulations (students, workers/administrative staff, and academic personnel) were interviewed with respect to their water consumption habits. The results showed that 75% of the university community drinks only bottled water and that the consumption of tap water is low. The interviewees responded that the main reason for this preference is the organoleptic features of tap water independent of quality. In general, the participants in this study do not trust the quality of the tap water, which could be caused by the facilities that distribute bottled water encouraging a general disinterest in learning about the origin and management of the tap water that is distributed on campus.
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Targeting CDKN3 in cervical cancer.
Expert Opin. Ther. Targets
PUBLISHED: 08-25-2014
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The cyclin-dependent kinase inhibitor 3 gene (CDKN3), which is involved in mitosis, has been found upregulated and associated with low survival in cervical cancer (CC) patients. Therefore, as in other cancers, CDKN3 could be a potential target in CC.
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Association of TMEM106B rs1990622 Marker and Frontotemporal Dementia: Evidence for a Recessive Effect and Meta-Analysis.
J. Alzheimers Dis.
PUBLISHED: 08-07-2014
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Transmembrane Protein 106B SNP rs1990622 was recently shown to modify the risk of frontotemporal lobar degeneration with TDP-43 inclusions (FTD-TDP). An independent replication study of this genetic variant was performed in 381 individuals from Catalonia (Spain). By applying a recessive model, a tendency toward an association with FTD risk was observed in our case-control study (age- and gender-adjusted odds ratio = 0.57; p = 0.082). Importantly, meta-analysis of available studies also supports a recessive effect for rs1990622 CC genotype (OR = 0.70; CI 95% [0.57-0.85]; p = 0.0003) and demonstrates the existence of statistical heterogeneity due to an inherent pathological heterogeneity between series (p = 0.00014). We conclude that TMEM106B is associated with FTD, although the extent of this effect is difficult to be estimated by using clinical FTD series.
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BR-dependent phosphorylation modulates PIF4 transcriptional activity and shapes diurnal hypocotyl growth.
Genes Dev.
PUBLISHED: 08-03-2014
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Signaling by the hormones brassinosteroid (BR) and gibberellin (GA) is critical to normal plant growth and development and is required for hypocotyl elongation in response to dark and elevated temperatures. Active BR signaling is essential for GA promotion of hypocotyl growth and suppresses the dwarf phenotype of GA mutants. Cross-talk between these hormones occurs downstream from the DELLAs, as GA-induced destabilization of these GA signaling repressors is not affected by BRs. Here we show that the light-regulated PIF4 (phytochrome-interacting factor 4) factor is a phosphorylation target of the BR signaling kinase BRASSINOSTEROID-INSENSITIVE 2 (BIN2), which marks this transcriptional regulator for proteasome degradation. Expression of a mutated PIF41A protein lacking a conserved BIN2 phosphorylation consensus causes a severe elongated phenotype and strongly up-regulated expression of the gene targets. However, PIF41A is not able to suppress the dwarf phenotype of the bin2-1 mutant with constitutive activation of this kinase. PIFs were shown to be required for the constitutive BR response of bes1-D and bzr1-1D mutants, these factors acting in an interdependent manner to promote cell elongation. Here, we show that bes1-D seedlings are still repressed by the inhibitor BRZ in the light and that expression of the nonphosphorylatable PIF41A protein makes this mutant fully insensitive to brassinazole (BRZ). PIF41A is preferentially stabilized at dawn, coinciding with the diurnal time of maximal growth. These results uncover a main role of BRs in antagonizing light signaling by inhibiting BIN2-mediated destabilization of the PIF4 factor. This regulation plays a prevalent role in timing hypocotyl elongation to late night, before light activation of phytochrome B (PHYB) and accumulation of DELLAs restricts PIF4 transcriptional activity.
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Chronic stress as a risk factor for Alzheimer's disease.
Rev Neurosci
PUBLISHED: 05-16-2014
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Abstract This review aims to point out that chronic stress is able to accelerate the appearance of Alzheimer's disease (AD), proposing the former as a risk factor for the latter. Firstly, in the introduction we describe some human epidemiological studies pointing out the possibility that chronic stress could increase the incidence, or the rate of appearance of AD. Afterwards, we try to justify these epidemiological results with some experimental data. We have reviewed the experiments studying the effect of various stressors on different features in AD animal models. Moreover, we also point out the data obtained on the effect of chronic stress on some processes that are known to be involved in AD, such as inflammation and glucose metabolism. Later, we relate some of the processes known to be involved in aging and AD, such as accumulation of ?-amyloid, TAU hyperphosphorylation, oxidative stress and impairement of mitochondrial function, emphasizing how they are affected by chronic stress/glucocorticoids and comparing with the description made for these processes in AD. All these data support the idea that chronic stress could be considered a risk factor for AD.
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Circadian variation of melatonin, light exposure, and diurnal preference in day and night shift workers of both sexes.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 05-08-2014
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Light-at-night has been shown in experimental studies to disrupt melatonin production but this has only partly been confirmed in studies of night shift workers. In this cross-sectional study, we examined the circadian variation of melatonin in relation to shift status, individual levels of light-at-night exposure, and diurnal preference, an attribute reflecting personal preference for activity in the morning or evening.
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Octreotide LAR treatment of acromegaly in "real life": long-term outcome at a tertiary care center.
Pituitary
PUBLISHED: 05-01-2014
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To report our day-to day experience with the long-term use of octreotide LAR in the treatment of acromegaly.
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Cognitive, genetic, and brain perfusion factors associated with four year incidence of Alzheimer's disease from mild cognitive impairment.
J. Alzheimers Dis.
PUBLISHED: 04-02-2014
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There is a range of factors that predict the development of Alzheimer's disease (AD) dementia among patients with amnestic mild cognitive impairment (MCI).
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In vivo effect of apomorphine and haloperidol on MPP neurotoxicity.
Pharmacology
PUBLISHED: 02-19-2014
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The involvement of dopaminergic (DAergic) receptor drugs in the neuroprotection against the neurotoxic action of 1-methyl-4-phenylpyridinium (MPP(+)) in the DAergic terminals in striatum was studied using an intracerebral microdialysis technique. Twenty-four hours after surgery (day 1), apomorphine and haloperidol, alone or with 1 mmol/l of MPP(+) perfusion through the microdialysis probe, were systemically administered. Forty-eight hours after surgery (day 2), 1 mmol/l of MPP(+) was perfused for 15 min in all groups of animals and the output of dopamine was measured. The amount of dopamine was directly proportional to the remaining striatal DAergic terminals. The results show that: (1) subcutaneous administration of apomorphine before MPP(+) perfusion prevented MPP(+)-induced neurotoxicity, and (2) intraperitoneal administration of haloperidol before MPP(+) perfusion did not prevent MPP(+)-induced neurotoxicity.
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Chronic stress enhances microglia activation and exacerbates death of nigral dopaminergic neurons under conditions of inflammation.
J Neuroinflammation
PUBLISHED: 02-07-2014
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Parkinson's disease is an irreversible neurodegenerative disease linked to progressive movement disorders and is accompanied by an inflammatory reaction that is believed to contribute to its pathogenesis. Since sensitivity to inflammation is not the same in all brain structures, the aim of this work was to test whether physiological conditions as stress could enhance susceptibility to inflammation in the substantia nigra, where death of dopaminergic neurons takes place in Parkinson's disease.
