Efectos del entrenamiento en marcos relacionales de condicionalidad sobre el responder relacional deíctico / Effects of Training in Conditional Relational Framing on the Deictic Relational Responding

Resumen Desde la Teoría de los Marcos Relacionales, la toma de perspectiva se concibe como un patrón de responder relacional arbitrariamente aplicable bajo control de claves contextuales deícticas personales, espaciales y temporales. Además, se asume necesaria la capacidad para responder relacionalmente bajo el control de claves contextuales condicionales. Sin embargo, no se ha reportado evidencia empírica que permita identificar la relación existente entre los marcos de condicionalidad y la precisión en el responder relacional deíctico. El objetivo del estudio fue analizar si el entrenamiento en marco de condicionalidad podría facilitar el desempeño sobre el responder deíctico. Participaron cuatro niños con desarrollo normalizado que fueron divididos en dos condiciones experimentales (C1 y C2). Los participantes de ambas condiciones se expusieron a un protocolo de evaluación y entrenamiento en marcos deícticos. A su vez, solo los participantes de la C2 se expusieron a una fase de evaluación y entrenamiento en marcos de condicionalidad previo al entrenamiento en marcos deícticos. Los resultados mostraron que todos los participantes exhibieron mejoras en sus ejecuciones post-test en las relaciones deícticas y que los participantes de C2 obtuvieron mejores resultados con respecto a su pre-test en los niveles de mayor complejidad deíctica tras el entrenamiento en marcos condicionales. Se discute la necesidad de protocolos de toma de perspectiva más naturalistas que posibiliten indagar en cómo se desarrollan los términos relacionales y se abstrae la función de las claves contextuales que permiten interpretar, atribuir y predecir el comportamiento de otro.

Abstract According to Relational Frame Theory, perspective taking is conceived as an arbitrarily applicable relational pattern of relational responding under the control of personal, spatial, and temporal deictic contextual cues. Furthermore, the ability to respond relationally under the control of conditional contextual cues is assumed to be necessary. However, no empirical evidence has been reported to identify the relationship between conditionality frames and accuracy in deictic relational responding. The study aimed to analyze whether training in conditionality frames could facilitate performance on deictic responding. Four children with normalized development participated and were divided into two experimental conditions (C1 and C2). Participants in both conditions were exposed to an evaluation protocol and training on deictic frames. In turn, only C2 participants were exposed to an evaluation and training phase in conditionality frames before the training in deictic frames. Results showed that all the participants exhibited improvements in their post-test performances on deictic relations and that the C2 participants performed better with respect to their pre-test on the levels of greater deictic complexity after training in conditional frames. We discuss the need for more naturalistic perspective-taking protocols that allow us to investigate how relational terms are developed and abstract the role of contextual cues that allow us to interpret, attribute, and predict another's behavior.

Hepatocyte Ploidy Is a Diversity Factor for Liver Homeostasis.

Polyploidy, the existence of cells containing more than one pair of chromosomes, is a well-known feature of mammalian hepatocytes. Polyploid hepatocytes are found either as cells with a single polyploid nucleus or as multinucleated cells with diploid or even polyploid nuclei. In this study, we evaluate the degree of polyploidy in the murine liver by accounting both DNA content and number of nuclei per cell. We demonstrate that mouse hepatocytes with diploid nuclei have distinct metabolic characteristics compared to cells with polyploid nuclei. In addition to strong differential gene expression, comprising metabolic as well as signaling compounds, we found a strongly decreased insulin binding of nuclear polyploid cells. Our observations were associated with nuclear ploidy but not with total ploidy within a cell. We therefore suggest ploidy of the nuclei as an new diversity factor of hepatocytes and hypothesize that hepatocytes with polyploid nuclei may have distinct biological functions than mono-nuclear ones. This diversity is independent from the well-known heterogeneity related to the cells' position along the porto-central liver-axis.

Imaging Markers of Post-Stroke Depression and Apathy: a Systematic Review and Meta-Analysis.

