Impact of monotherapy on HIV-1 reservoir, immune activation, and co-infection with Epstein-Barr virus

Abstract Objectives Although monotherapy (mART) effectiveness in maintaining viral suppression and CD4 cell count has been extensively examined in HIV-1-infected patients, its impact on HIV-1 reservoir, immune activation, microbial translocation and co-infection with Epstein-Barr Virus (EBV) is unclear. Methods This retrospective study involved 32 patients who switched to mART; patients were studied at baseline, 48 and 96 weeks after mART initiation. Thirty-two patients who continued combined antiretroviral therapy (cART) over the same period of time were included in the study. Markers of HIV-1 reservoir (HIV-1 DNA and intracellular HIV-1 RNA) were quantified by real-time PCR. Markers of T-(CD3(+)CD8(+)CD38(+)) and B-(CD19(+)CD80/86(+) and CD19(+)CD10-CD21(low)CD27(+)) cell activation were evaluated by flow cytometry. Plasma levels of microbial translocation markers were quantified by real-time PCR (16S ribosomal DNA and mitochondrial [mt] DNA) or by ELISA (LPS and sCD14). EBV was typed and quantified by multiplex real-time PCR. Results At baseline, no differences were found between mART and cART groups. Three (10%) mART-treated patients had a virological failure vs none in the cART group. Levels of HIV-1 DNA, intracellular HIV-1 RNA and EBV-DNA remained stable in the mART group, while decreased significantly in the cART group. Percentages of T-and B-activated cells significantly increased in the mART-treated patients, while remained at low levels in the cART-treated ones (p = 0.014 and p<0.001, respectively). Notably, levels of mtDNA remained stable in the cART group, but significantly rose in the mART one (p<0.001). Conclusions Long-term mART is associated with higher levels of T-and B-cell activation and, conversely to cART, does not reduce the size of HIV-1 reservoir and EBV co-infection

Influence of Indomethacin on Steroid Metabolism: Endocrine Disruption and Confounding Effects in Urinary Steroid Profiling of Anti-Doping Analyses

Anabolic androgenic steroids (AAS) are prohibited as doping substances in sports by the World Anti-Doping Agency. Concentrations and concentration ratios of endogenous AAS (steroid profile markers) in urine samples collected from athletes are used to detect their administration. Certain (non-prohibited) drugs have been shown to influence the steroid profile and thereby sophisticate anti-doping analysis. It was shown in vitro that the non-steroidal anti-inflammatory drug (NSAID) indomethacin inhibits selected steroid-biotransformations catalyzed by the aldo-keto reductase (AKR) 1C3, which plays a key role in the endogenous steroid metabolism. Kinetic parameters for the indomethacin-mediated inhibition of the AKR1C3 catalyzed reduction in etiocholanolone were determined in vitro using two comparing methods. As NSAIDs are very frequently used (not only) by athletes, the inhibitory impact of indomethacin intake on the steroid metabolism was evaluated, and steroid profile alterations were detected in vivo (one male and one female volunteer). Significant differences between samples collected before, during or after the intake of indomethacin for selected steroid profile markers were observed. The presented results are of relevance for the interpretation of results from doping control analysis. Additionally, the administration of NSAIDs should be carefully reconsidered due to their potential as endocrine disruptors

Genetic variation for the duration of pre-anthesis development in durum wheat and its interaction with vernalization treatment and photoperiod

A recombinant inbred durum wheat population was grown under three contrasting regimes: long days following vernalization (LDV), long days without vernalization (LD), and short days following vernalization (SDV). The length of several pre-anthesis stages and the number of leaves and the phyllochron were measured. Different groups of genes were involved in determining the phenology in the three treatments, as demonstrated by a quantitative trait locus (QTL) analysis. The length of the period required to reach the terminal spikelet stage was correlated with the time to anthesis only in the case of LDV- and LD-grown plants where the timing of anthesis depended on the final leaf number. However, for SDV-grown plants, anthesis date was more dependent on the length of the period between the terminal spikelet stage and anthesis and was independent of leaf number. The involvement of the phyllochron in determining the duration of pre-anthesis development was also treatment-dependent. QTL mapping of the various flowering time associated traits uncovered some novel loci (such as those associated with the phyllochron), in addition to confirming the presence of several well-established loci