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Magnetic hyperthermia efficiency in the cellular environment for different nanoparticle designs.
Biomaterials
PUBLISHED: 01-28-2014
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Magnetic hyperthermia mediated by magnetic nanomaterials is one promising antitumoral nanotherapy, particularly for its ability to remotely destroy deep tumors. More and more new nanomaterials are being developed for this purpose, with improved heat-generating properties in solution. However, although the ultimate target of these treatments is the tumor cell, the heating efficiency, and the underlying mechanisms, are rarely studied in the cellular environment. Here we attempt to fill this gap by making systematic measurements of both hyperthermia and magnetism in controlled cell environments, using a wide range of nanomaterials. In particular, we report a systematic fall in the heating efficiency for nanomaterials associated with tumour cells. Real-time measurements showed that this loss of heat-generating power occurred very rapidly, within a matter of minutes. The fall in heating correlated with the magnetic characterization of the samples, demonstrating a complete inhibition of the Brownian relaxation in cellular conditions.
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Role of dopamine in the recruitment of immune cells to the nigro-striatal dopaminergic structures.
Neurotoxicology
PUBLISHED: 01-21-2014
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Research indicates that inflammation and microglial activation are involved in the initiation and progression of Parkinson's disease (PD). Neuroinflammation contributes to the infiltration of peripheral immune cells and blood-brain barrier (BBB) leakage, linking peripheral and central inflammatory events in the pathogenesis of PD. Dopamine (DA) likely plays a role in this process. In the present study, the dopaminergic toxin 6-hydroxydopamine (6-OHDA) was used to damage dopaminergic neurons. Injection of 6-OHDA within the nigrostriatal pathway produced loss of astrocytes, disruption of the BBB, microglia activation and a reduction in osteopontin (OPN) immunoreactivity. Depletion of DA content by alpha-methylparatyrosine (?-MPT, a tyrosine hydroxylase inhibitor) reduced the infiltration of peripheral macrophages as well as the 6-OHDA-induced increase in microglial cells. DA could therefore be relevant in sustaining inflammation and lymphocyte recruitment induced by 6-OHDA, supporting DA implication in the degeneration of dopaminergic neurons induced by inflammatory processes.
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Impact of gene dosage on gene expression, biological processes and survival in cervical cancer: a genome-wide follow-up study.
PLoS ONE
PUBLISHED: 01-01-2014
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We investigated the role of tumor copy number (CN)-altered genome (CN-AG) in the carcinogenesis of cervical cancer (CC), especially its effect on gene expression, biological processes, and patient survival. Fifty-nine human papillomavirus 16 (HPV16)-positive CCs were investigated with microarrays-31 for mapping CN-AG and 55 for global gene expression, with 27 CCs in common. Five-year survival was investigated in 55 patients. Deletions and amplifications >2.5 Mb were defined as CN alterations. The %CN-AG varied from 0 to 32.2% (mean?=?8.1±8.9). Tumors were classified as low (mean?=?0.5±0.6, n?=?11), medium (mean?=?5.4±2.4, n?=?10), or high (mean?=?19.2±6.6, n?=?10) CN. The highest %CN-AG was found in 3q, which contributed an average of 55% of all CN alterations. Genome-wide, only 5.3% of CN-altered genes were deregulated directly by gene dosage. In contrast, the rate in fully duplicated 3q was twice as high. Amplification of 3q explained 23.2% of deregulated genes in whole tumors (r2?=?0.232, p?=?0.006; analysis of variance), including genes located in 3q and other chromosomes. A total of 862 genes were deregulated exclusively in high-CN tumors, but only 22.9% were CN altered. This suggests that the remaining genes are not deregulated directly by gene dosage, but by mechanisms induced in trans by CN-altered genes. Anaphase-promoting complex/cyclosome (APC/C)-dependent proteasome proteolysis, glycolysis, and apoptosis were upregulated, whereas cell adhesion and angiogenesis were downregulated exclusively in high-CN tumors. The high %CN-AG and upregulated gene expression profile of APC/C-dependent proteasome proteolysis were associated with poor patient survival (p<0.05, log-rank test). Along with glycolysis, they were linearly associated with FIGO stage (r>0.38, p<0.01, Spearman test). Therefore, inhibition of APC/C-dependent proteasome proteolysis and glycolysis could be useful for CC treatment. However, whether they are indispensable for tumor growth remains to be demonstrated.
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Exposure to Brominated Trihalomethanes in Water During Pregnancy and Micronuclei Frequency in Maternal and Cord Blood Lymphocytes.
Environ. Health Perspect.
PUBLISHED: 10-31-2013
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Water disinfection by-products have been associated with an increased cancer risk. Micronuclei (MN) frequency in lymphocytes are markers of genomic damage and predict adult cancer risk.
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Roles of ubiquitination in the control of phosphate starvation responses in plants(f).
J Integr Plant Biol
PUBLISHED: 07-09-2013
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Throughout evolution, plants have evolved sophisticated adaptive responses that allow them to grow with a limited supply of phosphate, the preferential form in which the essential macronutrient phosphorus is absorbed by plants. Most of these responses are aimed to increase phosphate availability and acquisition through the roots, to optimize its usage in metabolic processes, and to protect plants from the deleterious effects of phosphate deficiency stress. Regulation of these adaptive responses requires fine perception of the external and internal phosphate levels, and a complex signal transduction pathway that integrates information on the phosphate status at the whole-plant scale. The molecular mechanisms that participate in phosphate homeostasis include transcriptional control of gene expression, RNA silencing mediated by microRNAs, regulatory non-coding RNAs of miRNA activity, phosphate transporter trafficking, and post-translational modification of proteins, such as phosphorylation, sumoylation and ubiquitination. Such a varied regulatory repertoire reflects the complexity intrinsic to phosphate surveying and signaling pathways. Here, we describe these regulatory mechanisms, emphasizing the increasing importance of ubiquitination in the control of phosphate starvation responses.
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Ectopic acromegaly due to a GH-secreting pituitary adenoma in the sphenoid sinus: a case report and review of the literature.
BMC Res Notes
PUBLISHED: 07-04-2013
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In more than 98% of cases, acromegaly is due to a GH-secreting pituitary adenoma. The term "ectopic acromegaly" includes neuroendocrine tumors secreting GH releasing hormone (GHRH), usually located in the lungs, thymus and endocrine pancreas. Considerably less frequent are cases of ectopic acromegaly due to GH-secreting tumors located out of the pituitary fossa; except for one isolated case of a well-documented GH-secreting lymphoma, the majority of these lesions are located in the sphenoid sinus.
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Intracranial injection of LPS in rat as animal model of neuroinflammation.
Methods Mol. Biol.
PUBLISHED: 07-02-2013
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Animal models of neuroinflammatory processes are needed to study the involvement of inflammation in neurodegenerative disorders such as Parkinsons and Alzheimers diseases. One of the models used is based on lipopolysaccharide (LPS) as brain inflammation-inducing agent. This toxin is a potent inducer of inflammation and has different effects on cells of the immune system, as microglial cells. This chapter describes a protocol for the model of brain inflammation in rats based on the unilateral stereotaxic injection of LPS, which mimics the inflammatory milieu produced in some brain diseases.