Several brain imaging markers have been studied in the development of post-stroke depression (PSD) and post-stroke apathy (PSA), but inconsistent associations have been reported. This systematic review and meta-analysis aims to provide a comprehensive and up-to-date evaluation of imaging markers associated with PSD and PSA. Databases (Medline, Embase, PsycINFO, CINAHL, and Cochrane Database of Systematic Reviews) were searched from inception to July 21, 2016. Observational studies describing imaging markers of PSD and PSA were included. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated to examine the association between PSD or PSA and stroke lesion laterality, type, and location, also stratified by study phase (acute, post-acute, chronic). Other imaging markers were reviewed qualitatively. The search retrieved 4502 studies, of which 149 studies were included in the review and 86 studies in the meta-analyses. PSD in the post-acute stroke phase was significantly associated with frontal (OR 1.72, 95% CI 1.34-2.19) and basal ganglia lesions (OR 2.25, 95% CI 1.33-3.84). Hemorrhagic stroke related to higher odds for PSA in the acute phase (OR 2.58, 95% CI 1.18-5.65), whereas ischemic stroke related to higher odds for PSA in the post-acute phase (OR 0.20, 95% CI 0.06-0.69). Frequency of PSD and PSA is modestly associated with stroke type and location and is dependent on stroke phase. These findings have to be taken into consideration for stroke rehabilitation programs, as this could prevent stroke patients from developing PSD and PSA, resulting in better clinical outcome.

Cytotoxic and genotoxic potential of food-borne nitriles in a liver in vitro model.

Isothiocyanates are the most intensively studied breakdown products of glucosinolates from Brassica plants and well recognized for their pleiotropic effects against cancer but also for their genotoxic potential. However, knowledge about the bioactivity of glucosinolate-borne nitriles in foods is very poor. As determined by GC-MS, broccoli glucosinolates mainly degrade to nitriles as breakdown products. The cytotoxicity of nitriles in human HepG2 cells and primary murine hepatocytes was marginal as compared to isothiocyanates. Toxicity of nitriles was not enhanced in CYP2E1-overexpressing HepG2 cells. In contrast, the genotoxic potential of nitriles was found to be comparable to isothiocyanates. DNA damage was persistent over a certain time period and CYP2E1-overexpression further increased the genotoxic potential of the nitriles. Based on actual in vitro data, no indications are given that food-borne nitriles could be relevant for cancer prevention, but could pose a certain genotoxic risk under conditions relevant for food consumption.

Longitudinal patterns of urine biomarkers in infants across gestational ages.

BACKGROUND: Urinary biomarkers may be indicators of acute kidney injury (AKI), although little is known of their developmental characteristics in healthy neonates across a full range of gestational age (GA). The purpose of this study was to examine patterns of urinary biomarkers across GA groups from birth to 3 months of age. METHODS: Fifty-two infants ranging from 24 to 41 weeks' GA had urine assayed from birth through 3 months of age for 7 biomarkers including albumin (ALB), beta-2-microglobulin (B2M), cystatin-C (CysC), epidermal growth factor (EGF), neutrophil-gelatinase-associated lipocalin (NGAL), osteopontin (OPN), and uromodulin (UMOD). RESULTS: Of the seven urinary biomarkers, EGF and UMOD increased while others decreased with advancing GA. By 3 months of age, EGF and UMOD had increased in preterm infants to levels similar to those of term infants. UMOD/ml and EGF/ml appeared to be predominantly developmental biomarkers distinguishing estimated glomerular filtration rate (GFR) <30 ml/min/1.73 m(2) with receiver operator characteristic area under the curve (ROC-AUC) of 0.82; p = 0.002. When factored by urine creatinine CysC/cr + ALB/cr were the most significant functional markers with AUC = 0.79; p = 0.004; sensitivity 96 %; specificity 58 %. CONCLUSIONS: Among healthy neonates, urinary biomarkers vary with GA. These data support the use of urinary biomarkers in the assessment of normal kidney development in the absence of injury.

The Brassica epithionitrile 1-cyano-2,3-epithiopropane triggers cell death in human liver cancer cells in vitro.

SCOPE: Glucosinolates are secondary metabolites present in Brassica vegetables. Alkenyl glucosinolates are enzymatically degraded forming nitriles or isothiocyanates, but in the presence of epithiospecifier protein, epithionitriles are released. However, studies on the occurrence of epithionitriles in Brassica food and knowledge about their biological effects are scarce. METHODS AND RESULTS: Epithionitrile formation from glucosinolates of seven Brassica vegetables was analyzed using GC-MS and HPLC-DAD. Bioactivity of synthetic and plant-derived 1-cyano-2,3-epithiopropane (CETP) - the predominant epithionitrile in Brassica vegetables - in three human hepatocellular carcinoma (HCC) cell lines and primary murine hepatocytes was also evaluated. The majority of the Brassica vegetables were producers of nitriles or epithionitriles as hydrolysis products and not of isothiocyanates. For example, Brussels sprouts and savoy cabbage contained up to 0.8 µmol CETP/g vegetable. Using formazan dye assays, concentrations of 380-1500 nM CETP were observed to inhibit the mitochondrial dehydrogenase activity of human HCC cells without impairment of cell growth. At 100-fold higher CETP concentrations, cell death was observed. Presence of plant matrix increased CETP-based toxicity. CONCLUSION: These in vitro data provide no indication that epithionitriles will severely affect human health by Brassica consumption. In contrast to isothiocyanates, no evidence of selective toxicity against HCC cells was found.

