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En este texto presento algunos planteamientos teórico-metodológicos para el estudio de las representaciones sociales en el campo educativo integrados en una propuesta sustentada en la lógica natural que permite analizar su dimensión discursiva. Describo los planteamientos centrales de dicha propuesta y muestro que la particularidad de este enfoque es que permite evidenciar el papel que juega el lenguaje en la construcción de las representaciones sociales, captar la manera en que el sujeto se relaciona con lo construido y el involucramiento del locutor en lo que enuncia. Basándome en investigaciones que he realizado en el campo educativo ilustro la propuesta con un estudio sobre la Reforma Educativa Mexicana de 2013.

There is a significant need to gain access to new and better antibacterial agents.

BACKGROUND Some studies suggest that inflammatory signaling dysregulation may contribute to eating disorder (ED) pathophysiology. However, little is known about the influence of inflammatory response on altered processes seen among patients with ED, such as emotional processing and reactivity. OBJECTIVES The objectives were: (a) to investigate the systemic inflammatory response in ED women; and (b) to analyze the role of inflammatory markers in emotional reactivity. METHOD Concentrations of several intercellular and intracellular inflammatory mediators (cytokines, prostaglandin by-products and enzymes, TBARS, and MAPK proteins) were quantified in plasma and PBMCs from 68 women with an ED (m = 22.01 years, SD = 9.15) and 35 healthy controls (m = 18.54 years, SD = 4.21). Moreover, emotional reactivity to affective pictures (those without either food or thinness content) was studied using the adult (>18 years old) sample (n = 41). RESULTS Between-group differences were revealed for most markers (TNF-α, PGE2 , COX2, and ratio of activated MAPK proteins), pointing to increased inflammatory response in patients (p

INTRODUCTION AND OBJECTIVEPost-COVID syndrome (PCS) is a poorly-known entity. Underlying low-grade inflammation (LGI) has been theorized as one of its pathophysiological mechanisms. We aimed to investigate a possible relationship between PCS and an increase in inflammation markers, in a sex-stratified analysis.PARTICIPANTS AND METHODSMild cases of COVID-19 according to the WHO classification followed-up in a Primary Care Center, were included. We collected epidemiological data (age, sex, body mass index -BMI-, smoking, and comorbidities -Charlson index-), variables of the acute COVID-19 episode, and data at 3 months of follow-up (clinical manifestations and inflammatory markers). Serum C-reactive protein (CRP), neutrophil and lymphocyte counts, neutrophil/lymphocyte ratio (NLR), lactate dehydrogenase (LDH), ferritin, fibrinogen, and D-dimer levels were analyzed. Low-grade inflammation (LGI) was defined as serum CRP between >0.3 and RESULTSWe analyzed 121 subjects with mild COVID-19 (56.2% women; mean age 46 years). The most common symptom in the acute episode was fever (60.3%), while it was fatigue in PCS (42.8%). Prevalence of PCS was 35.8% in women and 20.8% in men (p = 0.07).In women, after controlling for age, BMI, smoking, and comorbidities, the D1, D3, and D4 indices were consistently associated with PCS, with ORs of 5.14 (95% CI, 1.6-16.4), 4.20 (95% CI, 1.3-13.3), and 4.12 (95% CI, 1.3-13.1), respectively; in patients with post-COVID anosmia and ageusia, neutrophils were significantly elevated (3.43±0.3 vs 2.58±0.1; p = 0.014, and 3.89±0.3 vs 2.59±0.1; p = 0.002,respectively), after adjusting for confounders.In men, the D2 and D5 indices were associated with PCS, with adjusted ORs of 10.1 (95% CI, 1.2-85) and 17.5 (95% CI, 2-153), respectively. Furthermore, serum CRP in the LGI range was associated with PCS [adjusted OR=12.9 (95% CI, 1.3-121)], and in post-COVID persistent fatigue, the neutrophil count was significantly elevated (4.68±0.6 vs 3.37±0.1; p = 0.041), after controlling for confounders.CONCLUSIONSConsistent associations among PCS, anosmia, ageusia, and fatigue, with slight -but significant-elevated levels of inflammatory markers, have been observed. The neutrophil count was the most frequently involved marker. Sex-stratified analyses showed relevant differences between women and men concerning PCS and serum inflammatory markers.

Some types of cancer are commonly associated with intense pain even at the early stages of the disease. The mandible is particularly vulnerable to metastasis from breast cancer, and this process has been studied using a bioluminescent human breast cancer cell line (MDA-MB-231LUC+). Using this cell line and anatomic and neurophysiologic methods in the trigeminal ganglion (TG), we examined the impact of cancer seeding in the mandible on behavioral evidence of hypersensitivity and on trigeminal sensory neurons. Growth of cancer cells seeded to the mandible after arterial injection of the breast cancer cell line in Foxn1 animals (allogeneic model) induced behavioral hypersensitivity to mechanical stimulation of the whisker pad and desensitization of tactile and sensitization of nociceptive mechanically sensitive afferents. These changes were not restricted to the site of metastasis but extended to sensory afferents in all three divisions of the TG, accompanied by widespread overexpression of substance P and CGRP in neurons through the ganglion. Subcutaneous injection of supernatant from the MDA-MB-231LUC+ cell culture in normal animals mimicked some of the changes in mechanically responsive afferents observed with mandibular metastasis. We conclude that released products from these cancer cells in the mandible are critical for the development of cancer-induced pain and that the overall response of the system greatly surpasses these local effects, consistent with the widespread distribution of pain in patients. The mechanisms of neuronal plasticity likely occur in the TG itself and are not restricted to afferents exposed to the metastatic cancer microenvironment.