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Immunohistochemical detection of microglia.
Methods Mol. Biol.
PUBLISHED: 07-02-2013
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Immunohistochemistry (IHC) is a technique that allows the localization of antigens or proteins in tissue sections using the high specificity and affinity of antibodies to recognize molecules and join them. The commercial offer and the standardization of protocols make this technique a simple, fast, and powerful method. Microglia, the resident macrophage cells of the central nervous system, can exist in three different forms that can be identified using different antibodies. The aim of this chapter is to describe the methods to perform IHC using these different antibodies.
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Cajal-Retzius cells instruct neuronal migration by coincidence signaling between secreted and contact-dependent guidance cues.
Neuron
PUBLISHED: 06-17-2013
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Cajal-Retzius (CR) cells are a transient cell population of the CNS that is critical for brain development. In the neocortex, CR cells secrete reelin to instruct the radial migration of projection neurons. It has remained unexplored, however, whether CR cells provide additional molecular cues important for brain development. Here, we show that CR cells express the immunoglobulin-like adhesion molecule nectin1, whereas neocortical projection neurons express its preferred binding partner, nectin3. We demonstrate that nectin1- and nectin3-mediated interactions between CR cells and migrating neurons are critical for radial migration. Furthermore, reelin signaling to Rap1 promotes neuronal Cdh2 function via nectin3 and afadin, thus directing the broadly expressed homophilic cell adhesion molecule Cdh2 toward mediating heterotypic cell-cell interactions between neurons and CR cells. Our findings identify nectins and afadin as components of the reelin signaling pathway and demonstrate that coincidence signaling between CR cell-derived secreted and short-range guidance cues direct neuronal migration.
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Williams neural stem cells: new model for insight into microRNA dysregulation.
Front Biosci (Elite Ed)
PUBLISHED: 06-11-2013
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Williams syndrome (WS) is a neurodevelopmental genetic disorder, due to a 7q11.23 hemizygous deletion. WS has a characteristic neurocognitive profile that includes intellectual disability (ID). Haploinsufficiency of some of the deleted genes is partially associated with the cognitive phenotype. The aim of this paper is to determine the differences in the microRNA (miRNA) expression in WS patients, using a neural cell model from the patients olfactory neuroepithelium (ONE), and to establish the relationship with those genes involved in neurodevelopment and neural function. To assess these goals, we made a comparative analysis of the miRNAs expression profile between WS patients and controls. Through an in silico analysis, we established potential pathways and targets associated with neural tissue. The expression profile shows 14 dysregulated miRNAs, including nervous system (NS)-rich miRNAs such as miR-125b, let-7c and miR-200. Most of these miRNAs have potential targets associated with NS functions while others have been reported to have specific neuronal functions. These data suggest that miRNAs widely contribute to the regulation of neurodevelopmental intrinsic processes, and that specific miRNAs could participate in WS neurobiology.
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Evaluation of the persistence of functional and biological respiratory health effects in clean-up workers 6years after the Prestige oil spill.
Environ Int
PUBLISHED: 05-21-2013
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Fishermen who had participated in clean-up activities of the Prestige oil spill showed increased bronchial responsiveness and higher levels of respiratory biomarkers 2years later. We aimed to evaluate the persistence of these functional and biological respiratory health effects 6years after clean-up work. In 2008/2009 a follow-up study was done in 230 never-smoking fishermen who had been exposed to clean-up work in 2002/2003 and 87 non-exposed fishermen. Lung function and bronchial responsiveness testing and the determination of respiratory biomarkers in exhaled breath condensate were done identically as in the baseline survey in 2004/2005. Associations between participation in clean-up work and respiratory health parameters were assessed using linear and logistic regression analyses adjusting for sex and age. Information from 158 exposed (69%) and 57 non-exposed (66%) fishermen was obtained. Loss to follow-up in the non-exposed was characterised by less respiratory symptoms at baseline. During the 4-year follow-up period lung function, bronchial hyperresponsiveness and the levels of respiratory biomarkers of oxidative stress and growth factors had deteriorated notably more among non-exposed than among exposed. At follow-up, respiratory health indices were similar or better in clean-up workers than in non-exposed. No clear differences between highly exposed and moderately exposed clean-up workers were found. In conclusion, we could not detect long-term respiratory health effects in clean-up workers 6years after the Prestige oil spill. Methodological issues that need to be considered in this type of studies include the choice of a non-exposed control group and limitation of follow-up to subgroups such as never smokers.
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Cellular prion protein modulates ?-amyloid deposition in aged APP/PS1 transgenic mice.
Neurobiol. Aging
PUBLISHED: 05-16-2013
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Alzheimers disease and prion diseases are neuropathological disorders that are caused by abnormal processing and aggregation of amyloid and prion proteins. Interactions between amyloid precursor protein (APP) and PrP(c) proteins have been described at the neuron level. Accordingly to this putative interaction, we investigated whether ?-amyloid accumulation may affect prion infectivity and, conversely, whether different amounts of PrP may affect ?-amyloid accumulation. For this purpose, we used the APPswe/PS1dE9 mouse line, a common model of Alzheimers disease, crossed with mice that either overexpress (Tga20) or that lack prion protein (knock-out) to generate mice that express varying amounts of prion protein and deposit ?-amyloid. On these mouse lines, we investigated the influence of each protein on the evolution of both diseases. Our results indicated that although the presence of APP/PS1 and ?-amyloid accumulation had no effect on prion infectivity, the accumulation of ?-amyloid deposits was dependent on PrP(c), whereby increasing levels of prion protein were accompanied by a significant increase in ?-amyloid aggregation associated with aging.
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Persistence of Cushings disease symptoms and comorbidities after surgical cure: a long-term, integral evaluation.
Endocr Pract
PUBLISHED: 04-02-2013
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Successful surgery does not always resolve all the clinical consequences of hypercortisolism in patients with Cushings disease (CD). Our purpose was to integrally evaluate a group of CD patients cured by pituitary surgery and look for the persistence of CD symptoms, signs, and comorbidities.
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Agreement between medical record and parent report for evaluation of childhood febrile seizures.
Vaccine
PUBLISHED: 02-22-2013
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The monitoring of vaccine safety is critical to maintaining the public acceptance of vaccines required to ensure their continued success. Methods used to assess adverse events following immunization (AEFI) must accurately reflect their occurrence. Assessment of AEFI is often done via medical record review (MR) or via patient report (PR). However, these sources of data have not previously been compared for the analysis of AEFI. The objective of this study was to evaluate the concordance between MR and PR for young children identified as having had a febrile seizure (FS), an important AEFI, in an integrated health care system. The variables chosen for analysis were those recommended by the Brighton Collaboration Seizure Working Group for the evaluation of generalized seizure as an AEFI [1].
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Occupational exposure to immunologically active agents and risk for lymphoma: the European Epilymph case-control study.
Cancer Epidemiol
PUBLISHED: 02-13-2013
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Allergies and asthma may be protective for the development of lymphoma. We evaluated whether occupational allergens that provoke immune reactivity and asthma through an IgE-mediated pathway are protective for lymphoma.
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Mitosis is a source of potential markers for screening and survival and therapeutic targets in cervical cancer.
