Median ages at stages of sexual maturity and excess weight in school children

Abstract: Background: We aimed to estimate the median ages at specific stages of sexual maturity stratified by excess weight in boys and girls. Materials and method. This was a cross-sectional study made in 2007 in Florianopolis, Brazil, with 2,339 schoolchildren between 8 to 14 years of age (1,107 boys) selected at random in two steps (by region and type of school). The schoolchildren were divided into: i) those with excess weight and ii) those without excess weight, according to the WHO 2007 cut-off points for gender and age. Sexual maturity was self-evaluated by the subjects according to the Tanner sexual development stages, and utilizing median ages for the genitalia, breasts, and pubic hair stages. Results: In the boys with excess weight, precocity was observed in the stages 4 for genitals and pubic hair and 2 for pubic hair, with the values for excess and normal weight. The median ages at the beginning of puberty (stage 2–sexual development) for boys and girls in Florianopolis were 10.8 and 10.3 years, respectively. Conclusion: Excess weight is associated with lower median ages in the sexual maturity stages in boys and girls and that it should be taken into account when evaluating sexual maturity in children and adolescents.

Depletion of Langerhans cells in the tongue from patients with advanced-stage acquired immune deficiency syndrome: relation to opportunistic infections

Aims: To quantify and compare the expression of Langerhans cells (LCs) in the tongue mucosa of AIDS patients with different opportunistic infections, and from acquired immune deficiency syndrome (AIDS) and non-AIDS patients with normal tongues, using autopsy material. Methods and results: Human leucocyte antigen D-related (HLA-DR), CD1a and CD83 antibodies were used to identify and quantify LCs by immunohistochemistry in tongue tissue of 40 AIDS patients (10 with lingual candidiasis, 10 with lingual herpes, 10 with oral hairy leukoplakia and 10 with no lesions) and 23 tongues from human immunodeficiency virus (HIV)negative control patients. Quantification was performed by means of conventional morphometry in four different regions (anterior, middle, posterior and lateral) of the tongue. The results were expressed as positive cells per area of epithelium. The AIDS patients presented a lower density of CD1a(+) cells (P < 0.001), HLA-DR (P < 0.003) and CD83 (P < 0.001) in all regions of the tongue compared to the non-AIDS control group. However, no differences in any of the markers were found when AIDS patients with different opportunistic infections were compared with AIDS patients without tongue infection. Conclusions: Advanced stage AIDS patients showed a depletion of LCs in the tongue mucosa. HIV infection induces cytopathic changes in LCs, contributing to their depletion regardless of the presence of oral infections.

Naturally acquired antibodies to Plasmodium vivax blood-stage vaccine candidates (PvMSP-1(19) and PvMSP-3 alpha(359-798)) and their relationship with hematological features in malaria patients from the Brazilian Amazon

An important step when designing a vaccine is identifying the antigens that function as targets of naturally acquired antibodies. We investigated specific antibody responses against two Plasmodium vivax vaccine candidates, PvMSP-1(19) and PvMSP-3 alpha(359-798). Moreover, we assessed the relationship between these antibodies and morbidity parameters. PvMSP-1(19) was the most immunogenic antigen and the frequency of responders to this protein tended to increase in P. vivax patients with higher parasitemia. For both antigens, IgG antibody responses tended to be lower in patients who had experienced their first bout of malaria. Furthermore, anemic patients presented higher IgG antibody responses to PvMSP-3 alpha(359-798). Since the humoral response involves a number of antibodies acting simultaneously on different targets, we performed a Principal Component Analysis (PCA). Anemic patients had, on average, higher first principal component scores (IgG1/IgG2/IgG3/IgG4 anti-MSP3 alpha), which were negatively correlated with hemoglobin levels. Since antibodies against PfMSP-3 have been strongly associated with clinical protection, we cannot exclude the possibility of a dual role of PvMSP-3 specific antibodies in both immunity and pathogenesis of vivax malaria. Our results confirm the high immunogenicity of the conserved C terminus of PvMSP-1 and points to the considerable immunogenicity of polymorphic PvMSP-3 alpha(359-798) during natural infection. (C) 2012 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Lymphatic fluctuation in the parenchymal remodeling stage of acute interstitial pneumonia, organizing pneumonia, nonspecific interstitial pneumonia and idiopathic pulmonary fibrosis

