Safety and efficacy of SARS-CoV-2 vaccination in patients with immune thrombocytopenia:A two-centre review

Multiple studies have reported immune thrombocytopenia (ITP) relapse following SARS-CoV-2 vaccination, however baseline ITP relapse rate and antibody response to vaccination are not known. Patients with ITP who received at least one of the first three SARS-CoV-2 vaccination doses were included in the study. One hundred and twenty-four patients met the inclusion criteria. Relapse rate was 4.2% following a first vaccine dose, 9.1% after a second and 2.9% after a third; baseline relapse rate was 7.6%. Ninety-four per cent of patients who received three vaccine doses developed a clinical antibody response. SARS-CoV-2 vaccination appears to be safe and effective in patients with ITP.</p

Spacial and temporal dynamics of the volume fraction of the colloidal particles inside a drying sessile drop

Using lubrication theory, drying processes of sessile colloidal droplets on a solid substrate are studied. A simple model is proposed to describe temporal dynamics both the shape of the drop and the volume fraction of the colloidal particles inside the drop. The concentration dependence of the viscosity is taken into account. It is shown that the final shapes of the drops depend on both the initial volume fraction of the colloidal particles and the capillary number. The results of our simulations are in a reasonable agreement with the published experimental data. The computations for the drops of aqueous solution of human serum albumin (HSA) are presented.Comment: Submitted to EPJE, 7 pages, 8 figure

Structural and functional stabilization of bacteriophage particles within the aqueous core of a W/O/W multiple emulsion: a potential biotherapeutic system for the inhalational treatment of bacterial pneumonia

The increase of antibiotic-resistant bacteria is growing every day, most likely associated with the indiscriminate use of these antimicrobials or even with evolutionary adaptability of bacteria to their environment. This situation brings a need to develop new alternatives to conventional antibiotics, and thus the application of strictly lytic bacteriophages has been proposed as an alternative (or complement) to the former, allowing release of the natural predators of bacteria directly where they are needed the most: the infection site. The main advantages of bacteriophages to treat infections is the maintenance of a high concentration of bacteriophage particles in the action site while any viable target bacteria still exist, coupled to the production of enzymes that hydrolyze the polymeric matrix of bacterial biofilms promoting penetration and antibacterial action. In the research effort entertained herein, the potential for protection and stabilization of strictly lytic bacteriophages with broad spectrum capable of infecting Pseudomonas aeruginosa, so as to maintain their structure and functionality, was investigated via encapsulation within the aqueous-core of lipid nanodroplets integrating a W/O/W multiple emulsion system, aiming at developing isotonic derivative solutions thereof for administration by nebulization.Project funding by FAPESP (São Paulo, Brazil; Refs. No. 2013/ 03181-6 (Project PneumoPhageKill), 2016/08884-3 (Project PneumoPhageColor) and 2016/12234-4 (Project TransAppIL)), is hereby gratefully acknowledged. This work also received support from CNPq, in the form of a Research Productivity (PQ)fellowship granted to Victor M. Balcão (Ref. No. 306113/2014-7). The authors are grateful to the LME facility at LNNano/CNPEM (Campinas, Brazil) for the use of the TEM microscope. The authors have no conflicts of interest whatsoever to declare.info:eu-repo/semantics/publishedVersio

Prior COVID-19 infection may increase risk for developing endothelial dysfunction following hematopoietic cell transplantation

Endothelial dysfunction underlies many of the major complications following hematopoietic cell transplantation (HCT), including transplant-associated thrombotic microangiopathy (TA-TMA), veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), and engraftment syndrome (ES). Emerging evidence similarly implicates endothelitis and microangiopathy in severe COVID-19-related multi-system organ dysfunction. Given the overlap in these two illness states, we hypothesize that prior COVID-19 infection may increase risk for HCT-related endotheliopathies. This retrospective, multicenter study included patients aged 0-25 years who underwent autologous or allogeneic HCT for any indication between January 1, 2020 and September 21, 2021, with close attention to those infected with COVID-19 in either the six months prior to transplant or twelve months following transplant. Incidences of TA-TMA, VOD/SOS, and ES were compared among patients with COVID-19 infection pre-HCT and post-HCT, as well as with historical controls who were never infected with SARS-CoV-2. Those who underwent HCT following COVID-19 infection displayed significantly increased rates of TA-TMA compared to those who were never infected. Additionally, our data suggests a similar trend for increased VOD/SOS and ES rates, although this did not reach statistical significance. Therefore, a history of COVID-19 infection prior to undergoing HCT may be a nonmodifiable risk factor for endothelial-related complications following HCT. Further studies are warranted to better clarify this relationship among larger cohorts and in the era of the Omicron SARS-CoV-2 variants