PLoS ONE
PUBLISHED: 01-04-2013
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The effect of preventive human papillomavirus (HPV) vaccination on the reduction of the cervical cancer (CC) burden will not be known for 30 years. Therefore, its still necessary to improve the procedures for CC screening and treatment. The objective of this study was to identify and characterize cellular targets that could be considered potential markers for screening or therapeutic targets. A pyramidal strategy was used. Initially the expression of 8,638 genes was compared between 43 HPV16-positive CCs and 12 healthy cervical epitheliums using microarrays. A total of 997 genes were deregulated, and 21 genes that showed the greatest deregulation were validated using qRT-PCR. The 6 most upregulated genes (CCNB2, CDC20, PRC1, SYCP2, NUSAP1, CDKN3) belong to the mitosis pathway. They were further explored in 29 low-grade cervical intraepithelial neoplasias (CIN1) and 21 high-grade CIN (CIN2/3) to investigate whether they could differentiate CC and CIN2/3 (CIN2+) from CIN1 and controls. CCNB2, PRC1, and SYCP2 were mostly associated with CC and CDC20, NUSAP1, and CDKN3 were also associated with CIN2/3. The sensitivity and specificity of CDKN3 and NUSAP1 to detect CIN2+ was approximately 90%. The proteins encoded by all 6 genes were shown upregulated in CC by immunohistochemistry. The association of these markers with survival was investigated in 42 CC patients followed up for at least 42 months. Only CDKN3 was associated with poor survival and it was independent from clinical stage (HR?=?5.9, 95%CI?=?1.4-23.8, p?=?0.01). CDKN3 and NUSAP1 may be potential targets for the development of screening methods. Nevertheless, further studies with larger samples are needed to define the optimal sensitivity and specificity. Inhibition of mitosis is a well-known strategy to combat cancers. Therefore, CDKN3 may be not only a screening and survival marker but a potential therapeutic target in CC. However, whether its indispensable for tumor growth remains to be demonstrated.
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Blood amyloid Beta levels in healthy, mild cognitive impairment and Alzheimers disease individuals: replication of diastolic blood pressure correlations and analysis of critical covariates.
PLoS ONE
PUBLISHED: 01-01-2013
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Plasma amyloid beta (A?) levels are being investigated as potential biomarkers for Alzheimers disease. In AB128 cross-sectional study, a number of medical relevant correlates of blood A?40 or A?42 were analyzed in 140 subjects (51 Alzheimers disease patients, 53 healthy controls and 36 individuals diagnosed with mild cognitive impairment). We determined the association between multiple variables with A?40 and A?42 levels measured in three different blood compartments called i) A? directly accessible (DA) in the plasma, ii) A? recovered from the plasma matrix (RP) after diluting the plasma sample in a formulated buffer, and iii) associated with the remaining cellular pellet (CP). We confirmed that diastolic blood pressure (DBP) is consistently correlated with blood DA A?40 levels (r=-0.19, P=0.032). These results were consistent in the three phenotypic groups studied. Importantly, the observation resisted covariation with age, gender or creatinine levels. Observed effect size and direction of A?40 levels/DBP correlation are in accordance with previous reports. Of note, DA A?40 and the RP A?40 were also strongly associated with creatinine levels (r=0.599, P<0.001) and to a lesser extent to urea, age, hematocrit, uric acid and homocysteine (p<0.001). DBP and the rest of statistical significant correlates identified should be considered as potential confounder factors in studies investigating blood A? levels as potential AD biomarker. Remarkably, the factors affecting A? levels in plasma (DA, RP) and blood cell compartments (CP) seem completely different.
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Chromosomal bands affected by acute oil exposure and DNA repair errors.
PLoS ONE
PUBLISHED: 01-01-2013
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In a previous study, we showed that individuals who had participated in oil clean-up tasks after the wreckage of the Prestige presented an increase of structural chromosomal alterations two years after the acute exposure had occurred. Other studies have also reported the presence of DNA damage during acute oil exposure, but little is known about the long term persistence of chromosomal alterations, which can be considered as a marker of cancer risk.
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Cut-off Scores of a Brief Neuropsychological Battery (NBACE) for Spanish Individual Adults Older than 44 Years Old.
PLoS ONE
PUBLISHED: 01-01-2013
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The neuropsychological battery used in Fundació ACE (NBACE) is a relatively brief, and easy to administer, test battery that was designed to detect cognitive impairment in the adulthood. The NBACE includes measures of cognitive information processing speed, orientation, attention, verbal learning and memory, language, visuoperception, praxis and executive functions. The aim of the present study was to establish the cut-off scores for impairment for different levels of age and education that could be useful in the cognitive assessment of Spanish subjects who are at risk for cognitive impairment, especially dementia. Data from 1018 patients with a mild dementia syndrome, and 512 cognitively healthy subjects, older than 44 years, from the Memory Clinic of Fundació ACE (Barcelona, Spain) were analyzed. In the whole sample, cut-off scores and sensitivity/specificity values were calculated for six conditions after combining 3 age ranges (44 to 64; 65 to 74; and older than 74 years old) by 2 educational levels (until Elementary school; and more than Elementary school). Moreover, general cut-offs are reported for Catalan and Spanish speakers. The results showed that most of NBACE tests reached good sensitivity and specificity values, except for Ideomotor praxis, Repetition and Verbal Comprehension tests, which had a ceiling effect. Word List Learning from the Wechsler Memory Scale-III and Semantic Verbal Fluency were the most useful tests to discriminate between cognitively healthy and demented subjects. The NBACE has been shown to be a useful tool able to detect cognitive impairment, especially dementia, in older than 44 years Spanish persons.
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Dermoscopy of non-pigmented eccrine poromas: study of Mexican cases.
Dermatol Pract Concept
PUBLISHED: 01-01-2013
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Eccrine poroma is a benign neoplasm that can mimick a malignant neoplasm dermoscopically. The characteristic vascular pattern of this tumor has not been established.
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Quantifying the reduction in potential health risks by determining the sensitivity of poliovirus type 1 chat strain and rotavirus SA-11 to electron beam irradiation of iceberg lettuce and spinach.
Appl. Environ. Microbiol.
PUBLISHED: 12-16-2011
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Fresh produce, such as lettuce and spinach, serves as a route of food-borne illnesses. The U.S. FDA has approved the use of ionizing irradiation up to 4 kGy as a pathogen kill step for fresh-cut lettuce and spinach. The focus of this study was to determine the inactivation of poliovirus and rotavirus on lettuce and spinach when exposed to various doses of high-energy electron beam (E-beam) irradiation and to calculate the theoretical reduction in infection risks that can be achieved under different contamination scenarios and E-beam dose applications. The D(10) value (dose required to reduce virus titers by 90%) (standard error) of rotavirus on spinach and lettuce was 1.29 (± 0.64) kGy and 1.03 (± 0.05) kGy, respectively. The D(10) value (standard error) of poliovirus on spinach and lettuce was 2.35 (± 0.20) kGy and 2.32 (± 0.08) kGy, respectively. Risk assessment of data showed that if a serving (?14 g) of lettuce was contaminated with 10 PFU/g of poliovirus, E-beam irradiation at 3 kGy will reduce the risk of infection from >2 in 10 persons to approximately 6 in 100 persons. Similarly, if a serving size (?0.8 g) of spinach is contaminated with 10 PFU/g of rotavirus, E-beam irradiation at 3 kGy will reduce infection risks from >3 in 10 persons to approximately 5 in 100 persons. The results highlight the value of employing E-beam irradiation to reduce public health risks but also the critical importance of adhering to good agricultural practices that limit enteric virus contamination at the farm and in packing houses.