Assessment of Poly(ADP-ribose) Polymerase1 (PARP1) expression and activity in cells purified from blood and milk of dairy cattle

Poly(ADP-ribosyl)ation (PAR) is a post-translational protein modification catalysed by enzyme member of the poly(ADP-ribose) polymerases (PARPs) family. The activation of several PARPs is triggered by DNA strand breakage and the main PARP enzyme involved in this process is PARP1. Besides its involvement in DNA repair, PARP1 is involved in several cellular processes including transcription, epigenetics, chromatin re-modelling as well as in the maintenance of genomic stability. Moreover, several studies in human and animal models showed PARP1 activation in various inflammatory disorders. The aims of the study were (1) to characterize PARP1 expression in bovine peripheral blood mononuclear cells (PBMC) and (2) to evaluate PAR levels as a potential inflammatory marker in cells isolated from blood and milk samples following different types of infection, including mastitis. Our results show that (i) bovine PBMC express PARP1; (ii) lymphocytes exhibit higher expression of PARP1 than monocytes; (iii) PARP1 and PAR levels were higher in circulating PBMCs of infected cows; (iv) PAR levels were higher in cells isolated from milk with higher Somatic Cell Counts (SCC > 100,000 cells/mL) than in cells from milk with low SCCs. In conclusion, these findings suggest that PARP1 is activated during mastitis, which may prove to be a useful biomarker of mastitis

New insights into the significance of PARP-1 activation: flow cytometric detection of poly(ADP-ribose) as marker of bovine intramammary infection

Bovine intramammary infections are common diseases affecting dairy cattle worldwide and represent a major focus of veterinary research due to financial losses and food safety concerns. The identification of new biomarkers of intramammary infection, useful for monitoring dairy cows’ health and wellness verification, represents a key advancement having potential beneficial effects on public health. In vitro experiments, using bovine peripheral blood mononuclear cells (PBMC) stimulated with the bacterial endotoxin lipopolysaccharide (LPS) allowed to perform a flow cytometric assay to evaluate in vivo poly-ADP-ribose (PAR) levels. Results showed a significant increase of PAR after 1h of treatment, which is consistent with the involvement of PARP activity in the inflammatory response. This study investigated PARP-1 activation in leukocyte subpopulations from bovine milk samples during udder infection. A flow cytometric assay was therefore performed to evaluate the PAR content on milk leukocytes subsets of cows with and without intramammary infection (IMI). Results showed that milk lymphocytes and macrophages isolated from cows with IMI had a significant increase of PAR content compared to uninfected samples. These results suggest mastitis as a new model for the study of the role of PARP in zoonotic inflammatory diseases, thereby opening new horizons for the "One Health" perspective connecting animal and human health

Unilateral condylar hyperplasia recurrence after orthognathic surgery: a case report

Introduction: Unilateral Condylar Hyperplasia (UCH) is an uncommon condition resulting in facial asymmetry and malocclusion. At the time of diagnosis, an accurate evaluation of condylar activity through bone SPECT is necessary to determine the most appropriate surgical treatment. The Authors present a case of a UCH recurrence after orthognathic surgery in order to discuss about the clinical role of condylar SPECT in UCH therapeutic management. Case report: A 60-years old female patient was referred to the Department of Maxillo-Facial Surgery of Sapienza University of Rome for a relapse of mandibular laterodeviation. At the age of 24, she underwent orthognathic surgery after a diagnosis of UCH without condylar SPECT evaluation. As part of our clinical routine, condylar SPECT was performed and a significant difference in radiotracer uptake (20%) was found between the left condylar region and the contralateral one. She underwent high condilectomy and Bilateral Mandibular Sagittal Osteotomy. She had no evidence of recurrence till today. Discussion: Optimal surgical management of UCH is still controversial. In the diagnostic phase of UCH, a functional evaluation of condylar growth status by bone SPECT is an essential step to avoid long-term recurrence of mandibular asymmetry. On the basis of condylar metabolic activity, UCH can be classified in an active phase or a stationary phase. Clinical and functional evaluation of patients with mandibular asymmetry should be standardized in order to plan the most appropriate surgical and orthodontic treatment