Most studies of eating disorders (ED) among adolescents have relied on the use of self-report questionnaires given its cost-effectiveness compared to interviews approaches. The Eating Disorders Examination Questionnaire (EDE-Q) is one of the most commonly used self-report measures of eating psychopathology, despite issues regarding the underlying latent structure and its validity in this population. Given the lack of validated measures among Hispanic clinical samples, the current study aimed to validate previously suggested models for the adolescent version (EDE-Q-A) among female teenage patients with ED in Spain (

Oxytocin reduces primary sensory afferent excitability and produces analgesia in part through a peripheral mechanism, yet its actions on physiologically characterized, mechanically sensitive afferents in normal and neuropathic conditions are unknown. We recorded intracellularly from L4 dorsal root ganglion neurons characterized as low-threshold mechanoreceptors (LTMRs) or high-threshold mechanoreceptors (HTMRs) in female rats 1 week after L5 partial spinal nerve injury or sham control (n = 24 rats/group) before, during, and after ganglionic perfusion with oxytocin, 1 nM. Nerve injury desensitized and hyperpolarized LTMRs (membrane potential [Em] was -63 ± 1.8 mV in sham vs -76 ± 1.4 mV in nerve injury; P < 0.001), and sensitized HTMRs without affecting Em. In nerve-injured rats, oxytocin depolarized LTMRs towards normal (Em = -69 ± 1.9 mV) and, in 6 of 21 neurons, resulted in spontaneous action potentials. By contrast, oxytocin hyperpolarized HTMRs (Em = -68 ± 2.7 mV before vs -80 ± 3.2 mV during oxytocin exposure; P < 0.01). These effects were reversed after removal of oxytocin, and oxytocin had minimal effects in neurons from sham surgery animals. Sensory afferent neurons immunopositive for the vasopressin 1a receptor were larger (34 ± 6.3 μm, range 16-57 μm) than immunonegative neurons (26 ± 3.4 μm, range 15-43 μm; P < 0.005). These data replicate findings that neuropathic injury desensitizes LTMRs while sensitizing HTMRs and show rapid and divergent oxytocin effects on these afferent subtypes towards normal, potentially rebalancing input to the central nervous system. Vasopressin 1a receptors are present on medium to large diameter afferent neurons and could represent oxytocin's target.

There is a significant need to gain access to new and better antibacterial agents. Acalypha arvensis, a plant from the Euphorbiaceae family, has been used in traditional medicine for centuries to treat infectious diseases. This manuscript reports the isolation, characterization, and antibacterial screening of 8 natural products extracted from maceration of aerial parts of Acalypha arvensis. Specifically, three extracts were assessed (n-hexane, ethyl acetate, and ethanol), in which antibacterial activity was evaluated against diverse bacterial strains. The ethanolic extract showed the best activity against methicillin-sensitive and methicillin-resistant Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa strains, which supports the medicinal properties attributed to this plant. The chromatographic fractions AaR4 and AaR5 were the most bioactive, in which the ellagitannin natural product known as corilagin (1) was identified for the first time in this plant. Therefore, it can be said that this is the main chemical responsible for the observed antibacterial activity. However, we also identified chlorogenic acid (2), rutin (3), quercetin-3-O-glucoside (4), caffeic acid (5), among others (6–8). Hence, this plant can be considered to be a good alternative to treat health-related issues caused by various bacteria.

A high ω6/ω3 ratio [fatty acid (FA) index] in the cell membrane has been associated with inadequate brain development. It has started to be used as a biomarker of treatment efficacy in human diseases. The aim of this study was to investigate if omega-3 supplementation improves erythrocyte membrane ω6/ω3, plasma antioxidant status (TAS) and autistic behaviors. A randomized, crossover, placebo-controlled study was designed to investigate the effect of 8 weeks of supplementation with ω3 (962mg/d and 1155mg/d for children and adolescents, respectively). Sixty-eight children and adolescents with Autism Spectrum Disorders (ASD) completed the full protocol. Primary outcome measures were erythrocyte membrane FA composition and TAS. Secondary outcome measures were Social Responsiveness Scale and Clinical Global Impression-Severity. Treatment with ω3 improved the erythrocyte membrane ω6/ω3 ratio (treatment effect p

