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Purpose: The aim of this narrative review is to sumarize data about the use and role of telemedicine in maternal fetal medicine (MFM)., Methods: We searched pubmed and scopus to find articles about telemedicine in MFM by using the terms telmedicine or telehealth and maternal fetal medicine., Results: Telehealth has been widely used for several medical specialties. During the coronavirus disease 2019 (COVID-19) pandemic, telehealth has gained investment and further research. Even though telemedicine in MFM has not been frequently applied, from 2020 onwards it has increased in both implementation and acceptance worldwide. The need to screen the patients in overloaded centers in a pandemic scenario required telemedicine in MFM, which has exhibited consistently good results concerning health and budget. The aim of this study was to review the telehealth programs and research focused on MFM around the world. Few studies have been applied to MFM and even fewer in developing and undeveloped countries. The majority of studies were concentrated in the USA and in Europe., Conclusion: Further research is needed, especially in non-developed countries, to comprehend the potential role of telemedicine in MFM for improving the life quality of the patients, health professionals, and to be cost-efficient., Competing Interests: Conflict of InterestNone declared., (© The Author(s) under exclusive licence to International Union for Physical and Engineering Sciences in Medicine (IUPESM) 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Introduction: Posterior urethral valve (PUV) is a congenital malformation characterized by a membranous structure located in the prostatic portion of the male posterior urethra that obstructs the urinary flow. Efforts have been made to determine the degree of impairment of fetal kidney function in this condition., Objective: This study aimed to measure the levels of urinary biomarkers of glomerular and tubular functions in fetuses with PUV and to compare with the levels of the same molecules in healthy male premature newborns., Study Design: Urine samples from 43 fetuses with PUVs were collected and compared with urine samples from 40 healthy male newborns of the same gestational age (controls). Tubular and glomerular biomarkers levels were measured in urine samples by MILLIPLEX® assay kits. Levels of the molecules were related to creatinine (Cr) measurements at same urine samples and expressed as pg/mg Cr. Results were analysed with Graphpad Prism version 7.0 and SPSS version 20.0., Results: Fetuses with PUV showed a significant reduction in urine levels of Epidermal Growth Factor (EGF), Calbindin, Osteoactivin, Molecule Renal Injury 1 (KIM-1 and Factor of trefoil 3 (TFF-3) when compared to controls. On the other hand, urine levels of cystatin C and renin were higher in PUV fetuses. The levels of molecules also differed according to urine osmolality and grade of hydronephrosis., Discussion: Some urinary excreted molecules may indicate kidney damage in several segments along the nephron, while others may exert important functions. Mechanical and immunological mechanisms related to PUV might significantly modulate the synthesis of cytokines related to glomerular and tubular physiology, leading to alterations in urinary concentrations of those molecules. These biomarkers can be used as future diagnostic and prognostic markers in clinical practice., Conclusion: Early kidney structural and functional impairment influenced the synthesis of glomerular and tubular molecules related to kidney physiological processes in fetuses with PUV., (Copyright © 2022 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Objective: Posterior urethral valve is the most common lower urinary tract obstruction in male children. A high percentage of patients with posterior urethral valve evolve to end-stage renal disease. Previous studies showed that cytokines, chemokines, and components of the renin-angiotensin system contribute to the renal damage in obstructive uropathies. The authors recently found that urine samples from fetuses with posterior urethral valve have increased levels of inflammatory molecules. The aim of this study was to measure renin-angiotensin system molecules and to investigate their correlation with previously detected inflammatory markers in the same urine samples of fetuses with posterior urethral valve., Methods: Urine samples from 24 fetuses with posterior urethral valve were collected and compared to those from 22 healthy male newborns at the same gestational age (controls). Renin-angiotensin system components levels were measured by enzyme-linked immunosorbent assay., Results: Fetuses with posterior urethral valve presented increased urinary levels of angiotensin (Ang) I, Ang-(1-7) and angiotensin-converting enzyme 2 in comparison with controls. ACE levels were significantly reduced and Ang II levels were similar in fetuses with posterior urethral valve in comparison with controls., Conclusions: Increased urinary levels of angiotensin-converting enzyme 2 and of Ang-(1-7) in fetuses with posterior urethral valve could represent a regulatory response to the intense inflammatory process triggered by posterior urethral valve., (Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

