Clinico-genetic aspects of a pediatric non-neurofibromatosis type 1 malignant triton tumor with loss of chromosome X

Malignant triton tumor (MTT) is an aggressive peripheral nerve sheath tumor with rhabdomyoblastic differentiation. Less than 100 cases have been described, being mostly male children with type 1 neurofibromatosis. We report a 6-year-old female with MTT and no diagnostic criteria for neurofibromatosis type 1. Cytogenetic analysis showed a 46,X,-X[4]/46,XX[16] karyotype. She underwent a transfemoral amputation and chemotherapy and is free of disease 15 months after diagnosis. The few cytogenetic studies of MTT described in the literature have been inconclusive. Further cytogenetic analyses are needed to understand the role of chromosome X monosomy in the pathogenesis of this rare tumor. Pediatr Blood Cancer 2012; 59: 13201323. (C) 2012 Wiley Periodicals, Inc.

Loss of male secondary sexual structures in allopatry in the Neotropical butterfly genus Arcas (Lycaenidae: Iheclinae: Eumaeini)

Male secondary sexual characters in Lepidoptera may be present or absent in species that otherwise appear to be closely related, an observation that has led to differences of opinion over the taxonomic usefulness of these structures above the species level. An evolutionary issue raised by this debate is whether male secondary sexual characters (1) can be regained after being lost evolutionarily, (2) are not lost after being evolved, or (3) are 'switched on and off' by genes that regulate development. A second evolutionary issue is the conditions under which male secondary sexual characters might be lost or gained evolutionarily. Because these structures are thought to promote species recognition, theory predicts evolutionary losses to be most likely in allopatry; evolutionary gains to be most likely during the process of secondarily establishing sympatry or during sympatric speciation. We updated the species-level taxonomy of the brilliant emerald winged Neotropical lycaenid butterfly genus Arcas and performed an analysis of phylogenetic relations among species to assess these evolutionary issues. We morphologically detail a scent pouch on the ventral hindwing of Areas and report that six species possess the pouch with androconia, one possesses the pouch without androconia, and the remaining two species have neither pouch nor androconia. In addition, eight Areas species have a morphologically species-specific male forewing scent pad, and one lacks a scent pad. This variation appears to be the result of three evolutionary losses and no gains of male secondary sexual organs. The four Areas species lacking a scent pouch or a scent pad are allopatric with their closest phylogenetic relatives while four of five with both of these structures are sympatric. Although Arcas is a small genus, these results are significantly more extreme than predicted by chance. For taxonomy, this study provides a rationale for the evolutionary loss of male secondary sexual structures and suggests that their absence, but itself, does not indicate a lack of relationship above the species level.

Endurance exercise training increases APPL1 expression and improves insulin signaling in the hepatic tissue of diet-induced obese mice, independently of weight loss

Hepatic insulin resistance is the major contributor to fasting hyperglycemia in type 2 diabetes. The protein kinase Akt plays a central role in the suppression of gluconeogenesis involving forkhead box O1 (Foxo1) and peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1a), and in the control of glycogen synthesis involving the glycogen synthase kinase beta (GSK3 beta) in the liver. It has been demonstrated that endosomal adaptor protein APPL1 interacts with Akt and blocks the association of Akt with its endogenous inhibitor, tribbles-related protein 3 (TRB3), improving the action of insulin in the liver. Here, we demonstrated that chronic exercise increased the basal levels and insulin-induced Akt serine phosphorylation in the liver of diet-induced obese mice. Endurance training was able to increase APPL1 expression and the interaction between APPL1 and Akt. Conversely, training reduced both TRB3 expression and TRB3 and Akt association. The positive effects of exercise on insulin action are reinforced by our findings that showed that trained mice presented an increase in Foxo1 phosphorylation and Foxo1/PGC-1a association, which was accompanied by a reduction in gluconeogenic gene expressions (PEPCK and G6Pase). Finally, exercised animals demonstrated increased at basal and insulin-induced GSK3 beta phosphorylation levels and glycogen content at 24?h after the last session of exercise. Our findings demonstrate that exercise increases insulin action, at least in part, through the enhancement of APPL1 and the reduction of TRB3 expression in the liver of obese mice, independently of weight loss. J. Cell. Physiol. 227: 29172926, 2012. (C) 2011 Wiley Periodicals, Inc.