Inositol-requiring enzyme 1[α] (IRE1[α])–X-box binding protein spliced (XBP1) signaling maintains endoplasmic reticulum (ER) homeostasis while controlling immunometabolic processes. Yet, the physiological consequences of IRE1a–XBP1 activation in leukocytes remain unexplored. We found that induction of prostaglandin-endoperoxide synthase 2 (Ptgs2/Cox-2) and prostaglandin E synthase (Ptges/mPGES-1) was compromised in IRE1a-deficient myeloid cells undergoing ER stress or stimulated through pattern recognition receptors. Inducible biosynthesis of prostaglandins, including the pro-algesic mediator prostaglandin E2 (PGE2), was decreased in myeloid cells that lack IRE1a or XBP1 but not other ER stress sensors. Functional XBP1 transactivated the human PTGS2 and PTGES genes to enable optimal PGE2 production. Mice that lack IRE1α–XBP1 in leukocytes, or that were treated with IRE1a inhibitors, demonstrated reduced pain behaviors in PGE2-dependent models of pain. Thus, IRE1a–XBP1 is a mediator of prostaglandin biosynthesis and a potential target to control pain.

Some types of cancer are commonly associated with intense pain even at the early stages of the disease. The mandible is particularly vulnerable to metastasis from breast cancer, and this process has been studied using a bioluminescent human breast cancer cell line (MDA-MB-231LUC+). Using this cell line and anatomic and neurophysiologic methods in the trigeminal ganglion (TG), we examined the impact of cancer seeding in the mandible on behavioral evidence of hypersensitivity and on trigeminal sensory neurons. Growth of cancer cells seeded to the mandible after arterial injection of the breast cancer cell line in Foxn1 animals (allogeneic model) induced behavioral hypersensitivity to mechanical stimulation of the whisker pad and desensitization of tactile and sensitization of nociceptive mechanically sensitive afferents. These changes were not restricted to the site of metastasis but extended to sensory afferents in all three divisions of the TG, accompanied by widespread overexpression of substance P and CGRP in neurons through the ganglion. Subcutaneous injection of supernatant from the MDA-MB-231LUC+ cell culture in normal animals mimicked some of the changes in mechanically responsive afferents observed with mandibular metastasis. We conclude that released products from these cancer cells in the mandible are critical for the development of cancer-induced pain and that the overall response of the system greatly surpasses these local effects, consistent with the widespread distribution of pain in patients. The mechanisms of neuronal plasticity likely occur in the TG itself and are not restricted to afferents exposed to the metastatic cancer microenvironment.

Background Metastatic cancer to bone is well-known to produce extreme pain. It has been suggested that the magnitude of this perceived pain is associated with disease progression and poor prognosis. These data suggest a potential cross-talk between cancer cells and nociceptors that contribute not only to pain, but also to cancer aggressiveness although the underlying mechanisms are yet to be stablished. Methods The in vitro dose dependent effect of neuropeptides (NPs) (substance P [SP], calcitonin gene-related peptide and neurokinin A [NKA]) and/or its combination, on the migration and invasion of MDA-MB-231LUC+ were assessed by wound healing and collagen-based cell invasion assays, respectively. The effect of NPs on the expression of its receptors (SP [NK1] and neurokinin A receptors [NK2], CALCRL and RAMP1) and kininogen (high-molecular-weight kininogen) release to the cell culture supernatant of MDA-MB-231LUC+, were measured using western-blot analysis and an ELISA assay, respectively. Statistical significance was tested using one-way ANOVA, repeated measures ANOVA, or the paired t-test. Post-hoc testing was performed with correction for multiple comparisons as appropriate. Results Our data show that NPs strongly modify the chemokinetic capabilities of a cellular line commonly used as a model of metastatic cancer to bone (MDA-MB-231LUC+) and increased the expression of their receptors (NK1R, NK2R, RAMP1, and CALCRL) on these cells. Finally, we demonstrate that NPs also trigger the acute release of HMWK (Bradykinin precursor) by MDA-MB-231LUC+, a molecule with both tumorigenic and pro-nociceptive activity. Conclusions Based on these observations we conclude that NPs exposure modulates this breast cancer cellular line aggressiveness by increasing its ability to migrate and invade new tissues. Furthermore, these results also support the pro nociceptive and cancer promoter role of the peripheral nervous system, during the initial stages of the disease.