The hippocampal mossy fibers contain a substantial quantity of loosely-bound zinc in their glutamatergic presynaptic vesicles, which is released in synaptic transmission processes. Despite the large number of studies about this issue, the zinc changes related to short and long-term forms of potentiation are not totally understood. This work focus on zinc signals associated with chemically-induced mossy fiber synaptic plasticity, in particular on postsynaptic zinc signals evoked by KCl depolarization. The signals were detected using the medium affinity fluorescent zinc indicator Newport Green. The application of large concentrations of KCl, 20 mM and 60 mM, in the extracellular medium evoked zinc potentiations that decreased and remained stable after washout of the first and the second media, respectively. These short and long-lasting enhancements are considered to be due to zinc entry into postsynaptic neurons. We have also observed that following established zinc potentiation, another application of 60 mM KCl only elicited further enhancement when combined with external zinc. These facts support the idea that the KCl-evoked presynaptic depolarization causes higher zinc release leading to zinc influx into the postsynaptic region.

Purpose: To analyze the effects of aortic anatomy and endovascular aneurysm repair (EVAR) inside and outside the instructions for use (IFU) on outcomes in patients treated for ruptured abdominal aortic aneurysms (rAAA)., Methods: All 112 patients (mean age 73 years; 102 men) treated with standard EVAR for rAAA between 2000 and 2012 in 3 European centers were included in the retrospective analysis. Patients were grouped based on aortic anatomy and whether EVAR was performed inside or outside the IFU. Data on complications, secondary interventions, and mortality were extracted from the patient records. Cox regression analysis was performed to assess predictors of mortality and complications; results are presented as the hazard ratio (HR) with 95% confidence interval (CI). Survival was analyzed using the Kaplan-Meier method., Results: Of the 112 patients examined, 61 (54%) were treated inside the IFU, 43 (38%) outside the IFU, and 8 patients lacked adequate preoperative computed tomography scans for determination. Median follow-up of those surviving 30 days was 2.5 years. Mortality at 30 days was 15% (95% CI 6% to 24%) inside the IFU vs 30% (95% CI 16% to 45%) outside (p=0.087). Three-year mortality estimates were 33.8% (95% CI 20.0% to 47.5%) inside the IFU vs 56% (95% CI 39.7% to 72.2%) outside (p=0.016). At 5 years, mortality was 48% (95% CI 30% to 66%) inside the IFU vs 74% (95% CI 54% to 93%) outside (p=0.015). Graft-related complications occurred in 6% (95% CI 0% to 13%) inside the IFU and 30% (95% CI 14% to 42%) outside (p=0.015). The rate of graft-related secondary interventions was 14% (95% CI 4% to 22%) inside the IFU vs 35% (95% CI 14% to 42%) outside (p=0.072). In the multivariate analysis, neck length <15 mm (HR 8.1, 95% CI 3.0 to 21.9, p<0.001) and angulation >60° (HR 3.1, 95% CI 1.0 to 9.3, p=0.045) were independent predictors of late graft-related complications. Aneurysm neck diameter >29 mm (HR 2.5, 95% CI 1.1 to 5.9, p=0.035) was an independent predictor of overall mortality., Conclusion: Long-term mortality and complications after rEVAR are associated with aneurysm anatomy. The role of adjunct endovascular techniques and the outcome of open repair in cases with challenging anatomy warrant further study., (© The Author(s) 2016.)

The DNA damage checkpoint (DDC) is an evolutionarily conserved signaling pathway that is crucial to maintain genomic integrity. In response to DNA damage, DDC kinases are rapidly activated and phosphorylate an elaborate network of substrates involved in multiple cellular processes. An important role of the DDC response is to assemble protein complexes. However, for most of the DDC substrates, how the DDC-dependent phosphorylation modulates their network of interactions remains to be established. Here, we present a protocol for the identification of DDC-dependent protein-protein interactions based on Stable Isotope Labeling of Amino acids in Cell culture (SILAC) followed by affinity-tagged protein purification and quantitative mass spectrometry analysis. Based on a model study using Saccharomyces cerevisiae, we provide a method that can be generally applied to study the role of kinases in mediating protein-protein interactions.