Because the superficial lymphatics in the lungs are distributed in the subpleural, interlobular and peribroncovascular interstitium, lymphatic impairment may occur in the lungs of patients with idiopathic interstitial pneumonias (IIPs) and increase their severity. We investigated the distribution of lymphatics in different remodeling stages of IIPs by immunohistochemistry using the D2-40 antibody. Pulmonary tissue was obtained from 69 patients with acute interstitial pneumonia/diffuse alveolar damage (AIP/DAD, N = 24), cryptogenic organizing pneumonia/organizing pneumonia (COP/OP, N = 6), nonspecific interstitial pneumonia (NSIP/NSIP, N = 20), and idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP, N = 19). D2-40+ lymphatic in the lesions was quantitatively determined and associated with remodeling stage score. We observed an increase in the D2-40+ percent from DAD (6.66 +/- 1.11) to UIP (23.45 +/- 5.24, P = 0.008) with the advanced process of remodeling stage of the lesions. Kaplan-Meier survival curves showed a better survival for patients with higher lymphatic D2-40+ expression than 9.3%. Lymphatic impairment occurs in the lungs of IIPs and its severity increases according to remodeling stage. The results suggest that disruption of the superficial lymphatics may impair alveolar clearance, delay organ repair and cause severe disease progress mainly in patients with AIP/DAD. Therefore, lymphatic distribution may serve as a surrogate marker for the identification of patients at greatest risk for death due to IIPs.

Pre- and post-puberty physiological plasma oxytocin concentrations in male domestic cats (Felis silvestris catus)

Souza J.O.T., Andriolo A., Franci C.R. & Genaro G. 2012. Pre- and post-puberty physiological plasma oxytocin concentrations in male domestic cats (Felis silvestris catus). Pesquisa Veterinaria Brasileira 32(11):1196-1198. Programa de Pos-Graduacao em Psicobiologia, Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto, Universidade de Sao Paulo, Cx. Postal 390, Ribeirao Preto, SP 14001-970, Brazil. E-mail: gelsongenaro@hotmail.com The hormone oxytocin is released by the neuropituitary gland through stimulation of the neurons of the supraoptic and paraventricular nuclei of the hypothalamus. In order to determine the physiological concentrations of this hormone in domestic cats, blood samples were collected from 15 male animals (Felis silvestris catus) during the pre- and post-puberty periods (at four and eight months of age, respectively). Oxytocin determination was accomplished by radioimmunoassay. The average oxytocin concentrations measured in the pre- and post-puberty periods were 2.54 +/- 0.24 (mu g/dL) and 2.53 +/- 0.28 (mu g/dL), respectively, and there were no statistical differences between these measurements. Because there are few literature on the analysis of this hormone, especially in the case of male Felis silvestris catus, more studies on the influence of oxytocin on the physiology and reproduction of this species should be conducted under maintenance and situations of stress (such as transportation), and other routine events.

Different morphology, stage and treatment affect immune cell infiltration and long-term outcome in patients with non-small-cell lung carcinoma

Aims: Development of effective immune-based therapies for patients with non-small-cell lung carcinoma (NSCLC) depends on an accurate characterization of complex interactions that occur between immune cells and the tumour environment. Methods and results: Innate and adaptive immune responses were evaluated in relation to prognosis in 65 patients with surgically excised NSCLC. Immunohistochemistry and morphometry were used to determine the abundance and distribution of immune cells. We found low numbers of immune cells and levels of cytokines in the tumour environment when compared with surrounding parenchyma. Smoking was associated inversely with the adaptive immune response and directly with innate immunity. We observed a prominent adaptive immune response in squamous cell carcinomas (SCC) but greater innate immune responses in adenocarcinomas and large cell carcinomas. Cox model analysis showed a low risk of death for smoking <41 packs/year, N-0 tambour stage, squamous carcinoma, CD4(+) > 16.81% and macrophages/monocytes >4.5%. Collectively, the data indicate that in NSCLC there is not a substantive local immune cell infiltrate within the tumour. Conclusion: Although immune cell infiltration is limited in NSCLC it appears to have an impact on prognosis and this may be of relevance for new immunotherapeutic approaches.

