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Introduction: Fetal growth restriction may be the consequence of maternal, fetal, or placental factors. The insulin-like growth factors (IGFs) are major determinants of fetal growth, and are expressed in the mother, fetus and placenta in most species. Previously we reported higher placental protein content of IGF-I, IGF-IR, and AKT in small (SGA) compared with those from appropriate for gestational age (AGA) placentas. The protein Klotho, has been reported in placenta and may regulate IGF-I activity. In this study we determined Klotho gene expression and protein immunostaining in term (T-SGA y T-AGA) and preterm (PT-SGA y PT-AGA) human placentas. In addition, we assessed the effect of Klotho on the IGF-IR and AKT activation induced by IGF-I.Methods: Placentas (n = 1 17) from 32 T-SGA (birth weight (BW) = −1.74 ± 0.08 SDS), 37 T-AGA (BW = 0.12 ± 0.12 SDS), 20 PT-SGA (BW = −2.08 ± 0.14 SDS), and 28 PT-AGA (BW = −0.43 ± 0.13 SDS) newborns were collected. mRNA expression by RT-PCR in the chorionic (CP) and basal (BP) plates of the placentas, and the presence of Klotho was evaluated by immunohistochemistry (integral optical density, IOD). In addition, we developed placental explants that were incubated with IGF-I in the presence or absence of Klotho.Results: We found a lower mRNA expression and protein immunoreactivity of Klotho in the CP of SGA (term and preterm) compared with AGA placentas. We also observed a significant reduction in IGF-IR tyrosine activation induced by IGF-I 10 nM when preincubated with 2.0 nM of Klotho (2.4 ± 0.5 arbitrary units vs. 1.3 ± 0.3 AU), and similar results we observed on AKT and ERK42/44 activation.Conclusion: We describe for the first time that Klotho mRNA and protein varies according to fetal growth and gestational age. In addition, Klotho appears to down-regulate the activation induced by IGF-I on IGF-IR and AKT, suggesting that Klotho may be regulating IGF-I activity in human placentas according to intrauterine fetal growth.

IntroductionThe human placenta expresses the IGF-I and IGF-IR proteins and their intracellular signal components (IRS-1, AKT and mTOR). The aim of this study was to assess the IGF-IR content and activation of downstream signaling molecules in placentas from newborns who were classified by gestational age and birth weight. We studied placentas from 25 term appropriate (T-AGA), 26 term small (T-SGA), 22 preterm AGA (PT-AGA), and 20 preterm SGA (PT-SGA) newborns. The total and phosphorylated IGF-IR, IRS-1, AKT, and mTOR contents were determined by Western Blot and normalized by actin or with their respective total content. The effect of IGF-I was determined by stimulating placental explants with recombinant IGF-I 10-8 mol/L for 15, 30, and 60 minutes.ResultsThe IGF-IR content was higher in T-SGA compared to T-AGA placentas, and the IRS-1 content was higher in PT-placentas compared with their respective T-placentas. The effect of IGF-I on the phosphorylated forms of IGF-IR was increased in T-SGA (150%) and PT-SGA (300%) compared with their respective AGA placentas. In addition, AKT serine phosphorylation was higher in PT-SGA compared to PT-AGA and T-SGA placentas (90% and 390% respectively).ConclusionThe higher protein content and response to IGF-I of IGF-IR, IRS-1, and AKT observed in SGA placentas may represent a compensatory mechanism in response to fetal growth restriction.

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Rhinosporidiosis is a chronic mucosal infection caused by Rhinosporidium seeberi, an aquatic protistan parasite. It presents as nasal or ocular polypoidal or vascularized masses. It is endemic in tropical and subtropical areas, especially in South Asia; R. seeberi´s endemicity in the Americas is often overlooked. The objective of this study was to describe the demographic and clinical characteristics of patients with rhinosporidiosis in the Americas, its management, and patient outcomes. This study is a systematic review of cases of human rhinosporidiosis in the Americas reported in the literature from 1896 to February 28, 2019. This review screened 1,994 reports, of which 115 were eligible for further analysis. The selected reports described 286 cases of human rhinosporidiosis between 1896 and 2019. Cases were diagnosed in Brazil (32.2%), Colombia (24.4%), Paraguay (12.6%), and the United States (11.9%). The majority of the cases (91%) occurred in geographic areas with altitudes < 1,000 m above sea level and in areas with median temperatures ≥ 25°C (67.3%). Most of the patients presented nasal (65%) and ocular involvement (35%). Surgical treatment was provided for 99.6% of patients, but 19.8% of them recurred. This review describes the under-recognized geographic distribution and clinical presentation of rhinosporidiosis in the Americas and highlights clinical differences to cases in Asia, specifically in reference to a higher prevalence of ocular disease and higher relapse rates.

During human pregnancy, the trophoblast develops as the fetal compartment, while in bidirectional communication with the maternal decidua. The trophoblast is responsible for the adequate implantation of the embryo, supply of nutrients and environmental protection of the fetus along the progress of pregnancy. To perform these functions trophoblast cells, undergo a complex and finely tuned differentiation into specialized groups of cells, in a process regulated by several hormones, growth factors and cytokines. Abnormalities in trophoblast function result in several pregnancy complications. In this review, we focus our attention on two growth factors with pivotal roles during human pregnancy. The Insulin-like growth factor (IGF) family and the Transforming growth factor (TGF-β) axis are important regulators of the proliferation, differentiation, apoptosis, migration and invasion of human trophoblasts. We summarize what is described in the literature on how these factors and their receptors are expressed on the different subsets of trophoblasts, the signaling pathways that transduce their corresponding actions and functional biological effects. We describe the associations that have been found between these growth factors and the group of pathologies known as Gestational Trophoblastic Diseases (GTD).

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Concrete Encased Steel (CES) structural system consisting of steel and fiber reinforced concrete (FRC) is a new proposed composite structural system. The aim of this research program is to evaluate the deformability under seismic actions of the CES columns with encased-steel of H-shaped section. In existing studies by the authors the influence of the axial force ratio, the H-shaped steel ratio and the shear span ratio on the deformation capacity were presented. Also a formulation for the evaluation of the column deformation capacity was proposed. In this study the influence of the concrete fiber contents ratio (percentage of fiber volume to concrete volume), and the flange width of H-shaped steel on the deformation capacity is examined Using the above five parameters, a new formulation was proposed and its validity was verified by comparing it with the test results in this paper.