Renal medullary carcinoma and sickle cell trait: A systematic review.

Sickle cell trait (SCT) carries a small risk of renal medullary carcinoma (RMC). We conducted a systematic literature review and reported new four RMC cases (total N = 217). Eighty eight percent had SCT and 8% had sickle cell disease; 50% were children. Males had 2.4× risk than females. Isolated hematuria or in combination with abdominal or flank pain was the presenting sign in 66% cases. Tumor-related mortality was 95%. Four non-metastatic patients were long-term disease-free survivors. Although risk appears to be very low, individuals with SCT should be informed about the low risk of RMC with the hope of early diagnosis. Hematuria should prompt immediate investigation.

Heterotopic gastric mucosa mimicking a Meckel's diverticulum in a young girl.

Heterotopic gastric mucosa (HGM) is a rare, but acknowledged source of gastrointestinal pathology in pediatric patients. Sometimes clinically confused with a Meckel's diverticulum, HGM diagnosis is often made postoperatively by pathology. We present a case of jejunal HGM with a positive technetium pertechnetate scan in the right lower quadrant that resembled a Meckel's diverticulum.

Congenital Anomalies of the Kidney and the Urinary Tract (CAKUT).

This article reviews the majority of Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) with emphasis in Pediatric Pathology describing and illustrating lesions as varied as ureteral duplications, ureteropelvic junction obstruction, horseshoe kidney, posterior urethral valve and prune belly syndrome, obstructive renal dysplasia, nonmotile ciliopathies and several syndromes associated with renal malformations (Meckel-Joubert, short rib, Bardet-Biedl, asplenia/polysplenia, hereditary renal adysplasia, Zellweger, trisomies, VACTER-L, Potter, caudal dysplasia, and sirenomelia), as well as ADPK, and ARPK. The purpose of this review is not only to describe the congenital renal anomalies, but also to analyze the more recent therapeutic interventions that may modify the natural history of some of these severe conditions.

Myosin 5b loss of function leads to defects in polarized signaling: implication for microvillus inclusion disease pathogenesis and treatment.

Microvillus inclusion disease (MVID) is an autosomal recessive condition resulting in intractable secretory diarrhea in newborns due to loss-of-function mutations in myosin Vb (Myo5b). Previous work suggested that the apical recycling endosomal (ARE) compartment is the primary location for phosphoinositide-dependent protein kinase 1 (PDK1) signaling. Because the ARE is disrupted in MVID, we tested the hypothesis that polarized signaling is affected by Myo5b dysfunction. Subcellular distribution of PDK1 was analyzed in human enterocytes from MVID/control patients by immunocytochemistry. Using Myo5b knockdown (kd) in Caco-2BBe cells, we studied phosphorylated kinases downstream of PDK1, electrophysiological parameters, and net water flux. PDK1 was aberrantly localized in human MVID enterocytes and Myo5b-deficient Caco-2BBe cells. Two PDK1 target kinases were differentially affected: phosphorylated atypical protein kinase C (aPKC) increased fivefold and phosohoprotein kinase B slightly decreased compared with control. PDK1 redistributed to a soluble (cytosolic) fraction and copurified with basolateral endosomes in Myo5b kd. Myo5b kd cells showed a decrease in net water absorption that could be reverted with PDK1 inhibitors. We conclude that, in addition to altered apical expression of ion transporters, depolarization of PDK1 in MVID enterocytes may lead to aberrant activation of downstream kinases such as aPKC. The findings in this work suggest that PDK1-dependent signaling may provide a therapeutic target for treating MVID.

Twin infant with lymphatic dysplasia diagnosed with Noonan syndrome by molecular genetic testing.

Noonan Syndrome is an autosomal dominant disorder characterized by short stature, congenital heart defects, developmental delay, dysmorphic facial features and occasional lymphatic dysplasias. The features of Noonan Syndrome change with age and have variable expression. The diagnosis has historically been based on clinical grounds. We describe a child that was born with congenital refractory chylothorax and subcutaneous edema suspected to be secondary to pulmonary lymphangiectasis. The infant died of respiratory failure and anasarca at 80 days. The autopsy confirmed lymphatic dysplasia in lungs and mesentery. The baby had no dysmorphic facial features and was diagnosed postmortem with Noonan syndrome by genomic DNA sequence analysis as he had a heterozygous mutation for G503R in the PTPN11 gene.

A unique presentation and rare pathological finding for urachal sinus.