Bone mineral density and body composition in girls with idiopathic central precocious puberty before and after treatment with a gonadotropin-releasing hormone agonist

OBJECTIVES: Idiopathic central precocious puberty and its postponement with a (gonadotropin-releasing hormone) GnRH agonist are complex conditions, the final effects of which on bone mass are difficult to define. We evaluated bone mass, body composition, and bone remodeling in two groups of girls with idiopathic central precocious puberty, namely one group that was assessed at diagnosis and a second group that was assessed three years after GnRH agonist treatment. METHODS: The precocious puberty diagnosis and precocious puberty treatment groups consisted of 12 girls matched for age and weight to corresponding control groups of 12 (CD) and 14 (CT) girls, respectively. Bone mineral density and body composition were assessed by dual X-ray absorptiometry. Lumbar spine bone mineral density was estimated after correction for bone age and the mathematical calculation of volumetric bone mineral density. CONEP: CAAE-0311.0.004.000-06. RESULTS: Lumbar spine bone mineral density was slightly increased in individuals diagnosed with precocious puberty compared with controls; however, after correction for bone age, this tendency disappeared (CD = -0.74 +/- 0.9 vs. precocious puberty diagnosis = -1.73 +/- 1.2). The bone mineral density values of girls in the precocious puberty treatment group did not differ from those observed in the CT group. CONCLUSION: There is an increase in bone mineral density in girls diagnosed with idiopathic central precocious puberty. Our data indicate that the increase in bone mineral density in girls with idiopathic central precocious puberty is insufficient to compensate for the marked advancement in bone age observed at diagnosis. GnRH agonist treatment seems to have no detrimental effect on bone mineral density.

Oocyte meiotic-stage-specific differences in spindle depolymerization in response to temperature changes monitored with polarized field microscopy and immunocytochemistry

Objective: To compare the polymerization status of mouse oocyte spindles exposed to various temperatures at various stages of meiosis. Design: Experimental animal study. Setting: University animal laboratory. Animal(s): CF1 mice. Intervention(s): Immature oocytes matured to metaphase I (MI), telophase I (TI), and metaphase II (MII) were incubated at 37 degrees C (control), room temperature (RT), or 4 degrees C for 0, 10, 30, and 60 minutes. Spindle analysis subsequently was performed using polarized field microscopy and immunocytochemistry. Spindles of TI and MII oocytes that underwent vitrification and warming were analyzed also by immunocytochemistry. Main Outcome Measure(s): Detection of polymerized meiotic spindles. Result(s): At RT, and after 60 minutes at 4 degrees C, a significant time-dependent decrease in the percentage of polymerized meiotic spindles was observed in MI and MII oocytes, but not in TI oocytes. The polymerization of TI spindles at 4 degrees C was similar to that of TI spindles at 4 degrees C that underwent vitrification and warming. Conclusion(s): Significant differences in the microtubule dynamics of MI, TI, and MII oocytes incubated at different temperatures were observed. In particular, meiotic spindles in TI oocytes exhibited less depolymerization than did metaphase spindles. (Fertil Steril (R) 2012; 97: 714-9. (C) 2012 by American Society for Reproductive Medicine.)

Chronic Conventional resistance exercise reduces blood pressure in stage 1 Hypertensive men

Moraes, MR, Bacurau, RFP, Casarini, DE, Jara, ZP, Ronchi, FA, Almeida, SS, Higa, EMS, Pudo, MA, Rosa, TS, Haro, AS, Barros, CC, Pesquero, JB, Wurtele, M, and Araujo, RC. Chronic conventional resistance exercise reduces blood pressure in stage 1 hypertensive men. J Strength Cond Res 26(4): 1122-1129, 2012-To investigate the antihypertensive effects of conventional resistance exercise (RE) on the blood pressure (BP) of hypertensive subjects, 15 middle-aged (46 +/- 3 years) hypertensive volunteers, deprived of antihypertensive medication (reaching 153 +/- 6/93 +/- 2 mmHg systolic/diastolic BP after a 6-week medication washout period) were submitted to a 12-week conventional RE training program (3 sets of 12 repetitions at 60% 1 repetition maximum, 3 times a week on nonconsecutive days). Blood pressure was measured in all phases of the study (washout, training, detraining). Additionally, the plasma levels of several vasodilators or vasoconstrictors that potentially could be involved with the effects of RE on BP were evaluated pre- and posttraining. Conventional RE significantly reduced systolic, diastolic, and mean BP, respectively, by an average of 16 (p < 0.001), 12 (p < 0.01), and 13 mm Hg (p < 0.01) to prehypertensive values. There were no significant changes of vasoactive factors from the kallikrein-kinin or renin-angiotensin systems. After the RE training program, the BP values remained stable during a 4-week detraining period. Taken together, this study shows for the first time that conventional moderate-intensity RE alone is able to reduce the BP of stage 1 hypertensive subjects free of antihypertensive medication. Moreover, the benefits of BP reduction achieved with RE training remained unchanged for up to 4 weeks without exercise.