What We Already Know about This Topic What This Article Tells Us That Is New Background Recovery from pain after surgery is faster after cesarean delivery than after other abdominal procedures. The authors hypothesized that recovery in rats after surgery could be reversed by antagonism of spinal oxytocin or vasopressin receptors, that there may be a sex difference, and that spinal oxytocin innervation could change after surgery. Methods Male and female rats underwent partial spinal nerve ligation surgery. Effects of nonselective and selective oxytocin and vasopressin 1A receptor antagonists on mechanical hypersensitivity during partial recovery were assessed (n = 8 to 14/group). Oxytocin immunoreactivity in the dorsal horn of the spinal cord (n = 7 to 8/group) and messenger RNA (mRNA) expression for oxytocin-binding receptors in dorsal root ganglia and spinal cord (n = 8/group) were measured. Results Intrathecal injection of oxytocin and vasopressin receptor antagonists were similarly effective at reducing withdrawal threshold (in all experiments from 22 [19, 26] median [first quartile, third quartile]) g to 8.3 [6.4, 12] g after injection) in both sexes, while having no or minimal effects in animals without surgery. Oxytocin fiber immunoreactivity was 3- to 5-fold greater in lumbar than other regions of the spinal cord and was increased more than 2-fold in lumbar cord ipsilateral to surgery. Injury was also associated with a 6.5-fold increase in oxytocin receptor and a 2-fold increase in vasopressin 1A receptor messenger RNA expression in the L4 dorsal root ganglion ipsilateral to surgery. Conclusions : These findings suggest that the capacity for oxytocin signaling in the spinal cord increases after surgery and that spinal oxytocin signaling plays ongoing roles in both sexes in recovery from mechanical hypersensitivity after surgery with known nerve injury.

Background and objective Unlike migraine and migraine with aura, little information exists regarding chronic migraine (CM) as a risk factor for cardiovascular disease. In this study we aim to determine whether an association between CM and endothelial dysfunction exists. Methods Individuals 18 years and older diagnosed with episodic migraine (EM) and CM according to ICHD criteria were studied. After an overnight fast and abstinence from vasoactive drugs, ultrasound studies were performed and blood samples taken from patients and matched controls according to internationally agreed on protocols. Results A total of 113 individuals were enrolled (35 CM, 37 EM, 41 controls). CM patients had a lower percentage of flow-mediated vasodilation (FMD; difference of means = 5.03%; p = 1.0E-6) and breath-holding index (BHI; difference of means 0.754; p = 2.0E-6), as well as increased carotid intima media thickness (cIMT; difference of means = 0.128 mm; p = 7.0E-5) than controls. The EM patients and controls comparison found similar, but less pronounced, differences: decreased BHI ( p = 0.031), and increased cIMT ( p = 0.028). Fibrinogen ( r = 0.277; p = 0.006), C-reactive protein ( r = 0.288; p = 0.003), and erythrocyte rate sedimentation ( r = 0.298; p = 0.002) also correlated with cIMT, and inversely with BHImV and FMD. Conclusions Migraine is associated with systemic and cerebral endothelial dysfunction demonstrated by ultrasound studies and biological markers. The degree of these changes was strongly associated with the severity of migraine. Our data indicate that migraine may be a cerebral disorder with systemic endothelial damage.

Los medios masivos de comunicación desempeñan un papel central en la configuración de la cultura moderna, ya que son los mediadores necesarios y omnipresentes entre el acontecer social y los individuos. Dada la importancia del discurso informativo como vehículo para transmitir información y opiniones el propósito de este artículo es exponer e ilustrar un esquema metodológico que puede ser útil para el análisis de textos periodísticos. La especificidad de esta propuesta es que en ella se agrupan en un sólo esquema los diferentes niveles de análisis que serían necesarios contemplar en el caso del género periodístico.

Chronic pain after nerve injury is often accompanied by hypersensitivity to mechanical stimuli, yet whether this reflects altered input, altered processing, or both remains unclear. Spinal nerve ligation or transection results in hypersensitivity to mechanical stimuli in skin innervated by adjacent dorsal root ganglia, but no previous study has quantified the changes in receptive field properties of these neurons in vivo. To address this, we recorded intracellularly from L4dorsal root ganglion neurons of anesthetized young adult rats, 1 wk after L5partial spinal nerve ligation (pSNL) or sham surgery. One week after pSNL, hindpaw mechanical withdrawal threshold in awake, freely behaving animals was decreased in the L4distribution on the nerve-injured side compared with sham controls. Electrophysiology revealed that high-threshold mechanoreceptive cells of A-fiber conduction velocity in L4were sensitized, with a seven-fold reduction in mechanical threshold, a seven-fold increase in receptive field area, and doubling of maximum instantaneous frequency in response to peripheral stimuli, accompanied by reductions in after-hyperpolarization amplitude and duration. Only a reduction in mechanical threshold (minimum von Frey hair producing neuronal activity) was observed in C-fiber conduction velocity high-threshold mechanoreceptive cells. In contrast, low-threshold mechanoreceptive cells were desensitized, with a 13-fold increase in mechanical threshold, a 60% reduction in receptive field area, and a 40% reduction in instantaneous frequency to stimulation. No spontaneous activity was observed in L4ganglia, and the likelihood of recording from neurons without a mechanical receptive field was increased after pSNL. These data suggest massively altered input from undamaged sensory afferents innervating areas of hypersensitivity after nerve injury, with reduced tactile and increased nociceptive afferent response. These findings differ importantly from previous preclinical studies, but are consistent with clinical findings in most patients with chronic neuropathic pain.