Loss of Y-chromosome does not correlate with age at onset of head and neck carcinoma: a case-control study

Loss of Y-chromosome has been correlated with older age in males. Furthermore, current evidence indicates that Y-chromosome loss also occurs in several human tumors, including head and neck carcinomas. However, the association between Y nullisomy and the occurrence of neoplasias in elderly men has not been well established. In the present study, the association between Y-chromosome loss and head and neck carcinomas was evaluated by comparison to cells from peripheral blood lymphocytes and normal mucosa of cancer-free individuals matched for age using dual-color fluorescence in situ hybridization. Twenty-one patients ranging in age from 28 to 68 years were divided into five-year groups for comparison with 16 cancer-free individuals matched for age. The medical records of all patients were examined to obtain clinical and histopathological data. None of the patients had undergone radiotherapy or chemotherapy before surgery. In all groups, the frequency of Y-chromosome loss was higher among patients than among normal reference subjects (P < 0.0001) and was not age-dependent. These data suggest that Y-chromosome loss is a tumor-specific alteration not associated with advanced age in head and neck carcinomas.

Risk factors for magnetic resonance imaging-detected patellofemoral and tibiofemoral cartilage loss during a six-month period: The Joints On Glucosamine study

Objective To assess several baseline risk factors that may predict patellofemoral and tibiofemoral cartilage loss during a 6-month period. Methods For 177 subjects with chronic knee pain, 3T magnetic resonance imaging (MRI) of both knees was performed at baseline and followup. Knees were semiquantitatively assessed, evaluating cartilage morphology, subchondral bone marrow lesions, meniscal morphology/extrusion, synovitis, and effusion. Age, sex, and body mass index (BMI), bone marrow lesions, meniscal damage/extrusion, synovitis, effusion, and prevalent cartilage damage in the same subregion were evaluated as possible risk factors for cartilage loss. Logistic regression models were applied to predict cartilage loss. Models were adjusted for age, sex, treatment, and BMI. Results Seventy-nine subregions (1.6%) showed incident or worsening cartilage damage at followup. None of the demographic risk factors was predictive of future cartilage loss. Predictors of patellofemoral cartilage loss were effusion, with an adjusted odds ratio (OR) of 3.5 (95% confidence interval [95% CI] 1.39.4), and prevalent cartilage damage in the same subregion with an adjusted OR of 4.3 (95% CI 1.314.1). Risk factors for tibiofemoral cartilage loss were baseline meniscal extrusion (adjusted OR 3.6 [95% CI 1.310.1]), prevalent bone marrow lesions (adjusted OR 4.7 [95% CI 1.119.5]), and prevalent cartilage damage (adjusted OR 15.3 [95% CI 4.947.4]). Conclusion Cartilage loss over 6 months is rare, but may be detected semiquantitatively by 3T MRI and is most commonly observed in knees with Kellgren/Lawrence grade 3. Predictors of patellofemoral cartilage loss were effusion and prevalent cartilage damage in the same subregion. Predictors of tibiofemoral cartilage loss were prevalent cartilage damage, bone marrow lesions, and meniscal extrusion.

Loss of Interleukin-10 Signaling and Infantile Inflammatory Bowel Disease: Implications for Diagnosis and Therapy