Three time-based scale formulations for the two-stage lot sizing and scheduling in process industries

In this paper, we propose three novel mathematical models for the two-stage lot-sizing and scheduling problems present in many process industries. The problem shares a continuous or quasi-continuous production feature upstream and a discrete manufacturing feature downstream, which must be synchronized. Different time-based scale representations are discussed. The first formulation encompasses a discrete-time representation. The second one is a hybrid continuous-discrete model. The last formulation is based on a continuous-time model representation. Computational tests with state-of-the-art MIP solver show that the discrete-time representation provides better feasible solutions in short running time. On the other hand, the hybrid model achieves better solutions for longer computational times and was able to prove optimality more often. The continuous-type model is the most flexible of the three for incorporating additional operational requirements, at a cost of having the worst computational performance. Journal of the Operational Research Society (2012) 63, 1613-1630. doi:10.1057/jors.2011.159 published online 7 March 2012

Stage, Grade and Behavior of Bladder Urothelial Carcinoma Defined by the MicroRNA Expression Profile

Purpose: We identified miRNA expression profiles in urothelial carcinoma that are associated with grade, stage, and recurrence-free and disease specific survival. Materials and Methods: The expression of 14 miRNAs was evaluated by quantitative reverse transcriptase-polymerase chain reaction in surgical specimens from 30 patients with low grade, noninvasive (pTa) and 30 with high grade, invasive (pT2-3) urothelial carcinoma. Controls were normal bladder tissue from 5 patients who underwent surgical treatment for benign prostatic hyperplasia. Endogenous controls were RNU-43 and RNU-48. miRNA profiles were compared and Kaplan-Meier curves were constructed to analyze disease-free and disease specific survival. Results: miR-100 was under expressed in 100% of low grade pTa specimens (p <0.001) and miR-10a was over expressed in 73.3% (p <0.001). miR-21 and miR-205 were over expressed in high grade pT2-3 disease (p = 0.02 and <0.001, respectively). The other miRNAs were present at levels similar to those of normal bladder tissue or under expressed in each tumor group. miR-21 over expression (greater than 1.08) was related to shorter disease-free survival in patients with low grade pTa urothelial carcinoma. Higher miR-10a levels (greater than 2.30) were associated with shorter disease-free and disease specific survival in patients with high grade pT2-3 urothelial carcinoma. Conclusions: Four miRNAs were differentially expressed in the 2 urothelial carcinoma groups. miR-100 and miR-10a showed under expression and over expression, respectively, in low grade pTa tumors. miR-21 and miR-205 were over expressed in pT2-3 disease. In addition, miR-10a and miR-21 over expression was associated with shorter disease-free and disease specific survival. miRNAs could be incorporated into the urothelial carcinoma molecular pathway. These miRNAs could also serve as new diagnostic or prognostic markers and new target drugs.