In the present work, we show that oxidized silicon may be successfully used to image multivalent cation-induced DNA condensates under the Atomic Force Microscope (AFM). The images thus obtained are good enough, allowing us to distinguish between different condensate forms and to perform nanometer-sized measurements. Qualitative results previously obtained using mica as a substrate are recovered here. We additionally show that the interactions between the cation spermidine (the condensing agent) and the DNA molecules are not significantly disturbed by the silicon surface, since the phase behavior of an ensemble of DNA molecules deposited on the silicon substrate as a function of the cation concentration is very similar to that found in solution., (Copyright © 2011 Elsevier B.V. All rights reserved.)

This article describes trends in nuclear medicine in the developing world as noted by nuclear medicine professionals at the International Atomic Energy Agency (IAEA). The trends identified are based on data gathered from several sources, including information gathered through a database maintained by the IAEA; evaluation of country program frameworks of various IAEA Member States; personal interactions with representatives in the nuclear medicine field from different regions of the world; official proceedings and meeting reports of the IAEA; participation in numerous national, regional, and international conferences; discussions with the leadership of major professional societies; and relevant literature. The information presented in this article relied on both objective and subjective observations. The aims of this article were to reflect on recent developments in the specialty of nuclear medicine and to envision the directions in which it is progressing. These issues are examined in terms of dimensions of practice, growth, and educational and training needs in the field of nuclear medicine. This article will enable readers to gain perspective on the status of nuclear medicine practice, with a specific focus on the developing world, and to examine needs and trends arising from the observations.

Background: The helminth Schistosoma mansoni parasite resides in mesenteric veins where fecundated female worms lay hundred of eggs daily. Some of the egg antigens are trapped in the liver and induce a vigorous granulomatous response. High Mobility Group Box 1 (HMGB1), a nuclear factor, can also be secreted and act as a cytokine. Schistosome HMGB1 (SmHMGB1) is secreted by the eggs and stimulate the production of key cytokines involved in the pathology of schistosomiasis. Thus, understanding the mechanism of SmHMGB1 release becomes mandatory. Here, we addressed the question of how the nuclear SmHMGB1 can reach the extracellular space., Principal Findings: We showed in vitro and in vivo that CK2 phosphorylation was involved in the nucleocytoplasmic shuttling of SmHMGB1. By site-directed mutagenesis we mapped the two serine residues of SmHMGB1 that were phosphorylated by CK2. By DNA bending and supercoiling assays we showed that CK2 phosphorylation of SmHMGB1 had no effect in the DNA binding activities of the protein. We showed by electron microscopy, as well as by cell transfection and fluorescence microscopy that SmHMGB1 was present in the nucleus and cytoplasm of adult schistosomes and mammalian cells. In addition, we showed that treatments of the cells with either a phosphatase or a CK2 inhibitor were able to enhance or block, respectively, the cellular traffic of SmHMGB1. Importantly, we showed by confocal microscopy and biochemically that SmHMGB1 is significantly secreted by S. mansoni eggs of infected animals and that SmHMGB1 that were localized in the periovular schistosomotic granuloma were phosphorylated., Conclusions: We showed that secretion of SmHMGB1 is regulated by phosphorylation. Moreover, our results suggest that egg-secreted SmHMGB1 may represent a new egg antigen. Therefore, the identification of drugs that specifically target phosphorylation of SmHMGB1 might block its secretion and interfere with the pathogenesis of schistosomiasis.

The platyhelminth parasite Schistosoma mansoni, the causative agent of schistosomiasis, is a dioecious parasite with a complex life cycle that includes two different hosts and two free-living stages. Yet very little is known about the biochemical details connected to these different transitions. In the present work, results will be presented showing the most recent results in S. mansoni regarding the characterization of transcription factors and coactivators that act directly on the transcriptional machinery and those that are involved with chromatin remodeling. It is hoped that the information gathered here may contribute towards the understanding of crucial events in the parasite life cycle. Likewise, the development of new drugs that could interfere with oogenesis and sexual maturation may eventually profit from the information contained herein.