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Normative data of a brief neuropsychological battery for Spanish individuals older than 49.
J Clin Exp Neuropsychol
PUBLISHED: 12-13-2011
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There is an increasing need for standardized assessment of cognition in older patients that is relatively brief, easy to administer, and has normative data adjusted for age and educational attainment. We tested 332 literate, cognitively normal, Spanish persons older than 49 years from the Memory Clinic of Fundació ACE, Institut Català de Neurociències Aplicades (Barcelona, Spain) with measures of cognitive information processing speed, orientation, attention, verbal learning and memory, language, visuoperception, praxis, and executive functions. Several of the tests were affected by age, education, and/or gender, but the language of administration (i.e., Spanish or Catalan) did not affect the test scores. Standardized scores and percentile ranks were calculated for each age and/or education group for use by clinical neuropsychologists.
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Discontinuation of octreotide LAR after long term, successful treatment of patients with acromegaly: is it worth trying?
Eur. J. Endocrinol.
PUBLISHED: 10-12-2011
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Somatostatin analogs (SA) have been used for over 25 years in the treatment of acromegaly. A major disadvantage is the need to continue therapy indefinitely.
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Clinical and biochemical characteristics of acromegalic patients with different abnormalities in glucose metabolism.
Pituitary
PUBLISHED: 09-29-2011
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To determine the prevalence of diabetes, glucose intolerance and impaired fasting glucose in Mexican patients with acromegaly and establish associations with clinical, anthropometric and biochemical variables. 257 patients with acromegaly were evaluated by a 75 g-oral glucose tolerance test with measurements of both GH and glucose (0, 30, 60, 90 120 min) as well as baseline IGF-1. Normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and diabetes (DM) were defined based on the 2003 ADA criteria. NGT, IFG, IGT and DM were found in 27.6, 8.9, 31.6 and 31.9% of the subjects, respectively; 42 of the DM patients were unaware of the diagnosis. Patients with diabetes were older than subjects in the other 3 categories (P = 0.001), and the proportion of women was significantly higher in the DM (74%) and IGT (68%) groups than in the NGT group (52%) (P = 0.004). Odds ratio for the development of DM was 3.29 (95% CI 3.28-3.3). GH and IGF-1 levels were comparable among the different groups. In a multivariable analysis DM was significantly associated with age, presence of a macroadenoma, disease duration and a basal GH > 30 ?g/dl. DM and probably IGT are more prevalent in acromegaly than in the general Mexican population. DM was more frequent in females of all ages, in subjects with severely elevated GH concentrations, in patients with macroadenomas, and long-standing disease duration. The odds ratio for DM in our subjects with acromegaly is more than 3 times higher than in the general population.
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Efficacy and safety of radiotherapy in acromegaly.
Arch. Med. Res.
PUBLISHED: 03-08-2011
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Transsphenoidal surgery remains the treatment of choice in acromegaly, yet 40-50% of patients require secondary forms of therapy such as radiation therapy (RT) and somatostatin analogues (SA). We undertook this study to evaluate the efficacy and safety of RT in acromegaly.
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Ulcerative colitis exacerbates lipopolysaccharide-induced damage to the nigral dopaminergic system: potential risk factor in Parkinson`s disease.
J. Neurochem.
PUBLISHED: 08-19-2010
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Peripheral inflammation could play a role in the origin and development of certain neurodegenerative disorders. To ascertain this possibility, a model of dopaminergic neurodegeneration based on the injection of the inflammatory agent lipopolysaccharide (LPS) within the substantia nigra was assayed in rats with ulcerative colitis (UC) induced by the ingestion of dextran sulphate sodium. We found an increase in the levels of inflammatory markers from serum (tumor necrosis factor-?, IL-1?, IL-6 and the acute phase protein C-reactive protein) and substantia nigra (tumor necrosis factor-?, IL-1?, IL-6, inducible nitric oxide synthase, intercellular adhesion molecule-1, microglial and astroglial populations) of rats with UC, as well as an alteration of the blood-brain barrier permeability and the loss of dopaminergic neurons. UC reinforced the inflammatory and deleterious effects of LPS. On the contrary, clodronate encapsulated in liposomes (ClodLip), which depletes peripheral macrophages, ameliorated the effect of LPS and UC. Peripheral inflammation might represent a risk factor in the development of Parkinsons disease.
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Embryonic MGE precursor cells grafted into adult rat striatum integrate and ameliorate motor symptoms in 6-OHDA-lesioned rats.
Cell Stem Cell
PUBLISHED: 01-05-2010
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We investigated a strategy to ameliorate the motor symptoms of rats that received 6-hydroxydopamine (6-OHDA) lesions, a rodent model of Parkinsons disease, through transplantation of embryonic medial ganglionic eminence (MGE) cells into the striatum. During brain development, embryonic MGE cells migrate into the striatum and neocortex where they mature into GABAergic interneurons and play a key role in establishing the balance between excitation and inhibition. Unlike most other embryonic neurons, MGE cells retain the capacity for migration and integration when transplanted into the postnatal and adult brain. We performed MGE cell transplantation into the basal ganglia of control and 6-OHDA-lesioned rats. Transplanted MGE cells survived, differentiated into GABA(+) neurons, integrated into host circuitry, and modified motor behavior in both lesioned and control rats. Our data suggest that MGE cell transplantation into the striatum is a promising approach to investigate the potential benefits of remodeling basal ganglia circuitry in neurodegenerative diseases.
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Comparative study of enteric viruses, coliphages and indicator bacteria for evaluating water quality in a tropical high-altitude system.
Environ Health
PUBLISHED: 10-27-2009
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Bacteria used as indicators for pathogenic microorganisms in water are not considered adequate as enteric virus indicators. Surface water from a tropical high-altitude system located in Mexico City that receives rainwater, treated and non-treated wastewater used for irrigation, and groundwater used for drinking, was studied.
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[Case report of mucormycosis in a patient with secondary methimazole-induced agranulocytosis].
Gac Med Mex
PUBLISHED: 08-19-2009
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Agranulocytosis is a rare side effect of antithyroid drugs, it occurs in less than 0.5% of patients, usually during the first few months of treatment. It is considered to be the most serious adverse effect of these medications since it may be complicated by serious, life-threatening infections. Mucormycosis is a severe mycotic infection that usually develops in immunocompromised hosts, such aspatients with diabetes mellitus, hematologic malignancies or immunosuppressive therapy. The association of mucormycosis with methimazole-induced agranulocytosis has not been previously described. The objective of this case presentation is to analyze the case ofa woman with diffuse toxic goiter and methimazole-induced agranulocytosis who developed rhino-palatal mucormycosis.
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Two separate subtypes of early non-subplate projection neurons in the developing cerebral cortex of rodents.