Lactation stage and udder health status of Santa Ines ewes

FAPESP [2003/08582-7]

Matrix Metalloproteinase (MMP)-2 Genetic Variants Modify the Circulating MMP-2 Levels in End-Stage Kidney Disease

Background: Matrix metalloproteinases (MMPs) play important roles in the pathophysiology of renal diseases, and imbalanced MMP-2 and its endogenous inhibitor (the tissue inhibitor of metalloproteinases-2; TIMP-2) are implicated in the vascular alterations of end-stage kidney disease (ESKD) patients. We have examined whether MMP-2 gene polymorphisms and haplotypes modify MMP-2 and TIMP-2 levels in ESKD patients as well as the effects of hemodialysis on the concentrations of these biomarkers. Methods: We determined MMP-2 and TIMP-2 plasma levels by gelatin zymography and ELISA, respectively, in 98 ESKD patients and in 38 healthy controls. Genotypes for two relevant MMP-2 polymorphisms (C-T-1306 and C-T-735 in the promoter region) were determined by TaqMan (R) allele discrimination assay and real-time polymerase chain reaction. The software program PHASE 2.1 was used to estimate the haplotype frequencies. Results: We found increased plasma MMP-2 and TIMP-2 levels in ESKD patients compared to controls (p<0.05), and hemodialysis decreased MMP-2 (but not TIMP-2) levels (p<0.05). The T allele for the C-T-735 polymorphism and the C-T haplotype were associated with higher MMP-2 (but not TIMP-2) levels (p<0.05), whereas the C-T-1306 had no effects. Hemodialysis decreased MMP-2 (but not TIMP-2) levels independently of MMP-2 genotypes or haplotypes (p<0.05). Conclusions: MMP-2 genotypes or haplotypes modify MMP-2 levels in ESKD patients, and may help to identify patients with increased MMP-2 activity in plasma. Hemodialysis reduces MMP-2 levels independently of MMP-2 genetic variants. Copyright (C) 2012 S. Karger AG, Basel

The Influence of Osteoblast Differentiation Stage on Bone Formation in Autogenously Implanted Cell-Based Poly(Lactide-Co-Glycolide) and Calcium Phosphate Constructs

We tested the hypothesis that the osteoblast differentiation status of bone marrow stem cells (BMSCs) combined with a three-dimensional (3D) structure modulates bone formation when autogenously implanted. Rat BMSCs were aspirated, expanded, and seeded into a 3D composite of poly(lactide-co-glycolide) and calcium phosphate (PLGA/CaP) to produce a hybrid biomaterial. Calvarial defects were implanted with (1) scaffold without cells (SC/NC), (2) scaffold and BMSCs (SC + BMSC), (3) scaffold and osteoblasts differentiated for 7 days (SC + OB7), and (4) for 14 days (SC + OB14). After 4 weeks, there was more bone formation in groups combining scaffold and cells, SC + BMSC and SC + OB7. A nonsignificant higher amount of bone formation was observed on SC + OB14 compared with SC/NC. Additionally, more blood vessels were counted within all hybrid biomaterials, without differences among them, than into SC/NC. These findings provide evidences that the cell differentiation status affects in vivo bone formation in autogenously implanted cell-based constructs. Undifferentiated BMSCs or osteoblasts in early stage of differentiation combined with PLGA/CaP scaffold favored bone formation compared with plain scaffold and that one associated with more mature osteoblasts.

Absence of Functional LIN28B Mutations in a Large Cohort of Patients with Idiopathic Central Precocious Puberty

Aim: To investigate LIN28B gene variants in children with idiopathic central precocious puberty (CPP). Patients and Methods: We studied 178 Brazilian children with CPP (171 girls, 16.8% familial cases). A large multiethnic group (1,599 subjects; Multiethnic Cohort, MEC) was used as control. DNA analysis and biochemical in vitro studies were performed. Results: A heterozygous LIN28B variant, p. H199R, was identified in a girl who developed CPP at 5.2 years. This variant was absent in 310 Brazilian control individuals, but it was found in the same allele frequency in women from the MEC cohort, independent of the age of menarche. Functional studies revealed that when ectopically expressed in cells, the mutant protein was capable of binding pre-let-7 microRNA and inhibiting let-7 expression to the same extent as wild-type Lin28B protein. Other rare LIN28B variants (p.P173P, c.198+32_33delCT, g.9575731A>C and c.-11C>T) were identified in CPP patients and controls. Therefore, no functional mutation was identified. Conclusion: In vitro studies revealed that the rare LIN28B p.H199R variant identified in a girl with CPP does not affect the Lin28B function in the regulation of let-7 expression. Although LIN28B SNPs were associated with normal pubertal timing, rare variations in this gene do not seem to be commonly involved in the molecular pathogenesis of CPP. Copyright (C) 2012 S. Karger AG, Basel