Thermodynamic Behavior of Polyalcohols and Speciation Studies in the Presence of Divalent Metal Cations

The acid–base properties and complexing ability of some biologically relevant polyalcohols (erythritol, sorbitol, maltol, and ethylmaltol) toward bivalent metal cations have been determined by pote..

Mechanical properties of the most common European woods: a literature review

Wood is an orthotropic material used since ancient time. A literature research about the mechanical properties of density, fracture toughness, modulus of elasticity, and Poisson’s ratio has been done to have a broader view on the subject. The publications relating to the topic were found through the two search engines Scopus and Google Scholar that have yielded several papers, including articles and book sections. In general, there is no standardization on the method of analysis carried out on wood, underlining the great difficulty in studying this complex material. The parameter of density has a great variability and needs a deeper investigation; fracture toughness is not always available in literature, not even in the different directions of the wood sample. Interesting is the modulus of elasticity, which provides a correlation with density, especially in longitudinal section but, again, it needs to be studied in detail. The parameter of Poisson’s ratio is provided as single values in three different directions, but mainly for softwood. All the parameters require a more in-depth study for both softwood and hardwood. Furthermore, the type of analysis, whether experimental or modelling, needs to be standardized to have more comparable results

Insights into the Structure of Dot@Rod and Dot@Octapod CdSe@CdS Heterostructures

CdSe@CdS dot@rods with diameter around 6 nm and length of either 20, 27, or 30 nm and dot@octapods with pod diameters of ?15 nm and lengths of ?50 nm were investigated by X-ray absorption spectroscopy. These heterostructures are prepared by seed-mediated routes, where the structure, composition, and morphology of the CdSe nanocrystals used as a seed play key roles in directing the growth of the second semiconducting domain. The local structural environment of all the elements in the CdSe@CdS heterostructures was investigated at the Cd, S, and Se K-edges by taking advantage of the selectivity of X-ray absorption spectroscopy, and was compared to pure reference compounds. We found that the structural features of dot@rods are independent of the size of the rods. These structures can be described as made of a CdSe dot and a CdS rod, both in the wurtzite phase with a high crystallinity of both the core and the rod. This result supports the effectiveness of high temperature colloidal synthesis in promoting the formation of core@shell nanocrystals with very low defectivity. On the other hand, data on the CdSe@CdS with octapod morphology suggest the occurrence of a core composed of a CdSe cubic sphalerite phase with eight pods made of CdS wurtzite phase. Our findings are compared to current models proposed for the design of functional heterostructures with controlled nanoarchitecture

Electrospun Structures Made of a Hydrolyzed Keratin-Based Biomaterial for Development of in vitro Tissue Models

The aim of this study is the analysis and characterization of a hydrolyzed keratin-based biomaterial and its processing using electrospinning technology to develop in vitro tissue models. This biomaterial, extracted from poultry feathers, was mixed with type A porcine gelatin and cross-linked with γ-glycidyloxy-propyl-trimethoxy-silane (GPTMS) to be casted initially in the form of film and characterized in terms of swelling, contact angle, mechanical properties, and surface charge density. After these chemical-physical characterizations, electrospun nanofibers structures were manufactured and their mechanical properties were evaluated. Finally, cell response was analyzed by testing the efficacy of keratin-based structures in sustaining cell vitality and proliferation over 4 days of human epithelial, rat neuronal and human primary skin fibroblast cells