Front Neuroanat
PUBLISHED: 08-06-2009
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The preplate of the cerebral cortex contains projection neurons that connect the cortical primordium with the subpallium. These are collectively named pioneer neurons. After preplate partition, most of these pioneer neurons become subplate neurons. Certain preplate neurons, however, never associate with the subplate but rather with the marginal zone. In the present overview, we propose a novel classification of non-subplate pioneer neurons in rodents into two subtypes. In rats, the neurons of the first subtype are calbindin(+) (CB), calretinin(+) (CR) and L1(+) and are situated in the upper part of the preplate before its partition. Neurons of the second subtype are TAG-1(+) and are located slightly deeper to the previous population in the preplate. After the preplate partition, the CB(+), CR(+) and L1(+) neurons remain in the marginal zone whereas TAG-1(+) neurons become transiently localized in the upper cortical plate. In mice, by contrast, calcium binding proteins did not label pioneer neurons. We define in mice two subtypes of non-subplate pioneer neurons, either L1(+) or TAG-1(+)/cntn2(+). We propose these to be the homologues of the two subtypes of non-subplate pioneer neurons of rats. The anatomical distribution of these neuron populations is similar in rats and mice. The two populations of non-subplate pioneer neurons differ in their axonal projections. Axons of L1(+) pioneer neurons project to the ganglionic eminences and the anterior preoptic area, but avoid entering the posterior limb of the internal capsule towards the thalamus. Axons of TAG-1(+) pioneer neurons project to the lateral parts of the ganglionic eminences at the early stages of cortical histogenesis examined.
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Degeneration of dopaminergic neurons induced by thrombin injection in the substantia nigra of the rat is enhanced by dexamethasone: role of monoamine oxidase enzyme.
Neurotoxicology
PUBLISHED: 07-08-2009
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Anti-inflammatory strategies receive growing attention for their potential to prevent pathological deterioration in disorders such as Parkinsons disease, which is accompanied by inflammatory reactions that might play a critical role in the degeneration of nigral dopaminergic neurons. We investigated the influence of dexamethasone - a potent synthetic member of the glucocorticoids class of steroid hormones that acts as an anti-inflammatory - on the degeneration of the dopaminergic neurons of rats observed after intranigral injection of thrombin, a serine protease that induces inflammation through microglia proliferation and activation. We evaluated tyrosine hydroxylase (TH)-positive neurons as well as astroglial and microglial populations; dexamethasone prevented the loss of astrocytes but was unable to stop microglial proliferation induced by thrombin. Moreover, dexamethasone produced alterations in the levels of nexin and the thrombin receptor PAR-1, and facilitated accumulation of alpha-synuclein induced by thrombin in dopaminergic neurons. Dexamethasone increased oxidative stress and expression of monoamine oxidase A and B, along with changes on different MAP kinases related to degenerative processes, resulting in a bigger loss of dopaminergic neurons after intranigral injection of thrombin in dexamethasone-treated animals. It is interesting to ascertain that inhibition of monoamine oxidase by tranylcypromine prevented neurodegeneration of dopaminergic neurons, thus suggesting that the deleterious effects of dexamethasone might be mediated by monoamine oxidase.
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Ecological assessment of executive functions in mild cognitive impairment and mild Alzheimers disease.
J Int Neuropsychol Soc
PUBLISHED: 07-02-2009
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Although memory deficits are typically the earliest and most profound symptoms of Alzheimers disease (AD) and mild cognitive impairment (MCI), there is increasing recognition of subtle executive dysfunctions in these patients. The purpose of the present study was to determine the sensitivity of the Behavioral Assessment of the Dysexecutive Syndrome (BADS), and to detect early specific signs of the dysexecutive syndrome in the transition from normal cognition to dementia. The BADS was administered to 50 MCI subjects, 50 mild AD patients, and 50 normal controls. Statistically significant differences were found among the three groups with the AD patients performing most poorly, and the MCI subjects performing between controls and AD patients. The Rule Shift Cards and the Action Program subtests were the most highly discriminative between MCI and controls; the Zoo Map and Modified Six Elements between MCI and AD; and the Action Program, Zoo Map, and Modified Six Elements between AD and controls. These results demonstrate that the BADS is clinically useful in discriminating between normal cognition and progressive neurodegenerative conditions. Furthermore, these data confirm the presence of a dysexecutive syndrome even in mildly impaired elderly subjects.
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Surgical reintervention in acromegaly: is it still worth trying?
Endocr Pract
PUBLISHED: 06-04-2009
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There has not been a formal evaluation of how frequently and to what extent surgical reintervention in patients with persistently active acromegaly may achieve significant, albeit incomplete, reductions in growth hormone (GH) and insulinlike growth factor-I (IGF-I) levels. Of importance, recent studies suggest that the response to radiotherapy and pharmacotherapy is better with lower degrees of hypersomatotropism. The objective of this study was to evaluate the outcome of surgical reintervention in patients with active acromegaly at our institution between 1995 and 2005.
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Modification of the technique for subclavian-vein catheterization.
Rev. Invest. Clin.
PUBLISHED: 03-02-2009
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In invasive monitoring, subclavian-vein puncture is a routine procedure indicated for central vein cathe-terization. It is indicated in patients according to hospital stay, including the administration of drugs and the treatment of chronic and cardiac disease. The techniques described to date include infraclavicular percutaneous puncture; others place catheters using angiographic methods, and the use of magnetic resonance imaging and ultrasound has also been reported. Studies have been done in cadavers to get a better understanding of the procedure since the relationship between vascular elements and surrounding tissues are obtained. The usual technique is with the patient in Trendelenburg position, with the arm in adduction, the placement of an interscapular roll, and the head turned away from the puncture site.
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Assessment of a primary and tertiary care integrated management model for chronic obstructive pulmonary disease.
BMC Public Health
PUBLISHED: 02-24-2009
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The diagnosis and treatment of patients with chronic obstructive pulmonary disease (COPD) in Spain continues to present challenges, and problems are exacerbated when there is a lack of coordinated follow-up between levels of care. This paper sets out the protocol for assessing the impact of an integrated management model for the care of patients with COPD. The new model will be evaluated in terms of 1) improvement in the rational utilization of health-care services and 2) benefits reflected in improved health status and quality of life for patients.
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The intranigral injection of tissue plasminogen activator induced blood-brain barrier disruption, inflammatory process and degeneration of the dopaminergic system of the rat.
Neurotoxicology
PUBLISHED: 02-05-2009
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Tissue-type plasminogen activator (tPA) is the only drug approved for the treatment of thromboembolic stroke, but it might lead to some neurotoxic side effects. tPA is a highly specific serine proteinase, one of the two principal plasminogen activators and one of the three trypsin-like serine proteinases of the tissue kallikrein family. We have observed that tPA injection in the SN leads to the degeneration of the dopaminergic neurons in a dose-dependent manner, without affecting the GABAergic neurons. We also found that tPA injected in the substantia nigra of rats produced the disruption of the blood-brain barrier (BBB) integrity, the induction of microglial activation, the loss of astroglia and the expression of aquaporin 4 (AQP4), as well as an increase in the expression of NMDA receptors and the brain derived neurothrophic factor (BDNF). All these effects, along with the changes produced in the phosphorylated forms of several MAP kinases and the transcription factor CREB, and the increase in the expression of nNOS and iNOS observed under our experimental conditions, could be involved in the loss of dopaminergic neurons.