The use of soluble and highly oxidizing Ag(III) in the form of the tetrahydroxoargentate ion Ag(OH)

Background The pathogenesis of Eating Disorders is still unknown. However, a growing body of evidence shows that there are changes in cytokine levels and an alteration in the stress response in patients with anorexia nervosa (AN). For this reason, we decided to test whether there are differences in immune parameters involved in the regulation of the inflammatory response between female adolescents with AN and healthy adolescents. Methods The sample 27 drug-naive AN patients the study sample included 27 AN patients at a very early stage of the disease and 23 healthy controls. Plasma and peripheral blood mononuclear cells (PBMCs) were obtained for biochemical study. Results Plasma levels of the pro-inflammatory cytokines TNF-α and IL-1β were significantly increased in patients with AN, while the levels of prostaglandins PGE2 (proinflammatory) and 15d-PGJ2, (anti-inflammatory) were lower compared with controls. Protein expression in PBMCs of cyclooxygenase-2 (COX-2) and the activated forms of the mitogen-activated protein kinases p38 and ERK were also increased in the AN group. Expression levels of the anti-inflammatory factor peroxisome proliferator-activated receptor gamma (PPARγ) were significantly decreased in patients. Plasma levels of lipid peroxidation markers –TBARS- were not increased in patients with AN. Components of the biochemical inflammatory response (COX-2, PGE2, TBARS, 15d-PGJ2, ERK, p65 NFκB) and glucocorticoid receptor –GR- expression and the scores on the impulsivity measures in the BARRATT, EDI and BITE questionnaires showed a significant correlation within the AN patients group. Conclusions The results for female adolescent patients with AN indicate that there is a dysfunction of intra- and intercellular inflammatory pathways characterized by higher levels of pro-inflammatory parameters in plasma and a decrease in one of the controlling cytoplasmic-nuclear pathways implicated in their modulation (i.e. PPARγ) with, at this very early stage of the disease, no effect on oxidative stress markers plasma levels. Most notably, higher severity of illness (restrictive and purging behaviour) correlated with higher levels of inflammatory markers.

Background: Recovery from pain after surgery exhibits large interindividual variability, with very slow recovery equated to chronic pain. Surgical injury in the postpartum period modestly increases initial recovery after major nerve injury. In this study, the authors use a nerve injury that recovers over 2 to 3 months and apply growth curve modeling to further understand the effect of the postpartum period on speed of recovery. Methods: Withdrawal threshold to mechanical stimulus on the hind paw was determined in 41 Sprague–Dawley rats before and for 10 weeks after partial spinal nerve ligation. Age-matched male and female rats and postpartum females with pups or those separated from pups at delivery were studied. Growth curve analyses were applied to model recovery after surgery despite varying timing of measurements across groups and missing data, and these results were compared with those of two-way repeated-measures ANOVA. Results: The recovery time course was similar between males and females. In contrast, recovery was hastened in the postpartum groups, with nonoverlapping 95% CIs of modeled trajectories between days 6 and 66 after surgery. CIs were more precise at most time periods with growth curve analysis compared with ANOVA. Conclusions: The authors describe a method of analysis to quantify recovery from hypersensitivity after surgery in rats with several distinct advantages over traditionally used methods. Study results do not support a sex difference in trajectory of recovery but confirm and extend previous observations that injury at the time of obstetric delivery is associated with an abnormally rapid recovery.

Se prepararon membranas de Nafion® dopadas con TiO2 en fase anatasa por medio del método recast, con diferentes porcentajes de óxido, 5%, 10%, 15%, y una membrana de referencia. Con la finalidad de evaluar los efectos y las mejorías que presenta este composito en la estabilidad estructural y en el rendimiento electroquímico de la celda de combustible. Las membranas preparadas fueron caracterizadas mediante DRX, microscopía SEM, capacidad de intercambio iónico, análisis mecánico dinámico, y probadas en una celda de combustible en diferentes condiciones de temperatura.

BACKGROUND Physical injury, including surgery, can result in chronic pain; yet chronic pain following childbirth, including cesarean delivery in women, is rare. The mechanisms involved in this protection by pregnancy or delivery have not been explored. METHODS We examined the effect of pregnancy and delivery on hypersensitivity to mechanical stimuli of the rat hindpaw induced by peripheral nerve injury (spinal nerve ligation) and after intrathecal oxytocin, atosiban, and naloxone. Additionally, oxytocin concentration in lumbar spinal cerebrospinal fluid was determined. RESULTS Spinal nerve ligation performed at mid-pregnancy resulted in similar hypersensitivity to nonpregnant controls, but hypersensitivity partially resolved beginning after delivery. Removal of pups after delivery prevented this partial resolution. Cerebrospinal fluid concentrations of oxytocin were greater in normal postpartum rats prior to weaning. To examine the effect of injury at the time of delivery rather than during pregnancy, spinal nerve ligation was performed within 24 h of delivery. This resulted in acute hypersensitivity that partially resolved over the next 2-3 weeks. Weaning of pups resulted only in a temporary return of hypersensitivity. Intrathecal oxytocin effectively reversed the hypersensitivity following separation of the pups. Postpartum resolution of hypersensitivity was transiently abolished by intrathecal injection of the oxytocin receptor antagonist, atosiban. CONCLUSIONS These results suggest that the postpartum period rather than pregnancy protects against chronic hypersensitivity from peripheral nerve injury and that this protection may reflect sustained oxytocin signaling in the central nervous system during this period.