BACKGROUND & AIMS: Homozygous loss of function mutations in interleukin-10 (IL10) and interleukin-10 receptors (IL10R) cause severe infantile (very early onset) inflammatory bowel disease (IBD). Allogeneic hematopoietic stem cell transplantation (HSCT) was reported to induce sustained remission in 1 patient with IL-10R deficiency. We investigated heterogeneity among patients with very early onset IBD, its mechanisms, and the use of allogeneic HSCT to treat this disorder. METHODS: We analyzed 66 patients with early onset IBD (younger than 5 years of age) for mutations in the genes encoding IL-10, IL-10R1, and IL-10R2. IL-10R deficiency was confirmed by functional assays on patients' peripheral blood mononuclear cells (immunoblot and enzyme-linked immunosorbent assay analyses). We assessed the therapeutic effects of standardized allogeneic HSCT. RESULTS: Using a candidate gene sequencing approach, we identified 16 patients with IL-10 or IL-10R deficiency: 3 patients had mutations in IL-10, 5 had mutations in IL-10R1, and 8 had mutations in IL-10R2. Refractory colitis became manifest in all patients within the first 3 months of life and was associated with perianal disease (16 of 16 patients). Extraintestinal symptoms included folliculitis (11 of 16) and arthritis (4 of 16). Allogeneic HSCT was performed in 5 patients and induced sustained clinical remission with a median follow-up time of 2 years. In vitro experiments confirmed reconstitution of IL-10R-mediated signaling in all patients who received the transplant. CONCLUSIONS: We identified loss of function mutations in IL-10 and IL-10R in patients with very early onset IBD. These findings indicate that infantile IBD patients with perianal disease should be screened for IL-10 and IL-10R deficiency and that allogeneic HSCT can induce remission in those with IL-10R deficiency.

Disabling hearing loss prevalence in Juiz de Fora, Brazil

Data on the prevalence of disabling hearing loss (DHL) in Brazil is scarce, which impacts healthcare professionals' knowledge on the extent of the problem. Objectives: This study aimed at estimating DHL prevalence in the municipality of Juiz de Fora, Minas Gerais, to identify individual-related variables and find risk areas. Materials and Methods: This was a descriptive sectional population study held from January to October of 2009. We randomly selected 349 households with 1,050 individuals who with ages ranging between 4 days and 95 years. The data collection instruments were: WHO structured questionnaire, ENT examination and laboratory tests. Chi-square and Poisson regression models were used for analyses. Results: DHL prevalence was estimated at 5.2% (95% CI = 3.1 to 7.3) which was classified as moderate in 3.9% (95% CI = 0.001 to 0.134), severe in 0.9% (95% CI = 0.001 to 0.107) and profound in 0.4% (95% CI = 0.001 to 0.095). We found correlation between DHL and tinnitus; age over 60 years and low educational level. Conclusions: Our data obtained pointed to the need to create hearing health programs targeted to specific risk groups, promoting quality of life for hearing impaired patients.

Comparison of screening methods for conductive hearing loss identification in children: low-cost proposal

Objective To evaluate the effectiveness of two screening methods (imitanciometry screening and questionnaire) to identify children at risk for conductive hearing loss, comparing this data with complete audiologic evaluation. Methods Of 507 children aged between three and six, 111 completed all procedures. The observational methods used were: imitanciometry screening, a questionnaire to identify risk factors for hearing loss and complete audiologic evaluation. Results obtained in the first two instruments were compared with results from complete audiologic evaluation (gold standard). From these comparisons, sensitivity and specificity, accuracy, positive and negative predictive values, and odds ratio were determined for the two screening methods and for the combination of both methods. Results The two methods applied in series (questionnaire and after imitanciometry screening) showed a greater odds ratio and better correlation between sensitivity and proportion of false-positives (ROC curve). Conclusion Combining the two tests in series improved screening accuracy. This combination was the best tool for identifying children at risk for conductive hearing loss.