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Detection of visuoperceptual deficits in preclinical and mild Alzheimers disease.
J Clin Exp Neuropsychol
PUBLISHED: 01-14-2009
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Exhaustive neuropsychological assessment of mild cognitive impairment (MCI) subjects frequently identifies cognitive deficits other than memory. However, visuoperception has rarely been investigated in MCI. The 15-Objects Test (15-OT), a visual discrimination task based on the Poppelreuter Test, consists of 15 overlapping objects. Poppelreuter-type tests are frequently used to detect visual agnosia. However, more complex tests, such as the 15-OT, are required to detect visuoperceptual signs in those patients who perform correctly on simple tests. The aim of the present study was to investigate visuoperceptual deficits in MCI patients and to assess the usefulness of the 15-OT to discriminate Alzheimers disease (AD) and MCI patients from controls. The 15-OT, and a neuropsychological battery included in the diagnostic assessment, was administered to 44 healthy controls, 44 MCI patients, and 44 mild AD patients. Performance on the 15-OT was significantly different between groups. MCI scored between AD and controls. When MCI and AD patients had relatively normal performance on simple tests (Poppelreuter), increased significant abnormalities were found by a more difficult visuoperceptual test (15-OT). Regression analyses showed that the 15-OT was a significant predictor of group membership, but the Poppelreuter Test did not significantly contribute to the models. Visuoperceptual processing is impaired early in the clinical course of AD. The 15-OT allows detection of visuoperceptual deficits in the preclinical and mild AD stages, when classical tests are still unable to detect subtle deficits. So, its inclusion in neuropsychological batteries that are nowadays used in the clinical practice would allow increasing their diagnostic potential.
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Detection of Epstein-Barr virus and genotyping based on EBNA2 protein in Mexican patients with hodgkin lymphoma: a comparative study in children and adults.
Clin Lymphoma Myeloma Leuk
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Epstein-Barr virus (EBV) is a member of the Herpesviridae family and is associated with Hodgkin lymphoma (HL). Isolates of EBV are classified according to sequence variation in the latency genes such as Epstein-Barr virus nuclear antigen (EBNA). EBNA2 contains the most divergent locus and is classified into type 1 and type 2 or EBNA2A and EBNA2B, respectively. We compared the frequency of EBV and the distribution of EBNA genotypes in Mexican children and adults with HL.
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The double life of Ceratobasidium: orchid mycorrhizal fungi and their potential for biocontrol of Rhizoctonia solani sheath blight of rice.
Mycologia
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Ceratobasidium includes orchid mycorrhizal symbionts, plant pathogens and biocontrol agents of soilborne plant pathogens. It is not known to what extent members of the first guild also can participate in the others. Ceratobasidium spp. were isolated from roots of Colombian orchids and identified by phylogeny based on nrITS sequences. Phylogenetic grouping of Ceratobasidium spp. isolates corresponded to orchid host substrate (epiphytic vs. terrestrial). Isolates were tested for virulence on rice and for biocontrol of Rhizoctonia solani, causal agent of sheath blight of rice. All Ceratobasidium spp. isolates caused some signs of sheath blight but significantly less than a pathogenic R. solani used as a positive control. When Ceratobasidium spp. isolates were inoculated on rice seedlings 3 d before R. solani, they significantly reduced disease expression compared to controls inoculated with R. solani alone. The use of Ceratobasidium spp. from orchids for biological control is novel, and biodiverse countries such as Colombia are promising places to look for new biocontrol agents.
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Fate-restricted neural progenitors in the mammalian cerebral cortex.
Science
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During development of the mammalian cerebral cortex, radial glial cells (RGCs) generate layer-specific subtypes of excitatory neurons in a defined temporal sequence, in which lower-layer neurons are formed before upper-layer neurons. It has been proposed that neuronal subtype fate is determined by birthdate through progressive restriction of the neurogenic potential of a common RGC progenitor. Here, we demonstrate that the murine cerebral cortex contains RGC sublineages with distinct fate potentials. Using in vivo genetic fate mapping and in vitro clonal analysis, we identified an RGC lineage that is intrinsically specified to generate only upper-layer neurons, independently of niche and birthdate. Because upper cortical layers were expanded during primate evolution, amplification of this RGC pool may have facilitated human brain evolution.
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Connexin 36 is expressed in beta and connexins 26 and 32 in acinar cells at the end of the secondary transition of mouse pancreatic development and increase during fetal and perinatal life.
Anat Rec (Hoboken)
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To identify when during fetal development connexins (Cxs) 26 (Cx26) 32 (Cx32), and 36 (Cx36) begin to be expressed, as well as to characterize their spatial distribution, real time polymerase chain reaction and immunolabeling studies were performed. Total RNA from mouse pancreases at 13 and 18 days postcoitum (dpc) and 3 days postpartum (dpp) was analyzed. In addition, pancreatic sections of mouse at 13, 14, 15, 16, 18 dpc and 3 dpp and of rat at term were double labeled with either anti-insulin or anti-?-amylase and anti-Cx26 or -Cx32 or -Cx36 antibodies and studied with confocal microscopy. From day 13 dpc, Cxs 26, 32, and 36 transcripts were identified and their levels increased with age. At 13-14 dpc, Cxs 26 and 32 were localized in few acinar cells, whereas Cx36 was distributed in small beta cell clumps. From day 14 dpc onwards, the number of labeled cells and relative immunofluorescent reactivity of all three Cxs at junctional membranes of the respective cell types increased. Cxs 26 and 32 colocalized in fetal acinar cells. In rat pancreas at term, a similar connexin distribution was found. Relative Cxs levels evaluated by immunoblotting also increased (two-fold) in pancreas homogenates from day 18 dpc to 3 dpp. The early cell specific, wide distribution, and age dependent expression of Cxs 26, 32, and 36 during fetal pancreas ontogeny suggests their possible involvement in pancreas differentiation and prenatal maturation.
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Water-soluble iron oxide nanocubes with high values of specific absorption rate for cancer cell hyperthermia treatment.
ACS Nano
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Iron oxide nanocrystals (IONCs) are appealing heat mediator nanoprobes in magnetic-mediated hyperthermia for cancer treatment. Here, specific absorption rate (SAR) values are reported for cube-shaped water-soluble IONCs prepared by a one-pot synthesis approach in a size range between 13 and 40 nm. The SAR values were determined as a function of frequency and magnetic field applied, also spanning technical conditions which are considered biomedically safe for patients. Among the different sizes tested, IONCs with an average diameter of 19 ± 3 nm had significant SAR values in clinical conditions and reached SAR values up to 2452 W/g(Fe) at 520 kHz and 29 kAm(-1), which is one of the highest values so far reported for IONCs. In vitro trials carried out on KB cancer cells treated with IONCs of 19 nm have shown efficient hyperthermia performance, with cell mortality of about 50% recorded when an equilibrium temperature of 43 °C was reached after 1 h of treatment.
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Amplified genes may be overexpressed, unchanged, or downregulated in cervical cancer cell lines.