PRAME is a tumor associated antigen (TAA) of particular interest since it is widely expressed by lymphoid and myeloid malignancies. Several studies have associated high PRAME RNA levels with good prognosis in acute myeloid leukemia (AML). PRAME expression is regulated at the epigenetic level. For this reason inhibitors of DNA methylation, such as 5-azacytidine, can modulate the expression of this TAAs. In the current study we analyzed the effect of 5-azaC on the expression of PRAME in blasts versus CD34+ cells from healthy donors in an attempt to increase its expression, thus inducing a potential target for therapeutic strategies.

The present study examined the role of endogenous noradrenaline on glial and neuronal plasticity in the spinal cord in rats after peripheral nerve injury. An intrathecal injection of dopamine-β-hydroxylase antibody conjugated to saporin (DβH-saporin) completely depleted noradrenergic axons in the spinal cord and also reduced noradrenergic neurons in the locus coeruleus (A6) and A5 noradrenergic nucleus in the brainstem and noradrenergic axons in the paraventricular nucleus of the hypothalamus. DβH-saporin treatment itself did not alter mechanical withdrawal threshold, but enhanced mechanical hypersensitivity and intrathecal clonidine analgesia after L5-L6 spinal nerve ligation. In the spinal dorsal horn of spinal nerve ligation rats, DβH-saporin treatment increased choline acetyltransferase immunoreactivity as well as immunoreactivity in microglia of ionized calcium binding adaptor molecule 1[IBA1] and in astrocytes of glial fibrillary acidic protein, and brain-derived nerve growth factor content. DβH-saporin treatment did not, however, alter the fractional release of acetylcholine from terminals by dexmedetomidine after nerve injury. These results suggest that endogenous tone of noradrenergic fibers is not necessary for the plasticity of α2-adrenoceptor analgesia and glial activation after nerve injury, but might play an inhibitory role on glial activation. Perspective This study demonstrates that endogenous noradrenaline modulates plasticity of glia and cholinergic neurons in the spinal cord after peripheral nerve injury and hence influences the pathophysiology of spinal cord changes associated with neuropathic pain.

The influenza virus establishes close functional and structural connections with the nucleus of the infected cell. Thus, viral ribonucleoproteins (RNPs) are closely bound to chromatin components and the main constituent of viral RNPs, the nucleoprotein (NP) protein, interacts with histone tails. Using a yeast two-hybrid screening, we previously found that the PA influenza virus polymerase subunit interacts with the CHD6 protein, a member of the CHD family of chromatin remodelers. Here we show that CHD6 also interacts with the viral polymerase complex and colocalizes with viral RNPs in the infected cells. To study the relationships between RNPs, chromatin and CHD6, we have analysed whether NP and CHD6 binds to peptides representing trimethylated lysines of histone 3 tails that mark transcriptionally active or inactive chromatin. Upon infection, NP binds to marks of repressed chromatin and, interestingly an important recruitment of CHD6 to these heterochromatin marks occurs in this situation. Silencing experiments indicate that CHD6 acts as a negative modulator of influenza virus replication. Hence, the CHD6 association with inactive chromatin could be part of a process where the influenza virus triggers modifications of chromatin-associated proteins that could contribute to the pathogenic events used by the virus to induce host cell shut-off.

Developmental differences in peripheral neuron characteristics and functionality exist. Direct measurement of active and passive electrophysiologic and receptive field characteristics of single mechanosensitive neurons in glabrous skin was performed and phenotypic characterization of fiber subtypes was applied to analyze developmental differences in peripheral mechanosensitive afferents. After Institutional approval, male Sprague-Dawley infant (P7: postnatal day 7) and juvenile (P28) rats were anesthetized and single cell intracellular electrophysiology was performed in the dorsal root ganglion (DRG) soma of mechanosensitive cells with receptive field (RF) in the glabrous skin of the hindpaw. Passive and active electrical properties of the cells and RF size and characteristics determined. Fiber subtype classification was performed and developmental differences in fiber subtype properties analyzed. RF size was smaller at P7 for both low and high threshold mechanoreceptor (LTMR and HTMR) with no differences between A- and C-HTMR (AHTMR and CHTMR). The RF size was also correlated to anatomic location on glabrous skin, toes having smaller RF. Conduction velocity (CV) was adequate at P28 for AHTMR and CHTMR classification, but not at P7. Only width of the action potential at half height (D50) was significantly different between HTMR at P7, while D50, CV and Amplitude of the AP were significant for HTMR at P28. RF size is determined in part by the RF distribution of the peripheral neuron. Developmental differences in RF size occur with larger RF sizes occurring in younger animals. This is consistent with RF size differences determined by measuring RF in the spinal cord, except the peripheral RF is much smaller, more refined, and in some cases pinpoint. Developmental differences make CV alone unreliable for neuron classification. Utilizing integration of all measured parameters allows classification of neurons into subtypes even at the younger ages. This will prove important in understanding changes that occur in the peripheral sensory afferents in the face of ongoing development and injury early in life.