We report an otherwise well developing 2-year-old girl who presented with a urachal sinus with its opening located at the midline between umbilicus and the pubic symphysis. Diagnosis was made by ultrasound preoperatively, and confirmed during surgery. Additionally, columnar epithelium was found in the portion of sinus tract traversing the abdominal wall. Metaplasia of the sinus tract is worrisome, as urachal carcinomas have been traditionally characterized to result from this process.

Disseminated nontuberculous mycobacterial infection in two children with different immune responses.

A diffuse, infiltrating abdominal mass accompanied with fever and anemia in a child raises the possibility of a benign or malignant tumor, pseudotumor, or infection. Herein, we describe a 9-year-old girl and a 14-year-old boy with multiple large abdominal masses, fever, weight loss, and anemia. During the evaluation of the children, the girl was found to be immunocompetent, while the boy was found to be immunocompromised. Computerized tomography of the abdomen in both cases demonstrated multiple large intra-abdominal masses. Tumors in the girl were composed of wide-spread necrotizing granulomas and necrosis with dystrophic calcifications. In the boy, non-necrotic, homogenous histiocytic infiltrates with rare multinucleated giant cells and lymphocytes were observed histologically. Review of histologic sections identified gram-positive, nonbranching acid-fast bacillary organisms in both cases. Diagnoses of Mycobacterium fortuitum (MF) and Mycobacterium avium-intracellulare complex (MAC) were confirmed by tissue microbiologic cultures in the girl and boy, respectively. The girl with MF infection was appropriately treated and is currently doing well. The boy with MAC was found to have human immunodeficiency virus infection/acquired immune deficiency syndrome (AIDS) and is currently undergoing AIDS treatment. These cases highlight the striking contrast between responses to nontuberculous mycobacteria infection based on immune status.

Gender differences in pain severity, disability, depression, and widespread pressure pain sensitivity in patients with fibromyalgia syndrome without comorbid conditions.

OBJECTIVES: To determine the differences in pain, disability, depression, and pressure sensitivity between men and women with fibromyalgia syndrome (FMS), and to analyze the relationship between pain and pressure sensitivity in FMS. DESIGN: A cross-sectional study. SETTING: Gender differences in pain sensitivity in individuals with FMS have not been yet clarified. PATIENTS: Twenty-four men (age: 52 ± 6 years) and 24 age-matched women (age: 52 ± 5 years) with FMS diagnosed according to 1990 American College of Rheumatology criteria participated. OUTCOME MEASURES: Pressure pain thresholds (PPTs) over the 18 tender points and over the second metacarpal and tibialis anterior muscle were assessed. The intensity and duration of pain, tender point count, the Fibromyalgia Impact Questionnaire, and depression (Beck Depression Inventory-II) were calculated. RESULTS: Women reported higher intensity of pain, tender point count, and depression than men (P < 0.01). Men reported a longer history of pain and disability than women (P = 0.005). Women showed bilateral lower PPT over suboccipital, cervical spine, second rib, supraspinatus, lateral epicondyle, gluteal region, and second metacarpal than men (P < 0.05). Negative associations between tender point count and PPT were found in men and women. In men, negative correlations between the intensity of ongoing pain and PPT over the cervical spine were found. No significant association between PPT and other clinical outcome was seen. CONCLUSIONS: Women with FMS showed higher pain severity and lower PPT than men, whereas men exhibited longer duration of symptoms and disability. In men with FMS, the intensity of ongoing pain was positively correlated to pressure hyperalgesia over the neck. This study suggests that FMS could show a different phenotype in women and men and confirm that women exhibit lower PPT than men.

Segmental absence of intestinal musculature: an increasingly reported pathology.

BACKGROUND: Segmental absence of the intestinal musculature (SAIM) is a known but clinically rare entity involving partial or complete absence of the intestinal muscularis propria. Clinical presentation is consistent with peritonitis, and treatment involves an emergent laparotomy, bowel resection, and reanastamosis or possible ostomy creation. Diagnosis results from histopathologic evaluation of the resected intestinal specimen. Most of the publications are case reports. METHODS: We retrospectively reviewed all surgical pathology files at a tertiary pediatric hospital from 2003 to 2010, identifying children who were noted to have absence of intestinal musculature on pathology. Patients meeting criteria were reviewed in detail, and data regarding clinical presentation, diagnostic testing, radiologic findings, treatment, and outcome were recorded. RESULTS: Five patients were identified between 2003 and 2010 who received the diagnosis of SAIM. Patient age ranged from 1 to 99 days of life. All children were born preterm by cesarean section, had a mean birth weight of 828 ± 338 g, and were intubated after birth. CONCLUSIONS: The 5 patients presented are reviewed and contrasted with previous cases presented in the literature. Theories of pathogenesis and classification are discussed, and the cases are labeled as primary versus secondary SAIM.