Eukaryotic LIM domain proteins contain zinc finger forming motifs rich in cysteine and histidine that enable them to interact with other proteins. A cDNA clone isolated from an adult schistosome cDNA library revealed a sequence that coded for a novel class of proteins bearing 6 LIM domains and an N-terminal PET domain, SmLIMPETin. Phylogeny reconstruction of SmLIMPETin and comparison of its sequence to invertebrate homologues and to the vertebrate four-and-a-half LIM domains protein family (FHLs), uncovered a novel LIM domain protein family, the invertebrate LIM and PET domain protein family (LIMPETin). Northern blots, RT-PCR and Western blot showed that SmLIMPETin gene was less expressed in sexually mature adult females compared to sexually immature adult females and sexually mature and immature adult males, and not expressed in schistosomula.

The transcriptional co-activator GCN5, a histone acetyltransferase (HAT), is part of large multimeric complexes that are required for chromatin remodeling and transcription activation. As in other eukaryotes, the DNA from the parasite Schistosome mansoni is organized into nucleosomes and the genome encodes components of chromatin-remodeling complexes. Using a series of synthetic peptides we determined that Lys-14 of histone H3 was acetylated by the recombinant SmGCN5-HAT domain. SmGCN5 was also able to acetylate schistosome non-histone proteins, such as the nuclear receptors SmRXR1 and SmNR1, and the co-activator SmNCoA-62. Electron microscopy revealed the presence of SmGCN5 protein in the nuclei of vitelline cells. Within the nucleus, SmGCN5 was found to be located in interchromatin granule clusters (IGCs), which are transcriptionally active structures. The data suggest that SmGCN5 is involved in transcription activation.

The parasitic helminth Schistosoma mansoni contains three HMGB proteins, HMGB1, HMGB2 and HMGB3, of primary amino acid sequences highly similar to vertebrate proteins. In this report we describe the characterization of the HMGB1 proteins and their genes from S. mansoni and Schistosoma japonicum. The deduced amino acid sequences of HMGB1 proteins from both schistosome species are identical, and comprise 176 residues. The proteins contain the two evolutionarily highly conserved HMG-box domains, A and B, exhibiting 60% similarity to mammalian HMGB1. Unlike the human HMGB1 which contains an unbroken run of 30 glutamic or aspartic residues, the SmHMGB1 or SjHMGB1 proteins possess unusually short acidic C-terminal tails (5 acidic residues interrupted by 2 serines). Southern hybridization and DNA sequencing revealed a single copy HMGB1 gene, composed of 3 exons and two introns, in S. mansoni. The exon/intron boundaries are identical to those of the human HMGB1 gene, with the exception that the second exon of the SmHMGB1 gene which is not split into two exons as in the human HMGB1 gene. RNA blot analysis revealed that the SmHMGB1 gene is constitutively expressed in similar levels both in male and female worms. The single-sized mRNA for SmHMGB1 is consistent with the size derived from the cDNA. Although DNA binding properties of SmHMGB1 (or SjHMGB1) protein seem to be similar to those previously reported with human HMGB1, i.e., preferential binding to supercoiled DNA over linear DNA, specific recognition of DNA four-way junctions, DNA-induced supercoiling in the presence of topoisomerase I, and DNA bending, we have observed two important differences relative to those observed with the human HMGB1: (i) the inability of the isolated SmHMGB1 domain A to bend DNA (as revealed by T4 ligase-mediated circularization assay), and (ii) higher DNA supercoiling and bending potential of the SmHMGB1 protein as compared to its human counterpart. The latter finding may indicate that the long acidic C-tail of human HMGB1 has much stronger repressive role on DNA bending or DNA supercoiling by topoisomerase I at physiological ionic strength than the short C-tail of the SmHMGB1 protein. Considering the important role of HMGB1 in DNA replication, transcription, recombination, and in particularly, the mediation of inflammation responses in mammalian cells, further studies on schistosome HMGB proteins may provide valuable information related to schistosomiasis, where inflammation plays a critical role in this disease.