Structural and functional stabilization of protein entities: state-of-the-art

Within the context of biomedicine and pharmaceutical sciences, the issue of (therapeutic) protein stabilization assumes particular relevance. Stabilization of protein and protein-like molecules translates into preservation of both structure and functionality during storage and/or targeting, and such stabilization is mostly attained through establishment of a thermodynamic equilibrium with the (micro)environment. The basic thermodynamic principles that govern protein structural transitions and the interactions of the protein molecule with its (micro)environment are, therefore, tackled in a systematic fashion. Highlights are given to the major classes of (bio)therapeutic molecules, viz. enzymes, recombinant proteins, (macro)peptides, (monoclonal) antibodies and bacteriophages. Modification of the microenvironment of the biomolecule via multipoint covalent attachment onto a solid surface followed by hydrophilic polymer co-immobilization, or physical containment within nanocarriers, are some of the (latest) strategies discussed aiming at full structural and functional stabilization of said biomolecules.Financial support to Victor M. Balcao, via an Invited Research Scientist fellowship (FAPESP Ref. No. 2011/51077-8), and project funding (FAPESP Ref. No. 2013/03181-6, Project PneumoPhageKill) by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Sao Paulo, Brazil), is hereby gratefully acknowledged. The authors are also grateful to Claudio M. Barroso (BSc.), Graphic Designer at University of Sorocaba (UNISO), for computer-designing the schemes/drawings integrating this review paper

Transcription factor induction of vascular blood stem cell niches in vivo

The hematopoietic niche is a supportive microenvironment composed of distinct cell types, including specialized vascular endothelial cells that directly interact with hematopoietic stem and progenitor cells (HSPCs). The molecular factors that specify niche endothelial cells and orchestrate HSPC homeostasis remain largely unknown. Using multi-dimensional gene expression and chromatin accessibility analyses in zebrafish, we define a conserved gene expression signature and cis-regulatory landscape that are unique to sinusoidal endothelial cells in the HSPC niche. Using enhancer mutagenesis and transcription factor overexpression, we elucidate a transcriptional code that involves members of the Ets, Sox, and nuclear hormone receptor families and is sufficient to induce ectopic niche endothelial cells that associate with mesenchymal stromal cells and support the recruitment, maintenance, and division of HSPCs in vivo. These studies set forth an approach for generating synthetic HSPC niches, in vitro or in vivo, and for effective therapies to modulate the endogenous niche

Mechanisms and models of dehydration and slow freezing damage to cell membranes

University of Minnesota Ph.D. dissertation. October 2010. Major: Mechanical Engineering. Advisor: Alptekin Aksan. 1 computer file (PDF) xviii, 199 pages.Cell preservation is accomplished primarily by two methods: cryopreservation and dehydration, with the former being the standard technique used. In order to optimize and develop cell preservation protocols for cells that are difficult to preserve or whose end application is incompatible with current cell preservation protocls and to advance preservation by dehydration, a better understanding of the freeze- and dehydration-induced changes to the cell membrane is required. Despite a large body of literature on the topic, the mechanisms of damage to cells during slow freezing and dehydration are still ambiguous. The objective of this study is to investigate the mechanisms of damage to the cell membrane during slow freezing and dehydration and expand our outlook beyond the cell membrane to its underlying support, the cytoskeleton. In this study, we used several model systems to investigate slow freezing and dehydration. We used a liposome model to gather basic information on changes that can occur to a simple membrane system during freezing. This study revealed that eutectic formation was capable of dehydrating the membrane at low temperatures which may be contribute to alteration of the post-thaw membrane structure. We used a bacteria model to investigate the role of the phase transition and immediate versus slow osmotic stress on post-rehydration viability. This study revealed that going through a lyotropic membrane phase transition was detrimental to post-rehydration viability. This study also demonstrated that a rapidly applied osmotic stress was more detrimental to the structure/ organization of the membrane than gradual osmotic stress. We then subjected a model mammalian cell to both hyperosmotic stress and freeze-thaw and investigated both the membrane and cytoskeletal responses. Osmotic stress experiments suggested that alterations in membrane structure (i.e., surface defects and lipid dissolution) were directly dependent on the change in the chemical potential of water. These experiments also suggest that cell shrinkage and the resulting formation of membrane protrusions negatively affect viability upon return to isotonic conditions. It was found that membrane morphology in the dehydrated state and post-hyperosmotic viability was dependent on the stiffness of the cytoskeleton. Freeze/ thaw experiments suggested that ice-cell interaction decreases post-thaw viability. However, similar to osmotic stress experiments, cell shrinkage and cytoskeletal stiffness negatively impact post-thaw viability. We suggest the resulting membrane morphology due to cell shrinkage is also responsible for damage during freeze/ thaw. The various mechanisms discovered and the models proposed can be used in developing new protocols for cell preservation and for cell destruction (e.g. cryosurgery)