Connective tissue growth factor antibody therapy attenuates hyperoxia-induced lung injury in neonatal rats.

Despite recent advances in neonatal intensive care and surfactant therapy, bronchopulmonary dysplasia (BPD) continues to be one of the most common long-term pulmonary complications associated with preterm birth. Clinical efforts to prevent and treat BPD have been largely unsuccessful due to its multifactorial nature and poorly understood disease process. Connective tissue growth factor (CTGF) is a matricellular protein that plays an important role in tissue development and remodeling. Previous studies have demonstrated that hyperoxia exposure up-regulates CTGF expression in neonatal rat lungs. Whether CTGF overexpression plays a role in the pathogenesis of BPD, and whether CTGF antagonism has a therapeutic potential for BPD, are unknown. In the present study, we examined CTGF expression in lung autopsy specimens from patients with BPD and control subjects with no BPD. We assessed the effect of a CTGF-neutralizing monoclonal antibody (CTGF Ab) on preventing hyperoxia-induced lung injury in neonatal rats. Our study demonstrates that CTGF expression is increased in BPD lungs. In newborn rats, exposure to 90% oxygen for 14 days resulted in activation of ß-catenin signaling, decreased alveolarization and vascular development, and physiological and histological evidence of pulmonary hypertension (PH). However, treatment with CTGF Ab prevented ß-catenin signaling activation, improved alveolarization and vascular development, and attenuated PH during hyperoxia. These data indicate that CTGF-ß-catenin signaling plays a critical role in the pathogenesis of experimental BPD. CTGF antagonism may offer a novel therapeutic strategy to alleviate BPD and PH in neonates.

Comparative immunohistochemical study of multicystic dysplastic kidneys with and without obstruction.

Etiology of multicystic dysplastic kidney (MCDK) remains unknown. Not all cases are associated with obstruction. We compared by immunohistochemistry 17 cases of MCDK (10 cases with and seven without obstruction) to 17 controls and 20 fetal kidneys. TGF-ß was negative in obstructive MCDKs and positive in nonobstructive MCDK. IGF2 was overexpressed in obstructive and underexpressed in nonobstructive MCDKs. PAX2, BCL-2, and ß-catenin were expressed equally in obstructive and nonobstructive dysplasia. TGF-ß and IGF2 work by different mechanisms in obstructive and nonobstructive MCDKs, but there are no differences among PAX 2, BCL-2, and ß-catenin in obstructive versus nonobstructive dysplasia.

Long-term risk of chronic kidney disease in unilateral multicystic dysplastic kidney.

The clinical spectrum of renal dysplasia includes the non-functioning multicystic dysplastic kidney (MCDK). We report our experience of the outcome of unilateral MCDK and its contralateral kidney in 101 children with the diagnosis of MCDK from 1985 to 2009. Data collected included urine protein/creatinine ratio, estimated GFR (eGFR), blood pressure, surgical intervention, renal length and abnormalities of the contralateral kidney, and the involution rate. There was a predominance of left-sided MCDK. Diagnosis was made prenatally in 86.7%. Contralateral abnormalities included vesicoureteral reflux (16.8%), UPJ obstruction (4.1%), and megaureter (2.4%). Complete involution of MCDK occurred within 5 years in 60%. Compensatory hypertrophy of the contralateral kidney to >97% occurred in 74.1%. Nephrectomy was performed in 19.8%. There was an increased risk of chronic kidney disease (CKD) stage ≥ 2, and hypertension in those with contralateral abnormalities (p<0.0001; p<0.001 respectively). In those without contralateral abnormalities, hyperfiltration with mean eGFR of 149 ± 13 ml/min/1.73 m(2) was seen in 32% and proteinuria in 9.8%. There was a significantly inverse relationship between proteinuria and eGFR (p<0.0001). In conclusion, children with contralateral abnormalities are at risk for developing decreased kidney function, whereas a substantial number of patients with no obvious contralateral abnormalities have markers of renal injury. Therefore, systematic follow-up of all patients is recommended.

Renal glomus tumor in an adolescent: a conservative approach.

The most common renal neoplasms in the second decade of life are renal cell carcinomas and Wilms' tumors. Glomus tumors arising in the kidney are rare. We report an adolescent with a benign renal glomus tumor excised by wedge resection. Nephron-sparing surgery is the therapy of choice for children with benign renal tumors. Glomus tumor should be considered in the differential diagnosis of a renal mass in a young patient.