Graft-versus-host disease (GVHD) is the major cause of morbidity and mortality among patients undergoing allogeneic hematopoietic stem cell transplantation. Although animal models have been clearly established for the study of skin, liver, and gut, currently there is no equivalent experiemental model for analyzing ocular involvement, which is rather common, especially among patients diagnosed with chronic GVHD. In the current study we have developed a murine model of ocular GVHD and, for the first time, we describe the histopathologic features involving cornea and limbus, which could play a role in the physiopathology of the disease at the ocular level. Our results represent a major finding that allows us to define a model for evaluating new therapeutic strategies for treating ocular GVHD prior to their use in clinical setting.

Background Prevalence of asthma in developed countries increased between the 1970s and the 1990s. One factor that might contribute to the trends in asthma is the increased use of acetaminophen vs aspirin in children and pregnant women. Objective To examine relationships between in utero exposure to acetaminophen and incidence of respiratory symptoms in the first year of life. Methods A total of 345 women were recruited in the first trimester of pregnancy and followed up with their children through the first year of life. Use of acetaminophen in pregnancy was determined by questionnaire and related to incidence of respiratory symptoms. Results Use of acetaminophen in middle to late but not early pregnancy was significantly related to wheezing (odd ratio, 1.8; 95% confidence interval, 1.1-3.0) and to wheezing that disturbed sleep (odds ratio, 2.1; 95% confidence interval, 1.1-3.8) in the first year of life after control for potential confounders. Conclusion This study suggests that use of acetaminophen in middle to late but not early pregnancy may be related to respiratory symptoms in the first year of life. Additional follow-up will examine relationships of maternal and early childhood use of acetaminophen with incidence of asthma at ages 3 to 5 years, when asthma diagnosis is more firmly established.

Mandates to include women and minority populations in research have heightened the need to identify successful recruitment strategies. This paper describes the recruitment and retention strategies used as part of a randomized controlled trial (RCT) of a physical activity and dietary intervention targeting low-income, predominantly Latino patients in a primary health care clinic. Data on the recruitment and retention rates and the representativeness of participants are presented. Strategies included hiring bilingual staff, translating and culturally adapting intervention materials and soliciting ongoing consultation from patients, clinicians and organizations providing services to the Latino community. The primary recruitment procedure involved letters from physicians followed by phone calls from project staff to patients identified from electronic medical records. Two hundred patients were recruited into the RCT (78% of those reached and eligible), with 69 and 81% reached for the 6-week and 6-month follow-ups, respectively. Women were more likely to both participate and remain in the trial, and there was a trend toward greater recruitment and retention of Spanish speakers. By engaging the community, clinicians and patients, this study was able to successfully recruit and retain a large proportion of this often difficult to reach Latino sub-population of patients with multiple chronic conditions.

In HeLa cells, histamine induces production of inositol 1,4,5-trisphosphate (InsP3) and release of Ca2+ from the endoplasmic reticulum (ER). Ca2+ release is typically biphasic, with a fast and brief initial phase, followed by a much slower and prolonged one. In the presence of inhibitors of protein kinase C (PKC), including staurosporine and the specific inhibitors GF109203X and Ro-31-8220, the fast phase continued until the ER became fully empty. On the contrary, treatment with phorbol 12,13-dibutyrate inhibited Ca2+ release. Staurosporine had no effect on InsP3-induced Ca2+ release in permeabilized cells and did not modify either histamine-induced InsP3 production. These data suggest that histamine induces Ca2+ release and with a short lag activates PKC to down-regulate it. Consistently, Ca2+ oscillations induced by histamine were increased in amplitude and decreased in frequency in the presence of PKC inhibitors. We show also that mitochondrial [Ca2+] was much more sensitive to changes in ER-Ca2+ release induced by PKC modulation than cytosolic [Ca2+]. PKC inhibitors increased the histamine-induced mitochondrial [Ca2+] peak by 4-fold but increased the cytosolic [Ca2+] peak only by 20%. On the contrary, PKC activation inhibited the mitochondrial [Ca2+] peak by 90% and the cytosolic one by only 50%. Similarly, the combination of PKC inhibitors with the mitochondrial Ca2+ uniporter activator SB202190 led to dramatic increases in mitochondrial [Ca2+] peaks, with little effect on cytosolic ones. This suggests that activation of ER-Ca2+ release by PKC inhibitors could be involved in apoptosis induced by staurosporine. In addition, these mechanisms allow flexible and independent regulation of cytosolic and mitochondrial [Ca2+] during cell stimulation.