PLoS ONE
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Several copy number-altered regions (CNAs) have been identified in the genome of cervical cancer, notably, amplifications of 3q and 5p. However, the contribution of copy-number alterations to cervical carcinogenesis is unresolved because genome-wide there exists a lack of correlation between copy-number alterations and gene expression. In this study, we investigated whether CNAs in the cell lines CaLo, CaSki, HeLa, and SiHa were associated with changes in gene expression. On average, 19.2% of the cell-line genomes had CNAs. However, only 2.4% comprised minimal recurrent regions (MRRs) common to all the cell lines. Whereas 3q had limited common gains (13%), 5p was entirely duplicated recurrently. Genome-wide, only 15.6% of genes located in CNAs changed gene expression; in contrast, the rate in MRRs was up to 3 times this. Chr 5p was confirmed entirely amplified by FISH; however, maximum 33.5% of the explored genes in 5p were deregulated. In 3q, this rate was 13.4%. Even in 3q26, which had 5 MRRs and 38.7% recurrently gained SNPs, the rate was only 15.1%. Interestingly, up to 19% of deregulated genes in 5p and 73% in 3q26 were downregulated, suggesting additional factors were involved in gene repression. The deregulated genes in 3q and 5p occurred in clusters, suggesting local chromatin factors may also influence gene expression. In regions amplified discontinuously, downregulated genes increased steadily as the number of amplified SNPs increased (p<0.01, Spearmans correlation). Therefore, partial gene amplification may function in silencing gene expression. Additional genes in 1q, 3q and 5p could be involved in cervical carcinogenesis, specifically in apoptosis. These include PARP1 in 1q, TNFSF10 and ECT2 in 3q and CLPTM1L, AHRR, PDCD6, and DAP in 5p. Overall, gene expression and copy-number profiles reveal factors other than gene dosage, like epigenetic or chromatin domains, may influence gene expression within the entirely amplified genome segments.
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Delineation of commonly deleted chromosomal regions in meningiomas by high-density single nucleotide polymorphism genotyping arrays.
Genes Chromosomes Cancer
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Despite recent advances in the identification of the cytogenetic profiles of meningiomas, a significant group of tumors still show normal karyotypes or few chromosomal changes. The authors analyzed the cytogenetic profile of 50 meningiomas using fluorescence in situ hybridization and high-density (500 K) single nucleotide polymorphism (SNP) arrays. Our results confirm that del(22q) (52%) and del(1p) (16%) (common deleted regions: 22q11.21-22q13.3. and 1p31.2-p36.33) are the most frequent alterations. Additionally, recurrent monosomy 14 (8%), del(6q) (10%), del(7p) (10%), and del(19q) (4%) were observed, while copy number patterns consistent with recurrent chromosomal gains, gene amplification, and copy number neutral loss of heterozygosity (cnLOH) were either absent or rare. Based on their overall SNP profiles, meningiomas could be classified into: (i) diploid cases, (ii) meningiomas with a single chromosomal change [e.g., monosomy 22/del(22q)] and (iii) tumors with ?2 altered chromosomes. In summary, our results confirm and extend on previous observations showing that the most recurrent chromosomal abnormalities in meningiomas correspond to chromosome losses localized in chromosomes 1, 22 and less frequently in chromosomes 6, 7, 14, and 19, while chromosomal gains and cnLOH are restricted to a small proportion of cases. Finally, a set of cancer-associated candidate genes associated with the TP53, MYC, CASP3, HDAC1, and TERT signaling pathways was identified, in cases with coexisting monosomy 14 and del(1p).
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The Amerindian mtDNA haplogroup B2 enhances the risk of HPV for cervical cancer: de-regulation of mitochondrial genes may be involved.
J. Hum. Genet.
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Although human papillomavirus (HPV) infection is the main causal factor for cervical cancer (CC), there are data suggesting that genetic factors could modulate the risk for CC. Sibling studies suggest that maternally inherited factors could be involved in CC. To assess whether mitochondrial DNA (mtDNA) polymorphisms are associated to CC, HPV infection and HPV types, a case-control study was performed in the Mexican population. Polymorphism of mtDNA D-loop was investigated in 187 CC patients and 270 healthy controls. HPV was detected and typed in cervical scrapes. The expression of 29 mitochondrial genes was analyzed in a subset of 45 tumor biopsies using the expression microarray ST1.0. The Amerindian haplogroup B2 increased the risk for CC (odds ratio (OR)=1.6; 95% confidence interval (CI): 1.05-2.58) and enhanced 36% (OR=208; 95% CI: 25.2-1735.5) the risk conferred by the HPV alone (OR=152.9; 95% CI: 65.4-357.5). In cases, the distribution of HPV types was similar in all haplogroups but one (D1), in which is remarkable the absence of HPV18, a very low frequency of HPV16 and high frequencies of HPV45, HPV31 and other HPV types. Two mtDNA genes (mitochondrial aspartic acid tRNA (MT-TD), mitochondrial lysine tRNA (MT-TK)) could be involved in the increased risk conferred by the haplogroup B2, as they were upregulated exclusively in B2 tumors (P<0.01, t-test). Although the association of mtDNA with CC and HPV infection is clear, other studies with higher sample size will be needed to elucidate the role of mtDNA in cervical carcinogenesis.
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Peripheral inflammation increases the deleterious effect of CNS inflammation on the nigrostriatal dopaminergic system.
Neurotoxicology
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Evidence supports the role of inflammation in the development of neurodegenerative diseases. In this work, we are interested in inflammation as a risk factor by itself and not only as a factor contributing to neurodegeneration. We tested the influence of a mild to moderate peripheral inflammation (injection of carrageenan into the paws of rats) on the degeneration of dopaminergic neurons in an animal model based on the intranigral injection of lipopolysaccharide (LPS), a potent inflammatory agent. Overall, the treatment with carrageenan increased the effect of the intranigral injection of LPS on the loss of dopaminergic neurons in the SN along with all the other parameters studied, including: serum levels of the inflammatory markers TNF-?, IL-1?, IL-6 and C-reactive protein; activation of microglia, expression of proinflammatory cytokines, the adhesion molecule ICAM and the enzyme iNOS, loss of astrocytes and damage to the blood brain barrier (BBB). The possible implication of BBB rupture in the increased loss of dopaminergic neurons has been studied using another Parkinsons disease animal model based on the intraperitoneal injection of rotenone. In this experiment, loss of dopaminergic neurons was also strengthened by carrageenan, without affecting the BBB. In conclusion, our data show that a mild to moderate peripheral inflammation can exacerbate the degeneration of dopaminergic neurons caused by a harmful stimulus.
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The role of primary pharmacological therapy in acromegaly.
Pituitary
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Primary pharmacological therapy may be the only viable treatment option for many patients with acromegaly, especially those presenting with advanced disease with large inoperable tumors. Long-acting somatostatin analogs are currently the first-line treatment of choice in this setting, where they provide biochemical control and reduce tumor size in a significant proportion of patients. We herein present a brief overview of the role of primary pharmacological therapy in the treatment of acromegaly within the context of Latin America and support this with a representative case study.
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Patient-focussed outcomes in acromegaly.
Pituitary
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Health-related quality of life (QoL) is severely impaired in acromegaly due to the physical and psychological consequences of the disease. Pharmacological and surgical treatments, when available, can improve QoL and life expectancy.
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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.