The most studied arginine methyltransferase is the type I enzyme, which catalyzes the transfer of an S-adenosyl-L-methionine to a broad spectrum of substrates, including histones, RNA-transporting proteins, and nuclear hormone receptor coactivators. We cloned a cDNA encoding a protein arginine methyltransferase in Schistosoma mansoni (SmPRMT1). SmPRMT1 is highly homologous to the vertebrate PRMT1 enzyme. In vitro methylation assays showed that SmPRMT1 recombinant protein was able to specifically methylate histone H4. Two schistosome proteins likely to be involved in RNA metabolism, SMYB1 and SmSmD3, that display a number of RGG motifs, were strongly methylated by SmPRMT1. In vitro GST pull-down assays showed that SMYB1 and SmSmD3 physically interacted with SmPRMT1. Additional GST pull-down assay suggested the occurrence of a ternary complex including SmPRMT1, SmRXR1 nuclear receptor, and the p160 (SRC-1) nuclear receptor coactivator. Together, these data suggest a mechanism by which SmPRMT1 plays a role in nuclear receptor-mediated chromatin remodeling and RNA transactions.

Rhodnius prolixus is a blood-sucking bug whose saliva contains a family of nitric oxide-carrying proteins named nitrophorins (NPs). Saliva is injected into the host bloodstream during insect feeding. Nitric oxide is then released from NPs and will act on vascular smooth muscle, promoting vasodilation. Epithelial cells of salivary glands then undergo a massive synthesis of antihemostatics including NPs which produces saliva for the next blood meal. Here, we demonstrate the transient activation of a protein kinase in the salivary glands of R. prolixus after a blood meal. Biochemical, immunological, and pharmacological assays were used to identify this enzyme as protein kinase CK2. CK2 is activated after a blood meal and decreases to basal levels when salivary gland refilling is resumed. Inhibition of CK2 blocked [(35)S]methionine incorporation into newly synthesized salivary gland proteins in cultured tissue. Dissected salivary glands were then incubated with the heme fluorescent analog palladium (II) mesoporphyrin IX (Pd-MP) in the presence of a selective cell-permeable CK2 inhibitor, TBB (4,5,6,7-tetrabromobenzotriazole). NP synthesis was quantified based on fluorescence of the Pd-MP group bound to the NP heme pocket. TBB dramatically blocked NP synthesis. Altogether, these data are the first demonstration to show that antihemostatic synthesis in a blood-sucking arthropods is under protein phosphorylation control.

PUR-alpha is a highly conserved protein in eukaryotes belonging to the family of single-stranded DNA-binding proteins. Because PUR-alpha is a multifunctional protein that participates in several regulatory events at the level of gene transcription, it became relevant to investigate the structural features of Schistosoma mansoni PUR-alpha (SmPUR-alpha) that could be correlated to its mode of action. Using deletion constructs on a dot blot assay we mapped the domains of GST-SmPUR-alpha fusion protein involved in the interactions with DNA and RNA. Individually, the N-terminal amino acid residues 1-26 and the C-terminal residues 196-276 of GST-SmPUR-alpha which did not contain nucleic acid-binding domains, did not bind ssDNA or RNA. In contrast, domains encompassing the N-terminal and Class I and C-terminal plus Class I exhibited the highest binding affinity. Seemingly, the latter (GST-SmPUR-alpha 174-276) played a major role in nucleic acid interaction as judged by affinity alone. Other combinations of the deletion constructs displayed either intermediary or no binding affinity to the DNA or RNA probes. Gel shift competition assay showed that GST-SmPUR-alpha bound to ssDNA with higher affinity than to RNA. Because SmPUR-alpha contains two putative phosphorylation sites the protein was tested as a substrate to casein kinase II. GST-SmPUR-alpha could be phosphorylated in vitro by casein kinase II at both, the N- and C-terminus of the protein. The multifunctional nature of SmPUR-alpha was demonstrated by experiments measuring the physical interaction between SmPUR-alpha and the transcription factor SMYB1. This was determined in vivo (yeast two hybrid) and in vitro (GST-pull down). Furthermore, we showed that SmPUR-alpha and SMYB1 acted synergistically to bind preferentially to pyrimidine-rich sequences.