"Las emociones están presentes prácticamente en todas las actividades que desempeñamos. En el discurso religioso las emociones, afectos y sentimientos actúan como modos de afiliación a una comunidad, son maneras de comunicarse y de permanecer juntos. En este artículo presentamos cómo son movilizadas las emociones en un programa radiofónico de corte religioso con una característica peculiar: se ofrece al público una experiencia emocional a partir de la adquisición de un bien material."

Acute lymphoblastic leukemia is a common malignancy in childhood. Managing adverse events during treatment can result in very complex situations. A previously healthy adolescent diagnosed with T-cell acute lymphoblastic leukemia developed on day +55 of induction chemotherapy hemiparesis, dysesthesia, and facial palsy. Blood tests and brain imaging techniques were unremarkable. The patient was diagnosed with a conversion disorder, which completely resolved. Although rare in clinical practice, children and adolescents with cancer do not always have organic pathology explaining their symptoms. Psychiatric disorders such as those of the somatoform spectrum must be considered, particularly in patients with anxiety or depression.

Introduction Intensity Modulated Radiation Therapy (IMRT) allows creating complex dose distributions. The Monte Carlo (MC) is considered the gold standard method to perform dose calculations. A recent new MC user-friendly interface named PRIMO was developed targeting External Radiotherapy environment. Nevertheless, advanced features such as IMRT are not yet introduced. Purpose To assess the capability of PRIMO to simulate IMRT procedures. Materials and methods Two Radiotherapy units, both using Varian 2300CD LINAC head were simulated. While one uses Millennium120, the other has 120HD as Multi Leaf Collimator (MLC). Static simulations were performed to validate LINAC heads and MLC models. Homemade software was developed to configure PRIMO to reproduce MLC modulation as planned by the Treatment Planning System and create dose distribution images at specific planes from PRIMO output files. For each unit, a dynamic MLC delivery was split into a number of static segments and simulated on solid water phantom. Gafchromic films were used to measure the actual dose and make comparisons with the simulations. Assessments were performed using the 2D Gamma analysis. Results More than 95% of Gamma points Conclusion A workflow was found to drive PRIMO to simulate IMRT procedures. The results of simulations agree with the experimental measurements, indicating PRIMO software as a potential tool for clinical implementation of MC simulations of IMRT technique. Disclosure The author has no relevant financial or nonfinancial relationships to disclose.

Maturation of the nervous system results in changes in both central and peripheral processing. To better understand responses to injury in the young, developmental differences in the acute response to incision were investigated in both tactile and nociceptive myelinated peripheral mechanosensitive afferent neurons in vivo. Neuronal intrasomal recordings were performed in juvenile and infant rats in 34 L5 dorsal root ganglia, and each neuron was phenotypically defined. Neurons had a mechanosensitive receptive field in the glabrous skin on the plantar surface of the hind paw, which was characterized at baseline and for up to 45 min after incision. Fundamental maturational differences in the effect of incision were clear: in high-threshold nociceptive mechanoreceptors, the mechanical threshold decreased immediately and the receptive field size increased rapidly in juvenile rats but not in infant rats. Additionally, a divergence in changes in the instantaneous response frequency of tactile afferents occurred between the two ages. These differences may help explain maturational differences in responses to peripheral injury and suggest that differences in central nervous system responses may be partially mitigated by spatially confined and frequency-dependent differences resulting from tactile and nociceptive mechanosensitive input.

Studies using animal models have shown that general anesthetics such as ketamine trigger widespread and robust apoptosis in the infant rodent brain. Recent clinical evidence suggests that the use of general anesthetics on young children (at ages equivalent to those used in rodent studies) can promote learning deficits as they mature. Thus, there is a growing need to develop strategies to prevent this injury. In this study, we describe a number of independent approaches to address therapeutic intervention. Postnatal day 7 (P7) rats were injected with vehicle (sterile PBS) or the NMDAR antagonist ketamine (20 mg/kg). After 8 h, we prepared brains for immunohistochemical detection of the pro-apoptotic enzyme activated caspase-3 (AC3). Focusing on the somatosensory cortex, AC3-positive cells were then counted in a non-biased stereological manner. We found AC3 levels were markedly increased in ketamine-treated animals. In one study, microarray analysis of the somatosensory cortex from ketamine-treated P7 pups revealed that expression of activity dependent neuroprotective protein (ADNP) was enhanced. Thus, we injected P7 animals with the ADNP peptide fragment NAPVSIPQ (NAP) 15 min before ketamine administration and found we could dose-dependently reverse the injury. In separate studies, pretreatment of P6 animals with 20 mg/kg vitamin D3 or a nontoxic dose of ketamine (5 mg/kg) also prevented ketamine-induced apoptosis at P7. In contrast, pretreatment of P7 animals with aspirin (30 mg/kg) 15 min before ketamine administration actually increased AC3 counts in some regions. These data show that a number of unique approaches can be taken to address anesthesia-induced neurotoxicity in the infant brain, thus providing MDs with a variety of alternative strategies that enhance therapeutic flexibility.