Polymorphisms in antithrombin and in tissue factor pathway inhibitor genes are associated with recurrent pregnancy loss

Recurrent pregnancy loss (RPL) is a multifactorial condition. The effect of antithrombin (SERPINC1), protein C (PROC), thrombomodulin (THBD) and tissue factor pathway inhibitor (TFPI) single nucleotide polymorphisms (SNPs) on the risk of RPL is thus far unknown. Our objective was to determine the association of SNPs in the above mentioned genes with RPL. We included 117 non-pregnant women with three or more consecutive losses prior to 20 weeks of pregnancy without a previous history of carrying a fetus to viability, and 264 healthy fertile non-pregnant women who had at least two term deliveries and no known pregnancy losses. The PROC (rs1799809 and rs1799808), SERPINC1 (rs2227589), THBD (rs1042579) and TFPI (rs10931292, rs8176592 and rs10153820) SNPs were analysed by Real Time PCR. Genotype frequencies for PROC 2418A > G, PROC 2405C > T, THBD 1418C > T, TFPI (T-33C and TFPI C-399T) SNPs were similar in cases and controls. The carriers of SERPINC1 786A allele (GA + AA genotypes) had an increased risk for RPL (odds ratio [OR]: 1.77, 95% confidence interval [CI]: 1.05-3.00, p=0.034) while women carrying the TFPI-287C allele (TC + CC genotypes) had a protection effect on having RPL (OR: 0.46, 95% CI: 0.26 - 0.83, p=0.009). The TCC haplotype for TFPI T-33C/TFPI T-287C/TFPI C-399T SNPs was less frequent in cases (5.7%) than in controls (11.6%) (OR: 0.45, 95% CI: 0.23 - 0.90, p=0.025). In conclusion, our data indicate that SERPINC1 786G > A variant increases the risk for RPL, while TFPI T-287C variant is protective; however, further studies are required to confirm our findings.

DXA, bioelectrical impedance, ultrasonography and biometry for the estimation of fat and lean mass in cats during weight loss

Background: Few equations have been developed in veterinary medicine compared to human medicine to predict body composition. The present study was done to evaluate the influence of weight loss on biometry (BIO), bioimpedance analysis (BIA) and ultrasonography (US) in cats, proposing equations to estimate fat (FM) and lean (LM) body mass, as compared to dual energy x-ray absorptiometry (DXA) as the referenced method. For this were used 16 gonadectomized obese cats (8 males and 8 females) in a weight loss program. DXA, BIO, BIA and US were performed in the obese state (T0; obese animals), after 10% of weight loss (T1) and after 20% of weight loss (T2). Stepwise regression was used to analyze the relationship between the dependent variables (FM, LM) determined by DXA and the independent variables obtained by BIO, BIA and US. The better models chosen were evaluated by a simple regression analysis and means predicted vs. determined by DXA were compared to verify the accuracy of the equations. Results: The independent variables determined by BIO, BIA and US that best correlated (p < 0.005) with the dependent variables (FM and LM) were BW (body weight), TC (thoracic circumference), PC (pelvic circumference), R (resistance) and SFLT (subcutaneous fat layer thickness). Using Mallows'Cp statistics, p value and r(2), 19 equations were selected (12 for FM, 7 for LM); however, only 7 equations accurately predicted FM and one LM of cats. Conclusions: The equations with two variables are better to use because they are effective and will be an alternative method to estimate body composition in the clinical routine. For estimated lean mass the equations using body weight associated with biometrics measures can be proposed. For estimated fat mass the equations using body weight associated with bioimpedance analysis can be proposed.

Lean and Fat Mass Loss in Obese Patients Before and After Roux-en-Y Gastric Bypass: A New Application for Ultrasound Technique

This study aims to evaluate the thickness of the femoral quadriceps and biceps brachii and brachialis muscles bilaterally and the adjacent subcutaneous fat in patients undergoing gastric bypass Roux-en-Y before and after surgery, using ultrasound as the diagnostic method of choice. We studied 12 patients undergoing this surgical method preoperatively and during the first, third, and sixth postoperative months. During these periods, patients were evaluated by ultrasound to determine the thickness of subcutaneous adipose tissue and muscle of the upper and lower limbs. Postoperatively, these patients showed a reduction in the thickness of the upper and lower extremities muscle and adipose tissue as compared to their preoperative values. There was a significant difference in the loss of muscle thickness in all postoperative months and in the thickness of fatty tissue in the sixth month after surgery, compared to the preoperative muscle and fatty tissue thickness. Ultrasound can be considered as the diagnostic method of choice when assessment of the fat and lean body mass is required in morbidly obese patients before and after bariatric surgery.

Vascular smooth muscle cells exhibit a progressive loss of rigidity with serial culture passaging

One drawback of in vitro cell culturing is the dedifferentiation process that cells experience. Smooth muscle cells (SMC) also change molecularly and morphologically with long term culture. The main objective of this study was to evaluate if culture passages interfere in vascular SMC mechanical behavior. SMC were obtained from five different porcine arterial beds. Optical magnetic twisting cytometry (OMTC) was used to characterize mechanically vascular SMC from different cultures in distinct passages and confocal microscopy/western blotting, to evaluate cytoskeleton and extracellular matrix proteins. We found that vascular SMC rigidity or viscoelastic complex modulus (G) decreases with progression of passages. A statistically significant negative correlation between G and passage was found in four of our five cultures studied. Phalloidin-stained SMC from higher passages exhibited lower mean signal intensity per cell (confocal microscopy) and quantitative western blotting analysis showed a decrease in collagen I content throughout passages. We concluded that vascular SMC progressively lose their stiffness with serial culture passaging. Thus, limiting the number of passages is essential for any experiment measuring viscoelastic properties of SMC in culture.

Self-reported hearing loss among elderly individuals in the city of Sao Paulo, Brazil: prevalence and associated factors (SABE Study, 2006)

This article describes the prevalence of self-reported hearing loss in an elderly population in the city of Sao Paulo, Brazil, and associated factors, based on a cross-sectional descriptive and quantitative study. The sample consisted of individuals over 65 years of age selected from census tracts in two stages, with replacement and probability proportional to the population 75 years of age or older. Statistical analysis used Stata 10 with weighted data, Rao-Scott test, and backward stepwise Poisson regression. 1,115 elders were interviewed. Prevalence of self-reported hearing loss was 30.4%, and higher levels were associated with age over 75 years, male gender, self-reported musculoskeletal conditions, dizziness, visual impairment, and difficulty using the telephone. Increased knowledge of factors associated with hearing loss would support public policies on hearing. The high prevalence found in this study underlines the importance of addressing this issue among the elderly.

Influence of Osmotic Dehydration on Ascorbic Acid Loss in Pickled Dry Peppers (Capsicum chinense)

The objective of this work was (1) to develop a dehydrated pepper with 45% humidity, determining the drying curves for pepper, with and without osmotic pre-treatment and (2) to evaluate the influence of both drying and osmotic treatment on the content ascorbic acid (vitamin C) in fresh pepper and pepper with 45% humidity. The experiments were carried out using the peppers cut in half, with and without osmotic pre-treatment, followed by drying in an oven at 70 degrees C. The results showed that the osmotic pretreatment did not influence the retention of ascorbic acid during the drying of pepper. The sensory analysis regarding the color, flavor, and texture attributes revealed that there was no difference in the acceptability.

Effect of Plastic Deformation on the Excess Loss of Electrical Steel

The interpretation of the effect of plastic deformation on the calculated excess loss component (anomalous-loss) supports the concept of loss separation. Magnetic losses and Barkhausen noise of nonoriented electrical steel sheets were measured on Epstein strips taken from a single coil of 0.8% Si nonoriented electrical steel. Sheets were extracted in the annealed condition, without any skin pass and with a grain size of 18 mu m. This material was cold rolled in order to obtain sets of samples with true strain from 2% up to 29%. X-ray diffraction was used to estimate the dislocation density. The analysis of magnetic properties was performed by Barkhausen noise measurements and also by analyzing the hysteresis loops obtained from Epstein frame measurements for different inductions and different frequencies (including the quasi-static regime for hysteresis loss measurements). These data allowed us to observe that most of the well known total loss increase with plastic deformation is due to an increase in the hysteresis loss component, while excess loss decreases to become negligible. This behavior can be explained if it is assumed that the plastic deformation lead to an increase in the number of domain walls per unit volume, thereby decreasing the excess loss. Barkhausen peak area increases with plastic deformation, reproducing results taken from samples of different silicon content.